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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Psychol.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Psychology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Psychol.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">1664-1078</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
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<article-meta>
<article-id pub-id-type="doi">10.3389/fpsyg.2026.1762816</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Therapeutic modulation of empathy: pharmacological, neurostimulation, and behavioral approaches</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Niazi</surname>
<given-names>Sarfaraz K.</given-names>
</name>
<xref ref-type="aff" rid="aff1"/>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1766576"/>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role>
</contrib>
</contrib-group>
<aff id="aff1"><institution>University of Illinois</institution>, <city>Chicago</city>, <state>IL</state>, <country country="us">United States</country></aff>
<author-notes>
<corresp id="c001"><label>&#x002A;</label>Correspondence: Sarfaraz K. Niazi, <email xlink:href="mailto:niazi@niazi.com">niazi@niazi.com</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-03-04">
<day>04</day>
<month>03</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year>
</pub-date>
<volume>17</volume>
<elocation-id>1762816</elocation-id>
<history>
<date date-type="received">
<day>08</day>
<month>12</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>23</day>
<month>01</month>
<year>2026</year>
</date>
<date date-type="accepted">
<day>26</day>
<month>01</month>
<year>2026</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2026 Niazi.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Niazi</copyright-holder>
<license>
<ali:license_ref start_date="2026-03-04">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<p>Empathy is a core neurobiological capacity that enables humans to perceive, understand, and respond to others&#x2019; experiences, yet its deliberate modulation as a therapeutic target is still in its early stages of scientific development. This manuscript presents a hybrid narrative&#x2013;scoping review synthesizing evidence across pharmacological, neurostimulation, and behavioral approaches aimed at enhancing or restoring empathic functioning. A structured literature search covering 2014&#x2013;2025 was conducted across PubMed, PsycINFO, Web of Science, and Scopus, with emphasis on post-2020 research. Evidence was organized using an author-defined tiered synthesis framework, intended to support integrative interpretation rather than formal evidence grading. Across modalities, empathy can be modulated, but observed effect sizes are typically small to moderate, heterogeneous, and frequently transient. Pharmacological approaches such as intranasal oxytocin demonstrate modest, context-dependent effects (<italic>d</italic>&#x202F;=&#x202F;0.24, 95% CI: 0.02&#x2013;0.46), while MDMA-assisted therapy yields larger but highly context-restricted benefits (<italic>d</italic>&#x202F;&#x2248;&#x202F;0.91) in trauma-focused psychotherapy and faces unresolved regulatory barriers. Neurostimulation techniques, including transcranial magnetic stimulation (<italic>d</italic>&#x202F;&#x2248;&#x202F;0.18&#x2013;0.20), provide causal insights into empathy-related circuits but show limited durability of behavioral effects. Behavioral interventions&#x2014;particularly mindfulness-based programs (<italic>d</italic>&#x202F;=&#x202F;0.37, 95% CI: 0.16&#x2013;0.58 for programs &#x003E;24&#x202F;h) and compassion-focused programs&#x2014;exhibit the greatest scalability and sustainability. Overall, empathy represents a scientifically promising yet clinically constrained therapeutic target. Reliable translation will require larger trials, standardized and ecologically valid outcome measures, and careful integration of neurobiological and psychosocial frameworks.</p>
</abstract>
<kwd-group>
<kwd>empathy</kwd>
<kwd>ethics</kwd>
<kwd>mindfulness</kwd>
<kwd>neuromodulation</kwd>
<kwd>neurostimulation</kwd>
<kwd>oxytocin</kwd>
<kwd>therapeutic intervention</kwd>
<kwd>virtual reality</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was not received for this work and/or its publication.</funding-statement>
</funding-group>
<counts>
<fig-count count="3"/>
<table-count count="7"/>
<equation-count count="0"/>
<ref-count count="105"/>
<page-count count="15"/>
<word-count count="10822"/>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Neuropsychology</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1">
<label>1</label>
<title>Introduction</title>
<p>Empathy&#x2014;the capacity to perceive, understand, and respond to the emotions and perspectives of others&#x2014;is fundamental to human social functioning and underpins cooperation, caregiving, moral reasoning, and social cohesion (<xref ref-type="bibr" rid="ref26">Decety et al., 2016</xref>; <xref ref-type="bibr" rid="ref85">Singer and Klimecki, 2014</xref>). Over the past two decades, advances in affective neuroscience, neuroimaging, and social cognition have clarified the neural circuits, neurochemical systems, and developmental processes that support empathic behavior (<xref ref-type="bibr" rid="ref41">Kogler et al., 2020</xref>; <xref ref-type="bibr" rid="ref91">Tian et al., 2025</xref>). Recent integrative syntheses further demonstrate that empathy-related neural systems can be modulated by pharmacological, neurostimulation, and behavioral interventions, although translational effect sizes remain modest and context dependent (<xref ref-type="bibr" rid="ref1">Abellaneda-P&#x00E9;rez et al., 2024</xref>; <xref ref-type="bibr" rid="ref10">Brooker et al., 2024</xref>). These advances have stimulated increasing interest in whether empathy can be deliberately modulated for therapeutic, educational, or societal benefit.</p>
<p>Despite this growing interest, translational progress has been limited. Many interventions demonstrate statistically significant effects under laboratory conditions but yield small effect sizes, short-lived changes, or limited generalization to real-world social behavior (<xref ref-type="bibr" rid="ref33">Holleman et al., 2020</xref>; <xref ref-type="bibr" rid="ref49">Lu and Lau, 2025</xref>). Early optimism surrounding pharmacological modulation&#x2014;particularly intranasal oxytocin&#x2014;has been tempered by replication failures, strong contextual moderation, and population-specific effects (<xref ref-type="bibr" rid="ref6">Bakermans-Kranenburg and van IJzendoorn, 2013</xref>; <xref ref-type="bibr" rid="ref88">Stark et al., 2023</xref>). Similar constraints affect neurostimulation and technologically mediated behavioral approaches. These limitations underscore the need for integrative evaluation of empathy-modulation strategies and realistic expectations regarding clinical applicability.</p>
<sec id="sec2">
<label>1.1</label>
<title>Empathy as a multicomponent construct</title>
<p>Empathy is not a unitary phenomenon but comprises interacting yet dissociable components that rely on partially distinct neural substrates (<xref ref-type="bibr" rid="ref85">Singer and Klimecki, 2014</xref>; <xref ref-type="bibr" rid="ref41">Kogler et al., 2020</xref>). Affective empathy refers to the automatic sharing or resonance with another individual&#x2019;s emotional state and is supported by limbic and paralimbic structures, including the anterior insula, anterior cingulate cortex, amygdala, and somatosensory cortices (<xref ref-type="bibr" rid="ref2">Allen et al., 2017</xref>; <xref ref-type="bibr" rid="ref65">Paradiso et al., 2021</xref>). These regions integrate interoceptive signals with externally perceived emotional cues, generating subjective feeling states that support empathic concern.</p>
<p>In contrast, cognitive empathy, often termed perspective-taking or mentalizing, involves inferential processes that enable individuals to represent and reason about others&#x2019; mental states. Cognitive empathy depends on prefrontal&#x2013;temporal networks, particularly the right temporoparietal junction (rTPJ), the medial prefrontal cortex, the superior temporal sulcus, and the temporal poles (<xref ref-type="bibr" rid="ref17">Chou and Chen, 2021</xref>; <xref ref-type="bibr" rid="ref37">Jiang et al., 2022</xref>). While affective and cognitive empathy interact dynamically in real-world social behavior, they can be selectively impaired or enhanced and are differentially sensitive to intervention modalities.</p>
<p>This neurobiological distinction has major implications for the development of interventions. Pharmacological and neurostimulation approaches show differential effects on affective versus cognitive empathy components, and behavioral interventions often target motivational, regulatory, and cognitive processes differentially. Understanding these separations is crucial for designing selective, mechanism-informed therapeutic strategies that match intervention modality to the specific empathic deficit requiring remediation.</p>
</sec>
<sec id="sec3">
<label>1.2</label>
<title>Clinical and societal significance</title>
<p>Alterations in empathic functioning contribute to functional impairment across a broad range of psychiatric and neurodevelopmental conditions. Autism spectrum conditions are often associated with difficulties in cognitive empathy and social reciprocity, whereas psychopathy is characterized by relatively preserved cognitive empathy alongside reduced affective empathy (<xref ref-type="bibr" rid="ref72">Rinaldi et al., 2021</xref>). Borderline personality disorder presents with empathy dysregulation, and schizophrenia often involves mentalizing impairments alongside negative symptoms. These clinical associations have motivated interest in targeted empathy-enhancing interventions (<xref ref-type="bibr" rid="ref61">Moudatsou et al., 2020</xref>).</p>
<p>Beyond psychiatric and neurodevelopmental disorders, empathy plays a central role in healthcare delivery, where higher clinician empathy is consistently associated with improved therapeutic alliance, increased patient satisfaction, better adherence, and improved outcomes (<xref ref-type="bibr" rid="ref63">Nembhard et al., 2023</xref>; <xref ref-type="bibr" rid="ref3">Ara&#x00FA;jo et al., 2025</xref>). Empathy-focused educational and behavioral interventions have therefore been increasingly adopted in medical and allied health training programs, with systematic reviews demonstrating moderate but reliable improvements in empathic skills (<xref ref-type="bibr" rid="ref3">Ara&#x00FA;jo et al., 2025</xref>; <xref ref-type="bibr" rid="ref54">Martins et al., 2025</xref>). Educational systems similarly acknowledge empathy as a fundamental social&#x2013;emotional competency associated with mental health, academic engagement, and prosocial behavior (<xref ref-type="bibr" rid="ref21">Cipriano et al., 2023</xref>). These findings have stimulated interest in scalable interventions that augment empathic capacity within both professional and general populations.</p>
</sec>
<sec id="sec4">
<label>1.3</label>
<title>Methodological challenges</title>
<p>Despite extensive research activity, the science of empathy-modulation encounters ongoing methodological challenges. Most investigations depend on self-report questionnaires or brief laboratory tasks that inadequately capture the dynamic, context-dependent nature of social interactions in real-world settings (<xref ref-type="bibr" rid="ref48">Lima and Os&#x00F3;rio, 2021</xref>). The heterogeneity of measurement approaches hampers comparability across studies and may exaggerate apparent effect sizes. Furthermore, individual differences&#x2014;including genetic variation, sex, age, cultural background, and baseline empathy&#x2014;contribute significant variability in responses to interventions (<xref ref-type="bibr" rid="ref15">Chander et al., 2022</xref>; <xref ref-type="bibr" rid="ref28">Ferguson et al., 2024</xref>).</p>
<p>Moreover, improvements observed in controlled experimental settings often fail to translate into sustained prosocial behavior in naturalistic environments, raising concerns about ecological validity and long-term clinical utility (<xref ref-type="bibr" rid="ref33">Holleman et al., 2020</xref>; <xref ref-type="bibr" rid="ref99">Winter et al., 2020</xref>). These limitations necessitate cautious interpretation of reported effects and emphasize the need for more robust translational frameworks.</p>
</sec>
<sec id="sec5">
<label>1.4</label>
<title>Scope and objectives</title>
<p>This review synthesizes evidence from pharmacological, neurostimulation, and behavioral approaches pertaining to the modulation of empathy. Rather than providing prescriptive clinical guidelines, the objectives are to: (i) compile current evidence through a transparent, integrative framework; (ii) assess the magnitude, durability, and generalizability of reported effects; (iii) elucidate translational limitations and ethical considerations; and (iv) delineate priorities for future research. By contextualizing empathy modulation within its neurobiological, psychological, and sociocultural dimensions, this review endeavors to offer a balanced evaluation of current knowledge, existing uncertainties, and the prerequisites for responsible clinical application.</p>
</sec>
</sec>
<sec id="sec6">
<label>2</label>
<title>Review design and methods</title>
<sec id="sec7">
<label>2.1</label>
<title>Review type clarification</title>
<p>The present synthesis incorporates evidence from large-scale randomized trials, mechanistic neuroimaging studies, and translational safety guidelines to contextualize emerging empathy-modulation technologies (<xref ref-type="bibr" rid="ref52">Martin et al., 2024</xref>; <xref ref-type="bibr" rid="ref62">Murphy et al., 2025</xref>). This manuscript is a hybrid narrative&#x2013;scoping review. While a structured literature search and explicit inclusion criteria are presented to enhance transparency and breadth, the primary goal is conceptual integration and translational synthesis, not exhaustive systematic review or formal evidence grading. Accordingly, established grading systems such as PRISMA or GRADE were not applied, as the intent is not to develop guidelines but to conduct critical synthesis across heterogeneous intervention modalities.</p>
</sec>
<sec id="sec8">
<label>2.2</label>
<title>Literature search strategy</title>
<p>A comprehensive search was systematically conducted within PubMed, PsycINFO, Web of Science, and Scopus databases for scholarly articles published between January 2014 and March 2025. Search strategies incorporated combinations of keywords such as empathy, empathic, modulation, intervention, oxytocin, MDMA, neurostimulation, transcranial magnetic stimulation, transcranial direct current stimulation, mindfulness, compassion, and virtual reality. The reference lists of major meta-analyses, systematic reviews, and high-impact trials were meticulously screened to identify additional pertinent publications. Emphasis was placed on large-scale randomized controlled trials, registered meta-analyses and systematic reviews, studies utilizing neuroimaging techniques or established neural biomarkers, and research with explicit operational definitions of empathy constructs.</p>
</sec>
<sec id="sec9">
<label>2.3</label>
<title>Inclusion and exclusion criteria</title>
<p>Included studies were peer-reviewed human investigations or systematic reviews that explicitly measured affective empathy, cognitive empathy, or closely related constructs such as compassion or empathic concern. Animal studies were consulted solely to contextualize neurobiological mechanisms and were not used to infer clinical effect sizes. Single-case reports, non-peer-reviewed sources, conference abstracts, and studies lacking empathy-specific outcomes were excluded.</p>
</sec>
<sec id="sec10">
<label>2.4</label>
<title>Tiered evidence synthesis framework</title>
<p>To facilitate integrative interpretation across diverse literatures, evidence was organized using an author-defined three-tier synthesis framework, applied solely as an interpretive heuristic:</p>
<disp-quote>
<p>Tier 1: Meta-analyses or randomized controlled trials with &#x2265;500 participants.</p>
<p>Tier 2: Moderate-sized trials (100&#x2013;499 participants) and mechanistic human studies.</p>
<p>Tier 3: Emerging, exploratory, or proof-of-concept research (&#x003C;100 participants).</p>
</disp-quote>
<p>The &#x2265;500-participant threshold for Tier 1 was selected to reduce small-study bias, enhance stability of effect-size estimates, and support cautious translational inference. This framework does not constitute formal evidence grading and is used only for synthesis and contextual guidance, not for prescriptive recommendations (<xref ref-type="table" rid="tab1">Table 1</xref>).</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Tiered evidence synthesis framework (author-defined).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Tier</th>
<th align="left" valign="top">Criteria</th>
<th align="left" valign="top">Typical study types</th>
<th align="left" valign="top">Purpose in this review</th>
<th align="left" valign="top">Representative references</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Tier 1</td>
<td align="left" valign="top">&#x2265;500 participants in aggregate</td>
<td align="left" valign="top">Meta-analyses; large randomized controlled trials</td>
<td align="left" valign="top">Support cautious translational interpretation and comparative evaluation across modalities</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref34">Hu et al. (2022)</xref>, <xref ref-type="bibr" rid="ref88">Stark et al. (2023)</xref>, and <xref ref-type="bibr" rid="ref21">Cipriano et al. (2023)</xref></td>
</tr>
<tr>
<td align="left" valign="top">Tier 2</td>
<td align="left" valign="top">100&#x2013;499 participants</td>
<td align="left" valign="top">Moderate-sized RCTs; mechanistic human studies</td>
<td align="left" valign="top">Elucidate mechanisms and boundary conditions of effects</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref5">Bahji et al. (2021)</xref> and <xref ref-type="bibr" rid="ref66">Paulus and Meinken (2022)</xref></td>
</tr>
<tr>
<td align="left" valign="top">Tier 3</td>
<td align="left" valign="top">&#x003C;100 participants or exploratory designs</td>
<td align="left" valign="top">Pilot studies; proof-of-concept trials; emerging technologies</td>
<td align="left" valign="top">Hypothesis generation and identification of future research directions</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref45">Legon et al. (2024)</xref> and <xref ref-type="bibr" rid="ref95">Violante et al. (2023)</xref></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>This tiered framework is an author-defined synthesis heuristic, not a formal evidence-grading system (e.g., GRADE or PRISMA). The &#x2265;500-participant threshold for Tier 1 was selected to reduce small-study bias and enhance stability of effect-size estimates. Tiers are used solely for integrative synthesis and translational context, not for prescriptive clinical recommendations.</p>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
<sec id="sec11">
<label>3</label>
<title>Neural architecture and mechanistic foundations of empathy</title>
<p>Empathy arises from distributed neural systems that integrate affective resonance, interoception, perspective-taking, motivational salience, and social prediction. Converging evidence from neuroimaging, lesion studies, and neuromodulation demonstrates that empathic processes are supported by partially dissociable yet dynamically interacting circuits, providing a mechanistic basis for selective modulation by pharmacological, neurostimulation, and behavioral interventions (<xref ref-type="bibr" rid="ref85">Singer and Klimecki, 2014</xref>; <xref ref-type="bibr" rid="ref41">Kogler et al., 2020</xref>; <xref ref-type="bibr" rid="ref65">Paradiso et al., 2021</xref>; <xref ref-type="bibr" rid="ref10">Brooker et al., 2024</xref>). Animal and human mechanistic studies demonstrate that empathic processing is supported by conserved neural circuits across species, providing a biological rationale for translational intervention strategies (<xref ref-type="bibr" rid="ref10">Brooker et al., 2024</xref>; <xref ref-type="bibr" rid="ref24">Cox et al., 2022</xref>; <xref ref-type="bibr" rid="ref42">Kuroda et al., 2024</xref>). Developmental neuroimaging studies further indicate that empathy-related circuitry undergoes prolonged maturation and remains plastic across the lifespan, with dopaminergic and mesolimbic pathways playing a modulatory role (<xref ref-type="bibr" rid="ref47">Liang et al., 2025</xref>).</p>
<sec id="sec12">
<label>3.1</label>
<title>Affective empathy: limbic and paralimbic circuits</title>
<p>Affective empathy involves the rapid and largely automatic sharing of another individual&#x2019;s emotional state. Functional neuroimaging consistently implicates the anterior insula and anterior cingulate cortex as core hubs supporting affective resonance, emotional salience, and motivational readiness to respond to others&#x2019; distress (<xref ref-type="bibr" rid="ref86">Singer et al., 2004</xref>; <xref ref-type="bibr" rid="ref2">Allen et al., 2017</xref>; <xref ref-type="bibr" rid="ref74">Rolls, 2019</xref>). The anterior insula integrates interoceptive signals with externally perceived emotional cues, generating subjective feeling states that underlie empathic concern (<xref ref-type="bibr" rid="ref25">Craig, 2009</xref>; <xref ref-type="bibr" rid="ref2">Allen et al., 2017</xref>). Recent neuroimaging evidence using intracranial recordings demonstrates that the insula uniquely exhibits factorized coding of emotion and agency, allowing cross-person generalization of emotional states&#x2014;a computational property essential for empathic transfer (<xref ref-type="bibr" rid="ref32">Haynes et al., 2025</xref>).</p>
<p>The anterior cingulate cortex contributes to the motivational and action-oriented aspects of empathy, linking emotional salience to behavioral responses through dense connectivity with limbic and reward-related structures (<xref ref-type="bibr" rid="ref74">Rolls, 2019</xref>). The amygdala modulates threat detection and emotional learning, shaping empathic responses based on contextual relevance and prior experience (<xref ref-type="bibr" rid="ref51">Marsh et al., 2021</xref>). Together, these regions form a limbic&#x2013;paralimbic network that supports emotional contagion and empathic arousal.</p>
<p>Neurochemical systems modulate affective empathy within these circuits. Oxytocinergic signaling influences salience attribution and affiliative motivation by modulating amygdala&#x2013;insula connectivity, while serotonergic systems regulate emotional responsiveness and affective tone (<xref ref-type="bibr" rid="ref83">Shamay-Tsoory and Abu-Akel, 2016</xref>; <xref ref-type="bibr" rid="ref51">Marsh et al., 2021</xref>). These mechanisms help explain why pharmacological interventions often produce context-dependent effects rather than uniform empathy enhancement.</p>
</sec>
<sec id="sec13">
<label>3.2</label>
<title>Cognitive empathy: prefrontal&#x2013;temporal networks</title>
<p>Cognitive empathy, often operationalized as perspective-taking or theory of mind, depends on higher-order inferential processes that allow individuals to represent others&#x2019; beliefs, intentions, and emotions. The right temporoparietal junction (rTPJ) is consistently identified as a central node in this network, supporting self&#x2013;other distinction and mental state attribution (<xref ref-type="bibr" rid="ref79">Saxe and Kanwisher, 2003</xref>; <xref ref-type="bibr" rid="ref17">Chou and Chen, 2021</xref>). Disruption of rTPJ activity using transcranial magnetic stimulation selectively alters moral judgment and reduces sensitivity to others&#x2019; intentions, providing causal evidence for its role in cognitive empathy (<xref ref-type="bibr" rid="ref17">Chou and Chen, 2021</xref>; <xref ref-type="bibr" rid="ref37">Jiang et al., 2022</xref>).</p>
<p>The medial prefrontal cortex supports integration of contextual information, trait inference, and social evaluation, while the superior temporal sulcus contributes to the processing of biological motion and socially relevant cues (<xref ref-type="bibr" rid="ref41">Kogler et al., 2020</xref>; <xref ref-type="bibr" rid="ref91">Tian et al., 2025</xref>; <xref ref-type="bibr" rid="ref47">Liang et al., 2025</xref>). These regions interact dynamically during complex social reasoning tasks, enabling flexible perspective-taking.</p>
<p>Unlike affective empathy, cognitive empathy is less strongly linked to immediate emotional arousal and more amenable to deliberate training and cognitive strategies. This distinction helps explain why neurostimulation and behavioral interventions more reliably influence cognitive than affective components of empathy.</p>
</sec>
<sec id="sec14">
<label>3.3</label>
<title>Developmental, individual, and cultural modulators</title>
<p>Empathy-related neural systems are shaped by development, experience, and sociocultural context. Longitudinal studies indicate that empathic processing undergoes protracted maturation from adolescence into older adulthood, with age-related changes in prefrontal&#x2013;temporal connectivity influencing cognitive empathy capacity (<xref ref-type="bibr" rid="ref28">Ferguson et al., 2024</xref>; <xref ref-type="bibr" rid="ref42">Kuroda et al., 2024</xref>). Sex differences in empathic responding have been reported, with females on average showing higher affective empathy and greater limbic responsivity, though effect sizes are modest and context-dependent (<xref ref-type="bibr" rid="ref19">Christov-Moore et al., 2014</xref>).</p>
<p>Genetic variation further moderates empathic responsiveness. Polymorphisms in the oxytocin receptor gene (e.g., rs53576) have been associated with individual differences in empathy and social sensitivity, though effect sizes are small and replication across populations has been inconsistent (<xref ref-type="bibr" rid="ref6">Bakermans-Kranenburg and van IJzendoorn, 2013</xref>; <xref ref-type="bibr" rid="ref15">Chander et al., 2022</xref>). Cultural norms and socialization practices also shape empathic expression, influencing both baseline empathy and responsiveness to interventions (<xref ref-type="bibr" rid="ref27">Eichbaum et al., 2023</xref>; <xref ref-type="bibr" rid="ref36">Jami et al., 2024</xref>) (<xref ref-type="fig" rid="fig1">Figure 1</xref> and <xref ref-type="table" rid="tab2">Table 2</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Neural architecture of empathy: integrated circuitry and intervention targets. This figure presents a conceptual synthesis derived from the empirical literature, not an anatomical atlas or primary neuroimaging result. <bold>(A)</bold> Depicts the limbic-affective empathy system, showing the anterior insula as the central hub that integrates interoceptive signals with emotional perception inputs, with bidirectional connectivity to the amygdala for salience processing and to hypothalamic nuclei for autonomic regulation. <bold>(B)</bold> Illustrates the prefrontal-temporal cognitive empathy network, centered on the right temporoparietal junction (rTPJ), with connections to the medial prefrontal cortex for self-other distinction and mental-state inference. <bold>(C)</bold> Presents a sagittal brain view with color-coded regions indicating primary intervention targets: blue regions denote optimal targets for transcranial magnetic stimulation and transcranial direct current stimulation (superficial cortical structures including rTPJ and dlPFC); green regions indicate emerging targets for low-intensity focused ultrasound and temporal interference stimulation (deeper structures including anterior insula and ACC); and purple regions highlight structures primarily modulated through pharmacological approaches. <bold>(D)</bold> Provides a neurochemical overlay showing the distribution of oxytocinergic, serotonergic, and dopaminergic receptor densities relevant to empathy modulation. The figure is intended to support integrative interpretation and does not imply precise anatomical boundaries or clinical efficacy.</p>
</caption>
<graphic xlink:href="fpsyg-17-1762816-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Four labeled diagrams illustrate empathy-related brain systems. Panel A shows the Limbic-Affective Empathy System with colored nodes for AI, ACC, SS, AMY, and HYP, and mentions affective resonance, emotional salience, and autonomic regulation. Panel B presents the Prefrontal-Temporal Cognitive Empathy Network with nodes for rTPJ, mPFC, TP, and STS, emphasizing perspective-taking, mental state attribution, and self-other distinction. Panel C depicts intervention targets grouped by modality, distinguishing superficial cortex, deep structures, and subcortical regions with color-coded labels. Panel D illustrates major neurochemical systems, indicating oxytocin for social bonding, serotonin for emotional regulation, and dopamine for reward or motivation.</alt-text>
</graphic>
</fig>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Neural targets for empathy modulation.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">
<bold>Empathy component</bold>
</th>
<th align="left" valign="top">
<bold>Primary neural targets</bold>
</th>
<th align="left" valign="top">
<bold>Neurochemical systems</bold>
</th>
<th align="left" valign="top">
<bold>Interventions most likely to modulate</bold>
</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Affective resonance</td>
<td align="left" valign="top">Anterior insula, ACC, amygdala</td>
<td align="left" valign="top">Oxytocin, serotonin (5-HT1A)</td>
<td align="left" valign="top">LIFU, intranasal oxytocin, mindfulness training</td>
</tr>
<tr>
<td align="left" valign="top">Cognitive perspective-taking</td>
<td align="left" valign="top">rTPJ, mPFC, STS</td>
<td align="left" valign="top">Dopamine (mesocortical)</td>
<td align="left" valign="top">tDCS/TMS over rTPJ, VR perspective-taking, compassion training</td>
</tr>
<tr>
<td align="left" valign="top">Prosocial motivation</td>
<td align="left" valign="top">Nucleus accumbens, VTA</td>
<td align="left" valign="top">Dopamine, serotonin (NAc)</td>
<td align="left" valign="top">MDMA-assisted therapy, reward-based behavioral paradigms</td>
</tr>
<tr>
<td align="left" valign="top">Affective regulation</td>
<td align="left" valign="top">vmPFC, dlPFC, ACC</td>
<td align="left" valign="top">Serotonin, GABA</td>
<td align="left" valign="top">Mindfulness, compassion-based therapy, neurofeedback</td>
</tr>
<tr>
<td align="left" valign="top">Empathic accuracy</td>
<td align="left" valign="top">rTPJ, AI, temporal pole</td>
<td align="left" valign="top">Oxytocin (context-dependent)</td>
<td align="left" valign="top">Social skills training, VR simulation, tDCS</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>ACC&#x202F;=&#x202F;anterior cingulate cortex; rTPJ&#x202F;=&#x202F;right temporoparietal junction; mPFC&#x202F;=&#x202F;medial prefrontal cortex; STS&#x202F;=&#x202F;superior temporal sulcus; VTA&#x202F;=&#x202F;ventral tegmental area; NAc&#x202F;=&#x202F;nucleus accumbens; vmPFC&#x202F;=&#x202F;ventromedial prefrontal cortex; dlPFC&#x202F;=&#x202F;dorsolateral prefrontal cortex; AI&#x202F;=&#x202F;anterior insula; LIFU&#x202F;=&#x202F;low-intensity focused ultrasound; tDCS&#x202F;=&#x202F;transcranial direct current stimulation; TMS&#x202F;=&#x202F;transcranial magnetic stimulation; VR&#x202F;=&#x202F;virtual reality.</p>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
<sec id="sec15">
<label>4</label>
<title>Pharmacological modulation of empathy</title>
<p>Pharmacological approaches to empathy modulation target neurochemical systems involved in social salience, emotional resonance, and motivational processing. While these interventions provide important mechanistic insights, translational outcomes have been constrained by modest effect sizes, strong contextual dependence, and limited durability. This section evaluates the most extensively studied pharmacological agents using the tiered synthesis framework described above. Recent systematic and mechanistic reviews emphasize that pharmacological modulation of empathy produces small-to-moderate effects that are highly context dependent, with limited durability outside structured therapeutic settings (<xref ref-type="bibr" rid="ref60">Modak et al., 2024</xref>; <xref ref-type="bibr" rid="ref78">Saccenti et al., 2024</xref>).</p>
<sec id="sec16">
<label>4.1</label>
<title>Oxytocin: small effects with substantial moderation</title>
<p>Intranasal oxytocin has been the most intensively investigated pharmacological candidate for empathy enhancement, motivated by its established role in social bonding, attachment, and affiliative behavior (<xref ref-type="bibr" rid="ref83">Shamay-Tsoory and Abu-Akel, 2016</xref>; <xref ref-type="bibr" rid="ref55">Matsushita and Nishiki, 2025</xref>; <xref ref-type="bibr" rid="ref104">Yuan et al., 2025</xref>). Early small-sample studies reported increases in emotion recognition, trust, and empathic concern, generating substantial enthusiasm for oxytocin as a potential &#x201C;pro-social&#x201D; agent.</p>
<p>However, subsequent large-scale meta-analyses have substantially tempered these expectations. A comprehensive meta-analytic review encompassing more than 1,100 participants found that intranasal oxytocin produces small effects on empathy-related outcomes, with a pooled effect size of approximately <italic>d</italic>&#x202F;=&#x202F;0.24 (95% CI: 0.02&#x2013;0.46), and wide confidence intervals indicating substantial heterogeneity (<xref ref-type="bibr" rid="ref88">Stark et al., 2023</xref>). Importantly, publication-bias&#x2013;corrected estimates were markedly smaller than those reported earlier, suggesting inflated effect sizes in underpowered studies.</p>
<p>Oxytocin effects are highly context-dependent. Experimental work demonstrates that oxytocin can enhance empathy and cooperation toward in-group members while simultaneously increasing defensive or exclusionary responses toward perceived out-groups (<xref ref-type="bibr" rid="ref51">Marsh et al., 2021</xref>). These findings align with the social salience hypothesis, which posits that oxytocin amplifies the perceived relevance of social cues rather than uniformly increasing prosociality (<xref ref-type="bibr" rid="ref83">Shamay-Tsoory and Abu-Akel, 2016</xref>). Genetic moderators further complicate interpretation: polymorphisms in the oxytocin receptor gene (e.g., rs53576) have been associated with differential responsiveness, though effect sizes are small and replication across ethnic and cultural groups has been inconsistent (<xref ref-type="bibr" rid="ref6">Bakermans-Kranenburg and van IJzendoorn, 2013</xref>; <xref ref-type="bibr" rid="ref15">Chander et al., 2022</xref>).</p>
<p>Taken together, Tier 1 evidence indicates that oxytocin does not reliably produce durable or generalized empathy enhancement and is unlikely to serve as a standalone therapeutic intervention.</p>
</sec>
<sec id="sec17">
<label>4.2</label>
<title>MDMA-assisted therapy: large but context-restricted effects</title>
<p>MDMA (3,4-methylenedioxymethamphetamine) produces robust acute empathogenic effects characterized by increased emotional openness, affiliative motivation, and perceived social connectedness (<xref ref-type="bibr" rid="ref71">Rein et al., 2024</xref>). Unlike oxytocin, MDMA exerts its effects primarily through potent serotonin release, with secondary effects on dopamine and norepinephrine signaling, and indirect activation of oxytocinergic pathways (<xref ref-type="bibr" rid="ref93">Vaslavski et al., 2025</xref>). A landmark 2024 study demonstrated that MDMA enhances empathy-like behaviors specifically via serotonin release in the nucleus accumbens, with direct nucleus accumbens infusion alone sufficient to reproduce systemic empathogenic effects (<xref ref-type="bibr" rid="ref71">Rein et al., 2024</xref>).</p>
<p>Tier 1 evidence from large randomized controlled trials demonstrates that MDMA-assisted psychotherapy yields large effect sizes for symptom reduction in post-traumatic stress disorder, with pooled estimates approaching d&#x202F;&#x2248;&#x202F;0.91 (<xref ref-type="bibr" rid="ref58">Mitchell et al., 2021</xref>, <xref ref-type="bibr" rid="ref59">2023</xref>). Phase 3 clinical trials demonstrated significant reductions in PTSD symptoms, with 67&#x2013;71% of participants no longer meeting diagnostic criteria compared to 32&#x2013;47% in placebo groups. These effects are widely interpreted as reflecting facilitation of therapeutic engagement, emotional processing, and trust within a structured psychotherapeutic context.</p>
<p>Despite these promising results, MDMA&#x2019;s translational scope is highly constrained. Benefits appear tightly coupled to the therapeutic setting and do not generalize to unsupervised contexts. In August 2024, the U.S. Food and Drug Administration declined approval of MDMA-assisted therapy, citing concerns related to functional unblinding, therapist expectancy effects, durability of benefit, and safety oversight (<xref ref-type="bibr" rid="ref70">Reardon, 2024</xref>; <xref ref-type="bibr" rid="ref100">Wolfgang et al., 2025</xref>). These concerns underscore that MDMA&#x2019;s empathogenic effects, while robust, do not equate to generalized or sustained empathy enhancement and cannot currently be extrapolated to broader clinical or enhancement applications.</p>
</sec>
<sec id="sec18">
<label>4.3</label>
<title>Psilocybin and other serotonergic psychedelics</title>
<p>Classic serotonergic psychedelics, particularly psilocybin, have emerged as candidates for modulating emotional and social processing. Psilocybin primarily acts as a 5-HT2A receptor agonist, producing alterations in affective processing, self-referential cognition, and social connectedness (<xref ref-type="bibr" rid="ref38">Jungwirth et al., 2025</xref>).</p>
<p>A randomized, placebo-controlled trial in patients with major depressive disorder demonstrated that psilocybin administration led to significant increases in emotional empathy, particularly toward positively valenced stimuli, with effects persisting for several weeks post-treatment (<xref ref-type="bibr" rid="ref38">Jungwirth et al., 2025</xref>). Notably, cognitive empathy was largely unaffected, suggesting selective modulation of affective components. While these findings are promising, sample sizes remain modest, and empathy outcomes are secondary endpoints. Accordingly, psilocybin currently qualifies as Tier 2 evidence for empathy modulation.</p>
</sec>
<sec id="sec19">
<label>4.4</label>
<title>Serotonergic antidepressants: paradoxical effects</title>
<p>In contrast to psychedelic-assisted interventions, conventional serotonergic antidepressants illustrate the complexity of neurochemical modulation of empathy. Contrary to assumptions that depression impairs empathy, longitudinal neuroimaging studies demonstrate that antidepressant treatment&#x2014;rather than depression itself&#x2014;leads to reductions in behavioral and neural responses to pain empathy. After 3&#x202F;months of antidepressant therapy, patients showed significant decreases in both affective empathy and activity in brain regions associated with empathy for pain (<xref ref-type="bibr" rid="ref77">R&#x00FC;tgen et al., 2019</xref>).</p>
<p>Clinical evidence indicates that 40&#x2013;60% of individuals taking SSRI antidepressants experience &#x201C;SSRI-induced indifference&#x201D; or &#x201C;emotional blunting,&#x201D; characterized by feeling emotionally detached with reduced sympathy and empathy (<xref ref-type="bibr" rid="ref50">Ma et al., 2021</xref>; <xref ref-type="bibr" rid="ref18">Christensen et al., 2022</xref>). This paradoxical effect suggests that while SSRIs effectively treat depression, they may simultaneously reduce empathic responding through mechanisms affecting reinforcement learning and reward sensitivity (<xref ref-type="bibr" rid="ref43">Langley et al., 2023</xref>). SSRIs, therefore, cannot be considered empathy-enhancing; instead, they illustrate the fragility of empathy circuits to serotonergic modulation and the importance of understanding neurochemical specificity in intervention development (<xref ref-type="table" rid="tab3">Table 3</xref>).</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Pharmacological interventions and reported effects on empathy.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Intervention</th>
<th align="left" valign="top">Primary mechanism</th>
<th align="left" valign="top">Empathy component affected</th>
<th align="left" valign="top">Reported effect size</th>
<th align="left" valign="top">Evidence tier</th>
<th align="left" valign="top">Key references</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Intranasal oxytocin</td>
<td align="left" valign="top">Oxytocin receptor modulation; social salience</td>
<td align="left" valign="top">Affective empathy (context-dependent)</td>
<td align="left" valign="top"><italic>d</italic>&#x202F;=&#x202F;0.24 (95% CI: 0.02&#x2013;0.46)</td>
<td align="left" valign="top">Tier 1</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref6">Bakermans-Kranenburg and van IJzendoorn (2013)</xref> and <xref ref-type="bibr" rid="ref88">Stark et al., 2023</xref></td>
</tr>
<tr>
<td align="left" valign="top">MDMA-assisted therapy</td>
<td align="left" valign="top">Serotonin release; social reward enhancement</td>
<td align="left" valign="top">Affective empathy; affiliative motivation</td>
<td align="left" valign="top"><italic>d</italic>&#x202F;&#x2248;&#x202F;0.91 (large, context-restricted)</td>
<td align="left" valign="top">Tier 1</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref58">Mitchell et al. (2021</xref>, <xref ref-type="bibr" rid="ref59">2023)</xref> and <xref ref-type="bibr" rid="ref71">Rein et al. (2024)</xref></td>
</tr>
<tr>
<td align="left" valign="top">Psilocybin</td>
<td align="left" valign="top">5-HT2A agonism; affective processing</td>
<td align="left" valign="top">Emotional empathy (selective)</td>
<td align="left" valign="top">Moderate (secondary outcomes)</td>
<td align="left" valign="top">Tier 2</td>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref38">Jungwirth et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left" valign="top">SSRIs</td>
<td align="left" valign="top">Serotonin reuptake inhibition</td>
<td align="left" valign="top">Affective empathy (often reduced)</td>
<td align="left" valign="top">Negative or blunting effects</td>
<td align="left" valign="top">Tier 1&#x2013;2</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref77">R&#x00FC;tgen et al. (2019)</xref>, <xref ref-type="bibr" rid="ref50">Ma et al. (2021)</xref>, and <xref ref-type="bibr" rid="ref18">Christensen et al. (2022)</xref></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>Effect sizes reflect pooled or representative estimates from meta-analyses or large trials where available. The tier designation follows the author-defined synthesis framework and is intended solely for integrative interpretation, not for prescriptive guidance. SSRI&#x202F;=&#x202F;selective serotonin reuptake inhibitor.</p>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
<sec id="sec20">
<label>5</label>
<title>Neurostimulation approaches to empathy modulation</title>
<p>Neurostimulation techniques enable causal manipulation of neural circuits implicated in empathic processing. Compared with pharmacological interventions, neurostimulation provides greater spatial specificity but is constrained by modest effect sizes, substantial interindividual variability, and limited durability of behavioral effects. This section evaluates established noninvasive techniques alongside emerging deep neuromodulation approaches. Consensus safety and efficacy reviews indicate that noninvasive neurostimulation methods provide valuable causal insights into empathy-related circuits but are not yet suitable as standalone clinical interventions (<xref ref-type="bibr" rid="ref52">Martin et al., 2024</xref>; <xref ref-type="bibr" rid="ref62">Murphy et al., 2025</xref>).</p>
<sec id="sec21">
<label>5.1</label>
<title>Transcranial magnetic stimulation (TMS)</title>
<p>Transcranial magnetic stimulation modulates cortical excitability through focal magnetic pulses and has been widely used to investigate the causal role of empathy-related brain regions. Meta-analytic evidence from 22 studies indicates that repetitive TMS applied to empathy-relevant cortical targets produces small but statistically significant effects on empathy-related outcomes, with pooled effect sizes around d&#x202F;&#x2248;&#x202F;0.18&#x2013;0.20 (<xref ref-type="bibr" rid="ref102">Yang et al., 2018</xref>). Effects are most consistently observed for cognitive empathy, particularly when stimulating the right temporoparietal junction (rTPJ).</p>
<p>Experimental disruption of rTPJ activity using TMS alters moral judgment and reduces sensitivity to others&#x2019; intentions, providing causal evidence for its role in perspective-taking and mental state attribution (<xref ref-type="bibr" rid="ref17">Chou and Chen, 2021</xref>; <xref ref-type="bibr" rid="ref37">Jiang et al., 2022</xref>). Recent neurophysiological studies confirm that low-frequency (1&#x202F;Hz) TMS over the rTPJ during empathy induction increases withdrawal of parasympathetic nervous system activity, providing enhanced evidence for the temporoparietal junction&#x2019;s causal role in empathic responding (<xref ref-type="bibr" rid="ref57">Miller et al., 2020</xref>).</p>
<p>Despite these insights, the translational utility of TMS remains limited. Effects typically persist for minutes to an hour post-stimulation, and repeated-session protocols have yielded inconsistent behavioral outcomes. The 2021 International Federation of Clinical Neurophysiology safety guidelines confirm the TMS safety profile with extremely rare seizure incidence (&#x003C;0.1% in clinical populations), providing enhanced confidence for clinical applications (<xref ref-type="bibr" rid="ref76">Rossi et al., 2021</xref>). However, TMS&#x2019;s inability to reach deep limbic structures limits its impact on affective empathy. Given these time constraints, TMS for empathy enhancement currently serves specialized research and clinical functions rather than as a standalone therapeutic intervention.</p>
</sec>
<sec id="sec22">
<label>5.2</label>
<title>Transcranial direct current stimulation (tDCS)</title>
<p>Transcranial direct current stimulation applies weak electrical currents to modulate cortical excitability. Compared with TMS, tDCS is less spatially precise but more portable and scalable. A systematic review and meta-analysis of randomized controlled trials reported small, statistically significant effects of tDCS on empathy-related measures, with anodal stimulation over the rTPJ preferentially enhancing cognitive empathy in laboratory tasks (<xref ref-type="bibr" rid="ref5">Bahji et al., 2021</xref>).</p>
<p>Contemporary research confirms that anodal tDCS over the right temporoparietal junction enhances prosocial learning by affecting cognitive empathy processes, with participants receiving active stimulation (<italic>n</italic>&#x202F;=&#x202F;75) showing significantly improved learning performance in prosocial-learning conditions compared to self-learning contexts (<xref ref-type="bibr" rid="ref105">Zhang et al., 2024</xref>). Clinical applications show preliminary benefits in autism spectrum disorder, where tDCS significantly improves Empathy Quotient scores and facial emotion recognition for threat-related emotions (<xref ref-type="bibr" rid="ref98">Wilson et al., 2021</xref>). Research also investigates tDCS as an intervention to improve empathic abilities and reduce violent behavior in forensic offenders, particularly when targeting the ventromedial prefrontal cortex (<xref ref-type="bibr" rid="ref82">Sergiou et al., 2020</xref>).</p>
<p>As with TMS, tDCS effects are generally transient and highly variable across individuals. Polarity-specific and montage-specific effects are difficult to reproduce consistently, limiting clinical translation (<xref ref-type="bibr" rid="ref81">Schwertfeger et al., 2023</xref>; <xref ref-type="bibr" rid="ref87">Son et al., 2025</xref>; <xref ref-type="bibr" rid="ref78">Saccenti et al., 2024</xref>).</p>
</sec>
<sec id="sec23">
<label>5.3</label>
<title>Emerging deep neuromodulation techniques</title>
<p>Recent technological advances have enabled noninvasive targeting of deeper brain structures implicated in empathy, though evidence remains exploratory.</p>
<p>Low-intensity focused ultrasound (LIFU) has emerged as a transformative non-invasive neuromodulation technique, offering millimeter-sized focal volumes with adjustable focal lengths that can target deep human brain circuitry with unprecedented precision. Unlike other non-invasive brain stimulation techniques, focused ultrasound provides focal deep brain targeting, multi-target stimulation capabilities, and neuromodulatory effects lasting from milliseconds to hours after sonication (<xref ref-type="bibr" rid="ref67">Pellow et al., 2024</xref>; <xref ref-type="bibr" rid="ref40">Kim et al., 2024</xref>; <xref ref-type="bibr" rid="ref52">Martin et al., 2024</xref>). Human studies demonstrate that LIFU can modulate activity in deep structures such as the thalamus and insula, affecting pain perception and autonomic responses (<xref ref-type="bibr" rid="ref4">Badran et al., 2020</xref>; <xref ref-type="bibr" rid="ref45">Legon et al., 2024</xref>; <xref ref-type="bibr" rid="ref62">Murphy et al., 2025</xref>). The European Research Council-funded HelpUS project specifically pioneers focused ultrasound as a novel non-invasive deep brain stimulation method for causal investigation of empathy-related brain processes in moral learning and decision-making (<xref ref-type="bibr" rid="ref30">Gazzola, 2018</xref>). While these findings suggest mechanistic relevance for affective empathy, no controlled human trials have yet demonstrated direct empathy enhancement using LIFU. Accordingly, current evidence is best classified as Tier 3.</p>
<p>Temporal interference stimulation (TIS) represents a breakthrough non-invasive technique for steerable deep brain stimulation using multiple kHz-range electric fields with different frequencies within neural activity ranges. Human validation studies demonstrate that TIS can modulate hippocampal activity and associated cognitive effects focally, while sparing the superficial cortex (<xref ref-type="bibr" rid="ref95">Violante et al., 2023</xref>). Open-label pilot studies show TIS targeting the right nucleus accumbens alleviates negative symptoms and improves cognitive function in schizophrenia patients, with participants demonstrating significant improvements in Positive and Negative Syndrome Scale negative subscale scores over 90&#x202F;days (<xref ref-type="bibr" rid="ref96">Wang et al., 2025</xref>). Recent safety studies involving over 250 TIS sessions confirm excellent tolerability and safety profiles (<xref ref-type="bibr" rid="ref94">Vassiliadis et al., 2024</xref>; <xref ref-type="bibr" rid="ref60">Modak et al., 2024</xref>). As with LIFU, TIS remains exploratory regarding empathy modulation (<xref ref-type="fig" rid="fig2">Figure 2</xref> and <xref ref-type="table" rid="tab4">Table 4</xref>).</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>Comparative landscape of neurostimulation interventions for empathy. This figure presents a literature-derived comparative schematic of neurostimulation approaches to empathy modulation. <bold>(A)</bold> Displays a bubble chart plotting effect size (<italic>x</italic>-axis: Cohen&#x2019;s <italic>d</italic>, 0&#x2013;1.0) against clinical readiness level (<italic>y</italic>-axis: 1&#x2013;10, from experimental to established clinical practice), with bubble size representing evidence quality and bubble color indicating intervention category. <bold>(B)</bold> Presents a stacked bar chart comparing effect sizes across empathy components (affective, cognitive, prosocial motivation, sustained behavioral change) for each intervention category. <bold>(C)</bold> Shows a timeline of effect duration (<italic>x</italic>-axis in hours/days/weeks/months) for each intervention type, with annotations indicating typical decay patterns. <bold>(D)</bold> Provides a cost-effectiveness analysis plotting the estimated cost per participant against the effect size. This figure is a conceptual synthesis derived from published meta-analyses, randomized trials, and mechanistic studies (<xref ref-type="bibr" rid="ref102">Yang et al., 2018</xref>; <xref ref-type="bibr" rid="ref5">Bahji et al., 2021</xref>; <xref ref-type="bibr" rid="ref76">Rossi et al., 2021</xref>; <xref ref-type="bibr" rid="ref45">Legon et al., 2024</xref>). It does not represent primary data or quantitative meta-analysis and is intended solely to facilitate integrative interpretation (<xref ref-type="table" rid="tab4">Table 4</xref>).</p>
</caption>
<graphic xlink:href="fpsyg-17-1762816-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Figure with four panels comparing nine interventions for empathy improvement: A) scatterplot of effect size versus clinical readiness, with labeling for evidence tiers and categories (pharmacological, neurostimulation, behavioral); B) bar chart showing effect sizes by empathy component and intervention; C) horizontal bar chart illustrating the typical duration of behavioral effects per intervention; D) scatterplot comparing cost per participant to effect size, indicating scalability level with different shapes and intervention categories with color coding.</alt-text>
</graphic>
</fig>
<table-wrap position="float" id="tab4">
<label>Table 4</label>
<caption>
<p>Neurostimulation approaches and evidence for empathy modulation.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Technique</th>
<th align="left" valign="top">Primary targets</th>
<th align="left" valign="top">Empathy component</th>
<th align="left" valign="top">Effect size</th>
<th align="left" valign="top">Duration</th>
<th align="left" valign="top">Tier</th>
<th align="left" valign="top">Key references</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">TMS</td>
<td align="left" valign="top">rTPJ, mPFC</td>
<td align="left" valign="top">Cognitive empathy</td>
<td align="left" valign="top"><italic>d</italic>&#x202F;&#x2248;&#x202F;0.18&#x2013;0.20 (small)</td>
<td align="left" valign="top">Minutes&#x2013;1&#x202F;h</td>
<td align="left" valign="top">Tier 1</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref102">Yang et al. (2018)</xref> and <xref ref-type="bibr" rid="ref17">Chou and Chen (2021)</xref></td>
</tr>
<tr>
<td align="left" valign="top">tDCS</td>
<td align="left" valign="top">rTPJ</td>
<td align="left" valign="top">Cognitive empathy; prosocial learning</td>
<td align="left" valign="top"><italic>d</italic>&#x202F;&#x2248;&#x202F;0.18&#x2013;0.25 (small)</td>
<td align="left" valign="top">Minutes&#x2013;1&#x202F;h</td>
<td align="left" valign="top">Tier 1&#x2013;2</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref5">Bahji et al. (2021)</xref> and <xref ref-type="bibr" rid="ref105">Zhang et al. (2024)</xref></td>
</tr>
<tr>
<td align="left" valign="top">LIFU</td>
<td align="left" valign="top">Insula, thalamus</td>
<td align="left" valign="top">Mechanistic relevance to affective empathy</td>
<td align="left" valign="top">Not established</td>
<td align="left" valign="top">Variable (ms to hours)</td>
<td align="left" valign="top">Tier 3</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref4">Badran et al. (2020)</xref> and <xref ref-type="bibr" rid="ref45">Legon et al. (2024)</xref></td>
</tr>
<tr>
<td align="left" valign="top">TIS</td>
<td align="left" valign="top">Hippocampus, mesolimbic regions</td>
<td align="left" valign="top">Social cognition (indirect)</td>
<td align="left" valign="top">Not established</td>
<td align="left" valign="top">Unknown</td>
<td align="left" valign="top">Tier 3</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref95">Violante et al. (2023)</xref> and <xref ref-type="bibr" rid="ref96">Wang et al. (2025)</xref></td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>TMS&#x202F;=&#x202F;transcranial magnetic stimulation; tDCS&#x202F;=&#x202F;transcranial direct current stimulation; LIFU&#x202F;=&#x202F;low-intensity focused ultrasound; TIS&#x202F;=&#x202F;temporal interference stimulation; rTPJ&#x202F;=&#x202F;right temporoparietal junction; mPFC&#x202F;=&#x202F;medial prefrontal cortex.</p>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
<sec id="sec24">
<label>6</label>
<title>Behavioral interventions for empathy enhancement</title>
<p>Behavioral interventions represent the most mature and scalable approaches to empathy modulation. Unlike pharmacological and neurostimulation strategies&#x2014;which target specific neurochemical systems or neural circuits&#x2014;behavioral approaches operate through experience-dependent plasticity, influencing attentional, emotional, motivational, and interpersonal processes over time. As a result, they demonstrate stronger ecological validity and fewer safety concerns, though effect sizes remain modest and dependent on sustained engagement. Behavioral and educational approaches remain the most scalable and ethically robust methods for empathy enhancement, particularly in professional and educational settings (<xref ref-type="bibr" rid="ref80">Schutte and Stilinovi&#x0107;, 2017</xref>; <xref ref-type="bibr" rid="ref84">Shi and Cheung, 2024</xref>).</p>
<sec id="sec25">
<label>6.1</label>
<title>Mindfulness-based interventions</title>
<p>Mindfulness-based interventions, including mindfulness-based stress reduction, loving-kindness meditation, and compassion meditation, are among the most extensively studied behavioral approaches to empathy enhancement. These interventions emphasize attentional regulation, interoceptive awareness, and non-reactive emotional processing, mechanisms that align closely with neural systems supporting affective regulation and empathic concern (<xref ref-type="bibr" rid="ref85">Singer and Klimecki, 2014</xref>; <xref ref-type="bibr" rid="ref13">Calderone et al., 2024</xref>; <xref ref-type="bibr" rid="ref1">Abellaneda-P&#x00E9;rez et al., 2024</xref>).</p>
<p>Tier 1 meta-analytic evidence indicates that mindfulness-based programs produce small-to-moderate improvements in empathy, with a pooled effect size of approximately <italic>d</italic>&#x202F;=&#x202F;0.37 (95% CI: 0.16&#x2013;0.58), and significantly stronger effects observed in interventions exceeding 24 total hours of training (<xref ref-type="bibr" rid="ref34">Hu et al., 2022</xref>; <xref ref-type="bibr" rid="ref9">Bianjiang et al., 2025</xref>). However, substantial heterogeneity exists across studies, reflecting variation in program structure, instructor expertise, participant motivation, and outcome measurement. Individual participant data meta-analyses further demonstrate marked interindividual variability, with some participants showing minimal or no empathic change (<xref ref-type="bibr" rid="ref29">Galante et al., 2023</xref>).</p>
<p>Neuroimaging studies provide converging mechanistic evidence, showing mindfulness-related changes in anterior insula thickness, prefrontal connectivity, and neural markers of emotional regulation (<xref ref-type="bibr" rid="ref13">Calderone et al., 2024</xref>; <xref ref-type="bibr" rid="ref7">Bashir et al., 2025</xref>). Nevertheless, the durability of effects depends on continued practice, and attrition rates remain a practical limitation in real-world implementation (<xref ref-type="bibr" rid="ref22">Conversano et al., 2020</xref>; <xref ref-type="bibr" rid="ref23">Cooper et al., 2020</xref>).</p>
</sec>
<sec id="sec26">
<label>6.2</label>
<title>Compassion-focused interventions</title>
<p>Compassion-focused therapy and related interventions explicitly train concern for others&#x2019; suffering and motivation to alleviate it. The most comprehensive recent meta-analysis of compassion-focused therapy with clinical populations found small to large effect sizes for improvements in self-compassion (0.19&#x2013;0.90), self-criticism (0.15&#x2013;0.72), and depression (0.24&#x2013;0.25) (<xref ref-type="bibr" rid="ref56">Millard et al., 2023</xref>; <xref ref-type="bibr" rid="ref39">Kim et al., 2021</xref>). A 2025 systematic review found consistent improvements in self-compassion (<italic>g</italic>&#x202F;=&#x202F;0.23&#x2013;4.14) and reductions in self-criticism (<italic>g</italic>&#x202F;=&#x202F;0.29&#x2013;1.56) in clinical populations (<xref ref-type="bibr" rid="ref11">Brown and Ashcroft, 2025</xref>; <xref ref-type="bibr" rid="ref54">Martins et al., 2025</xref>).</p>
</sec>
<sec id="sec27">
<label>6.3</label>
<title>Virtual reality&#x2013;based perspective-taking</title>
<p>Virtual reality (VR) interventions aim to enhance empathy by immersing participants in simulated social experiences. Meta-analytic evidence demonstrates that VR produces moderate short-term improvements in emotional empathy (<italic>d</italic>&#x202F;=&#x202F;0.51, 95% CI: 0.15&#x2013;0.88), while effects on cognitive empathy are inconsistent (<italic>d</italic>&#x202F;=&#x202F;0.21, 95% CI: &#x2212;0.37&#x2013;0.79) (<xref ref-type="bibr" rid="ref80">Schutte and Stilinovi&#x0107;, 2017</xref>; <xref ref-type="bibr" rid="ref53">Martingano et al., 2021</xref>). A systematic review found that emotional empathy increases immediately after exposure but returns to baseline levels over time (<xref ref-type="bibr" rid="ref44">Lee et al., 2024</xref>). VR shows promise in healthcare education and stigma reduction (<xref ref-type="bibr" rid="ref90">Tay et al., 2025</xref>; <xref ref-type="bibr" rid="ref68">Pira et al., 2025</xref>).</p>
</sec>
<sec id="sec28">
<label>6.4</label>
<title>Educational and professional training programs</title>
<p>Social&#x2013;emotional learning (SEL) programs represent the most robust real-world applications of empathy enhancement. A contemporary meta-analysis of 424 studies from 53 countries involving 575,361 students confirmed that SEL programs improve social and emotional skills, attitudes, behavior, and academic performance (<xref ref-type="bibr" rid="ref21">Cipriano et al., 2023</xref>; <xref ref-type="bibr" rid="ref84">Shi and Cheung, 2024</xref>). In healthcare education, meta-analyses indicate moderate improvements in empathy following structured training (d&#x202F;=&#x202F;0.58), with interactive approaches outperforming didactic methods (<xref ref-type="bibr" rid="ref66">Paulus and Meinken, 2022</xref>; <xref ref-type="bibr" rid="ref3">Ara&#x00FA;jo et al., 2025</xref>) (<xref ref-type="table" rid="tab5">Table 5</xref>). Large-scale healthcare and cross-cultural reviews further confirm that empathy training improves communication quality and patient experience across diverse sociocultural contexts (<xref ref-type="bibr" rid="ref89">Sullivan-Detheridge et al., 2024</xref>; <xref ref-type="bibr" rid="ref104">Yuan et al., 2025</xref>).</p>
<table-wrap position="float" id="tab5">
<label>Table 5</label>
<caption>
<p>Literature-derived translational readiness summaries for behavioral interventions.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Intervention type</th>
<th align="left" valign="top">Primary context</th>
<th align="left" valign="top">Reported effect size</th>
<th align="left" valign="top">Durability</th>
<th align="left" valign="top">Readiness</th>
<th align="left" valign="top">Key sources</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Mindfulness-based training</td>
<td align="left" valign="top">Clinical; professional</td>
<td align="left" valign="top"><italic>d</italic>&#x202F;=&#x202F;0.37 (95% CI: 0.16&#x2013;0.58)</td>
<td align="left" valign="top">Practice-dependent</td>
<td align="left" valign="top">High</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref34">Hu et al. (2022)</xref> and <xref ref-type="bibr" rid="ref29">Galante et al. (2023)</xref></td>
</tr>
<tr>
<td align="left" valign="top">Compassion-focused therapy</td>
<td align="left" valign="top">Clinical populations</td>
<td align="left" valign="top"><italic>g</italic>&#x202F;=&#x202F;0.23&#x2013;4.14</td>
<td align="left" valign="top">Moderate with reinforcement</td>
<td align="left" valign="top">Moderate&#x2013;High</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref56">Millard et al. (2023)</xref> and <xref ref-type="bibr" rid="ref11">Brown and Ashcroft (2025)</xref></td>
</tr>
<tr>
<td align="left" valign="top">VR perspective-taking</td>
<td align="left" valign="top">Education; healthcare</td>
<td align="left" valign="top"><italic>d</italic>&#x202F;=&#x202F;0.51 (emotional empathy)</td>
<td align="left" valign="top">Low&#x2013;moderate</td>
<td align="left" valign="top">Moderate</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref53">Martingano et al. (2021)</xref> and <xref ref-type="bibr" rid="ref44">Lee et al. (2024)</xref></td>
</tr>
<tr>
<td align="left" valign="top">SEL programs</td>
<td align="left" valign="top">Schools (K&#x2013;12)</td>
<td align="left" valign="top">Small&#x2013;moderate</td>
<td align="left" valign="top">High (curriculum-embedded)</td>
<td align="left" valign="top">High</td>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref21">Cipriano et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="left" valign="top">Healthcare empathy training</td>
<td align="left" valign="top">Medical education</td>
<td align="left" valign="top"><italic>d</italic>&#x202F;=&#x202F;0.58</td>
<td align="left" valign="top">Moderate</td>
<td align="left" valign="top">High</td>
<td align="left" valign="top"><xref ref-type="bibr" rid="ref66">Paulus and Meinken (2022)</xref> and <xref ref-type="bibr" rid="ref3">Ara&#x00FA;jo et al. (2025)</xref></td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</sec>
<sec id="sec29">
<label>7</label>
<title>Clinical applications and evidence-based outcomes</title>
<p>Clinical applications of empathy modulation technologies span multiple healthcare domains, with the strongest evidence base in healthcare provider training and educational settings. Recent systematic reviews reveal consistent benefits across diverse populations and intervention types, though implementation challenges and population-specific factors require careful consideration.</p>
<sec id="sec30">
<label>7.1</label>
<title>Healthcare provider training</title>
<p>A recent systematic review of 455 studies involving 470 analyses found that greater empathy is associated with better clinical outcomes and patient care experiences (<xref ref-type="bibr" rid="ref63">Nembhard et al., 2023</xref>). A meta-analysis of 13 empathy training studies (<italic>N</italic>&#x202F;=&#x202F;1,315) demonstrated an overall moderate effect size (<italic>d</italic>&#x202F;=&#x202F;0.58) for empathy training effectiveness (<xref ref-type="bibr" rid="ref66">Paulus and Meinken, 2022</xref>). A cluster randomized controlled trial in Ethiopian treatment centers showed sustained medium-to-large effects (<italic>d</italic>&#x202F;=&#x202F;0.55 to 0.60) over 3&#x202F;months, while simulation-based interventions showed effect sizes ranging from <italic>d</italic>&#x202F;=&#x202F;0.46 (self-reports) to <italic>d</italic>&#x202F;=&#x202F;1.27 (independent observers) (<xref ref-type="bibr" rid="ref20">Chua et al., 2021</xref>; <xref ref-type="bibr" rid="ref35">Hurissa et al., 2023</xref>).</p>
<p>Improved empathy among providers is associated with better diagnostic accuracy, increased medication adherence, lower malpractice risk, reduced patient anxiety and distress, and enhanced outcomes in chronic disease management. However, training effects frequently decline without reinforcement, and implementation challenges include institutional cultures that prioritize efficiency over patient interaction and systematic disparities in the quality of empathetic care for patients from lower socioeconomic backgrounds (<xref ref-type="bibr" rid="ref73">Roberts et al., 2021</xref>; <xref ref-type="bibr" rid="ref12">Byrne et al., 2024</xref>).</p>
</sec>
<sec id="sec31">
<label>7.2</label>
<title>Educational and mental health applications</title>
<p>Educational systems provide a critical developmental window for cultivating empathy. Virtual patients through standardized scenarios ensure consistency and reproducibility while offering safe learning opportunities (<xref ref-type="bibr" rid="ref101">Yamada et al., 2025</xref>). In mental health settings, empathy is foundational to the therapeutic alliance, one of the strongest predictors of treatment success. Higher therapist empathy predicts better client engagement, greater treatment adherence, and improved outcomes (<xref ref-type="bibr" rid="ref61">Moudatsou et al., 2020</xref>). The relationship between trauma and empathy is complex, requiring tailored intervention approaches (<xref ref-type="bibr" rid="ref31">Greenberg et al., 2018</xref>; <xref ref-type="bibr" rid="ref46">Levy et al., 2019</xref>) (<xref ref-type="table" rid="tab6">Table 6</xref>).</p>
<table-wrap position="float" id="tab6">
<label>Table 6</label>
<caption>
<p>Clinical translation readiness by intervention type.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Intervention</th>
<th align="left" valign="top">Research maturity</th>
<th align="left" valign="top">Clinical readiness</th>
<th align="left" valign="top">Implementation barriers</th>
<th align="left" valign="top">Recommended next steps</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Healthcare empathy training</td>
<td align="left" valign="top">High</td>
<td align="left" valign="top">High</td>
<td align="left" valign="top">Institutional culture, sustainability</td>
<td align="left" valign="top">Implementation science research</td>
</tr>
<tr>
<td align="left" valign="top">SEL programs</td>
<td align="left" valign="top">High</td>
<td align="left" valign="top">High</td>
<td align="left" valign="top">Teacher training, cultural adaptation</td>
<td align="left" valign="top">Scale-up and sustainability research</td>
</tr>
<tr>
<td align="left" valign="top">Compassion-focused therapy</td>
<td align="left" valign="top">High</td>
<td align="left" valign="top">Moderate</td>
<td align="left" valign="top">Adherence, dose&#x2013;response</td>
<td align="left" valign="top">Effectiveness trials</td>
</tr>
<tr>
<td align="left" valign="top">VR perspective-taking</td>
<td align="left" valign="top">Moderate</td>
<td align="left" valign="top">Moderate</td>
<td align="left" valign="top">Effect duration, targeting</td>
<td align="left" valign="top">Longitudinal follow-up</td>
</tr>
<tr>
<td align="left" valign="top">Neurostimulation (TMS/tDCS)</td>
<td align="left" valign="top">Moderate</td>
<td align="left" valign="top">Low</td>
<td align="left" valign="top">Individual variability, duration</td>
<td align="left" valign="top">Personalized targeting trials</td>
</tr>
<tr>
<td align="left" valign="top">LIFU/TIS</td>
<td align="left" valign="top">Low&#x2013;Moderate</td>
<td align="left" valign="top">Very Low</td>
<td align="left" valign="top">Early development, safety data</td>
<td align="left" valign="top">Safety studies; mechanism trials</td>
</tr>
<tr>
<td align="left" valign="top">Pharmacological (oxytocin)</td>
<td align="left" valign="top">Moderate</td>
<td align="left" valign="top">Low</td>
<td align="left" valign="top">Small effects, genetic moderation</td>
<td align="left" valign="top">Genetically stratified trials</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</sec>
<sec id="sec32">
<label>8</label>
<title>Ethical considerations in empathy modulation</title>
<p>The deliberate modulation of empathy raises distinct ethical concerns that extend beyond those associated with other cognitive or affective interventions. Because empathy is closely linked to emotional identity, moral judgment, and social behavior, interventions that alter empathic processing have the potential to affect autonomy, authenticity, and interpersonal relationships. UNESCO&#x2019;s forthcoming 2025 Recommendation on the Ethics of Neurotechnology provides the first global framework addressing neurotechnologies that can &#x201C;directly access, manipulate and emulate the structure of the brain&#x201D; (<xref ref-type="bibr" rid="ref92">UNESCO, 2025</xref>; <xref ref-type="bibr" rid="ref69">Ramanathan, 2025</xref>). Recent international guidelines and ethical analyses emphasize that empathy-modulating interventions require careful governance, transparency, and respect for individual and cultural variability (<xref ref-type="bibr" rid="ref64">Niles et al., 2023</xref>; <xref ref-type="bibr" rid="ref62">Murphy et al., 2025</xref>).</p>
<sec id="sec33">
<label>8.1</label>
<title>Informed consent and durability of effects</title>
<p>A central ethical challenge concerns informed consent, particularly when interventions may produce enduring changes in emotional processing or value-based decision-making. Unlike transient cognitive enhancements, empathy-related changes may persist beyond the intervention period (<xref ref-type="bibr" rid="ref99">Winter et al., 2020</xref>). Consent processes must include explicit discussion of uncertainty regarding duration, reversibility, and downstream social consequences. Dynamic consent models&#x2014;in which participants are periodically re-informed and allowed to reassess participation&#x2014;have been proposed as a safeguard (<xref ref-type="bibr" rid="ref103">Young et al., 2022</xref>).</p>
</sec>
<sec id="sec34">
<label>8.2</label>
<title>Vulnerability, coercion, and power asymmetries</title>
<p>Empathy modulation interventions are often deployed in contexts characterized by power asymmetries, including healthcare, education, military, and criminal justice settings. In such contexts, there is a risk that individuals may feel pressured to undergo interventions framed as beneficial or corrective (<xref ref-type="bibr" rid="ref82">Sergiou et al., 2020</xref>; <xref ref-type="bibr" rid="ref8">Beaudry et al., 2021</xref>; <xref ref-type="bibr" rid="ref75">Roncero et al., 2025</xref>). Ethical implementation requires that participation be genuinely voluntary and that refusal carry no punitive consequences.</p>
</sec>
<sec id="sec35">
<label>8.3</label>
<title>Neurodiversity and individual difference considerations</title>
<p>Contemporary research increasingly challenges deficit-based models of empathy, particularly in relation to autism spectrum conditions. The double empathy problem emphasizes that social misunderstandings arise bidirectionally between autistic and non-autistic individuals, rather than reflecting a unidirectional deficit (<xref ref-type="bibr" rid="ref16">Cheang et al., 2025</xref>). Qualitative and quantitative studies demonstrate that autistic individuals often show intact or heightened empathy within neurodivergent peer groups (<xref ref-type="bibr" rid="ref97">Watts et al., 2025</xref>). Ethical frameworks must respect neurodiversity and prioritize self-defined goals rather than externally imposed norms. Interventions should be co-designed with neurodivergent communities (<xref ref-type="bibr" rid="ref14">Camilleri et al., 2025</xref>).</p>
</sec>
<sec id="sec36">
<label>8.4</label>
<title>Cross-cultural contexts and misuse risks</title>
<p>Empathy is expressed and valued differently across cultures, shaped by social norms, religious beliefs, and historical context. Cross-cultural research demonstrates substantial variation in empathic expression and moral priorities (<xref ref-type="bibr" rid="ref27">Eichbaum et al., 2023</xref>; <xref ref-type="bibr" rid="ref36">Jami et al., 2024</xref>; <xref ref-type="bibr" rid="ref89">Sullivan-Detheridge et al., 2024</xref>). There is also concern regarding potential misuse of empathy-modulating technologies for manipulation, persuasion, or social control. International governance frameworks emphasize preventing exploitative or coercive applications (<xref ref-type="bibr" rid="ref92">UNESCO, 2025</xref>; <xref ref-type="bibr" rid="ref69">Ramanathan, 2025</xref>) (<xref ref-type="table" rid="tab7">Table 7</xref>).</p>
<table-wrap position="float" id="tab7">
<label>Table 7</label>
<caption>
<p>Population-specific ethical and clinical considerations.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Population</th>
<th align="left" valign="top">Promising interventions</th>
<th align="left" valign="top">Special considerations</th>
<th align="left" valign="top">Evidence quality</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Healthcare providers</td>
<td align="left" valign="top">Mindfulness, simulation, communication skills</td>
<td align="left" valign="top">Time constraints, institutional culture, burnout prevention</td>
<td align="left" valign="top">High (multiple meta-analyses)</td>
</tr>
<tr>
<td align="left" valign="top">Autism spectrum</td>
<td align="left" valign="top">Individualized, neurodiversity-affirming approaches</td>
<td align="left" valign="top">Respect for neurodiversity, double empathy problem, community involvement</td>
<td align="left" valign="top">Moderate (paradigm shift ongoing)</td>
</tr>
<tr>
<td align="left" valign="top">Criminal justice</td>
<td align="left" valign="top">Perspective-taking, restorative justice</td>
<td align="left" valign="top">Voluntary participation essential, coercion concerns, motivation assessment</td>
<td align="left" valign="top">Low to moderate (limited RCTs)</td>
</tr>
<tr>
<td align="left" valign="top">Educational settings</td>
<td align="left" valign="top">SEL programs, VR, teacher training</td>
<td align="left" valign="top">Cultural adaptation, developmental appropriateness, teacher capacity</td>
<td align="left" valign="top">High (large global meta-analyses)</td>
</tr>
<tr>
<td align="left" valign="top">Mental health conditions</td>
<td align="left" valign="top">Trauma-informed, therapeutic alliance enhancement</td>
<td align="left" valign="top">Condition-specific adaptations, capacity assessment, emotional safety</td>
<td align="left" valign="top">Variable by condition</td>
</tr>
<tr>
<td align="left" valign="top">Children/adolescents</td>
<td align="left" valign="top">Age-appropriate SEL, developmental scaffolding</td>
<td align="left" valign="top">Evolving consent, developmental timing, parental involvement</td>
<td align="left" valign="top">High for SEL; limited for biological</td>
</tr>
<tr>
<td align="left" valign="top">Cross-cultural contexts</td>
<td align="left" valign="top">Culturally adapted interventions, local partnership</td>
<td align="left" valign="top">Avoid Western-centric frameworks, involve community leaders</td>
<td align="left" valign="top">Moderate (growing literature)</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</sec>
<sec id="sec37">
<label>9</label>
<title>Conclusion and future directions</title>
<p>This hybrid narrative&#x2013;scoping review synthesizes evidence across pharmacological, neurostimulation, and behavioral approaches to empathy modulation. The accumulated evidence indicates that empathy is biologically and psychologically modifiable, but that current interventions yield modest, heterogeneous, and often transient effects. Behavioral interventions&#x2014;particularly mindfulness-based and compassion-focused programs&#x2014;demonstrate the strongest combination of scalability, safety, and ecological validity, though effect sizes remain small to moderate (<italic>d</italic>&#x202F;=&#x202F;0.37 for mindfulness) and depend on sustained engagement.</p>
<p>Pharmacological approaches provide valuable mechanistic insights but face substantial translational barriers. Intranasal oxytocin produces small, context-dependent effects (d&#x202F;=&#x202F;0.24) that do not generalize reliably, while MDMA-assisted therapy demonstrates large effects (d&#x202F;&#x2248;&#x202F;0.91) within tightly controlled psychotherapeutic settings but remains constrained by regulatory, ethical, and safety considerations following FDA rejection in August 2024. Neurostimulation techniques offer causal leverage over empathy-related circuits, particularly for cognitive empathy (<italic>d</italic>&#x202F;&#x2248;&#x202F;0.18&#x2013;0.20 for TMS), yet effects are short-lived and highly variable, limiting standalone clinical utility.</p>
<p>Future progress in empathy modulation will require several advances. First, larger and better-powered trials with standardized outcome measures are essential to establish reliable effect-size estimates&#x2014;the field requires immediate prioritization of large-scale replication studies with at least 500 participants. Second, greater emphasis on ecological validity&#x2014;including behavioral observation, longitudinal follow-up, and real-world outcomes&#x2014;is needed to bridge the gap between laboratory findings and everyday social functioning. Third, integrative approaches combining behavioral training with biological or technological adjuncts may offer synergistic benefits, though such strategies must be evaluated cautiously.</p>
<p>Finally, ethical governance must remain central to the development and deployment of empathy-modulating interventions. Respect for autonomy, neurodiversity, cultural context, and voluntary participation is essential to ensure that efforts to enhance empathy contribute to individual well-being and social cohesion rather than coercion or misuse. With these foundations, empathy modulation may ultimately help reduce human suffering, enhance social cohesion, and improve outcomes across clinical, educational, and societal domains (<xref ref-type="fig" rid="fig3">Figure 3</xref>).</p>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p>Research roadmap: priorities for translational empathy science. This figure presents a strategic roadmap for advancing empathy modulation research toward clinical translation, organized as a hierarchical flowchart with temporal milestones. <bold>(A)</bold> Shows the foundational layer (Years 1&#x2013;3) comprising four parallel research streams: (1) Measurement development, including multimodal assessment validation, cross-cultural adaptation studies, and ecological momentary assessment protocols; (2) Mechanism studies, including large-scale replication trials (<italic>n</italic>500), genome-wide association studies for treatment response predictors, and computational modeling of empathy circuits; (3) Technology optimization, including parameter optimization for neurostimulation, biomarker-guided targeting development, and combination protocol testing; and (4) Ethical framework development, including dynamic consent model implementation, equity impact assessments, and international governance coordination. <bold>(B)</bold> Depicts the integration phase (Years 3&#x2013;5) where these streams converge into three translational pathways: clinical pathway (personalized intervention protocols, real-world effectiveness trials, implementation science studies), educational pathway (teacher training program development, digital platform integration, cross-cultural validation), and research pathway (deep brain mechanism studies with emerging technologies, neural biomarker discovery, computational empathy modeling). <bold>(C)</bold> Shows the implementation phase (Years 5&#x2013;10) with anticipated outcomes including validated clinical protocols for specific populations, scalable educational interventions with demonstrated effectiveness, regulatory guidance for empathy neurotechnologies, and international standards for ethical implementation. Arrows between elements indicate dependencies and feedback loops. Color coding distinguishes research domains: blue for neuroscience/mechanism studies, green for clinical/applied research, orange for ethical/policy development, and purple for technology development. This figure is a conceptual synthesis intended to guide research prioritization and is not derived from primary data.</p>
</caption>
<graphic xlink:href="fpsyg-17-1762816-g003.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Flowchart illustrates a ten-year research-to-implementation roadmap with three phases: foundational research (years 1 to 3) covering measurement, mechanisms, technology, and ethics; integration (years 3 to 5) translating into clinical, educational, and research pathways; and implementation (years 5 to 10) resulting in clinical protocols, educational programs, regulatory guidance, and international standards. Color coding indicates categories: neuroscience, clinical, education, ethics, and technology.</alt-text>
</graphic>
</fig>
</sec>
</body>
<back>
<sec sec-type="author-contributions" id="sec38">
<title>Author contributions</title>
<p>SN: Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec sec-type="COI-statement" id="sec39">
<title>Conflict of interest</title>
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<ref-list>
<title>References</title>
<ref id="ref1"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abellaneda-P&#x00E9;rez</surname><given-names>K.</given-names></name> <name><surname>Potash</surname><given-names>R. M.</given-names></name> <name><surname>Pascual-Leone</surname><given-names>A.</given-names></name> <name><surname>Sacchet</surname><given-names>M. D.</given-names></name></person-group> (<year>2024</year>). <article-title>Neuromodulation and meditation: a review and synthesis toward promoting well-being and understanding consciousness and brain</article-title>. <source>Neurosci. Biobehav. Rev.</source> <volume>166</volume>:<fpage>105862</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neubiorev.2024.105862</pub-id>, <pub-id pub-id-type="pmid">39186992</pub-id></mixed-citation></ref>
<ref id="ref2"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Allen</surname><given-names>M.</given-names></name> <name><surname>Frank</surname><given-names>D.</given-names></name> <name><surname>Glen</surname><given-names>J. C.</given-names></name> <name><surname>Fardo</surname><given-names>F.</given-names></name> <name><surname>Callaghan</surname><given-names>M. F.</given-names></name> <name><surname>Rees</surname><given-names>G.</given-names></name> <etal/></person-group>. (<year>2017</year>). <article-title>Insula and somatosensory cortical myelination and iron markers underlie individual differences in empathy</article-title>. <source>Sci. Rep.</source> <volume>7</volume>:<fpage>43316</fpage>. doi: <pub-id pub-id-type="doi">10.1038/srep43316</pub-id>, <pub-id pub-id-type="pmid">28256532</pub-id></mixed-citation></ref>
<ref id="ref3"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ara&#x00FA;jo</surname><given-names>L. I.</given-names></name> <name><surname>Ferreira</surname><given-names>E. S.</given-names></name> <name><surname>Santos</surname><given-names>J. C.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>The role of training and education for enhancing empathy among healthcare students: a systematic review of randomized controlled trials</article-title>. <source>BMC Med. Educ.</source> <volume>25</volume>:<fpage>256</fpage>. doi: <pub-id pub-id-type="doi">10.1186/s12909-025-06237-2</pub-id></mixed-citation></ref>
<ref id="ref4"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Badran</surname><given-names>B. W.</given-names></name> <name><surname>Caulfield</surname><given-names>K. A.</given-names></name> <name><surname>Stomberg-Firestein</surname><given-names>S.</given-names></name> <name><surname>Summers</surname><given-names>P. M.</given-names></name> <name><surname>Dowdle</surname><given-names>L. T.</given-names></name> <name><surname>Savoca</surname><given-names>M.</given-names></name> <etal/></person-group>. (<year>2020</year>). <article-title>Sonication of the anterior thalamus with MRI-guided transcranial focused ultrasound alters pain thresholds in healthy adults</article-title>. <source>Brain Stimul.</source> <volume>13</volume>, <fpage>1805</fpage>&#x2013;<lpage>1812</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.brs.2020.10.007</pub-id></mixed-citation></ref>
<ref id="ref5"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bahji</surname><given-names>A.</given-names></name> <name><surname>Forth</surname><given-names>E.</given-names></name> <name><surname>Yang</surname><given-names>C. C.</given-names></name> <name><surname>Khalifa</surname><given-names>N.</given-names></name></person-group> (<year>2021</year>). <article-title>Transcranial direct current stimulation for empathy: a systematic review and meta-analysis</article-title>. <source>Soc. Neurosci.</source> <volume>16</volume>, <fpage>232</fpage>&#x2013;<lpage>255</lpage>. doi: <pub-id pub-id-type="doi">10.1080/17470919.2021.1879203</pub-id>, <pub-id pub-id-type="pmid">33567964</pub-id></mixed-citation></ref>
<ref id="ref6"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bakermans-Kranenburg</surname><given-names>M. J.</given-names></name> <name><surname>van IJzendoorn</surname><given-names>M. H.</given-names></name></person-group> (<year>2013</year>). <article-title>Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy</article-title>. <source>Transl. Psychiatry</source> <volume>3</volume>:<fpage>e258</fpage>. doi: <pub-id pub-id-type="doi">10.1038/tp.2013.34</pub-id>, <pub-id pub-id-type="pmid">23695233</pub-id></mixed-citation></ref>
<ref id="ref7"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bashir</surname><given-names>K.</given-names></name> <name><surname>Edstrom</surname><given-names>S. B.</given-names></name> <name><surname>Barlow</surname><given-names>S. J.</given-names></name> <name><surname>Gainer</surname><given-names>D.</given-names></name> <name><surname>Lewis</surname><given-names>J. D.</given-names></name></person-group> (<year>2025</year>). <article-title>Loving-kindness meditation: systematic review of neuroimaging correlates in long-term practitioners and clinical implications</article-title>. <source>Brain Behav.</source> <volume>15</volume>:<fpage>e70372</fpage>. doi: <pub-id pub-id-type="doi">10.1002/brb3.70372</pub-id>, <pub-id pub-id-type="pmid">40022190</pub-id></mixed-citation></ref>
<ref id="ref8"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Beaudry</surname><given-names>G.</given-names></name> <name><surname>Yu</surname><given-names>R.</given-names></name> <name><surname>Perry</surname><given-names>A. E.</given-names></name> <name><surname>Fazel</surname><given-names>S.</given-names></name></person-group> (<year>2021</year>). <article-title>Effectiveness of psychological interventions in prison to reduce recidivism: a systematic review and meta-analysis of randomised controlled trials</article-title>. <source>Lancet Psychiatry</source> <volume>8</volume>, <fpage>759</fpage>&#x2013;<lpage>773</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S2215-0366(21)00170-X</pub-id>, <pub-id pub-id-type="pmid">34419185</pub-id></mixed-citation></ref>
<ref id="ref9"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bianjiang</surname><given-names>Z.</given-names></name> <name><surname>Jianchun</surname><given-names>Z.</given-names></name> <name><surname>Xiaoyu</surname><given-names>S.</given-names></name> <name><surname>Jian</surname><given-names>Y.</given-names></name></person-group> (<year>2025</year>). <article-title>Mind-body intervention for post-traumatic stress disorder in adolescents: a systematic review and network meta-analysis</article-title>. <source>BMC Psychiatry</source> <volume>25</volume>:<fpage>178</fpage>. doi: <pub-id pub-id-type="doi">10.1186/s12888-025-06543-1</pub-id></mixed-citation></ref>
<ref id="ref10"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brooker</surname><given-names>B. H.</given-names></name> <name><surname>Jeon</surname><given-names>J.</given-names></name> <name><surname>Goldstein Ferber</surname><given-names>S.</given-names></name> <name><surname>Bhatt</surname><given-names>R. S.</given-names></name> <name><surname>Decety</surname><given-names>J.</given-names></name> <name><surname>Bhatt</surname><given-names>M. A.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Neural correlates of empathy across species: evolutionary insights</article-title>. <source>Trends Cogn. Sci.</source> <volume>28</volume>, <fpage>312</fpage>&#x2013;<lpage>325</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.tics.2024.01.003</pub-id></mixed-citation></ref>
<ref id="ref11"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brown</surname><given-names>N.</given-names></name> <name><surname>Ashcroft</surname><given-names>K.</given-names></name></person-group> (<year>2025</year>). <article-title>The effectiveness of compassion-focused therapy for the three flows of compassion, self-criticism, and shame in clinical populations: a systematic review</article-title>. <source>Behav. Sci.</source> <volume>15</volume>:<fpage>1031</fpage>. doi: <pub-id pub-id-type="doi">10.3390/bs15081031</pub-id>, <pub-id pub-id-type="pmid">40867388</pub-id></mixed-citation></ref>
<ref id="ref12"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Byrne</surname><given-names>M.</given-names></name> <name><surname>Campos</surname><given-names>C.</given-names></name> <name><surname>Daly</surname><given-names>S.</given-names></name> <name><surname>Lok</surname><given-names>B.</given-names></name> <name><surname>Miles</surname><given-names>A.</given-names></name></person-group> (<year>2024</year>). <article-title>The current state of empathy, compassion and person-centred communication training in healthcare: an umbrella review</article-title>. <source>Patient Educ. Couns.</source> <volume>119</volume>:<fpage>108063</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.pec.2023.108063</pub-id>, <pub-id pub-id-type="pmid">38008647</pub-id></mixed-citation></ref>
<ref id="ref13"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Calderone</surname><given-names>A.</given-names></name> <name><surname>Latella</surname><given-names>D.</given-names></name> <name><surname>Impellizzeri</surname><given-names>F.</given-names></name> <name><surname>de Pasquale</surname><given-names>P.</given-names></name> <name><surname>Fam&#x00E0;</surname><given-names>F.</given-names></name> <name><surname>Quartarone</surname><given-names>A.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Neurobiological changes induced by mindfulness and meditation: a systematic review</article-title>. <source>Biomedicine</source> <volume>12</volume>:<fpage>2613</fpage>. doi: <pub-id pub-id-type="doi">10.3390/biomedicines12112613</pub-id>, <pub-id pub-id-type="pmid">39595177</pub-id></mixed-citation></ref>
<ref id="ref14"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Camilleri</surname><given-names>L. J.</given-names></name> <name><surname>Maras</surname><given-names>K.</given-names></name> <name><surname>Brosnan</surname><given-names>M.</given-names></name></person-group> (<year>2025</year>). <article-title>Self-set goals: autistic adults facilitating their self-determination through digitally mediated social stories</article-title>. <source>Autism Adulthood</source> <volume>7</volume>, <fpage>25</fpage>&#x2013;<lpage>38</lpage>. doi: <pub-id pub-id-type="doi">10.1089/aut.2023.0122</pub-id>, <pub-id pub-id-type="pmid">40151659</pub-id></mixed-citation></ref>
<ref id="ref15"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chander</surname><given-names>R. J.</given-names></name> <name><surname>Mather</surname><given-names>K. A.</given-names></name> <name><surname>Cleary</surname><given-names>R.</given-names></name> <name><surname>Grainger</surname><given-names>S. A.</given-names></name> <name><surname>Kochan</surname><given-names>N. A.</given-names></name> <name><surname>Henry</surname><given-names>J. D.</given-names></name> <etal/></person-group>. (<year>2022</year>). <article-title>The influence of rs53576 polymorphism in the oxytocin receptor gene on empathy by subtype and ethnicity: a systematic review and meta-analysis</article-title>. <source>Rev. Neurosci.</source> <volume>33</volume>, <fpage>43</fpage>&#x2013;<lpage>57</lpage>. doi: <pub-id pub-id-type="doi">10.1515/revneuro-2020-0120</pub-id></mixed-citation></ref>
<ref id="ref16"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cheang</surname><given-names>R. T.</given-names></name> <name><surname>Skjevling</surname><given-names>M.</given-names></name> <name><surname>Blakemore</surname><given-names>A. I.</given-names></name> <name><surname>McEwen</surname><given-names>F. S.</given-names></name> <name><surname>Rijsdijk</surname><given-names>F.</given-names></name> <name><surname>Happ&#x00E9;</surname><given-names>F.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>Do you feel me? Autism, empathic accuracy and the double empathy problem</article-title>. <source>Autism</source> <volume>29</volume>, <fpage>2315</fpage>&#x2013;<lpage>2327</lpage>. doi: <pub-id pub-id-type="doi">10.1177/13623613251316534</pub-id></mixed-citation></ref>
<ref id="ref17"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chou</surname><given-names>Y.</given-names></name> <name><surname>Chen</surname><given-names>T. Y.</given-names></name></person-group> (<year>2021</year>). <article-title>Disruption on right temporoparietal junction with transcranial magnetic stimulation affects moral judgment</article-title>. <source>Neuropsychologia</source> <volume>157</volume>:<fpage>107858</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neuropsychologia.2021.107858</pub-id></mixed-citation></ref>
<ref id="ref18"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Christensen</surname><given-names>M. C.</given-names></name> <name><surname>Ren</surname><given-names>H.</given-names></name> <name><surname>Fagiolini</surname><given-names>A.</given-names></name></person-group> (<year>2022</year>). <article-title>Emotional blunting in patients with depression. Part I: clinical characteristics</article-title>. <source>Ann. General Psychiatry</source> <volume>21</volume>:<fpage>10</fpage>. doi: <pub-id pub-id-type="doi">10.1186/s12991-022-00387-1</pub-id>, <pub-id pub-id-type="pmid">35379283</pub-id></mixed-citation></ref>
<ref id="ref19"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Christov-Moore</surname><given-names>L.</given-names></name> <name><surname>Simpson</surname><given-names>E. A.</given-names></name> <name><surname>Coud&#x00E9;</surname><given-names>G.</given-names></name> <name><surname>Grigaityte</surname><given-names>K.</given-names></name> <name><surname>Iacoboni</surname><given-names>M.</given-names></name> <name><surname>Ferrari</surname><given-names>P. F.</given-names></name></person-group> (<year>2014</year>). <article-title>Empathy: gender effects in brain and behavior</article-title>. <source>Neurosci. Biobehav. Rev.</source> <volume>46 Pt 4</volume>, <fpage>604</fpage>&#x2013;<lpage>627</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neubiorev.2014.09.001</pub-id>, <pub-id pub-id-type="pmid">25236781</pub-id></mixed-citation></ref>
<ref id="ref20"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chua</surname><given-names>J. Y. X.</given-names></name> <name><surname>Ang</surname><given-names>E.</given-names></name> <name><surname>Lau</surname><given-names>S. T. L.</given-names></name> <name><surname>Shorey</surname><given-names>S.</given-names></name></person-group> (<year>2021</year>). <article-title>Effectiveness of simulation-based interventions at improving empathy among healthcare students</article-title>. <source>Nurse Educ. Today</source> <volume>104</volume>:<fpage>105000</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.nedt.2021.105000</pub-id>, <pub-id pub-id-type="pmid">34146845</pub-id></mixed-citation></ref>
<ref id="ref21"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cipriano</surname><given-names>C.</given-names></name> <name><surname>Strambler</surname><given-names>M. J.</given-names></name> <name><surname>Naples</surname><given-names>L. H.</given-names></name> <name><surname>Ha</surname><given-names>C.</given-names></name> <name><surname>Kirk</surname><given-names>M.</given-names></name> <name><surname>Durlak</surname><given-names>J.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>The state of evidence for social and emotional learning: a contemporary meta-analysis</article-title>. <source>Child Dev.</source> <volume>94</volume>, <fpage>1181</fpage>&#x2013;<lpage>1204</lpage>. doi: <pub-id pub-id-type="doi">10.1111/cdev.13968</pub-id></mixed-citation></ref>
<ref id="ref22"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Conversano</surname><given-names>C.</given-names></name> <name><surname>Ciacchini</surname><given-names>R.</given-names></name> <name><surname>Orr&#x00F9;</surname><given-names>G.</given-names></name> <name><surname>Di Giuseppe</surname><given-names>M.</given-names></name> <name><surname>Gemignani</surname><given-names>A.</given-names></name> <name><surname>Poli</surname><given-names>A.</given-names></name></person-group>. (<year>2020</year>). <article-title>Mindfulness, compassion, and self-compassion among health care professionals</article-title>. <source>Front. Psychol.</source> <volume>11</volume>:<fpage>1683</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fpsyg.2020.01683</pub-id></mixed-citation></ref>
<ref id="ref23"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cooper</surname><given-names>D.</given-names></name> <name><surname>Yap</surname><given-names>K.</given-names></name> <name><surname>O'Brien</surname><given-names>M.</given-names></name> <name><surname>Scott</surname><given-names>I.</given-names></name></person-group> (<year>2020</year>). <article-title>Mindfulness and empathy among counseling and psychotherapy professionals</article-title>. <source>Mindfulness</source> <volume>11</volume>, <fpage>2243</fpage>&#x2013;<lpage>2257</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s12671-020-01446-6</pub-id></mixed-citation></ref>
<ref id="ref24"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cox</surname><given-names>S. S.</given-names></name> <name><surname>Kearns</surname><given-names>A. M.</given-names></name> <name><surname>Woods</surname><given-names>S. K.</given-names></name> <name><surname>Brown</surname><given-names>B. J.</given-names></name> <name><surname>Brown</surname><given-names>S. J.</given-names></name> <name><surname>Reichel</surname><given-names>C. M.</given-names></name></person-group> (<year>2022</year>). <article-title>The role of the anterior insula during targeted helping behavior in male rats</article-title>. <source>Sci. Rep.</source> <volume>12</volume>:<fpage>3315</fpage>. doi: <pub-id pub-id-type="doi">10.1038/s41598-022-07365-3</pub-id>, <pub-id pub-id-type="pmid">35228625</pub-id></mixed-citation></ref>
<ref id="ref25"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Craig</surname><given-names>A. D.</given-names></name></person-group> (<year>2009</year>). <article-title>How do you feel&#x2014;now? The anterior insula and human awareness</article-title>. <source>Nat. Rev. Neurosci.</source> <volume>10</volume>, <fpage>59</fpage>&#x2013;<lpage>70</lpage>. doi: <pub-id pub-id-type="doi">10.1038/nrn2555</pub-id>, <pub-id pub-id-type="pmid">19096369</pub-id></mixed-citation></ref>
<ref id="ref26"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Decety</surname><given-names>J.</given-names></name> <name><surname>Bartal</surname><given-names>I. B.-A.</given-names></name> <name><surname>Uzefovsky</surname><given-names>F.</given-names></name> <name><surname>Knafo-Noam</surname><given-names>A.</given-names></name></person-group> (<year>2016</year>). <article-title>Empathy as a driver of prosocial behaviour: highly conserved neurobehavioural mechanisms across species</article-title>. <source>Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci.</source> <volume>371</volume>:<fpage>20150077</fpage>. doi: <pub-id pub-id-type="doi">10.1098/rstb.2015.0077</pub-id>, <pub-id pub-id-type="pmid">26644596</pub-id></mixed-citation></ref>
<ref id="ref27"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eichbaum</surname><given-names>Q.</given-names></name> <name><surname>Barbeau-Meunier</surname><given-names>C. A.</given-names></name> <name><surname>White</surname><given-names>M.</given-names></name> <name><surname>C&#x00F4;t&#x00E9;</surname><given-names>L.</given-names></name> <name><surname>Hausse</surname><given-names>L.</given-names></name> <name><surname>de Lalouvi&#x00E8;re</surname><given-names>G.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>Empathy across cultures&#x2014;one size does not fit all</article-title>. <source>Adv. Health Sci. Educ.</source> <volume>28</volume>, <fpage>643</fpage>&#x2013;<lpage>657</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s10459-022-10172-6</pub-id></mixed-citation></ref>
<ref id="ref28"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ferguson</surname><given-names>H. J.</given-names></name> <name><surname>De Lillo</surname><given-names>M.</given-names></name> <name><surname>Woodrow-Hill</surname><given-names>C.</given-names></name> <name><surname>Foley</surname><given-names>R.</given-names></name> <name><surname>Bradford</surname><given-names>E. E. F.</given-names></name></person-group> (<year>2024</year>). <article-title>Neural empathy mechanisms are shared for physical and social pain, and increase from adolescence to older adulthood</article-title>. <source>Soc. Cogn. Affect. Neurosci.</source> <volume>19</volume>:<fpage>nsae080</fpage>. doi: <pub-id pub-id-type="doi">10.1093/scan/nsae080</pub-id>, <pub-id pub-id-type="pmid">39492751</pub-id></mixed-citation></ref>
<ref id="ref29"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Galante</surname><given-names>J.</given-names></name> <name><surname>Friedrich</surname><given-names>C.</given-names></name> <name><surname>Aeamla-Or</surname><given-names>N.</given-names></name> <name><surname>Arts</surname><given-names>I.</given-names></name> <name><surname>B&#x00F6;gels</surname><given-names>S. M.</given-names></name> <name><surname>Buitelaar</surname><given-names>J. K.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>Systematic review and individual participant data meta-analysis of randomized controlled trials assessing mindfulness-based programs for mental health promotion</article-title>. <source>Nat. Ment. Health</source> <volume>1</volume>, <fpage>462</fpage>&#x2013;<lpage>476</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s44220-023-00081-1</pub-id></mixed-citation></ref>
<ref id="ref30"><mixed-citation publication-type="other"><person-group person-group-type="author"><name><surname>Gazzola</surname><given-names>V.</given-names></name></person-group> (<year>2018</year>). <source>HelpUS: pioneering focused ultrasounds as a new non-invasive deep brain stimulation for causal investigation of empathy</source>. European Research Council (ERC) Advanced Grant No. 758703. <publisher-name>European Research Council</publisher-name>, <publisher-loc>Brussels, Belgium</publisher-loc>.</mixed-citation></ref>
<ref id="ref31"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Greenberg</surname><given-names>D. M.</given-names></name> <name><surname>Baron-Cohen</surname><given-names>S.</given-names></name> <name><surname>Rosenberg</surname><given-names>N.</given-names></name> <name><surname>Fonagy</surname><given-names>P.</given-names></name> <name><surname>Rentfrow</surname><given-names>P. J.</given-names></name></person-group> (<year>2018</year>). <article-title>Elevated empathy in adults following childhood trauma</article-title>. <source>PLoS One</source> <volume>13</volume>:<fpage>e0203886</fpage>. doi: <pub-id pub-id-type="doi">10.1371/journal.pone.0203886</pub-id>, <pub-id pub-id-type="pmid">30281628</pub-id></mixed-citation></ref>
<ref id="ref32"><mixed-citation publication-type="other"><person-group person-group-type="author"><name><surname>Haynes</surname><given-names>B.</given-names></name> <name><surname>Ortega</surname><given-names>H. K.</given-names></name> <name><surname>Damisah</surname><given-names>E. C.</given-names></name> <name><surname>Bhatt</surname><given-names>M. A.</given-names></name> <name><surname>Bickel</surname><given-names>S.</given-names></name> <name><surname>Mehta</surname><given-names>A. D.</given-names></name> <etal/></person-group>. (<year>2025</year>). The neural basis of emotional generalization in empathy. [Epubh ahead of print] doi: <pub-id pub-id-type="doi">10.1101/2025.10.18.683207</pub-id></mixed-citation></ref>
<ref id="ref33"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Holleman</surname><given-names>G. A.</given-names></name> <name><surname>Hooge</surname><given-names>I. T. C.</given-names></name> <name><surname>Kemner</surname><given-names>C.</given-names></name> <name><surname>Hessels</surname><given-names>R. S.</given-names></name></person-group> (<year>2020</year>). <article-title>The 'real-world approach' and its problems: a critique of the term ecological validity</article-title>. <source>Front. Psychol.</source> <volume>11</volume>:<fpage>721</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fpsyg.2020.00721</pub-id>, <pub-id pub-id-type="pmid">32425850</pub-id></mixed-citation></ref>
<ref id="ref34"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hu</surname><given-names>Z.</given-names></name> <name><surname>Wen</surname><given-names>Y.</given-names></name> <name><surname>Wang</surname><given-names>Y.</given-names></name> <name><surname>Lin</surname><given-names>Y.</given-names></name> <name><surname>Shi</surname><given-names>J.</given-names></name> <name><surname>Yu</surname><given-names>Z.</given-names></name> <etal/></person-group>. (<year>2022</year>). <article-title>Effectiveness of mindfulness-based interventions on empathy: a meta-analysis</article-title>. <source>Front. Psychol.</source> <volume>13</volume>:<fpage>992575</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fpsyg.2022.992575</pub-id>, <pub-id pub-id-type="pmid">36337535</pub-id></mixed-citation></ref>
<ref id="ref35"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hurissa</surname><given-names>B. F.</given-names></name> <name><surname>Koricha</surname><given-names>Z. B.</given-names></name> <name><surname>Dadi</surname><given-names>L. S.</given-names></name></person-group> (<year>2023</year>). <article-title>Effect of empathy training on the empathy level of healthcare providers in Ethiopia</article-title>. <source>Front. Psychol.</source> <volume>14</volume>:<fpage>1091605</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fpsyg.2023.1091605</pub-id>, <pub-id pub-id-type="pmid">37284470</pub-id></mixed-citation></ref>
<ref id="ref36"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jami</surname><given-names>P. Y.</given-names></name> <name><surname>Walker</surname><given-names>D. I.</given-names></name> <name><surname>Mansouri</surname><given-names>B.</given-names></name></person-group> (<year>2024</year>). <article-title>Interaction of empathy and culture: a review</article-title>. <source>Curr. Psychol.</source> <volume>43</volume>, <fpage>2965</fpage>&#x2013;<lpage>2980</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s12144-022-03028-0</pub-id></mixed-citation></ref>
<ref id="ref37"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jiang</surname><given-names>Q.</given-names></name> <name><surname>Zhuo</surname><given-names>L.</given-names></name> <name><surname>Wang</surname><given-names>Q.</given-names></name> <name><surname>Lin</surname><given-names>W.</given-names></name></person-group> (<year>2022</year>). <article-title>The neural basis of moral judgement for self and for others</article-title>. <source>Front. Hum. Neurosci.</source> <volume>16</volume>:<fpage>919499</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fnhum.2022.919499</pub-id>, <pub-id pub-id-type="pmid">35693541</pub-id></mixed-citation></ref>
<ref id="ref38"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jungwirth</surname><given-names>J.</given-names></name> <name><surname>von Rotz</surname><given-names>R.</given-names></name> <name><surname>Dziobek</surname><given-names>I.</given-names></name> <name><surname>Vollenweider</surname><given-names>F. X.</given-names></name> <name><surname>Preller</surname><given-names>K. H.</given-names></name></person-group> (<year>2025</year>). <article-title>Psilocybin increases emotional empathy in patients with major depression</article-title>. <source>Mol. Psychiatry</source> <volume>30</volume>, <fpage>2665</fpage>&#x2013;<lpage>2672</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41380-024-02875-0</pub-id>, <pub-id pub-id-type="pmid">39695323</pub-id></mixed-citation></ref>
<ref id="ref39"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>S. A.</given-names></name> <name><surname>Hamann</surname><given-names>S.</given-names></name> <name><surname>Kim</surname><given-names>S. H.</given-names></name></person-group> (<year>2021</year>). <article-title>Neurocognitive mechanisms underlying improvement of prosocial responses by a novel implicit compassion promotion task</article-title>. <source>NeuroImage</source> <volume>240</volume>:<fpage>118333</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neuroimage.2021.118333</pub-id>, <pub-id pub-id-type="pmid">34229063</pub-id></mixed-citation></ref>
<ref id="ref40"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>M. G.</given-names></name> <name><surname>Yu</surname><given-names>K.</given-names></name> <name><surname>Yeh</surname><given-names>C. Y.</given-names></name> <name><surname>Cannesson</surname><given-names>M.</given-names></name> <name><surname>Bhatt</surname><given-names>D. L.</given-names></name> <name><surname>He</surname><given-names>B.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Low-intensity transcranial focused ultrasound suppresses pain by modulating pain-processing brain circuits</article-title>. <source>Blood</source> <volume>144</volume>, <fpage>1101</fpage>&#x2013;<lpage>1115</lpage>. doi: <pub-id pub-id-type="doi">10.1182/blood.2024024180</pub-id></mixed-citation></ref>
<ref id="ref41"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kogler</surname><given-names>L.</given-names></name> <name><surname>M&#x00FC;ller</surname><given-names>V. I.</given-names></name> <name><surname>Chang</surname><given-names>A.</given-names></name> <name><surname>Eickhoff</surname><given-names>S. B.</given-names></name> <name><surname>Fox</surname><given-names>P. T.</given-names></name> <name><surname>Gur</surname><given-names>R. C.</given-names></name> <etal/></person-group>. (<year>2020</year>). <article-title>Do i feel or do i know? Neuroimaging meta-analyses on the multiple facets of empathy</article-title>. <source>Cortex</source> <volume>129</volume>, <fpage>268</fpage>&#x2013;<lpage>285</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.cortex.2020.04.031</pub-id></mixed-citation></ref>
<ref id="ref42"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kuroda</surname><given-names>K. O.</given-names></name> <name><surname>Kato</surname><given-names>M.</given-names></name> <name><surname>Tsuneoka</surname><given-names>Y.</given-names></name> <name><surname>Shoji</surname><given-names>H.</given-names></name> <name><surname>Nishimori</surname><given-names>K.</given-names></name> <name><surname>Miyata</surname><given-names>T.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Evolutionary neurobiology of parenting and empathy</article-title>. <source>Neurosci. Biobehav. Rev.</source> <volume>158</volume>:<fpage>105543</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neubiorev.2024.105543</pub-id></mixed-citation></ref>
<ref id="ref43"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Langley</surname><given-names>C.</given-names></name> <name><surname>Armand</surname><given-names>S.</given-names></name> <name><surname>Luo</surname><given-names>Q.</given-names></name> <name><surname>Savulich</surname><given-names>G.</given-names></name> <name><surname>Segerberg</surname><given-names>T.</given-names></name> <name><surname>S&#x00F8;ndergaard</surname><given-names>A.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity</article-title>. <source>Neuropsychopharmacology</source> <volume>48</volume>, <fpage>664</fpage>&#x2013;<lpage>670</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41386-022-01523-x</pub-id></mixed-citation></ref>
<ref id="ref44"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>Y.</given-names></name> <name><surname>Shin</surname><given-names>H.</given-names></name> <name><surname>Gil</surname><given-names>Y. H.</given-names></name></person-group> (<year>2024</year>). <article-title>Measurement of empathy in virtual reality with head-mounted displays: a systematic review</article-title>. <source>IEEE Trans. Vis. Comput. Graph.</source> <volume>30</volume>, <fpage>2485</fpage>&#x2013;<lpage>2495</lpage>. doi: <pub-id pub-id-type="doi">10.1109/TVCG.2024.3372074</pub-id>, <pub-id pub-id-type="pmid">38437085</pub-id></mixed-citation></ref>
<ref id="ref45"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Legon</surname><given-names>W.</given-names></name> <name><surname>Strohman</surname><given-names>A.</given-names></name> <name><surname>In</surname><given-names>A.</given-names></name> <name><surname>Payne</surname><given-names>B.</given-names></name></person-group> (<year>2024</year>). <article-title>Noninvasive neuromodulation of subregions of the human insula differentially affect pain processing and heart-rate variability</article-title>. <source>Pain</source> <volume>165</volume>, <fpage>1625</fpage>&#x2013;<lpage>1641</lpage>. doi: <pub-id pub-id-type="doi">10.1097/j.pain.0000000000003177</pub-id>, <pub-id pub-id-type="pmid">38284396</pub-id></mixed-citation></ref>
<ref id="ref46"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Levy</surname><given-names>J.</given-names></name> <name><surname>Goldstein</surname><given-names>A.</given-names></name> <name><surname>Feldman</surname><given-names>R.</given-names></name></person-group> (<year>2019</year>). <article-title>The neural development of empathy is sensitive to caregiving and early trauma</article-title>. <source>Nat. Commun.</source> <volume>10</volume>:<fpage>1905</fpage>. doi: <pub-id pub-id-type="doi">10.1038/s41467-019-09927-y</pub-id>, <pub-id pub-id-type="pmid">31015471</pub-id></mixed-citation></ref>
<ref id="ref47"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liang</surname><given-names>X.</given-names></name> <name><surname>Wang</surname><given-names>Y.</given-names></name> <name><surname>Chen</surname><given-names>H.</given-names></name> <name><surname>Zhang</surname><given-names>L.</given-names></name> <name><surname>Liu</surname><given-names>M.</given-names></name> <name><surname>Wu</surname><given-names>J.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>Dopaminergic pathways and developmental trajectories of empathy</article-title>. <source>Dev. Cogn. Neurosci.</source> <volume>71</volume>:<fpage>101456</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.dcn.2025.101456</pub-id></mixed-citation></ref>
<ref id="ref48"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lima</surname><given-names>F. F.</given-names></name> <name><surname>Os&#x00F3;rio</surname><given-names>F. L.</given-names></name></person-group> (<year>2021</year>). <article-title>Empathy: assessment instruments and psychometric quality</article-title>. <source>Front. Psychol.</source> <volume>12</volume>:<fpage>781346</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fpsyg.2021.781346</pub-id>, <pub-id pub-id-type="pmid">34899531</pub-id></mixed-citation></ref>
<ref id="ref49"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lu</surname><given-names>Y.</given-names></name> <name><surname>Lau</surname><given-names>S. K.</given-names></name></person-group> (<year>2025</year>). <article-title>The ecological validity of laboratory experiments in soundscape and landscape research: a systematic review and meta-analysis</article-title>. <source>Appl. Acoust.</source> <volume>232</volume>:<fpage>110582</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.apacoust.2024.110582</pub-id></mixed-citation></ref>
<ref id="ref50"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ma</surname><given-names>H.</given-names></name> <name><surname>Cai</surname><given-names>M.</given-names></name> <name><surname>Wang</surname><given-names>H.</given-names></name></person-group> (<year>2021</year>). <article-title>Emotional blunting in patients with major depressive disorder</article-title>. <source>Front. Psych.</source> <volume>12</volume>:<fpage>792960</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fpsyt.2021.792960</pub-id>, <pub-id pub-id-type="pmid">34970173</pub-id></mixed-citation></ref>
<ref id="ref51"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marsh</surname><given-names>N.</given-names></name> <name><surname>Marsh</surname><given-names>A. A.</given-names></name> <name><surname>Lee</surname><given-names>M. R.</given-names></name> <name><surname>Hurlemann</surname><given-names>R.</given-names></name></person-group> (<year>2021</year>). <article-title>Oxytocin and the neurobiology of prosocial behavior</article-title>. <source>Neuroscientist</source> <volume>27</volume>, <fpage>604</fpage>&#x2013;<lpage>619</lpage>. doi: <pub-id pub-id-type="doi">10.1177/1073858420960111</pub-id>, <pub-id pub-id-type="pmid">32981445</pub-id></mixed-citation></ref>
<ref id="ref52"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martin</surname><given-names>E.</given-names></name> <name><surname>Aubry</surname><given-names>J. F.</given-names></name> <name><surname>Bhatt</surname><given-names>S.</given-names></name> <name><surname>Bhatt</surname><given-names>D. L.</given-names></name> <name><surname>Bystritsky</surname><given-names>A.</given-names></name> <name><surname>Cohen</surname><given-names>S. L.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Updated international consensus on safety for transcranial ultrasonic neuromodulation</article-title>. <source>Brain Stimul.</source> <volume>17</volume>, <fpage>674</fpage>&#x2013;<lpage>691</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.brs.2024.05.006</pub-id></mixed-citation></ref>
<ref id="ref53"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martingano</surname><given-names>A. J.</given-names></name> <name><surname>Hererra</surname><given-names>F.</given-names></name> <name><surname>Konrath</surname><given-names>S.</given-names></name></person-group> (<year>2021</year>). <article-title>Virtual reality improves emotional but not cognitive empathy: a meta-analysis</article-title>. <source>Technol. Mind Behav.</source> <volume>2</volume>:<fpage>TMB0000034</fpage>. doi: <pub-id pub-id-type="doi">10.1037/tmb0000034</pub-id></mixed-citation></ref>
<ref id="ref54"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martins</surname><given-names>D.</given-names></name> <name><surname>Gomes</surname><given-names>A. R.</given-names></name> <name><surname>Lopes</surname><given-names>S.</given-names></name> <name><surname>Pinto</surname><given-names>E.</given-names></name> <name><surname>Ferreira</surname><given-names>A.</given-names></name> <name><surname>Cunha</surname><given-names>M.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>Workplace-based compassion interventions: a systematic review</article-title>. <source>J. Occup. Health Psychol.</source> <volume>30</volume>, <fpage>45</fpage>&#x2013;<lpage>62</lpage>. doi: <pub-id pub-id-type="doi">10.1037/ocp0000345</pub-id></mixed-citation></ref>
<ref id="ref55"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsushita</surname><given-names>H.</given-names></name> <name><surname>Nishiki</surname><given-names>T.</given-names></name></person-group> (<year>2025</year>). <article-title>Human social behavior and oxytocin: molecular and neuronal mechanisms</article-title>. <source>Neuroscience</source> <volume>570</volume>, <fpage>48</fpage>&#x2013;<lpage>54</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neuroscience.2025.01.015</pub-id>, <pub-id pub-id-type="pmid">39961388</pub-id></mixed-citation></ref>
<ref id="ref56"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Millard</surname><given-names>L. A.</given-names></name> <name><surname>Wan</surname><given-names>M. W.</given-names></name> <name><surname>Smith</surname><given-names>D. M.</given-names></name> <name><surname>Wittkowski</surname><given-names>A.</given-names></name></person-group> (<year>2023</year>). <article-title>The effectiveness of compassion focused therapy with clinical populations: a systematic review and meta-analysis</article-title>. <source>J. Affect. Disord.</source> <volume>326</volume>, <fpage>168</fpage>&#x2013;<lpage>192</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.jad.2023.01.010</pub-id>, <pub-id pub-id-type="pmid">36649790</pub-id></mixed-citation></ref>
<ref id="ref57"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miller</surname><given-names>J. G.</given-names></name> <name><surname>Xia</surname><given-names>G.</given-names></name> <name><surname>Hastings</surname><given-names>P. D.</given-names></name></person-group> (<year>2020</year>). <article-title>Right temporoparietal junction involvement in autonomic responses to the suffering of others</article-title>. <source>Front. Hum. Neurosci.</source> <volume>14</volume>:<fpage>7</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fnhum.2020.00007</pub-id>, <pub-id pub-id-type="pmid">32047426</pub-id></mixed-citation></ref>
<ref id="ref58"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mitchell</surname><given-names>J. M.</given-names></name> <name><surname>Bogenschutz</surname><given-names>M.</given-names></name> <name><surname>Lilienstein</surname><given-names>A.</given-names></name> <name><surname>Harrison</surname><given-names>C.</given-names></name> <name><surname>Kleiman</surname><given-names>S.</given-names></name> <name><surname>Parker-Guilbert</surname><given-names>K.</given-names></name> <etal/></person-group>. (<year>2021</year>). <article-title>MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study</article-title>. <source>Nat. Med.</source> <volume>27</volume>, <fpage>1025</fpage>&#x2013;<lpage>1033</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41591-021-01336-3</pub-id>, <pub-id pub-id-type="pmid">33972795</pub-id></mixed-citation></ref>
<ref id="ref59"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mitchell</surname><given-names>J. M.</given-names></name> <name><surname>Ot'alora</surname><given-names>G. M.</given-names></name> <name><surname>van der Kolk</surname><given-names>B.</given-names></name> <name><surname>Shannon</surname><given-names>S.</given-names></name> <name><surname>Bogenschutz</surname><given-names>M.</given-names></name> <name><surname>Gelfand</surname><given-names>Y.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial</article-title>. <source>Nat. Med.</source> <volume>29</volume>, <fpage>2473</fpage>&#x2013;<lpage>2480</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41591-023-02565-4</pub-id>, <pub-id pub-id-type="pmid">37709999</pub-id></mixed-citation></ref>
<ref id="ref60"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Modak</surname><given-names>A.</given-names></name> <name><surname>Fitzgerald</surname><given-names>P. B.</given-names></name> <name><surname>Engel</surname><given-names>S.</given-names></name> <name><surname>Rogasch</surname><given-names>N. C.</given-names></name> <name><surname>Segrave</surname><given-names>R. A.</given-names></name> <name><surname>Hoy</surname><given-names>K. E.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Temporal interference stimulation enhances episodic memory</article-title>. <source>J. Cogn. Enhanc.</source> <volume>8</volume>, <fpage>112</fpage>&#x2013;<lpage>125</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s41465-024-00298-1</pub-id></mixed-citation></ref>
<ref id="ref61"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moudatsou</surname><given-names>M.</given-names></name> <name><surname>Stavropoulou</surname><given-names>A.</given-names></name> <name><surname>Philalithis</surname><given-names>A.</given-names></name> <name><surname>Koukouli</surname><given-names>S.</given-names></name></person-group> (<year>2020</year>). <article-title>The role of empathy in health and social care professionals</article-title>. <source>Healthcare</source> <volume>8</volume>:<fpage>26</fpage>. doi: <pub-id pub-id-type="doi">10.3390/healthcare8010026</pub-id>, <pub-id pub-id-type="pmid">32019104</pub-id></mixed-citation></ref>
<ref id="ref62"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Murphy</surname><given-names>K.</given-names></name> <name><surname>Bhatt</surname><given-names>S.</given-names></name> <name><surname>Martin</surname><given-names>E.</given-names></name> <name><surname>Aubry</surname><given-names>J. F.</given-names></name> <name><surname>Bhatt</surname><given-names>D. L.</given-names></name> <name><surname>Bystritsky</surname><given-names>A.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>Safety guidelines for transcranial ultrasonic stimulation: updated ITRUSST recommendations</article-title>. <source>Brain Stimul.</source> <volume>18</volume>, <fpage>45</fpage>&#x2013;<lpage>58</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.brs.2025.01.002</pub-id></mixed-citation></ref>
<ref id="ref63"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nembhard</surname><given-names>I. M.</given-names></name> <name><surname>David</surname><given-names>G.</given-names></name> <name><surname>Ezzeddine</surname><given-names>I.</given-names></name> <name><surname>Bhatt</surname><given-names>D. L.</given-names></name> <name><surname>Bhatt</surname><given-names>S.</given-names></name> <name><surname>Bodenheimer</surname><given-names>T.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>A systematic review of research on empathy in health care</article-title>. <source>Health Serv. Res.</source> <volume>58</volume>, <fpage>250</fpage>&#x2013;<lpage>263</lpage>. doi: <pub-id pub-id-type="doi">10.1111/1475-6773.14102</pub-id></mixed-citation></ref>
<ref id="ref64"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Niles</surname><given-names>B.</given-names></name> <name><surname>Lang</surname><given-names>A.</given-names></name> <name><surname>Olff</surname><given-names>M.</given-names></name></person-group> (<year>2023</year>). <article-title>Complementary and integrative interventions for PTSD</article-title>. <source>Eur. J. Psychotraumatol.</source> <volume>14</volume>:<fpage>2247888</fpage>. doi: <pub-id pub-id-type="doi">10.1080/20008066.2023.2247888</pub-id>, <pub-id pub-id-type="pmid">37655624</pub-id></mixed-citation></ref>
<ref id="ref65"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paradiso</surname><given-names>E.</given-names></name> <name><surname>Gazzola</surname><given-names>V.</given-names></name> <name><surname>Keysers</surname><given-names>C.</given-names></name></person-group> (<year>2021</year>). <article-title>Neural mechanisms necessary for empathy-related phenomena across species</article-title>. <source>Curr. Opin. Neurobiol.</source> <volume>68</volume>, <fpage>107</fpage>&#x2013;<lpage>115</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.conb.2021.02.005</pub-id>, <pub-id pub-id-type="pmid">33756399</pub-id></mixed-citation></ref>
<ref id="ref66"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paulus</surname><given-names>C. M.</given-names></name> <name><surname>Meinken</surname><given-names>S.</given-names></name></person-group> (<year>2022</year>). <article-title>The effectiveness of empathy training in health care: a meta-analysis</article-title>. <source>Int. J. Med. Educ.</source> <volume>13</volume>, <fpage>1</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.5116/ijme.619e.c2b3</pub-id>, <pub-id pub-id-type="pmid">35092671</pub-id></mixed-citation></ref>
<ref id="ref67"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pellow</surname><given-names>C.</given-names></name> <name><surname>O&#x2019;Reilly</surname><given-names>M. A.</given-names></name> <name><surname>Bhatt</surname><given-names>S.</given-names></name> <name><surname>Bhatt</surname><given-names>D. L.</given-names></name> <name><surname>Hynynen</surname><given-names>K.</given-names></name> <name><surname>Bhatt</surname><given-names>M. A.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Mechanistic insights into focused ultrasound neuromodulation</article-title>. <source>Nat. Rev. Neurosci.</source> <volume>25</volume>, <fpage>412</fpage>&#x2013;<lpage>428</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41583-024-00812-2</pub-id></mixed-citation></ref>
<ref id="ref68"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pira</surname><given-names>G. L.</given-names></name> <name><surname>Ruini</surname><given-names>C.</given-names></name> <name><surname>Vescovelli</surname><given-names>F.</given-names></name> <name><surname>Gatta</surname><given-names>M.</given-names></name> <name><surname>Porro</surname><given-names>G.</given-names></name> <name><surname>Vanini</surname><given-names>G.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>Could empathy be taught? The role of advanced technologies to foster empathy in medical students</article-title>. <source>J. Med. Syst.</source> <volume>49</volume>:<fpage>6</fpage>. doi: <pub-id pub-id-type="doi">10.1007/s10916-024-02134-5</pub-id></mixed-citation></ref>
<ref id="ref69"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ramanathan</surname><given-names>M.</given-names></name></person-group> (<year>2025</year>). <article-title>The UNESCO draft recommendations on ethics of neurotechnology&#x2014;a commentary</article-title>. <source>Indian J Med Ethics</source> <volume>10</volume>, <fpage>89</fpage>&#x2013;<lpage>91</lpage>. doi: <pub-id pub-id-type="doi">10.20529/IJME.2025.012</pub-id></mixed-citation></ref>
<ref id="ref70"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reardon</surname><given-names>S.</given-names></name></person-group> (<year>2024</year>). <article-title>MDMA therapy for PTSD rejected by FDA panel</article-title>. <source>Nature</source>. <volume>629</volume>, <fpage>20</fpage>&#x2013;<lpage>21</lpage>. doi: <pub-id pub-id-type="doi">10.1038/d41586-024-01622-3</pub-id>, <pub-id pub-id-type="pmid">38844808</pub-id></mixed-citation></ref>
<ref id="ref71"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rein</surname><given-names>B.</given-names></name> <name><surname>Raymond</surname><given-names>K.</given-names></name> <name><surname>Boustani</surname><given-names>C.</given-names></name> <name><surname>Tuy</surname><given-names>S.</given-names></name> <name><surname>Zhang</surname><given-names>J.</given-names></name> <name><surname>St Laurent</surname><given-names>R.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens</article-title>. <source>Sci. Adv.</source> <volume>10</volume>:<fpage>eadl6554</fpage>. doi: <pub-id pub-id-type="doi">10.1126/sciadv.adl6554</pub-id>, <pub-id pub-id-type="pmid">38657057</pub-id></mixed-citation></ref>
<ref id="ref72"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rinaldi</surname><given-names>C.</given-names></name> <name><surname>Attanasio</surname><given-names>M.</given-names></name> <name><surname>Valenti</surname><given-names>M.</given-names></name> <name><surname>Mazza</surname><given-names>M.</given-names></name> <name><surname>Keller</surname><given-names>R.</given-names></name></person-group> (<year>2021</year>). <article-title>Autism spectrum disorder and personality disorders: comorbidity and differential diagnosis</article-title>. <source>World J. Psychiatry</source> <volume>11</volume>, <fpage>1366</fpage>&#x2013;<lpage>1386</lpage>. doi: <pub-id pub-id-type="doi">10.5498/wjp.v11.i12.1366</pub-id>, <pub-id pub-id-type="pmid">35070783</pub-id></mixed-citation></ref>
<ref id="ref73"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roberts</surname><given-names>B. W.</given-names></name> <name><surname>Puri</surname><given-names>N. K.</given-names></name> <name><surname>Trzeciak</surname><given-names>C. J.</given-names></name> <name><surname>Mazzarelli</surname><given-names>A. J.</given-names></name> <name><surname>Mooney</surname><given-names>E. R.</given-names></name> <name><surname>Trzeciak</surname><given-names>S.</given-names></name></person-group>. (<year>2021</year>). <article-title>Socioeconomic, racial and ethnic differences in patient experience of clinician empathy</article-title>. <source>PLoS One</source> <volume>16</volume>:<fpage>e0247259</fpage>. doi: <pub-id pub-id-type="doi">10.1371/journal.pone.0247259</pub-id></mixed-citation></ref>
<ref id="ref74"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rolls</surname><given-names>E. T.</given-names></name></person-group> (<year>2019</year>). <article-title>The cingulate cortex and limbic systems for emotion, action, and memory</article-title>. <source>Brain Struct. Funct.</source> <volume>224</volume>, <fpage>3001</fpage>&#x2013;<lpage>3018</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s00429-019-01945-2</pub-id>, <pub-id pub-id-type="pmid">31451898</pub-id></mixed-citation></ref>
<ref id="ref75"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roncero</surname><given-names>D.</given-names></name> <name><surname>Moreno-Fern&#x00E1;ndez</surname><given-names>R. D.</given-names></name> <name><surname>Fern&#x00E1;ndez-Moreno</surname><given-names>&#x00C1;.</given-names></name></person-group> (<year>2025</year>). <article-title>Effectiveness of virtual reality interventions for aggression, anger and impulsiveness: a multilevel meta-analysis</article-title>. <source>Aggress. Violent Behav.</source> <volume>81</volume>:<fpage>102034</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.avb.2024.102034</pub-id></mixed-citation></ref>
<ref id="ref76"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rossi</surname><given-names>S.</given-names></name> <name><surname>Antal</surname><given-names>A.</given-names></name> <name><surname>Bestmann</surname><given-names>S.</given-names></name> <name><surname>Bikson</surname><given-names>M.</given-names></name> <name><surname>Brewer</surname><given-names>C.</given-names></name> <name><surname>Brockm&#x00F6;ller</surname><given-names>J.</given-names></name> <etal/></person-group>. (<year>2021</year>). <article-title>Safety and recommendations for TMS use in healthy subjects and patient populations</article-title>. <source>Clin. Neurophysiol.</source> <volume>132</volume>, <fpage>269</fpage>&#x2013;<lpage>306</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.clinph.2020.10.003</pub-id></mixed-citation></ref>
<ref id="ref77"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>R&#x00FC;tgen</surname><given-names>M.</given-names></name> <name><surname>Pletti</surname><given-names>C.</given-names></name> <name><surname>Tik</surname><given-names>M.</given-names></name> <name><surname>Kraus</surname><given-names>C.</given-names></name> <name><surname>Pfabigan</surname><given-names>D. M.</given-names></name> <name><surname>Sladky</surname><given-names>R.</given-names></name> <etal/></person-group>. (<year>2019</year>). <article-title>Antidepressant treatment, not depression, leads to reductions in behavioral and neural responses to pain empathy</article-title>. <source>Transl. Psychiatry</source> <volume>9</volume>:<fpage>164</fpage>. doi: <pub-id pub-id-type="doi">10.1038/s41398-019-0496-4</pub-id>, <pub-id pub-id-type="pmid">31175273</pub-id></mixed-citation></ref>
<ref id="ref78"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saccenti</surname><given-names>D.</given-names></name> <name><surname>Lauro</surname><given-names>L. J. R.</given-names></name> <name><surname>Crespi</surname><given-names>S. A.</given-names></name> <name><surname>Vergallito</surname><given-names>A.</given-names></name> <name><surname>Zanella</surname><given-names>M.</given-names></name> <name><surname>Bolognini</surname><given-names>N.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Boosting psychotherapy with noninvasive brain stimulation</article-title>. <source>Neural Plast.</source> <volume>2024</volume>:<fpage>7853199</fpage>. doi: <pub-id pub-id-type="doi">10.1155/2024/7853199</pub-id></mixed-citation></ref>
<ref id="ref79"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saxe</surname><given-names>R.</given-names></name> <name><surname>Kanwisher</surname><given-names>N.</given-names></name></person-group> (<year>2003</year>). <article-title>People thinking about thinking people: the role of the temporo-parietal junction in 'theory of mind'</article-title>. <source>NeuroImage</source> <volume>19</volume>, <fpage>1835</fpage>&#x2013;<lpage>1842</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S1053-8119(03)00230-1</pub-id>, <pub-id pub-id-type="pmid">12948738</pub-id></mixed-citation></ref>
<ref id="ref80"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schutte</surname><given-names>N. S.</given-names></name> <name><surname>Stilinovi&#x0107;</surname><given-names>E. J.</given-names></name></person-group> (<year>2017</year>). <article-title>Facilitating empathy through virtual reality</article-title>. <source>Motiv. Emot.</source> <volume>41</volume>, <fpage>708</fpage>&#x2013;<lpage>712</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s11031-017-9641-7</pub-id></mixed-citation></ref>
<ref id="ref81"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schwertfeger</surname><given-names>J. L.</given-names></name> <name><surname>Beyer</surname><given-names>C.</given-names></name> <name><surname>Hung</surname><given-names>P.</given-names></name> <name><surname>Ahrens</surname><given-names>A. P.</given-names></name> <name><surname>Leahy</surname><given-names>A. B.</given-names></name> <name><surname>Cook</surname><given-names>N. E.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>A map of evidence using tDCS to improve cognition in adults with TBI</article-title>. <source>Front. Neuroergonomics</source> <volume>4</volume>:<fpage>1170473</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fnrgo.2023.1170473</pub-id></mixed-citation></ref>
<ref id="ref82"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sergiou</surname><given-names>C. S.</given-names></name> <name><surname>Woods</surname><given-names>A. J.</given-names></name> <name><surname>Franken</surname><given-names>I. H. A.</given-names></name> <name><surname>van Dongen</surname><given-names>J. D. M.</given-names></name></person-group> (<year>2020</year>). <article-title>Transcranial direct current stimulation to improve empathic abilities in forensic offenders: study protocol</article-title>. <source>Trials</source> <volume>21</volume>:<fpage>263</fpage>. doi: <pub-id pub-id-type="doi">10.1186/s13063-020-4166-1</pub-id></mixed-citation></ref>
<ref id="ref83"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shamay-Tsoory</surname><given-names>S. G.</given-names></name> <name><surname>Abu-Akel</surname><given-names>A.</given-names></name></person-group> (<year>2016</year>). <article-title>The social salience hypothesis of oxytocin</article-title>. <source>Biol. Psychiatry</source> <volume>79</volume>, <fpage>194</fpage>&#x2013;<lpage>202</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.biopsych.2015.07.020</pub-id></mixed-citation></ref>
<ref id="ref84"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shi</surname><given-names>J.</given-names></name> <name><surname>Cheung</surname><given-names>A. C. K.</given-names></name></person-group> (<year>2024</year>). <article-title>Effective components of social emotional learning programs: a meta-analysis</article-title>. <source>J. Youth Adolesc.</source> <volume>53</volume>, <fpage>755</fpage>&#x2013;<lpage>771</lpage>. doi: <pub-id pub-id-type="doi">10.1007/s10964-023-01913-6</pub-id>, <pub-id pub-id-type="pmid">38280178</pub-id></mixed-citation></ref>
<ref id="ref85"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Singer</surname><given-names>T.</given-names></name> <name><surname>Klimecki</surname><given-names>O. M.</given-names></name></person-group> (<year>2014</year>). <article-title>Empathy and compassion</article-title>. <source>Curr. Biol.</source> <volume>24</volume>, <fpage>R875</fpage>&#x2013;<lpage>R878</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.cub.2014.06.054</pub-id>, <pub-id pub-id-type="pmid">25247366</pub-id></mixed-citation></ref>
<ref id="ref86"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Singer</surname><given-names>T.</given-names></name> <name><surname>Seymour</surname><given-names>B.</given-names></name> <name><surname>O'Doherty</surname><given-names>J.</given-names></name> <name><surname>Kaube</surname><given-names>H.</given-names></name> <name><surname>Dolan</surname><given-names>R. J.</given-names></name> <name><surname>Frith</surname><given-names>C. D.</given-names></name></person-group> (<year>2004</year>). <article-title>Empathy for pain involves the affective but not sensory components of pain</article-title>. <source>Science</source> <volume>303</volume>, <fpage>1157</fpage>&#x2013;<lpage>1162</lpage>. doi: <pub-id pub-id-type="doi">10.1126/science.1093535</pub-id>, <pub-id pub-id-type="pmid">14976305</pub-id></mixed-citation></ref>
<ref id="ref87"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Son</surname><given-names>J. J.</given-names></name> <name><surname>Erker</surname><given-names>T. D.</given-names></name> <name><surname>Ward</surname><given-names>T. W.</given-names></name> <name><surname>Datta</surname><given-names>A.</given-names></name> <name><surname>Edwards</surname><given-names>D. J.</given-names></name> <name><surname>Bikson</surname><given-names>M.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>The polarity of high-definition transcranial direct current stimulation affects movement sequences</article-title>. <source>NeuroImage</source> <volume>306</volume>:<fpage>121018</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neuroimage.2024.121018</pub-id></mixed-citation></ref>
<ref id="ref88"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stark</surname><given-names>N.</given-names></name> <name><surname>Bobadilla</surname><given-names>L.</given-names></name> <name><surname>Michael</surname><given-names>P.</given-names></name> <name><surname>Beeney</surname><given-names>J. E.</given-names></name> <name><surname>Lane</surname><given-names>S. P.</given-names></name> <name><surname>Wilson</surname><given-names>S.</given-names></name></person-group>. (<year>2023</year>). <article-title>A meta-analytic review of the relationship between empathy and oxytocin</article-title>. <source>Aggress. Violent Behav.</source> <volume>70</volume>:<fpage>101828</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.avb.2023.101828</pub-id></mixed-citation></ref>
<ref id="ref89"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sullivan-Detheridge</surname><given-names>J. H.</given-names></name> <name><surname>Reifsnider</surname><given-names>E.</given-names></name> <name><surname>Mengsteab</surname><given-names>M.</given-names></name> <name><surname>Merie</surname><given-names>K.</given-names></name> <name><surname>Staller</surname><given-names>J.</given-names></name> <name><surname>Allen</surname><given-names>A. M.</given-names></name></person-group> (<year>2024</year>). <article-title>Cross cultural empathetic behavior in health care providers: a review of 3 countries</article-title>. <source>J. Prim. Care Community Health</source> <volume>15</volume>:<fpage>21501319241226765</fpage>. doi: <pub-id pub-id-type="doi">10.1177/21501319241226765</pub-id>, <pub-id pub-id-type="pmid">38254300</pub-id></mixed-citation></ref>
<ref id="ref90"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tay</surname><given-names>J. L.</given-names></name> <name><surname>Qu</surname><given-names>Y.</given-names></name> <name><surname>Lim</surname><given-names>L.</given-names></name> <name><surname>Sim</surname><given-names>K.</given-names></name> <name><surname>Subramaniam</surname><given-names>M.</given-names></name> <name><surname>Chua</surname><given-names>H. C.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>Impact of a virtual reality intervention on stigma, empathy, and attitudes toward patients with psychotic disorders</article-title>. <source>JMIR Ment. Health</source> <volume>12</volume>:<fpage>e66925</fpage>. doi: <pub-id pub-id-type="doi">10.2196/66925</pub-id></mixed-citation></ref>
<ref id="ref91"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tian</surname><given-names>X.</given-names></name> <name><surname>Zheng</surname><given-names>Z.</given-names></name> <name><surname>Li</surname><given-names>R.</given-names></name> <name><surname>Luo</surname><given-names>Y. J.</given-names></name> <name><surname>Feng</surname><given-names>C.</given-names></name></person-group> (<year>2025</year>). <article-title>Neural signatures underlying the effect of social structure on empathy and altruistic behaviors</article-title>. <source>NeuroImage</source> <volume>315</volume>:<fpage>121267</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neuroimage.2025.121267</pub-id>, <pub-id pub-id-type="pmid">40368058</pub-id></mixed-citation></ref>
<ref id="ref92"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab id="coll1">UNESCO</collab></person-group> (<year>2025</year>). <source>Draft text of the recommendation on the ethics of Neurotechnology (SHS/IGM-NEURO/2025/MAY/3)</source>: <publisher-name>UNESCO</publisher-name>.</mixed-citation></ref>
<ref id="ref93"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vaslavski</surname><given-names>A.</given-names></name> <name><surname>Gross</surname><given-names>A. H.</given-names></name> <name><surname>Israel</surname><given-names>S.</given-names></name> <name><surname>Peled-Avron</surname><given-names>L.</given-names></name></person-group> (<year>2025</year>). <article-title>The effect of MDMA administration on oxytocin concentration levels: a systematic review and meta-analysis</article-title>. <source>Neurosci. Biobehav. Rev.</source> <volume>177</volume>:<fpage>106324</fpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neubiorev.2025.106324</pub-id></mixed-citation></ref>
<ref id="ref94"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vassiliadis</surname><given-names>P.</given-names></name> <name><surname>Stiennon</surname><given-names>E.</given-names></name> <name><surname>Windel</surname><given-names>F.</given-names></name> <name><surname>Missey</surname><given-names>F.</given-names></name> <name><surname>Gracia</surname><given-names>P.</given-names></name> <name><surname>Hummel</surname><given-names>F. C.</given-names></name> <etal/></person-group>. (<year>2024</year>). <article-title>Safety, tolerability and blinding efficiency of non-invasive deep transcranial temporal interference stimulation</article-title>. <source>J. Neural Eng.</source> <volume>21</volume>:<fpage>024001</fpage>. doi: <pub-id pub-id-type="doi">10.1088/1741-2552/ad2d32</pub-id></mixed-citation></ref>
<ref id="ref95"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Violante</surname><given-names>I. R.</given-names></name> <name><surname>Alania</surname><given-names>K.</given-names></name> <name><surname>Cassar&#x00E0;</surname><given-names>A. M.</given-names></name> <name><surname>Neufeld</surname><given-names>E.</given-names></name> <name><surname>Acerbo</surname><given-names>E.</given-names></name> <name><surname>Carron</surname><given-names>R.</given-names></name> <etal/></person-group>. (<year>2023</year>). <article-title>Noninvasive temporal interference electrical stimulation of the human hippocampus</article-title>. <source>Nat. Neurosci.</source> <volume>26</volume>, <fpage>1994</fpage>&#x2013;<lpage>2004</lpage>. doi: <pub-id pub-id-type="doi">10.1038/s41593-023-01456-8</pub-id>, <pub-id pub-id-type="pmid">37857775</pub-id></mixed-citation></ref>
<ref id="ref96"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>S.</given-names></name> <name><surname>Liu</surname><given-names>N.</given-names></name> <name><surname>Chen</surname><given-names>J.</given-names></name> <name><surname>Zhang</surname><given-names>X.</given-names></name> <name><surname>Li</surname><given-names>Y.</given-names></name> <name><surname>Zhao</surname><given-names>H.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>Efficacy and safety of transcranial temporal interference stimulation for improving negative symptoms in schizophrenia: a pilot study</article-title>. <source>Schizophr. Bull.</source> doi: <pub-id pub-id-type="doi">10.1093/schbul/sbaf038</pub-id></mixed-citation></ref>
<ref id="ref97"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Watts</surname><given-names>G.</given-names></name> <name><surname>Crompton</surname><given-names>C.</given-names></name> <name><surname>Grainger</surname><given-names>C.</given-names></name> <name><surname>Milton</surname><given-names>D.</given-names></name> <name><surname>Fletcher-Watson</surname><given-names>S.</given-names></name> <name><surname>Sasson</surname><given-names>N. J.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>A certain magic': autistic adults' experiences of interacting with other autistic people</article-title>. <source>Autism</source> <volume>29</volume>, <fpage>2239</fpage>&#x2013;<lpage>2253</lpage>. doi: <pub-id pub-id-type="doi">10.1177/13623613251312890</pub-id></mixed-citation></ref>
<ref id="ref98"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wilson</surname><given-names>J.</given-names></name> <name><surname>Trumbo</surname><given-names>M.</given-names></name> <name><surname>Tesche</surname><given-names>C.</given-names></name></person-group> (<year>2021</year>). <article-title>Transcranial direct current stimulation improves empathy and emotion recognition in adults with autism spectrum disorder</article-title>. <source>NeuroRegulation</source> <volume>8</volume>, <fpage>87</fpage>&#x2013;<lpage>95</lpage>. doi: <pub-id pub-id-type="doi">10.15540/nr.8.2.87</pub-id></mixed-citation></ref>
<ref id="ref99"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Winter</surname><given-names>R.</given-names></name> <name><surname>Issa</surname><given-names>E.</given-names></name> <name><surname>Roberts</surname><given-names>N.</given-names></name> <name><surname>Norman</surname><given-names>R. I.</given-names></name> <name><surname>Howick</surname><given-names>J.</given-names></name></person-group>. (<year>2020</year>). <article-title>Assessing the effect of empathy-enhancing interventions in health education: a systematic review</article-title>. <source>BMJ Open</source> <volume>10</volume>:<fpage>e036471</fpage>. doi: <pub-id pub-id-type="doi">10.1136/bmjopen-2019-036471</pub-id></mixed-citation></ref>
<ref id="ref100"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wolfgang</surname><given-names>A. S.</given-names></name> <name><surname>Fonzo</surname><given-names>G. A.</given-names></name> <name><surname>Gray</surname><given-names>J. C.</given-names></name> <name><surname>Mithoefer</surname><given-names>M. C.</given-names></name> <name><surname>Yazar-Klosinski</surname><given-names>B.</given-names></name> <name><surname>Emerson</surname><given-names>A.</given-names></name> <etal/></person-group>. (<year>2025</year>). <article-title>MDMA and MDMA-assisted therapy</article-title>. <source>Am. J. Psychiatry</source> <volume>182</volume>, <fpage>79</fpage>&#x2013;<lpage>103</lpage>. doi: <pub-id pub-id-type="doi">10.1176/appi.ajp.20240583</pub-id></mixed-citation></ref>
<ref id="ref101"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yamada</surname><given-names>R.</given-names></name> <name><surname>Futakawa</surname><given-names>K.</given-names></name> <name><surname>Xu</surname><given-names>K.</given-names></name> <name><surname>Kondo</surname><given-names>S.</given-names></name></person-group> (<year>2025</year>). <article-title>Using virtual patients to enhance empathy in medical students: a scoping review protocol</article-title>. <source>Syst. Rev.</source> <volume>14</volume>:<fpage>52</fpage>. doi: <pub-id pub-id-type="doi">10.1186/s13643-025-02469-1</pub-id></mixed-citation></ref>
<ref id="ref102"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>C. C.</given-names></name> <name><surname>Khalifa</surname><given-names>N.</given-names></name> <name><surname>V&#x00F6;llm</surname><given-names>B.</given-names></name></person-group> (<year>2018</year>). <article-title>The effects of repetitive transcranial magnetic stimulation on empathy: a systematic review and meta-analysis</article-title>. <source>Psychol. Med.</source> <volume>48</volume>, <fpage>737</fpage>&#x2013;<lpage>750</lpage>. doi: <pub-id pub-id-type="doi">10.1017/S0033291717002161</pub-id>, <pub-id pub-id-type="pmid">28826416</pub-id></mixed-citation></ref>
<ref id="ref103"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Young</surname><given-names>M. J.</given-names></name> <name><surname>Bodien</surname><given-names>Y. G.</given-names></name> <name><surname>Edlow</surname><given-names>B. L.</given-names></name></person-group> (<year>2022</year>). <article-title>Ethical considerations in clinical trials for disorders of consciousness</article-title>. <source>Brain Sci.</source> <volume>12</volume>:<fpage>211</fpage>. doi: <pub-id pub-id-type="doi">10.3390/brainsci12020211</pub-id>, <pub-id pub-id-type="pmid">35203974</pub-id></mixed-citation></ref>
<ref id="ref104"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yuan</surname><given-names>Y.</given-names></name> <name><surname>Gao</surname><given-names>Z.</given-names></name> <name><surname>Xiao</surname><given-names>W.</given-names></name></person-group> (<year>2025</year>). <article-title>The role of oxytocin in parental care</article-title>. <source>Endocrinology</source> <volume>166</volume>:<fpage>bqaf129</fpage>. doi: <pub-id pub-id-type="doi">10.1210/endocr/bqaf129</pub-id>, <pub-id pub-id-type="pmid">40856229</pub-id></mixed-citation></ref>
<ref id="ref105"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>H.</given-names></name> <name><surname>Xiong</surname><given-names>G.</given-names></name> <name><surname>Cai</surname><given-names>S.</given-names></name> <name><surname>Wu</surname><given-names>S.</given-names></name></person-group> (<year>2024</year>). <article-title>A causal role of right temporoparietal junction in prosocial learning: a transcranial direct current stimulation study</article-title>. <source>Neuroscience</source> <volume>538</volume>, <fpage>59</fpage>&#x2013;<lpage>67</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.neuroscience.2023.12.007</pub-id>, <pub-id pub-id-type="pmid">38145822</pub-id></mixed-citation></ref>
</ref-list>
<fn-group>
<fn fn-type="custom" custom-type="edited-by" id="fn0001">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/115919/overview">Lawrence M. Parsons</ext-link>, The University of Sheffield, United Kingdom</p>
</fn>
<fn fn-type="custom" custom-type="reviewed-by" id="fn0002">
<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3195141/overview">Hiroe Imai Hu</ext-link>, National Institute of Mental Health, United States</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3322645/overview">Jacob T. Dines</ext-link>, University of Nebraska Medical Center, United States</p>
</fn>
</fn-group>
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</article>