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<journal-id journal-id-type="publisher-id">Front. Aging Neurosci.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Aging Neuroscience</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Aging Neurosci.</abbrev-journal-title>
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<issn pub-type="epub">1663-4365</issn>
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<publisher-name>Frontiers Media S.A.</publisher-name>
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<article-meta>
<article-id pub-id-type="doi">10.3389/fnagi.2025.1734432</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>Effect of deep brain stimulation on dysphagia in Parkinson&#x2019;s disease: mechanisms, evidence, and outlook</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Hofacker</surname>
<given-names>Jule</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Bahners</surname>
<given-names>Bahne H.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Huber</surname>
<given-names>Cinja</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Hartmann</surname>
<given-names>Christian J.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Claus</surname>
<given-names>Inga</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<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>
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<contrib contrib-type="author">
<name>
<surname>Suntrup-Krueger</surname>
<given-names>Sonja</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<contrib contrib-type="author">
<name>
<surname>Schnitzler</surname>
<given-names>Alfons</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Warnecke</surname>
<given-names>Tobias</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<xref ref-type="author-notes" rid="fn0001"><sup>&#x2020;</sup></xref>
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<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Labeit</surname>
<given-names>Bendix</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<aff id="aff1"><label>1</label><institution>Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Heinrich-Heine University Duesseldorf</institution>, <city>Duesseldorf</city>, <country country="de">Germany</country></aff>
<aff id="aff2"><label>2</label><institution>Medical Faculty and University Hospital Duesseldorf, Institute of Clinical Neuroscience and Medical Psychology, Heinrich-Heine University Duesseldorf</institution>, <city>Duesseldorf</city>, <country country="de">Germany</country></aff>
<aff id="aff3"><label>3</label><institution>Department of Neurology, University Hospital Muenster</institution>, <city>Muenster</city>, <country country="de">Germany</country></aff>
<aff id="aff4"><label>4</label><institution>Department of Neurology and Neurorehabilitation, Klinikum Osnabrueck &#x2013; Academic Teaching Hospital of the WWU</institution>, <city>Muenster</city>, <country country="de">Germany</country></aff>
<author-notes>
<corresp id="c001"><label>&#x002A;</label>Correspondence: Jule Hofacker, <email xlink:href="mailto:jule.hofacker@hhu.de">jule.hofacker@hhu.de</email></corresp>
<fn fn-type="equal" id="fn0001">
<label>&#x2020;</label>
<p>These authors have contributed equally to this work</p>
</fn>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-01-15">
<day>15</day>
<month>01</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2025</year>
</pub-date>
<volume>17</volume>
<elocation-id>1734432</elocation-id>
<history>
<date date-type="received">
<day>28</day>
<month>10</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>16</day>
<month>12</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>22</day>
<month>12</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2026 Hofacker, Bahners, Huber, Hartmann, Claus, Suntrup-Krueger, Schnitzler, Warnecke and Labeit.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Hofacker, Bahners, Huber, Hartmann, Claus, Suntrup-Krueger, Schnitzler, Warnecke and Labeit</copyright-holder>
<license>
<ali:license_ref start_date="2026-01-15">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>
<sec>
<title>Introduction</title>
<p>Oropharyngeal dysphagia (OD) is a common and significant complication of Parkinson&#x2019;s disease (PD), contributing to malnutrition, respiratory complications and impaired medication intake. The pathophysiology of OD in PD is heterogeneous, involving basal ganglia dysfunction with associated motor impairments in the oropharynx, cortical pathophysiology, and <italic>&#x03B1;</italic>-synuclein pathology in peripheral nerves. While deep brain stimulation (DBS) is an established intervention for motor symptom management in PD, its effects on swallowing function remain poorly understood and controversial. This narrative review aims to critically evaluate the current evidence on the effects of DBS on OD in PD and to outline potential future research directions, grounded in current understanding of OD pathophysiology and DBS mechanisms.</p>
</sec>
<sec>
<title>Methods</title>
<p>A narrative review of clinical studies examining the effects of DBS on swallowing function in people with PD was conducted. Studies were identified through database searching of MEDLINE, Embase and Cochrane Library, from inception of the databases until May 2025. Inclusion criteria encompassed clinical studies and case reports investigating DBS effects on swallowing outcomes in people with PD, with no language restrictions applied. Data regarding study design, DBS intervention and stimulation parameters, swallow-related outcomes and assessment methods were extracted and compiled systematically.</p>
</sec>
<sec>
<title>Results</title>
<p>A total of 24 clinical studies, including prospective and retrospective observational studies and case reports, were included in this review. Evidence regarding DBS effects remains inconsistent. Subthalamic DBS shows the greatest variability: some studies report improvements in aspiration frequency or pharyngeal timing, while others describe no change or even long-term deterioration in swallowing safety. Pallidal DBS appears to neither improve nor deteriorate swallowing function, however, evidence is limited to four mainly retrospective studies with small sample sizes. Evidence on combined or alternative targets remains sparse and heterogeneous. Patient-reported swallowing outcomes are often more favorable than instrumental measures.</p>
</sec>
<sec>
<title>Discussion</title>
<p>DBS may influence swallowing in PD, but outcomes likely depend on OD phenotypes, stimulation targets and parameters. Future research should recruit adequately powered cohorts, apply standardized instrumental assessments including detailed OD phenotyping, systematically explore stimulation parameters, distinguish short- from long-term effects, and integrate OD outcomes into DBS programming.</p>
</sec>
</abstract>
<kwd-group>
<kwd>deep brain stimulation</kwd>
<kwd>dysphagia</kwd>
<kwd>Parkinson&#x2019;s disease</kwd>
<kwd>swallowing function</kwd>
<kwd>narrative review</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) &#x2013; project number: 529859742 &#x2013; under the Walter Benjamin Program for BL. JH received a doctoral fellowship from the German Academic Scholarship Foundation (Studienstiftung des deutschen Volkes). BB gratefully acknowledges support by the Prof. Dr. Klaus Thiemann Foundation (Parkinson Fellowship 2022). SS-K was supported with an endowed professorship from the Else Kr&#x00F6;ner Fresenius-Foundation. The publication costs were funded by the Open-Access-Fund of Heinrich Heine University D&#x00FC;sseldorf and the Medical Faculty of Heinrich Heine University D&#x00FC;sseldorf.</funding-statement>
</funding-group>
<counts>
<fig-count count="1"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="100"/>
<page-count count="18"/>
<word-count count="13784"/>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Parkinson&#x2019;s Disease and Aging-related Movement Disorders</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1">
<label>1</label>
<title>Introduction</title>
<p>Oropharyngeal dysphagia (OD) is a common and clinically significant complication in people with Parkinson&#x2019;s disease (PD), with prevalence rates reaching 80% when the gold-standard assessments, Flexible Endoscopic Evaluation of Swallowing (FEES) and Videofluoroscopic Swallow Study (VFSS), are used (<xref ref-type="bibr" rid="ref26">Gong et al., 2022</xref>; <xref ref-type="bibr" rid="ref82">Takizawa et al., 2016</xref>). Although commonly associated with advanced stages of PD, OD can also manifest as an early symptom (<xref ref-type="bibr" rid="ref12">Claus et al., 2020</xref>; <xref ref-type="bibr" rid="ref65">Pflug et al., 2018</xref>). It poses serious health risks, including malnutrition (<xref ref-type="bibr" rid="ref28">G&#x00FC;ltekin et al., 2024</xref>), aspiration pneumonia, and other respiratory complications (<xref ref-type="bibr" rid="ref94">Won et al., 2020</xref>), increased mortality, secondary morbidity (<xref ref-type="bibr" rid="ref17">Di Luca et al., 2021</xref>) and hospitalizations (<xref ref-type="bibr" rid="ref18">Dilmaghani et al., 2022</xref>). Moreover, it can impair oral medication intake, potentially exacerbating motor fluctuations (<xref ref-type="bibr" rid="ref43">Labeit et al., 2022b</xref>). Reliable assessment and treatment of OD is therefore essential.</p>
<p>Patients with PD often present with reduced awareness of their swallowing difficulty (<xref ref-type="bibr" rid="ref7">Buhmann et al., 2019</xref>; <xref ref-type="bibr" rid="ref67">Rangwala et al., 2025</xref>; <xref ref-type="bibr" rid="ref59">Monteiro et al., 2014</xref>; <xref ref-type="bibr" rid="ref35">Kalf et al., 2012</xref>), and silent aspiration without overt protective reflexes is common (<xref ref-type="bibr" rid="ref57">Martell et al., 2024</xref>), which complicates detection of OD. Therefore, instrumental evaluations are essential for accurately detecting OD. Both FEES and VFSS are considered diagnostic gold standards, providing robust and reliable information on OD pathologies (<xref ref-type="bibr" rid="ref42">Labeit et al., 2022a</xref>). However, FEES is particularly well-suited for patients with PD, as symptom fluctuations may require repeated assessments without the risk of radiation exposure. Additionally, it enables characterization of the OD phenotype. Phenotyping of OD categorizes swallowing disorders based on characteristic instrumental patterns rather than severity alone (<xref ref-type="bibr" rid="ref87">Warnecke et al., 2021</xref>). Neurogenic OD represents a multietiologic syndrome with different phenotypic patterns depending on the underlying disease (<xref ref-type="bibr" rid="ref87">Warnecke et al., 2021</xref>).</p>
<p>Although clinically relevant, OD is rarely the primary focus when selecting and implementing treatments such as deep brain stimulation (DBS). DBS is an established advanced therapy for patients with PD and medication-refractory tremor or motor fluctuations, and has become standard of care with substantial advances in technology and clinical management in recent years (<xref ref-type="bibr" rid="ref39">Krauss et al., 2021</xref>). DBS involves the surgical implantation of electrodes into deep brain structures, commonly the subthalamic nucleus (STN) or the globus pallidus internus (GPi). These electrodes deliver continuous electrical stimulation with adjustable parameters including voltage, pulse width and frequency, to optimize therapeutic efficacy and minimize side effects. DBS effectively alleviates core motor symptoms such as tremor, rigidity, and bradykinesia, and often reduces dopaminergic medication needs (<xref ref-type="bibr" rid="ref29">Hartmann et al., 2019</xref>).</p>
<p>Current evidence on DBS effects on swallowing function remains limited and partly contradictory. While some studies suggest improvements (<xref ref-type="bibr" rid="ref11">Ciucci et al., 2008</xref>), others find no significant effect (<xref ref-type="bibr" rid="ref77">Smith-Hublou et al., 2024</xref>) or report deterioration (<xref ref-type="bibr" rid="ref84">Troche et al., 2014</xref>) in specific aspects of swallowing. These inconsistencies may stem from methodological differences, diverse patient populations, variations in stimulation targets and parameters, but also from the multifaceted nature of OD, which differs from other PD symptoms. Previous reviews on this topic have examined the effects of DBS on swallowing in PD in recent years. However, these publications largely provide descriptive summaries of study outcomes and do not integrate current advances in our understanding of OD pathophysiology, DBS mechanisms, stimulation parameter effects, or phenotype-specific swallowing patterns. The present review aims to address these gaps by offering a pathophysiology-based and mechanism-oriented synthesis of the evidence. In addition, we incorporate newly published clinical studies and systematically evaluate stimulation settings, swallowing protocol quality, and methodological limitations that critically shape interpretation of DBS effects. This approach provides a refined perspective on why swallowing outcomes remain heterogeneous and outlines how future studies can be designed to overcome the limitations of the existing evidence base.</p>
<sec id="sec2">
<label>1.1</label>
<title>Pathophysiology of OD in PD</title>
<p>The pathophysiology underlying OD in PD is not yet fully understood and is presumed to be heterogeneous, involving both central and peripheral mechanisms.</p>
<p>Among the central mechanisms, the dopaminergic basal ganglia system plays a pivotal role being both a primary site affected by neurodegeneration in PD and a critical component of the supramedullary motor control of swallowing (<xref ref-type="bibr" rid="ref91">Wei et al., 2024</xref>). Clinically, it is therefore unsurprising that classical motor symptoms of PD, such as rigidity and bradykinesia, may also affect the oropharynx and contribute to OD (<xref ref-type="bibr" rid="ref46">Labeit et al., 2020b</xref>). For example, analogous to freezing of gait, dysfunction in motor initiation and sequencing may present as episodic impairment of deglutition initiation, termed &#x201C;freezing of swallowing&#x201D; (<xref ref-type="bibr" rid="ref44">Labeit et al., 2020a</xref>; <xref ref-type="bibr" rid="ref53">Maetzler et al., 2016</xref>).</p>
<p>Beyond the basal ganglia, Lewy body pathology has also been identified in non-dopaminergic subcortical and cortical regions involved in the central control of swallowing (<xref ref-type="bibr" rid="ref89">Warnecke et al., 2022</xref>). Dual-task studies show that swallowing performance deteriorates in participants with PD when performed concurrently with cognitively or motor demanding tasks (<xref ref-type="bibr" rid="ref45">Labeit et al., 2021</xref>). This suggests that cognitive cortical reserve may compensate for OD but becomes compromised under increased cognitive load (<xref ref-type="bibr" rid="ref45">Labeit et al., 2021</xref>) and may be further constrained by PD-associated neurodegeneration.</p>
<p>Beyond central involvement, peripheral mechanisms influence OD manifestations. Phosphorylated <italic>&#x03B1;</italic>-synuclein accumulates in both central nervous system and peripheral nerves, as seen in olfactory impairment, a common preclinical symptom of PD (<xref ref-type="bibr" rid="ref1">Abraham et al., 2025</xref>). In oropharyngeal dysfunction, <italic>&#x03B1;</italic>-synuclein aggregates have been identified in pharyngeal motor and sensory nerves, mucosa, muscles, and salivary glands (<xref ref-type="bibr" rid="ref60">Mu et al., 2024</xref>). This pathology may contribute to pharyngeal muscle atrophy and enlarged pharyngeal areas in patients with PD, which are associated with impaired swallowing functions (<xref ref-type="bibr" rid="ref15">Curtis et al., 2020</xref>). <xref ref-type="bibr" rid="ref15">Curtis et al. (2020)</xref> measured normalized pharyngeal area from VFSS in people with PD and healthy older adults, using two-dimensional fluoroscopic tracing techniques and examined relationships between pharyngeal area and swallowing kinematics, efficiency (bolus clearance ratio), and safety (Penetration-Aspiration Scale) in PD. They found that larger pharyngeal areas in PD were associated with reduced constriction, shorter airway closure, and decreased swallowing safety.</p>
<p>Moreover, reduced salivary substance P levels in patients with PD may underlie sensory deficits and impaired airway protection, as this neuropeptide is involved in regulation of the cough reflex (<xref ref-type="bibr" rid="ref72">Schr&#x00F6;der et al., 2019</xref>).</p>
<p>These pathophysiological mechanisms commonly culminate in pharyngeal bolus retention after swallowing, particularly in the valleculae, the most common OD phenotype in PD (<xref ref-type="bibr" rid="ref87">Warnecke et al., 2021</xref>). Residue may spill over into the laryngeal vestibule, causing penetration or aspiration. Due to sensory impairments, patients often remain unaware of residue, preventing compensatory swallows. Other OD characteristics include delayed pharyngeal swallow initiation or premature spillage of the bolus into the pharynx resulting from impaired oral bolus containment (<xref ref-type="bibr" rid="ref87">Warnecke et al., 2021</xref>). Impaired respiratory&#x2013;swallow coordination may further increase airway invasion risks (<xref ref-type="bibr" rid="ref88">Warnecke et al., 2023</xref>; <xref ref-type="bibr" rid="ref68">Rangwala et al., 2023</xref>).</p>
<p>Oropharyngeal symptoms in PD vary across clinical motor phenotypes, suggesting benefits from phenotype-specific DBS adjustments, as with motor symptom control. A systematic review (<xref ref-type="bibr" rid="ref83">Thijs and Dumican, 2023</xref>) reported that participants with tremor-dominant PD tend to exhibit less severe laryngeal symptoms, including dysphagia, than those with non-tremor dominant phenotypes, like postural instability and gait difficulty. However, it remains unclear whether the motor deficits affecting oropharyngeal function mirror those observed in the limbs. <xref ref-type="bibr" rid="ref20">Dumican et al. (2024)</xref> found that oropharyngeal resting tremor significantly altered the timing of swallowing events, particularly shortening laryngeal vestibule closure duration and earlier airway reopening. These individuals demonstrated greater pharyngeal residue and more frequent aspiration/penetration, indicating that PD-related OD may involve distinct mechanisms in this subgroup requiring tremor-specific DBS programming.</p>
<p>Rigidity, another cardinal PD motor symptom, may also contribute to OD. A systematic review (<xref ref-type="bibr" rid="ref83">Thijs and Dumican, 2023</xref>) showed that individuals with an akinetic-rigid phenotype had higher penetration/aspiration rates and more delayed pharyngeal swallow initiations than those with a tremor-dominant phenotype. Axial postural tone assessment showed that people with PD exhibit the most pronounced muscle tone increases in the cervical region (<xref ref-type="bibr" rid="ref23">Franz&#x00E9;n et al., 2009</xref>), with neck muscle tone 75% higher than healthy controls, exceeding trunk (22%) and hip (32%) increases. Given the close anatomical and functional relationship between cervical muscle tone and oropharyngeal structures, elevated neck rigidity may contribute to OD.</p>
<p>While rigidity may affect the structural aspects of swallowing, bradykinesia impacts its temporal dynamics. Pharyngeal bradykinesia is associated with vallecular residue, a primary characteristic of OD in PD (<xref ref-type="bibr" rid="ref87">Warnecke et al., 2021</xref>) and was described to improve with levodopa-carbidopa intestinal gel (<xref ref-type="bibr" rid="ref46">Labeit et al., 2020b</xref>). Bradykinesia of the tongue and mandible prolongs oropharyngeal transit time (<xref ref-type="bibr" rid="ref86">Umemoto et al., 2011</xref>).</p>
<p>From a pathophysiological perspective, only certain components of OD, particularly those related to basal ganglia dysfunction such as tremorous, bradykinetic, rigid or freezing oropharyngeal motor patterns may be responsive to DBS. Other mechanisms, especially those involving non-dopaminergic or peripheral pathways, are less likely to be affected by DBS.</p>
</sec>
</sec>
<sec id="sec3">
<label>2</label>
<title>Current evidence on the effect of DBS on swallowing function</title>
<p>Studies were identified through database searches of MEDLINE, Embase and the Cochrane Library conducted in May 2025, using the search strategy: (&#x2018;parkinson disease&#x2019;/exp. OR &#x2018;parkinson&#x002A;&#x2019;) AND (&#x2018;deep brain stimulation&#x2019;/exp. OR &#x2018;deep brain stimulation&#x2019; OR &#x2018;DBS&#x2019;) AND (&#x2018;deglutition&#x2019;/exp. OR &#x2018;swallowing&#x2019;/exp. OR &#x2018;dysphagia&#x2019;/exp. OR deglutition OR swallowing OR dysphagia). Inclusion criteria encompassed clinical studies including prospective and retrospective observational studies and case reports, investigating effects of DBS on swallowing function in people with PD. No language restrictions were applied; all identified papers were published in English. Duplicates were removed using database tools followed by manual checking. As this is a narrative review, screening was conducted by one reviewer (JH). In total, 24 studies were included in this review, encompassing 535 participants with PD. A systematic review methodology including risk of bias assessment or reviewer reliability procedures was not followed, which aligns with the intended scope of a narrative synthesis. Key aspects of included studies are summarized in <xref ref-type="table" rid="tab1">Table 1</xref>.</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Characteristics and main findings of included studies examining deep brain stimulation effects on swallowing function in people with Parkinson&#x2019;s disease.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Study</th>
<th align="left" valign="top">Study design</th>
<th align="left" valign="top">Target(s)</th>
<th align="center" valign="top">
<italic>N</italic>
</th>
<th align="left" valign="top">Objective swallowing outcome (outcome measure)</th>
<th align="left" valign="top">Subjective swallowing outcome (outcome measure)</th>
<th align="left" valign="top">DBS setting</th>
<th align="left" valign="top">Testing conditions</th>
<th align="left" valign="top">Key findings</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref10">Cebi et al. (2024)</xref>
</td>
<td align="left" valign="top">RCT</td>
<td align="left" valign="top">Combined STN&#x202F;+&#x202F;SNr</td>
<td align="center" valign="top">20</td>
<td align="left" valign="top">FEES:<break/><list list-type="bullet">
<list-item>
<p>Penetration/Aspiration (PAS)</p>
</list-item>
<list-item>
<p>Swallow reflex (SOS)</p>
</list-item>
<list-item>
<p>Pharyngeal residue (VAS)</p>
</list-item>
<list-item>
<p>Oral preparation &#x0026; transport (TOMASS)</p>
</list-item>
<list-item>
<p>Functional level of oral intake of food &#x0026; liquid (FOIS)</p>
</list-item>
<list-item>
<p>Adverse events, e.g., coughing, asphyxia, bronchitis, aspiration pneumonia (patient diary)</p>
</list-item>
</list></td>
<td align="left" valign="top">Dysphagia associated quality of life (SWAL-QoL)</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>125&#x202F;Hz</p>
</list-item>
<list-item>
<p>60&#x202F;&#x03BC;s</p>
</list-item>
<list-item>
<p>0.5&#x2013;2.0&#x202F;mA</p>
</list-item>
<list-item>
<p>All participants received concurrent swallowing therapy (3x1h group sessions per week for 8&#x202F;weeks; strength-based exercises: Shaker-exercise, chin tuck- and tongue strengthening against resistance)</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V0: MED-off &#x0026; DBS-off/STN-on/SNr-on</p>
</list-item>
<list-item>
<p>V1 (1&#x2013;8&#x202F;days after V0): MED-on &#x0026; DBS-on</p>
</list-item>
<list-item>
<p>V2 (8&#x202F;weeks after V1): MED-on &#x0026; DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>No change in PAS score after intervention (STN vs. STN&#x202F;+&#x202F;SNr) (V1 vs. V2)</p>
</list-item>
<list-item>
<p>Sig. Improvement in PAS scores only when groups are pooled (V1 vs. V2)</p>
</list-item>
<list-item>
<p>Improvement in TOMASS&#x002A; and pharyngeal residue&#x002A; in STN group (V2)</p>
</list-item>
<list-item>
<p>SOS score: delayed initiation of pharyngeal reflex&#x002A; in STN group compared to STN-off (V0)</p>
</list-item>
<list-item>
<p>SWAL-QOL: no change (STN vs. STN&#x202F;+&#x202F;SNr)</p>
</list-item>
<list-item>
<p>Adverse events (2 mild, 1 severe)</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref11">Ciucci et al. (2008)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">14</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Pharyngeal transit time</p>
</list-item>
<list-item>
<p>Maximal hyoid bone excursion</p>
</list-item>
<list-item>
<p>Severity of impairment (Oral total composite score, Pharyngeal total composite score)</p>
</list-item>
</list></td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">not specified</td>
<td align="left" valign="top">V1: MED-off &#x0026; DBS-on/DBS-off</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>Improvement of pharyngeal composite score&#x002A; and pharyngeal transit time&#x002A; in DBS-ON compared to DBS-OFF</p>
</list-item>
<list-item>
<p>No change in oral parameters</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref21">Fagbami and Donato (2011)</xref>
</td>
<td align="left" valign="top">Case report</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">1</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Aspiration (not further defined)</p>
</list-item>
<list-item>
<p>Pulmonary restriction (pulmonary function testing)</p>
</list-item>
<list-item>
<p>Stridor</p>
</list-item>
<list-item>
<p>Throat spasms, paroxysmal, non-productive cough</p>
</list-item>
</list></td>
<td align="left" valign="top">Patient report</td>
<td align="left" valign="top">Original settings (monopolar):<break/><list list-type="bullet">
<list-item>
<p>Left: 130&#x202F;Hz, 90&#x202F;&#x03BC;s, and 1.6&#x202F;V</p>
</list-item>
<list-item>
<p>Right: 130&#x202F;Hz, 60&#x202F;&#x03BC;s, and 1.6&#x202F;V</p>
</list-item>
</list>Optimized settings (bipolar):<break/><list list-type="bullet">
<list-item>
<p>Left: 160&#x202F;Hz, 60&#x202F;&#x03BC;s, and 1.5&#x202F;V</p>
</list-item>
<list-item>
<p>Right: 160&#x202F;Hz, 60&#x202F;&#x03BC;s, and 2.1&#x202F;V</p>
</list-item>
</list></td>
<td align="left" valign="top">N/A</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>Stimulation-induced dysphagia and stridor</p>
</list-item>
<list-item>
<p>Immediate resolvement of cough and dysphagia symptoms when DBS was turned off</p>
</list-item>
<list-item>
<p>Subjective improvement by 80% in cough and swallowing</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref30">Henry et al. (2022)</xref>
</td>
<td align="left" valign="top">Retrospective analysis</td>
<td align="left" valign="top">STN or GPi</td>
<td align="center" valign="top">54</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Penetration/aspiration (verbal description converted into PAS-score)</p>
</list-item>
</list></td>
<td align="left" valign="top">MDS-UPDRS</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on</p>
</list-item>
<list-item>
<p>V2 (6&#x202F;months post-surgery): MED-on &#x0026; DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">No sig. changes in converted PAS-scores after intervention, neither between groups (GPi vs. STN)</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref36">Kitashima et al. (2013)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">18</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Swallowing function (VF dysphagia scale)</p>
</list-item>
<list-item>
<p>Oropharyngeal transit time, tongue movement, laryngeal elevation delay time</p>
</list-item>
</list></td>
<td align="left" valign="top">UPDRS</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on</p>
</list-item>
<list-item>
<p>V2 (6&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off</p>
</list-item>
</list>
</td>
<td align="left" valign="top">No change in VF dysphagia score (V1 vs. V2; V2), but changes in tongue movement&#x002A; and laryngeal elevation delay time&#x002A; (DBS on vs. off)</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref38">Krause et al. (2004)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">27</td>
<td align="left" valign="top">Not assessed</td>
<td align="left" valign="top">UPDRS</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>&#x2300; 148&#x202F;Hz</p>
</list-item>
<list-item>
<p>&#x2300; 2.9&#x202F;V</p>
</list-item>
<list-item>
<p>&#x2300; 73&#x202F;&#x03BC;s</p>
</list-item>
</list>
</td>
<td align="left" valign="top">Testing conditions not explicitly stated<break/><list list-type="bullet">
<list-item>
<p>V1 (pre-surgery)</p>
</list-item>
<list-item>
<p>V2 (12&#x202F;months post-surgery)</p>
</list-item>
</list>Additional annual follow-ups, last assessment &#x2300; 30&#x202F;months post-surgery</td>
<td align="left" valign="top">Reported dysphagia as an adverse event in 3 participants</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref40">Krygowska-Wajs et al. (2016)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">20</td>
<td align="left" valign="top">Not assessed</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>UPDRS</p>
</list-item>
<list-item>
<p>study-spefic questionnaire on gastro-intestinal dysfunction incl. dysphagia</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>130&#x202F;Hz</p>
</list-item>
<list-item>
<p>1&#x2013;2&#x202F;V</p>
</list-item>
<list-item>
<p>60&#x202F;&#x03BC;s</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on</p>
</list-item>
<list-item>
<p>V2 (3&#x202F;months post-surgery): MED-on &#x0026; DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">Improvement in swallowing-related item of questionnaire&#x002A; (V1 vs. V2)</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref41">Kulneff et al. (2013)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">11</td>
<td align="left" valign="top">FEES:<break/><list list-type="bullet">
<list-item>
<p>Penetration/aspiration (PAS)</p>
</list-item>
<list-item>
<p>Secretion status (secretion severity scale)</p>
</list-item>
<list-item>
<p>Residues (scale for pharyngeal residue and clearance)</p>
</list-item>
<list-item>
<p>Pre-swallow spillage (scale)</p>
</list-item>
</list></td>
<td align="left" valign="top">VAS for self-perception of swallowing</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-off/MED-on</p>
</list-item>
<list-item>
<p>V2 (6&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off</p>
</list-item>
<list-item>
<p>V3 (12&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>No changes in objective outcomes during FEES (any condition in V1 vs. V2)</p>
</list-item>
<list-item>
<p>Improvement in subjective perception&#x002A; (V1 MED-off vs. V2 MED-on &#x0026; DBS-on; both in V2 &#x0026; V3 in DBS-on vs. DBS-off)</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref50">Lengerer et al. (2012)</xref>
</td>
<td align="left" valign="top">Retrospective analysis</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">18</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Swallowing function (NZIMES Subscale One, Logemann-MBS-Parameters)</p>
</list-item>
<list-item>
<p>Maximal hyoid bone excursion</p>
</list-item>
</list></td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>65&#x2013;180&#x202F;Hz</p>
</list-item>
<list-item>
<p>0.5&#x2013;6.0&#x202F;V</p>
</list-item>
<list-item>
<p>60&#x2013;120&#x202F;&#x03BC;s</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on</p>
</list-item>
<list-item>
<p>V2 (&#x2300; 20.3&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="simple">
<list-item>
<p>Changes in:</p>
</list-item>
</list>
<list list-type="bullet">
<list-item>
<p>Reduced pharyngeal transit time&#x002A; (V1 vs. V2)</p>
</list-item>
<list-item>
<p>Reduced pharyngeal reaction time&#x002A; (V1 vs. V2 DBS-on)</p>
</list-item>
<list-item>
<p>Increased duration of cricopharyngeal opening&#x002A; (V2, DBS-on vs. DBS-off)</p>
</list-item>
<list-item>
<p>Reduced duration of cricopharyngeal opening&#x002A; (V1 vs. V2 DBS-on &#x0026; DBS-off)</p>
</list-item>
<list-item>
<p>Increased time between cricopharyngeal opening and laryngeal vestibule closure&#x002A; (V2, DBS-on vs. DBS-off)</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref64">Olchik et al. (2018)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">10</td>
<td align="left" valign="top">Non-instrumental assessment:<break/><list list-type="bullet">
<list-item>
<p>Swallowing function (clinical evaluation, water swallow test, cervical auscultation, oximeter)</p>
</list-item>
<list-item>
<p>Oral food intake (FOIS)</p>
</list-item>
</list></td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on</p>
</list-item>
<list-item>
<p>V2 (6&#x2013;12&#x202F;months post-surgery): MED-on &#x0026; DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">No sig. changes in swallowing function</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref66">Pflug et al. (2020)</xref>
</td>
<td align="left" valign="top">RCT</td>
<td align="left" valign="top">STN or combined STN&#x202F;+&#x202F;SNr</td>
<td align="center" valign="top">15</td>
<td align="left" valign="top">FEES:<break/><list list-type="bullet">
<list-item>
<p>Pharyngeal residues (solids) (6-point scale)</p>
</list-item>
<list-item>
<p>Penetration/aspiration (PAS)</p>
</list-item>
<list-item>
<p>Leakage (scale for bolus location)</p>
</list-item>
<list-item>
<p>Secretion (Murray score)</p>
</list-item>
<list-item>
<p>Capability to swallow pills (4-point scale)</p>
</list-item>
<list-item>
<p>Build-up phenomenon</p>
</list-item>
<list-item>
<p>Swallowing duration (mixed consistencies)</p>
</list-item>
</list></td>
<td align="left" valign="top">Self-perception of swallowing (VAS)</td>
<td align="left" valign="top">STN:<break/><list list-type="bullet">
<list-item>
<p>125&#x2013;130&#x202F;Hz</p>
</list-item>
<list-item>
<p>1.5&#x202F;V &#x2013; 4.5&#x202F;mA</p>
</list-item>
<list-item>
<p>60&#x202F;&#x03BC;s</p>
</list-item>
</list>STN&#x202F;+&#x202F;SNr:<break/><list list-type="bullet">
<list-item>
<p>125&#x2013;130&#x202F;Hz</p>
</list-item>
<list-item>
<p>max. 5.2&#x202F;mA</p>
</list-item>
<list-item>
<p>60&#x202F;&#x03BC;s</p>
</list-item>
</list></td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1: MED-on &#x0026; DBS-off</p>
</list-item>
<list-item>
<p>V2 (3&#x202F;weeks after V1): MED-on &#x0026; STN-on/STN&#x202F;+&#x202F;SNr-on</p>
</list-item>
<list-item>
<p>V3 (3&#x202F;weeks after V2): MED-on &#x0026; STN-on/STN&#x202F;+&#x202F;SNr-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>No sig. changes (V1 vs. any DBS-on in V2 and V3)</p>
</list-item>
<list-item>
<p>Simultaneous DBS-STN&#x202F;+&#x202F;SNr showed no added benefit compared to DBS-STN</p>
</list-item>
<list-item>
<p>No sig. influence of DBS mode on subjective perception</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref70">Robertson et al. (2011)</xref>
</td>
<td align="left" valign="top">RCT</td>
<td align="left" valign="top">STN or<break/>GPi</td>
<td align="center" valign="top">27</td>
<td align="left" valign="top">Mandibular movement (kinesiograph):<break/><list list-type="bullet">
<list-item>
<p>Jaw velocity</p>
</list-item>
<list-item>
<p>Voluntary jaw movement</p>
</list-item>
<list-item>
<p>Automatic jaw movement</p>
</list-item>
</list></td>
<td align="left" valign="top">UPDRS</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>130&#x2013;185&#x202F;Hz</p>
</list-item>
<list-item>
<p>&#x2300;3.28&#x202F;V</p>
</list-item>
<list-item>
<p>60&#x2013;150&#x202F;&#x03BC;s</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on/MED-off</p>
</list-item>
<list-item>
<p>V2 (6&#x202F;months post-surgery): MED-off &#x0026; DBS-off/DBS-on; MED-on &#x0026; DBS-off/DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>Reduced velocity&#x002A; in STN group compared to baseline (all conditions in V1 vs. V2)</p>
</list-item>
<list-item>
<p>Increased velocity&#x002A; in GPi group compared to baseline (V1 MED-off vs. V2 MED-off &#x0026; DBS-off)</p>
</list-item>
<list-item>
<p>No sig. change in velocity in GPi group in comparison V1 MED-on vs. V2 MED-on &#x0026; DBS-on</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref73">Silbergleit et al. (2012a)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">14</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Penetration/aspiration (4-point scale)</p>
</list-item>
<list-item>
<p>Oral phase characteristics, pharyngeal phase characteristics (4-point scale)</p>
</list-item>
</list></td>
<td align="left" valign="top">Self-perception of swallowing (DHI)</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on/MED-off</p>
</list-item>
<list-item>
<p>V2 (3&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off; MED-off &#x0026; DBS-on/DBS-off</p>
</list-item>
<list-item>
<p>V3 (12&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off; MED-off &#x0026; DBS-on/DBS-off</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>Improvements&#x002A; in subjective evaluation (DHI) (V1 vs. V2; V1 vs. V3)</p>
</list-item>
<list-item>
<p>Improved oral preparation of thin liquids&#x002A; (V3: MED-off &#x0026; DBS-on vs. MED-off &#x0026; DBS-off)</p>
</list-item>
<list-item>
<p>Improved swallowing response for solids&#x002A; (V3: MED-off &#x0026; DBS-on vs. MED-off &#x0026; DBS-off)</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref77">Smith-Hublou et al. (2024)</xref>
</td>
<td align="left" valign="top">Retrospective cross-sectional observational study</td>
<td align="left" valign="top">GPi</td>
<td align="center" valign="top">36</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Swallowing safety (PAS, DIGEST)</p>
</list-item>
<list-item>
<p>Swallowing timing measures</p>
</list-item>
<list-item>
<p>Relationships between swallowing safety and DBS settings</p>
</list-item>
</list></td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">Unilateral GPi-DBS (&#x2300;)<break/>Left:<break/><list list-type="bullet">
<list-item>
<p>155.83&#x202F;Hz</p>
</list-item>
<list-item>
<p>2.76&#x202F;V</p>
</list-item>
<list-item>
<p>88.33&#x202F;&#x03BC;s</p>
</list-item>
</list>Right:<break/><list list-type="bullet">
<list-item>
<p>168.75&#x202F;Hz</p>
</list-item>
<list-item>
<p>2.64&#x202F;V</p>
</list-item>
<list-item>
<p>86.25&#x202F;&#x03BC;s</p>
</list-item>
</list>Bilateral GPi-DBS (&#x2300;)<break/>Left:<break/><list list-type="bullet">
<list-item>
<p>151.56&#x202F;Hz</p>
</list-item>
<list-item>
<p>2.76&#x202F;V</p>
</list-item>
<list-item>
<p>91.88&#x202F;&#x03BC;s</p>
</list-item>
</list>Right:<break/><list list-type="bullet">
<list-item>
<p>152.81&#x202F;Hz</p>
</list-item>
<list-item>
<p>2.68&#x202F;V</p>
</list-item>
<list-item>
<p>86.25&#x202F;&#x03BC;s</p>
</list-item>
</list></td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>Pre-surgical evaluation: MED-on</p>
</list-item>
<list-item>
<p>Post-surgical evaluation: (&#x2300; 6.7&#x2013;7.5&#x202F;months post-surgery): unilateral-DBS-on &#x0026; MED-on; bilateral-DBS-on &#x0026; MED-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>No changes in pre- vs. post-surgical evaluation</p>
</list-item>
<list-item>
<p>No changes between DBS modalities (unilateral vs. bilateral GPi-DBS)</p>
</list-item>
<list-item>
<p>No associations between swallowing safety and stimulation frequency or pulse width</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref78">Sundstedt et al. (2017a)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">cZi</td>
<td align="center" valign="top">14</td>
<td align="left" valign="top">FEES:<break/><list list-type="bullet">
<list-item>
<p>Penetration/aspiration (PAS)</p>
</list-item>
<list-item>
<p>Secretion status (Secretion severity scale)</p>
</list-item>
<list-item>
<p>Pre-swallow spillage, pharyngeal residue, pharyngeal clearance (rated as present/absent)</p>
</list-item>
</list></td>
<td align="left" valign="top">UPDRS</td>
<td align="left" valign="top">125&#x2013;160&#x202F;Hz</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on</p>
</list-item>
<list-item>
<p>V2 (6&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off</p>
</list-item>
<list-item>
<p>V3 (12&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off</p>
</list-item>
</list>
</td>
<td align="left" valign="top">No sig. changes in any of the investigated outcomes pre- to post-surgery</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref79">Sundstedt et al. (2017b)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">cZi</td>
<td align="center" valign="top">9</td>
<td align="left" valign="top">Not assessed</td>
<td align="left" valign="top">Swallow-related Quality of Life (SWAL-QoL, VAS)</td>
<td align="left" valign="top">125&#x2013;160&#x202F;Hz</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on</p>
</list-item>
<list-item>
<p>V2 (12&#x202F;months post-surgery): MED-on &#x0026; DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">No sig. changes in swallow-related quality of life (V1 vs. V2)</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref80">Sundstedt et al. (2012)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">cZi</td>
<td align="center" valign="top">8</td>
<td align="left" valign="top">FEES:<break/><list list-type="bullet">
<list-item>
<p>Penetration/aspiration (PAS)</p>
</list-item>
<list-item>
<p>Secretion status (Secretion severity scale)</p>
</list-item>
<list-item>
<p>Preswallow spillage, pharyngeal residue, pharyngeal clearance (rated as present/absent)</p>
</list-item>
</list></td>
<td align="left" valign="top">Swallow-related quality of life (non-validated questionnaire, VAS)</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on/MED-off</p>
</list-item>
<list-item>
<p>V2 (6&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off</p>
</list-item>
<list-item>
<p>V3 (12&#x202F;months post-surgery): MED-on &#x0026; DBS-on/DBS-off</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>Reduced pre-swallow spillage&#x002A; (V1 MED-on vs. V2 both in DBS-off and DBS-on)</p>
</list-item>
<list-item>
<p>Increased pre-swallow spillage&#x002A; (V3 at DBS-on vs. DBS-off) (no sig. Difference to V1 MED-on state)</p>
</list-item>
<list-item>
<p>No sig. changes in subjective outcomes</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref84">Troche et al. (2014)</xref>
</td>
<td align="left" valign="top">Retrospective analysis</td>
<td align="left" valign="top">STN or GPi</td>
<td align="center" valign="top">33</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Penetration/aspiration (PAS)</p>
</list-item>
</list></td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>Swallow-related quality of life (SWAL-QOL)</p>
</list-item>
<list-item>
<p>UPDRS</p>
</list-item>
</list>
</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on</p>
</list-item>
<list-item>
<p>V2 (6&#x202F;months post-surgery): MED-on &#x0026; DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>No changes in PAS-scores in GPi-DBS group (V1 vs. V2)</p>
</list-item>
<list-item>
<p>Increase in PAS-score&#x002A; after STN-DBS (V1 vs. V2)</p>
</list-item>
<list-item>
<p>No change in swallowing-related quality of life pre- to post-surgery in neither group (V1 vs. V2)</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref85">Troche et al. (2016)</xref>
</td>
<td align="left" valign="top">Case report</td>
<td align="left" valign="top">Combined right STN&#x202F;+&#x202F;left GPi</td>
<td align="center" valign="top">1</td>
<td align="left" valign="top">VFSS<break/><list list-type="bullet">
<list-item>
<p>Swallowing function</p>
</list-item>
</list>Laryngoscopy:<break/><list list-type="bullet">
<list-item>
<p>Airway protective outcomes</p>
</list-item>
</list></td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">Optimized settings:<break/><list list-type="bullet">
<list-item>
<p>135&#x202F;Hz</p>
</list-item>
<list-item>
<p>3.8&#x202F;V</p>
</list-item>
<list-item>
<p>90&#x202F;&#x03BC;s</p>
</list-item>
</list></td>
<td align="left" valign="top">N/A</td>
<td align="left" valign="top">Immediate improvements in swallowing safety and airway protective outcomes with optimized DBS settings</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref93">Wolz et al. (2012)</xref>
</td>
<td align="left" valign="top">Prospective pre-post study</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">34</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">Water swallow test (200&#x202F;mL) if swallowing difficulties were observed, severity was rated by researcher on a VAS</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">V1 (at least 9&#x202F;months post-surgery): MED-off &#x0026; DBS-on/DBS-off</td>
<td align="left" valign="top">Subjective improvement&#x002A; in DBS-on vs. DBS-off state</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref96">Xie et al. (2015)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">7</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Frequency of aspiration (PAS)</p>
</list-item>
</list></td>
<td align="left" valign="top">Perceived swallowing difficulty (SDQ)</td>
<td align="left" valign="top">60&#x202F;Hz/130&#x202F;Hz/ Off<break/>Left:<break/><list list-type="bullet">
<list-item>
<p>60&#x202F;Hz</p>
</list-item>
<list-item>
<p>&#x2300;3.2&#x202F;&#x00B1;&#x202F;0.4&#x202F;V</p>
</list-item>
<list-item>
<p>&#x2300;90.0&#x202F;&#x00B1;&#x202F;24.5&#x202F;&#x03BC;s</p>
</list-item>
</list>Right:<break/><list list-type="bullet">
<list-item>
<p>60&#x202F;Hz</p>
</list-item>
<list-item>
<p>&#x2300;3.1&#x202F;&#x00B1;&#x202F;0.4&#x202F;V</p>
</list-item>
<list-item>
<p>&#x2300;81.4&#x202F;&#x00B1;&#x202F;14.6&#x202F;&#x03BC;s</p>
</list-item>
</list></td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1: MED-on &#x0026; DBS-60-Hz/130&#x202F;Hz/off</p>
</list-item>
<list-item>
<p>V2 (&#x2300; 6&#x202F;weeks after V1): MED-on &#x0026; DBS-60&#x202F;Hz</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>Reduced aspiration frequency&#x002A; with 60&#x202F;Hz vs. 130&#x202F;Hz (within V1)</p>
</list-item>
<list-item>
<p>Reduced perceived swallowing difficulty&#x002A; with 60&#x202F;Hz vs. 130&#x202F;Hz (within V1)</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref95">Xie et al. (2018)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">11</td>
<td align="left" valign="top">VFSS:<break/><list list-type="bullet">
<list-item>
<p>Frequency of aspiration (PAS)</p>
</list-item>
</list></td>
<td align="left" valign="top">Perceived swallowing difficulty (SDQ)</td>
<td align="left" valign="top">60&#x202F;Hz/130&#x202F;Hz/ Off<break/>Left:<break/><list list-type="bullet">
<list-item>
<p>60&#x202F;Hz</p>
</list-item>
<list-item>
<p>&#x2300;3.0&#x202F;V</p>
</list-item>
<list-item>
<p>&#x2300;76.0&#x202F;&#x03BC;s</p>
</list-item>
</list>Right:<break/><list list-type="bullet">
<list-item>
<p>60&#x202F;Hz</p>
</list-item>
<list-item>
<p>&#x2300;2.9&#x202F;V</p>
</list-item>
<list-item>
<p>&#x2300;68.0&#x202F;&#x03BC;s</p>
</list-item>
</list></td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1: MED-on &#x0026; DBS-60-Hz/130&#x202F;Hz/off</p>
</list-item>
<list-item>
<p>V2 (&#x2300;14,5&#x202F;months after V1): MED-on &#x0026; DBS-60&#x202F;Hz/130&#x202F;Hz/off</p>
</list-item>
</list>
</td>
<td align="left" valign="top">Short-term:<break/><list list-type="bullet">
<list-item>
<p>Reduced frequency of aspiration&#x002A; with 60&#x202F;Hz vs. 130&#x202F;Hz (no change in 60&#x202F;Hz vs. DBS-off) (within V1)</p>
</list-item>
<list-item>
<p>Reduced perceived swallowing difficulty&#x002A; with 60&#x202F;Hz vs. DBS-off (within V1)</p>
</list-item>
</list>Long-term:<break/><list list-type="bullet">
<list-item>
<p>No benefit of 60&#x202F;Hz in frequency of aspiration or perceived swallowing difficulty (V1 vs. V2)</p>
</list-item>
</list></td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref98">Xu et al. (2018)</xref>
</td>
<td align="left" valign="top">Retrospective analysis</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">80</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">UPDRS</td>
<td align="left" valign="top">Tremor-dominant type:<break/><list list-type="bullet">
<list-item>
<p>163.0&#x202F;&#x00B1;&#x202F;20.9&#x202F;Hz</p>
</list-item>
<list-item>
<p>2.9&#x202F;&#x00B1;&#x202F;0.5&#x202F;V</p>
</list-item>
<list-item>
<p>86.0&#x202F;&#x00B1;&#x202F;10.6&#x202F;&#x03BC;s</p>
</list-item>
</list>Akinetic-rigid type:<break/><list list-type="bullet">
<list-item>
<p>174.2&#x202F;&#x00B1;&#x202F;9.4&#x202F;Hz</p>
</list-item>
<list-item>
<p>2.9&#x202F;&#x00B1;&#x202F;0.4&#x202F;V</p>
</list-item>
<list-item>
<p>87.9&#x202F;&#x00B1;&#x202F;12.1&#x202F;&#x03BC;s</p>
</list-item>
</list>Mixed type:<break/><list list-type="bullet">
<list-item>
<p>168.5&#x202F;&#x00B1;&#x202F;13.4&#x202F;Hz</p>
</list-item>
<list-item>
<p>3.1&#x202F;&#x00B1;&#x202F;0.4&#x202F;V</p>
</list-item>
<list-item>
<p>87.2&#x202F;&#x00B1;&#x202F;12.0&#x202F;&#x03BC;s</p>
</list-item>
</list></td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on/MED-off</p>
</list-item>
<list-item>
<p>V2 (&#x2300; 4.9&#x202F;years post-surgery): MED-on/MED-off &#x0026; DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>No long-term benefit of STN-DBS</p>
</list-item>
<list-item>
<p>Swallowing&#x002A; deteriorated (V1 vs. V2)</p>
</list-item>
</list>
</td>
</tr>
<tr>
<td align="left" valign="top">
<xref ref-type="bibr" rid="ref100">Zibetti et al. (2007)</xref>
</td>
<td align="left" valign="top">Prospective pre-post design</td>
<td align="left" valign="top">STN</td>
<td align="center" valign="top">36</td>
<td align="left" valign="top">Not reported</td>
<td align="left" valign="top">UPDRS</td>
<td align="left" valign="top">At 12&#x202F;months:<break/><list list-type="bullet">
<list-item>
<p>136&#x202F;&#x00B1;&#x202F;14.8&#x202F;Hz</p>
</list-item>
<list-item>
<p>3.2&#x202F;&#x00B1;&#x202F;0.4&#x202F;V</p>
</list-item>
<list-item>
<p>63.3&#x202F;&#x00B1;&#x202F;9.5&#x202F;&#x03BC;s</p>
</list-item>
</list>At 24&#x202F;months:<break/><list list-type="bullet">
<list-item>
<p>136.1&#x202F;&#x00B1;&#x202F;12.5&#x202F;Hz</p>
</list-item>
<list-item>
<p>3.3&#x202F;&#x00B1;&#x202F;0.3&#x202F;V</p>
</list-item>
<list-item>
<p>65.0&#x202F;&#x00B1;&#x202F;11.3&#x202F;&#x03BC;s</p>
</list-item>
</list></td>
<td align="left" valign="top">
<list list-type="bullet">
<list-item>
<p>V1 (pre-surgery): MED-on/MED-off</p>
</list-item>
<list-item>
<p>V2 (12&#x202F;months post-surgery) MED-on/MED-off &#x0026; DBS-on</p>
</list-item>
<list-item>
<p>V3 (24&#x202F;months post-surgery) MED-on/MED-off &#x0026; DBS-on</p>
</list-item>
</list>
</td>
<td align="left" valign="top">Improved swallowing&#x002A; (V1 MED-off vs. V2 &#x0026; V3 MED-on &#x0026; DBS-on)</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>This table presents study characteristics including anatomical target, sample sizes, and swallowing outcomes (instrumental and subjective). DBS parameters and key findings are summarized for each study. Asterisks (&#x002A;) indicate statistically significant results, with <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05. Study visits are coded as: V0 (screening), V1 (baseline), V2&#x202F;+&#x202F;(follow-up measurements). DBS-on, active stimulation; DBS-off, inactive stimulation; DHI, dysphagia handicap index; FEES, flexible endoscopic evaluation of swallowing; FOIS, Functional oral intake scale; GPi, globus pallidus internus; MED-on, medication-on state; MED-off, medication-off state; NZIMES, New Zealand Index for Multidisciplinary Evaluation of Swallowing; PAS, penetration aspiration scale; SDQ, Swallowing Disturbance Questionnaire; SNr, substantia nigra; SOS, site of swallow reflex initiation; STN, subthalamic nuleus; SWAL-QoL, Swallowing Quality of Life Questionnaire; TOMASS, Test of Mastication and Swallowing Solids; UPDRS, Unified Parkinson&#x2019;s Disease Rating Scale; VAS, visual analog scale; VF dysphagia scale, Videofluoroscopic dysphagia scale; VFSS, videofluoroscopic swallow study.</p>
</table-wrap-foot>
</table-wrap>
<p>The included studies employed diverse methodological approaches to evaluate swallowing function. Instrumental assessment was performed in <italic>n</italic>&#x202F;=&#x202F;16 studies, with VFSS used in <italic>n</italic>&#x202F;=&#x202F;11 studies and FEES in <italic>n</italic>&#x202F;=&#x202F;5 studies. The most commonly reported outcome measure used for instrumental assessments was the Penetration-Aspiration Scale (PAS; <italic>n</italic>&#x202F;=&#x202F;10), a validated 8-point ordinal scale that rates the depth of airway invasion and the patient&#x2019;s response to material entering the airway (<xref ref-type="bibr" rid="ref71">Rosenbek et al., 1996</xref>) (see <xref ref-type="table" rid="tab2">Table 2</xref>). Other scales applied include the Dynamic Imaging Grade of Swallowing Toxicity [DIGEST (<xref ref-type="bibr" rid="ref32">Hutcheson et al., 2017</xref>); <italic>n</italic>&#x202F;=&#x202F;1] and the Secretion-Severity Scale (<xref ref-type="bibr" rid="ref61">Murray et al., 1996</xref>); (<italic>n</italic>&#x202F;=&#x202F;3). Patient-reported outcome measures included quality-of-life questionnaires (Swallowing Quality of Life Questionnaire [SWAL-QoL (<xref ref-type="bibr" rid="ref58">McHorney et al., 2002</xref>); <italic>n</italic>&#x202F;=&#x202F;3]) and Dysphagia Handicap Index [DHI (<xref ref-type="bibr" rid="ref74">Silbergleit et al., 2012b</xref>); <italic>n</italic>&#x202F;=&#x202F;1]). Separately, <italic>n</italic>&#x202F;=&#x202F;3 studies reported the dysphagia-related questions of the Unified Parkinson&#x2019;s Disease Rating Scale (UPDRS) (<xref ref-type="bibr" rid="ref25">Goetz et al., 2008</xref>; <xref ref-type="bibr" rid="ref22">Fahn et al., 1987</xref>), a general motor assessment tool while <italic>n</italic>&#x202F;=&#x202F;2 studies employed the Swallowing Disturbance Questionnaire (SDQ) (<xref ref-type="bibr" rid="ref56">Manor et al., 2007</xref>). A minority of studies used investigator-reported outcome measures including clinical bedside evaluation (<italic>n</italic>&#x202F;=&#x202F;1), a water swallow test (<italic>n</italic>&#x202F;=&#x202F;1), the Test of Mastication and Swallowing Solids [TOMASS (<xref ref-type="bibr" rid="ref31">Huckabee et al., 2018</xref>); <italic>n</italic>&#x202F;=&#x202F;1] and the Functional Oral Intake Scale [FOIS (<xref ref-type="bibr" rid="ref13">Crary et al., 2005</xref>); <italic>n</italic>&#x202F;=&#x202F;2]. Kinesiography and laryngoscopy were applied by one study, respectively.</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>The Penetration-Aspiration Scale (<xref ref-type="bibr" rid="ref71">Rosenbek et al., 1996</xref>).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">PAS-score</th>
<th align="left" valign="top">Description</th>
</tr>
</thead>
<tbody>
<tr>
<td align="center" valign="top">1</td>
<td align="left" valign="top">Material does not enter the airway.</td>
</tr>
<tr>
<td align="center" valign="top">2</td>
<td align="left" valign="top">Material enters the airway, remains above the vocal folds, and is ejected from the airway.</td>
</tr>
<tr>
<td align="center" valign="top">3</td>
<td align="left" valign="top">Material enters the airway, remains above the vocal folds, and is not ejected from the airway.</td>
</tr>
<tr>
<td align="center" valign="top">4</td>
<td align="left" valign="top">Material enters the airway, contacts the vocal folds, and is ejected from the airway.</td>
</tr>
<tr>
<td align="center" valign="top">5</td>
<td align="left" valign="top">Material enters the airway, contacts the vocal folds, and is not ejected from the airway.</td>
</tr>
<tr>
<td align="center" valign="top">6</td>
<td align="left" valign="top">Material enters the airway, passes below the vocal folds and is ejected into the larynx or out of the airway.</td>
</tr>
<tr>
<td align="center" valign="top">7</td>
<td align="left" valign="top">Material enters the airway, passes below the vocal folds, and is not ejected from the trachea despite effort.</td>
</tr>
<tr>
<td align="center" valign="top">8</td>
<td align="left" valign="top">Material enters the airway, passes below the vocal folds, and no effort is made to eject.</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>The following section provides a structured overview of included studies, organized by DBS targets, patient-reported outcome measures and stimulation settings.</p>
<sec id="sec4">
<label>2.1</label>
<title>DBS targets and mechanisms on swallowing</title>
<p>For PD motor symptom management, the STN and GPi represent common DBS targets. European treatment guidelines (<xref ref-type="bibr" rid="ref16">Deuschl et al., 2022</xref>) indicate no evidence-based preference for either target. Among included papers, 17 investigated DBS in STN (<xref ref-type="bibr" rid="ref11">Ciucci et al., 2008</xref>; <xref ref-type="bibr" rid="ref84">Troche et al., 2014</xref>; <xref ref-type="bibr" rid="ref30">Henry et al., 2022</xref>; <xref ref-type="bibr" rid="ref95">Xie et al., 2018</xref>; <xref ref-type="bibr" rid="ref96">Xie et al., 2015</xref>; <xref ref-type="bibr" rid="ref38">Krause et al., 2004</xref>; <xref ref-type="bibr" rid="ref21">Fagbami and Donato, 2011</xref>; <xref ref-type="bibr" rid="ref36">Kitashima et al., 2013</xref>; <xref ref-type="bibr" rid="ref40">Krygowska-Wajs et al., 2016</xref>; <xref ref-type="bibr" rid="ref41">Kulneff et al., 2013</xref>; <xref ref-type="bibr" rid="ref50">Lengerer et al., 2012</xref>; <xref ref-type="bibr" rid="ref64">Olchik et al., 2018</xref>; <xref ref-type="bibr" rid="ref70">Robertson et al., 2011</xref>; <xref ref-type="bibr" rid="ref73">Silbergleit et al., 2012a</xref>; <xref ref-type="bibr" rid="ref93">Wolz et al., 2012</xref>; <xref ref-type="bibr" rid="ref98">Xu et al., 2018</xref>; <xref ref-type="bibr" rid="ref100">Zibetti et al., 2007</xref>), four in GPi (<xref ref-type="bibr" rid="ref77">Smith-Hublou et al., 2024</xref>; <xref ref-type="bibr" rid="ref84">Troche et al., 2014</xref>; <xref ref-type="bibr" rid="ref30">Henry et al., 2022</xref>; <xref ref-type="bibr" rid="ref70">Robertson et al., 2011</xref>) and three in caudal zona incerta (cZI) (<xref ref-type="bibr" rid="ref78">Sundstedt et al., 2017a</xref>; <xref ref-type="bibr" rid="ref79">Sundstedt et al., 2017b</xref>; <xref ref-type="bibr" rid="ref80">Sundstedt et al., 2012</xref>). Two studies employed combined STN and substantia nigra (SNr) DBS (<xref ref-type="bibr" rid="ref10">Cebi et al., 2024</xref>; <xref ref-type="bibr" rid="ref66">Pflug et al., 2020</xref>), while one utilized combined STN&#x202F;+&#x202F;GPi-DBS (<xref ref-type="bibr" rid="ref85">Troche et al., 2016</xref>).</p>
<sec id="sec5">
<label>2.1.1</label>
<title>STN-DBS</title>
<p>STN-DBS is known to modulate both direct and indirect motor pathways (<xref ref-type="bibr" rid="ref9">Cavallo et al., 2025</xref>), including excitatory glutamatergic projections to the substantia nigra pars compacta (which influences dopaminergic output) and loops involving the brainstem (<xref ref-type="bibr" rid="ref24">Freestone et al., 2015</xref>).</p>
<p>Of 24 identified studies, eight clinical studies (<xref ref-type="bibr" rid="ref30">Henry et al., 2022</xref>; <xref ref-type="bibr" rid="ref95">Xie et al., 2018</xref>; <xref ref-type="bibr" rid="ref36">Kitashima et al., 2013</xref>; <xref ref-type="bibr" rid="ref41">Kulneff et al., 2013</xref>; <xref ref-type="bibr" rid="ref50">Lengerer et al., 2012</xref>; <xref ref-type="bibr" rid="ref64">Olchik et al., 2018</xref>; <xref ref-type="bibr" rid="ref73">Silbergleit et al., 2012a</xref>; <xref ref-type="bibr" rid="ref100">Zibetti et al., 2007</xref>) reported no significant changes in swallowing function after STN-DBS. Two studies reported positive effects of STN-DBS (<xref ref-type="bibr" rid="ref11">Ciucci et al., 2008</xref>; <xref ref-type="bibr" rid="ref96">Xie et al., 2015</xref>), while four studies (<xref ref-type="bibr" rid="ref84">Troche et al., 2014</xref>; <xref ref-type="bibr" rid="ref38">Krause et al., 2004</xref>; <xref ref-type="bibr" rid="ref70">Robertson et al., 2011</xref>; <xref ref-type="bibr" rid="ref98">Xu et al., 2018</xref>) described detrimental effects on swallowing.</p>
<sec id="sec6">
<label>2.1.1.1</label>
<title>Studies reporting positive or neutral STN-DBS outcomes</title>
<p>Using VFSS in 14 participants, <xref ref-type="bibr" rid="ref11">Ciucci et al. (2008)</xref> observed significant improvements in pharyngeal transit time and pharyngeal composite scores (encompassing swallowing safety, efficiency, and structural movement parameters) when comparing DBS-on with DBS-off in the medication-off state. Hyoid bone excursion and oral stage parameters remained unchanged. <xref ref-type="bibr" rid="ref96">Xie et al. (2015)</xref> investigated the impact of stimulation frequency on swallowing function in bilateral STN-DBS by comparing DBS-off, 60&#x202F;Hz, and 130&#x202F;Hz conditions in the medication-on state (<italic>n</italic>&#x202F;=&#x202F;7). They observed during VFSS that 60&#x202F;Hz significantly reduced aspiration frequency and subjective swallowing difficulty compared to 130&#x202F;Hz. However, no statistically significant difference was found when comparing 60&#x202F;Hz stimulation with DBS-off, suggesting that DBS with 60&#x202F;Hz does not inherently improve swallowing. Given the small sample size, this study was likely underpowered, impacting statistical analyses. <xref ref-type="bibr" rid="ref73">Silbergleit et al. (2012a)</xref> evaluated swallowing during VFSS across multiple medication and stimulation states (MED-on/off, DBS-on/off) at both 3 and 12&#x202F;months. Improvements in oral preparation of thin liquids and pharyngeal response for solids were observed at 12&#x202F;months post-surgery in MED-off/DBS-on conditions compared to MED-off/DBS-off, while global penetration/aspiration-based safety outcomes remained unchanged. <xref ref-type="bibr" rid="ref50">Lengerer et al. (2012)</xref> conducted VFSS with detailed timing measures (pharyngeal transit, reaction time, cricopharyngeal opening). Several timing parameters improved post-surgery in DBS-on vs. DBS-off conditions, although the retrospective design, heterogeneous DBS settings, and variable follow-up duration limit causal inferences. Moreover, <xref ref-type="bibr" rid="ref36">Kitashima et al. (2013)</xref> investigated swallowing function in DBS-on vs. DBS-off conditions and found no changes in videofluoroscopic dysphagia score between visits. However, significant changes in tongue movement and laryngeal elevation delay time were observed when comparing DBS-on vs. DBS-off states. <xref ref-type="bibr" rid="ref41">Kulneff et al. (2013)</xref> applied a comprehensive FEES protocol including PAS, secretion status, residue scoring and pre-swallow spillage after STN-DBS. For statistical analysis, all scales were transformed so the lowest score was 0 and the mean of each scale was derived. Although no changes were detected during FEES post-surgery, patients consistently reported improved subjective swallowing.</p>
</sec>
<sec id="sec7">
<label>2.1.1.2</label>
<title>Studies reporting negative STN-DBS outcomes</title>
<p>Other studies reported negative effects of STN-DBS on swallowing. <xref ref-type="bibr" rid="ref84">Troche et al. (2014)</xref> retrospectively analyzed the effects of unilateral STN-DBS on swallowing safety in 14 individuals with PD, comparing PAS scores before and 6&#x202F;months after surgery. The baseline assessment was conducted in the medication-on state, while the post-surgical evaluation was performed in medication-on and DBS-on state. The study found a significant increase in PAS scores postoperatively, indicating a decline in swallowing safety. Beyond pharyngeal swallowing function, one study examined the impact of STN-DBS on jaw movements. <xref ref-type="bibr" rid="ref70">Robertson et al.&#x2019;s (2011)</xref> research team conducted a prospective intervention study to evaluate the effects of DBS target site on bradykinetic jaw movements in participants with STN-DBS (<italic>n</italic>&#x202F;=&#x202F;14). They assessed mandibular movement through kinesiographic measurements and oromotor tasks. A chin-mounted magnet tracked by eyeglass sensors provided 3D mandibular data. Baseline assessments prior to surgery included both medication-off and -on states. The post-surgery testing included four different conditions: (1) medication-off and DBS-off; (2) medication-on and DBS-off (3) medication-off and DBS-on; (4) both medication-on and DBS-on. The authors reported a significant reduction in jaw velocity in the STN-DBS group in all conditions compared to medication-off in the baseline assessment. However, swallowing efficiency or safety were not assessed directly.</p>
<p><xref ref-type="bibr" rid="ref38">Krause et al. (2004)</xref> reported OD as an adverse event in 3 out of 27 participants in a study investigating the long-term effects of bilateral STN-DBS on overall motor symptoms in PD. However, neither a definition of OD nor criteria for adverse event classification were specified, limiting interpretation of these findings.</p>
</sec>
<sec id="sec8">
<label>2.1.1.3</label>
<title>STN-DBS mechanisms</title>
<p>While STN-DBS mechanisms often produce motor improvement, the STN lies adjacent to the internal capsule, especially with its lateral aspect (see <xref ref-type="fig" rid="fig1">Figure 1</xref>). If stimulation spreads toward the capsule with its corticobulbar fibers, which descend through the genu of the internal capsule and control facial, lingual, and pharyngeal muscles, this can result in capsular side effects such as dysarthria (<xref ref-type="bibr" rid="ref34">Jergas et al., 2025</xref>), facial pulling (<xref ref-type="bibr" rid="ref54">Mahlknecht et al., 2017</xref>), or potentially OD. This phenomenon may explain why some patients show negative effects on swallowing, especially in the medication-on state when STN-DBS and pharmacological pathways interact.</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Deep brain stimulation electrode placement in the basal ganglia showing subthalamic nucleus and globus pallidus internus targets in relation to the internal capsule. Anatomical structures are depicted based on the BigBrain atlas (<xref ref-type="bibr" rid="ref2">Amunts et al., 2013</xref>). DBS leads show typical positioning for therapeutic stimulation.</p>
</caption>
<graphic xlink:href="fnagi-17-1734432-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Medical imaging of the brain shows anteroposterior view with highlighted components in color. Yellow fibers represent the internal capsule (IC). Green represents the globus pallidus internus (GPI), and orange shows the subthalamic nucleus (STN). A close-up on the right provides a coronal view, detailing these structures.</alt-text>
</graphic>
</fig>
</sec>
</sec>
<sec id="sec9">
<label>2.1.2</label>
<title>GPi-DBS</title>
<p>As the principal output nucleus of the basal ganglia, the GPi sends GABAergic inhibitory projections to the thalamus and brainstem, both key regions involved in motor control, including bulbar function. In PD, overactivity in the GPi is considered to contribute to disrupted motor signaling (<xref ref-type="bibr" rid="ref19">Dostrovsky et al., 2001</xref>). DBS targeting the GPi may reduce this pathological overactivity, thereby improving the transmission of motor signals to brainstem centers such as the swallowing central pattern generator (CPG), potentially modulating swallowing function (<xref ref-type="bibr" rid="ref3">Au et al., 2021</xref>). The swallowing CPG, a neural network located in the brainstem, coordinates the sequential motor patterns required for swallowing and receives modulatory input from higher motor centers including basal ganglia pathways (<xref ref-type="bibr" rid="ref91">Wei et al., 2024</xref>). None of the four included studies investigating the impact of GPi on swallowing function found significant changes pre- to post-surgery. One of these studies was a prospective clinical trial (<xref ref-type="bibr" rid="ref70">Robertson et al., 2011</xref>), while three studies were retrospective chart reviews (<xref ref-type="bibr" rid="ref77">Smith-Hublou et al., 2024</xref>; <xref ref-type="bibr" rid="ref84">Troche et al., 2014</xref>; <xref ref-type="bibr" rid="ref30">Henry et al., 2022</xref>). The prospective trial by <xref ref-type="bibr" rid="ref70">Robertson et al. (2011)</xref> found that compared with baseline medication-off conditions, the GPi group (<italic>n</italic>&#x202F;=&#x202F;13) showed significant postoperative improvements in the DBS- and medication-off condition, with increased jaw opening and closing velocity (both <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05), and faster thin-elicited biting velocity (defined as the final, consistent peak velocity of the jaw, measured when the participant bites through a thin piece of raw carrot in a single, ballistic motion; <italic>p</italic>&#x202F;&#x003C;&#x202F;0.01), although their performance during combined DBS- and medication-on was not different from medication-on pre-surgery. These findings indicate that GPi-DBS may have produced persistent improvements in jaw function which could reflect several mechanisms including microlesion effect, as commonly observed in DBS. The absence of additional benefit when stimulation is active may reflect ceiling effects with medication. <xref ref-type="bibr" rid="ref77">Smith-Hublou et al. (2024)</xref> retrospectively assessed swallowing in 36 participants in a cross-sectional observational study with some overlapping participants. The team used PAS for swallowing safety and DIGEST (<xref ref-type="bibr" rid="ref32">Hutcheson et al., 2017</xref>) for both safety and efficiency, and timing parameters including pharyngeal transit time and laryngeal approximation reaction time. The primary outcome was the percentage of thin-liquid bolus trials rated &#x201C;unsafe,&#x201D; defined as PAS scores of &#x2265;3. No effect of GPi-DBS was found on any outcome. Similar findings were reported by <xref ref-type="bibr" rid="ref30">Henry et al. (2022)</xref>, who investigated 25 participants with bilateral GPi-DBS pre- and 6-months post-surgery and retrospectively reported their results. In this retrospective study, the researchers converted the verbal description from the report into a PAS score, a post-hoc scoring approach that may have introduced validity concerns. No significant difference in PAS score was detected when compared to baseline or to the other study group receiving STN-DBS (<italic>n</italic>&#x202F;=&#x202F;29). In contrast to the worsened PAS scores observed after STN-DBS, participants receiving GPi-DBS (<italic>n</italic>&#x202F;=&#x202F;19) in the study by <xref ref-type="bibr" rid="ref84">Troche et al. (2014)</xref> showed no significant change in PAS scores at 6&#x202F;months post-surgery.</p>
<sec id="sec10">
<label>2.1.2.1</label>
<title>GPi-DBS mechanisms</title>
<p>The findings described above align with the anatomical considerations for GPi targeting, as GPi-DBS is generally located at a safer distance from the internal capsule (see <xref ref-type="fig" rid="fig1">Figure 1</xref>), reducing the likelihood of corticobulbar side effects from stimulating the capsule that could impair swallowing. However, the larger anatomical size of the GPi may cause greater variability in electrode placement than the more compact STN. With only one study reporting precise GPi coordinates (<xref ref-type="bibr" rid="ref70">Robertson et al., 2011</xref>), direct comparisons and identification of an optimal stimulation site to target OD were not possible (see <xref rid="SM1" ref-type="supplementary-material">Supplementary Table 1</xref> for reported coordinate data). Furthermore, the larger dimensions of the GPi also require higher charge densities (<xref ref-type="bibr" rid="ref3">Au et al., 2021</xref>), so electrodes near the internal capsule may induce corticobulbar side effects at lower thresholds due to increased pulse rates and amplitudes.</p>
</sec>
</sec>
<sec id="sec11">
<label>2.1.3</label>
<title>cZI-DBS</title>
<p>The cZI has widespread connections to cortical, thalamic, and brainstem regions, including those involved in autonomic and bulbar functions (<xref ref-type="bibr" rid="ref49">Lau et al., 2020</xref>). Although not as well studied, stimulation in this region may modulate both dopaminergic and brainstem networks, potentially providing symptom relief with fewer capsular side effects due to its relative distance from the internal capsule (<xref ref-type="bibr" rid="ref55">Mai and Paxinos, 2012</xref>).</p>
<p>One research group investigated bilateral cZI-DBS in a prospective pre-post stimulation design and published findings on swallowing function and swallowing related quality of life across three different studies (<xref ref-type="bibr" rid="ref78">Sundstedt et al., 2017a</xref>; <xref ref-type="bibr" rid="ref79">Sundstedt et al., 2017b</xref>; <xref ref-type="bibr" rid="ref80">Sundstedt et al., 2012</xref>), with participant overlap between studies. The 2017 swallowing safety study (<xref ref-type="bibr" rid="ref78">Sundstedt et al., 2017a</xref>) (<italic>n</italic>&#x202F;=&#x202F;14) constituted an extended analysis of the 2012 study (<xref ref-type="bibr" rid="ref80">Sundstedt et al., 2012</xref>) (<italic>n</italic>&#x202F;=&#x202F;8), examining the same subset. Overall, the study team found no changes in swallowing related quality of life, swallowing safety measured during FEES by PAS and the Secretion Severity Scale (<xref ref-type="bibr" rid="ref61">Murray et al., 1996</xref>) nor in pre-swallow spillage, pharyngeal residue and pharyngeal clearance which were rated dichotomously (present/absent) (<xref ref-type="bibr" rid="ref78">Sundstedt et al., 2017a</xref>; <xref ref-type="bibr" rid="ref80">Sundstedt et al., 2012</xref>).</p>
</sec>
<sec id="sec12">
<label>2.1.4</label>
<title>Simultaneous DBS in different targets</title>
<p>Three studies reported on simultaneous DBS of different anatomical targets. Two of these were randomized double-blind clinical trials investigating combined DBS of STN and SNr.</p>
<p>The SNr connects to the pedunculopontine nucleus, superior colliculus, and the swallowing CPG, making it an intriguing target for bulbar symptom modulation (<xref ref-type="bibr" rid="ref92">Wichmann and Delong, 2011</xref>). Stimulation here may inhibit excessive neural firing and restore normal function in downstream brainstem networks. Importantly, the SNr is located further from the internal capsule, reducing the risk of corticospinal or corticobulbar activation and associated swallowing side effects (<xref ref-type="bibr" rid="ref55">Mai and Paxinos, 2012</xref>).</p>
<p><xref ref-type="bibr" rid="ref10">Cebi et al. (2024)</xref> compared the effects of STN-DBS versus combined STN&#x202F;+&#x202F;SNr-DBS in 20 participants with PD who had previously received STN-DBS for at least 6&#x202F;months prior to study enrollment in a double-blind randomized controlled trial. Following baseline assessment under existing STN-DBS settings, participants were randomized to receive either continued STN-DBS or combined STN&#x202F;+&#x202F;SNr-DBS for 8&#x202F;weeks before post-intervention evaluation. All participants received concurrent swallowing therapy consisting of group sessions (three times per week for 8&#x202F;weeks) with strength-based exercises (Shaker-exercise, chin tuck against resistance and tongue strengthening against resistance), precluding attribution of effects to DBS alone. The researchers conducted a power analysis determining that 10 participants per group would provide 81% power to detect significant PAS score changes and performed an intention-to-treat analysis on all 20 enrolled participants despite six drop-outs. The research group found no significant difference in PAS scores obtained during FEES when comparing STN-DBS with combined STN&#x202F;+&#x202F;SNr-DBS. A significant effect was only detected after pooling the data and comparing baseline with follow-up measurements. The study group used the median and interquartile ranges for statistical analysis of the PAS. Similarly, <xref ref-type="bibr" rid="ref66">Pflug et al. (2020)</xref> compared STN&#x202F;+&#x202F;SNr-DBS with conventional STN-DBS. Using a randomized, double-blind crossover study design, 15 participants with PD underwent baseline assessment followed by either STN-DBS or combined STN&#x202F;+&#x202F;SNr-DBS for 3&#x202F;weeks, with assessments conducted after each treatment period. Likewise, they did not find any positive effects on pharyngeal residue and penetration&#x2212;/aspiration events after simultaneous STN&#x202F;+&#x202F;SNr-DBS. Of the 15 included participants, four dropped out due to adverse events after starting combined STN&#x202F;+&#x202F;SNr-DBS. Although no significant group-level effects were observed, individual outcomes varied considerably compared to DBS-off: three participants showed worsening PAS scores for water under both stimulation modes, and two demonstrated improvements. In this study, PAS scores were grouped into three categories for analysis: &#x201C;non-pathological&#x201D; (PAS 1&#x2013;2), &#x201C;laryngeal penetration&#x201D; (PAS 3&#x2013;5), and &#x201C;aspiration&#x201D; (PAS 6&#x2013;8). While <xref ref-type="bibr" rid="ref66">Pflug et al. (2020)</xref> determined through power analysis that 11 participants provided sufficient statistical power for their cross-over design, the authors acknowledged that this small sample size could still limit detection of group-level differences in swallowing function. In a case report, <xref ref-type="bibr" rid="ref85">Troche et al. (2016)</xref> described a patient with VFSS-confirmed OD and bilateral DBS (STNand GPi). Airway protection improved after reprogramming, with final settings of 135&#x202F;Hz, 120&#x202F;&#x03BC;s, 2.9&#x202F;V (GPi) and 135&#x202F;Hz, 90&#x202F;&#x03BC;s, 3.8&#x202F;V (STN). Interpretation remains limited since baseline parameters were not provided.</p>
</sec>
</sec>
<sec id="sec13">
<label>2.2</label>
<title>Patient-reported outcome measures</title>
<p>Several studies used patient-reported outcome measures to evaluate swallowing. Some studies assessed swallowing using the UPDRS. One retrospective study of 80 participants examined the long-term effects of bilateral STN-DBS across Parkinson&#x2019;s disease motor subtypes and reported a decline in swallowing function after a mean follow-up of 4.9&#x202F;years (<xref ref-type="bibr" rid="ref98">Xu et al., 2018</xref>). In a study on long-term motor outcomes following bilateral STN-DBS, <xref ref-type="bibr" rid="ref38">Krause et al. (2004)</xref> described a worsening in mean swallowing scores from baseline to one year post-DBS surgery (0.3 vs. 1.1, respectively), though statistical significance of this difference was not reported. <xref ref-type="bibr" rid="ref100">Zibetti et al. (2007)</xref> observed significant improvements in swallowing at 12 and 24&#x202F;months post-surgery in 36 participants in the MED-on state with STN-DBS compared with the pre-surgical MED-off state. However, no significant differences were found when comparing the pre-operative MED-on state to the post-surgical DBS-ON &#x0026; MED-on states at 12 or 24 months. Therefore, the observed improvements cannot be solely attributed to DBS and may reflect medication effect. Overall, results derived from the UPDRS should be interpreted with caution, as the scale includes only a limited number of swallowing-related items and was not designed to provide a comprehensive or sensitive assessment of swallowing function or OD severity.</p>
<p><xref ref-type="bibr" rid="ref40">Krygowska-Wajs et al. (2016)</xref> used a study-specific gastrointestinal dysfunction questionnaire containing a single OD item rated on a 5-point severity scale. At 3&#x202F;months post STN-DBS surgery, fewer participants reported OD, and mean severity scores decreased significantly. <xref ref-type="bibr" rid="ref96">Xie et al. (2015)</xref> reported that 60-Hz stimulation reduced perceived swallowing difficulty by 80% compared to 130&#x202F;Hz in their 2015 study, though their 2018 study (<xref ref-type="bibr" rid="ref95">Xie et al., 2018</xref>) found this subjective benefit was not sustained at long-term follow-up at 14.5&#x202F;months.</p>
<p>Visual analog scales were employed in three studies. <xref ref-type="bibr" rid="ref66">Pflug et al. (2020)</xref> assessed self-perceived swallowing function and found no effect of stimulation target (STN vs. STN&#x202F;+&#x202F;SNr). <xref ref-type="bibr" rid="ref41">Kulneff et al. (2013)</xref> evaluated participants&#x2019; perceived percentage deterioration in swallowing and reported significantly improved swallowing during STN-DBS-on compared with STN-DBS-off conditions, while no significant effect was detected on FEES assessment. <xref ref-type="bibr" rid="ref79">Sundstedt et al. (2017b)</xref> found no clinically significant negative impact of cZI-DBS on participants&#x2019; self-perceived swallowing function.</p>
<p>Three studies used the SWAL-QOL to assess swallowing-related quality of life. <xref ref-type="bibr" rid="ref84">Troche et al. (2014)</xref> reported no pre- to post-surgical differences in either GPi-DBS or STN-DBS groups, despite significantly worsened mean PAS-scores in the STN-DBS group. Similarly, <xref ref-type="bibr" rid="ref79">Sundstedt et al. (2017b)</xref> found no change following cZI-DBS, and <xref ref-type="bibr" rid="ref10">Cebi et al. (2024)</xref> observed no clinically relevant changes pre- to post-surgery or between STN-DBS and STN&#x202F;+&#x202F;SNr-DBS groups. In contrast, <xref ref-type="bibr" rid="ref73">Silbergleit et al. (2012a)</xref> reported a significant improvement in DHI scores following STN-DBS.</p>
<p>In summary, patient-reported outcomes yielded inconsistent findings across studies. While validated, swallowing-specific quality-of-life measures generally indicated no deterioration following DBS, results derived from broader motor assessments were more variable.</p>
</sec>
<sec id="sec14">
<label>2.3</label>
<title>DBS stimulation settings and mechanisms</title>
<p>The impact of DBS stimulation settings on swallowing in PD has been investigated only rarely, and stimulation parameters were often incompletely reported. None of the included studies systematically adjusted settings based on swallowing outcomes, except for two case reports (<xref ref-type="bibr" rid="ref21">Fagbami and Donato, 2011</xref>; <xref ref-type="bibr" rid="ref85">Troche et al., 2016</xref>). Overall, swallowing function was generally not considered in DBS programming.</p>
<sec id="sec15">
<label>2.3.1</label>
<title>Stimulation parameters</title>
<p>DBS programming involves adjusting multiple stimulation parameters, including frequency (Hz), amplitude (V), and pulse width (&#x03BC;s), which can be individually optimized to maximize therapeutic benefit while minimizing adverse effects (<xref ref-type="bibr" rid="ref29">Hartmann et al., 2019</xref>). Frequency settings have been investigated for their differential effects on motor symptom subtypes. Low-frequency stimulation (LFS, &#x003C;100&#x202F;Hz) may restore physiological gamma-oscillations, while high-frequency stimulation (HFS, &#x003E;100&#x202F;Hz, typically 130&#x202F;Hz) suppresses pathological rhythms and is more effective for appendicular symptoms (<xref ref-type="bibr" rid="ref9">Cavallo et al., 2025</xref>; <xref ref-type="bibr" rid="ref24">Freestone et al., 2015</xref>). LFS may be more beneficial for axial symptoms such as gait (<xref ref-type="bibr" rid="ref34">Jergas et al., 2025</xref>).</p>
<p>With respect to swallowing, <xref ref-type="bibr" rid="ref77">Smith-Hublou et al. (2024)</xref> found no significant associations between swallowing safety (percentage of &#x201C;unsafe thin-liquid swallows,&#x201D; defined as PAS&#x202F;&#x003E;&#x202F;3) and stimulation parameters including frequency, pulse width, or voltage in their retrospective analysis of 36 participants with GPi-DBS. In contrast, <xref ref-type="bibr" rid="ref96">Xie et al. (2015)</xref> observed reduced aspiration frequency and improved self-reported swallowing difficulty under low-frequency STN-DBS (60&#x202F;Hz) compared to HFS (130&#x202F;Hz). Aspiration frequency was calculated by summing the number of swallows with a PAS rating of &#x2265; 6. These effects were only seen in a direct comparison and after 6&#x2013;8&#x202F;weeks of LFS however were not sustained at 14.5&#x202F;months (<xref ref-type="bibr" rid="ref95">Xie et al., 2018</xref>). Both studies by Xie et al. conducted power analyses but were underpowered due to lower recruitment, potentially limiting the magnitude of detected effects. Notably, participants had medication-refractory freezing of gait that improved under LFS, suggesting that alleviation of oropharyngeal freezing may have contributed to swallowing benefits. Therefore, findings may not be generalizable to the broader PD population. Moreover, stimulation voltage was not adjusted when switching from HFS to LFS, reducing total electrical energy delivered (TEED) and complicating interpretation. TEED represents the cumulative energy transferred during stimulation and is a function of the stimulation frequency, pulse width, voltage and the impedance between electrode and surrounding brain tissue (<xref ref-type="bibr" rid="ref37">Koss et al., 2005</xref>). TEED is proportional to the square of voltage. Therefore, maintaining constant voltage across different frequencies results in different total energy exposures, making it difficult to determine whether observed effects are due to frequency changes per se or to differences in TEED.</p>
<p>Given the limited body of literature specifically addressing swallowing outcomes, insights from related domains such as speech and voice may provide useful contextual information. Studies in these areas demonstrate highly variable effects, with high-frequency or high-amplitude stimulation often worsening speech and articulation, while lower frequencies or shorter pulse widths may offer some benefit (<xref ref-type="bibr" rid="ref75">Skodda, 2012</xref>; <xref ref-type="bibr" rid="ref81">Tabari et al., 2024</xref>); the anatomical target is also critical, as pallidal stimulation can improve voice quality but may worsen other speech features while other targets (STN, Thalamic, Zona Incerta) are more often linked to deterioration of vocal parameters (<xref ref-type="bibr" rid="ref4">Baudouin et al., 2023</xref>).</p>
</sec>
<sec id="sec16">
<label>2.3.2</label>
<title>Lead configuration: monopolar vs. bipolar DBS</title>
<p>Lead configuration strongly influences DBS effects. Monopolar stimulation produces a broad electric field and increases the risk of unintended activation of corticobulbar fibers in the internal capsule, which are essential for speech and swallowing and may underlie stimulation-induced dysarthria in STN-DBS (<xref ref-type="bibr" rid="ref91">Wei et al., 2024</xref>; <xref ref-type="bibr" rid="ref34">Jergas et al., 2025</xref>; <xref ref-type="bibr" rid="ref54">Mahlknecht et al., 2017</xref>; <xref ref-type="bibr" rid="ref51">Li&#x00E9;geois et al., 2016</xref>). Bipolar stimulation generates a more confined electric field, thereby reducing current spread. Recruitment also depends on the alignment between the electric field and fiber orientation. With cylindrical contacts, monopolar or simple bipolar configurations tend to bias activation toward fibers parallel to the lead (<xref ref-type="bibr" rid="ref76">Slopsema et al., 2018</xref>; <xref ref-type="bibr" rid="ref8">Butenko et al., 2025</xref>), further increasing the risk of corticobulbar involvement. In contrast, multipolar or directional stimulation can bias recruitment toward therapeutic pathways such as the hyperdirect tract (<xref ref-type="bibr" rid="ref76">Slopsema et al., 2018</xref>; <xref ref-type="bibr" rid="ref8">Butenko et al., 2025</xref>), and anatomy-guided programming may thus help clinicians reduce bulbar side effects.</p>
<p>Eight studies reported stimulation configuration: some applied mixed settings within individuals (<xref ref-type="bibr" rid="ref95">Xie et al., 2018</xref>; <xref ref-type="bibr" rid="ref96">Xie et al., 2015</xref>; <xref ref-type="bibr" rid="ref98">Xu et al., 2018</xref>; <xref ref-type="bibr" rid="ref100">Zibetti et al., 2007</xref>), while others included monopolar or bipolar stimulation exclusively (<xref ref-type="bibr" rid="ref50">Lengerer et al., 2012</xref>; <xref ref-type="bibr" rid="ref100">Zibetti et al., 2007</xref>; <xref ref-type="bibr" rid="ref10">Cebi et al., 2024</xref>). <xref ref-type="bibr" rid="ref21">Fagbami and Donato (2011)</xref> provided a clear case example: a patient developed OD with aspiration, stridor, and respiratory restriction under monopolar STN-DBS (130&#x202F;Hz, 90/60&#x202F;&#x03BC;s, 1.6&#x202F;V bilaterally). When DBS was suspended, symptoms improved and aspiration resolved; subsequent reprogramming to bipolar stimulation (160&#x202F;Hz, 60&#x202F;&#x03BC;s, 1.5&#x2013;2.1&#x202F;V) achieved sustained clinical improvement. The improvement may be attributed to reduced current spread to corticobulbar fibers.</p>
</sec>
<sec id="sec17">
<label>2.3.3</label>
<title>Stimulation directionality: omnidirectional vs. directional electrodes</title>
<p>Electrode design further affects DBS outcomes. In a homogeneous medium, traditional omnidirectional leads generate axially symmetric electric fields, which can spread into surrounding structures, whereas segmented leads allow directional current steering. Directional stimulation reduces the risk of activating corticospinal and corticobulbar tracts, which is especially relevant near the highly myelinated internal capsule, where current distribution can be altered (<xref ref-type="bibr" rid="ref33">Ineichen et al., 2018</xref>). Steering current away from these tracts may reduce stimulation-induced side effects such as OD. Various commercial and non-commercial methods are available to predict which brain tissue will be affected by DBS stimulation and to estimate the volume of neural activation.</p>
</sec>
<sec id="sec18">
<label>2.3.4</label>
<title>Tailored optimization</title>
<p>In addition to frequency and configuration, individualized optimization of stimulation settings has been reported in case studies (<xref ref-type="bibr" rid="ref21">Fagbami and Donato, 2011</xref>; <xref ref-type="bibr" rid="ref85">Troche et al., 2016</xref>). Similar to the previously outlined case study by <xref ref-type="bibr" rid="ref21">Fagbami and Donato (2011)</xref>, <xref ref-type="bibr" rid="ref85">Troche et al. (2016)</xref> described improved airway protection in a patient with bilateral DBS (STN and GPi) after tailored reprogramming, although specific stimulation parameter adjustments were not provided. Such cases illustrate the potential of individualized DBS programming to modulate swallowing outcomes, even though systematic protocols are currently lacking.</p>
</sec>
</sec>
</sec>
<sec sec-type="discussion" id="sec19">
<label>3</label>
<title>Discussion</title>
<p>In total, 24 studies were included: three randomized double-blind trials, 14 prospective pre&#x2013;post studies, five retrospective analyses, and two case reports. Some compared anatomical targets, while others examined stimulation settings, most commonly assessing pre- versus post-surgery or DBS-on versus -off. Many studies were open-label and/or retrospective in design, with small sample sizes. Additional limitations included suboptimal outcome measures for swallowing, as well as incomplete reporting of swallowing protocols, stimulation parameters, and medication status, which further compromised comparability across studies.</p>
<p>A major limitation across studies is the consistently small sample size, with power analyses only reported in four (<xref ref-type="bibr" rid="ref95">Xie et al., 2018</xref>; <xref ref-type="bibr" rid="ref96">Xie et al., 2015</xref>; <xref ref-type="bibr" rid="ref10">Cebi et al., 2024</xref>; <xref ref-type="bibr" rid="ref66">Pflug et al., 2020</xref>) of the 24 studies. As a result, most investigations were likely underpowered to detect clinically meaningful effects. This issue is further compounded by the heterogeneity of DBS effects, which can vary substantially within individuals. Without adequate sample sizes or stratification by OD phenotype, such variability is difficult to capture at the group level, limiting the interpretability and generalizability of findings.</p>
<p>Notably, four studies published between 2020 and April 2025 included two double-blind randomized controlled trials and two retrospective studies. All four utilized instrumental OD assessments, representing methodological improvement over earlier studies. However, participant selection may have introduced bias, as most individuals had no or only minimal swallowing safety impairment at baseline, based on reported PAS scores. Consequently, potential for observing treatment-related improvement was limited, and generalizability to broader clinical populations, particularly patients with severe OD remains restricted. However, most of these studies also examined outcomes beyond swallowing safety, measuring timing parameters such as pharyngeal swallow phase (<xref ref-type="bibr" rid="ref77">Smith-Hublou et al., 2024</xref>), mastication (<xref ref-type="bibr" rid="ref10">Cebi et al., 2024</xref>), or bolus location (<xref ref-type="bibr" rid="ref66">Pflug et al., 2020</xref>), to gain insights into how DBS impacts OD pathophysiology. Additionally, one trial included healthy, age-matched controls (<xref ref-type="bibr" rid="ref66">Pflug et al., 2020</xref>), enabling clearer attribution of swallowing impairments to PD while accounting for age-related changes in swallowing physiology.</p>
<p>The effect of levodopa on swallowing remains controversial in the literature. Some studies report beneficial effects on swallowing function (<xref ref-type="bibr" rid="ref46">Labeit et al., 2020b</xref>; <xref ref-type="bibr" rid="ref90">Warnecke et al., 2016</xref>). For instance, <xref ref-type="bibr" rid="ref89">Warnecke et al. (2022)</xref> proposed that specific manifestations of oropharyngeal dysphagia are related to dopaminergic deficiency and may therefore improve with levodopa therapy. When findings across the included studies are compared, these same manifestations, such as prolonged oral and pharyngeal transit times and increased pharyngeal residue, also appear to be at least partly responsive to DBS (<xref ref-type="bibr" rid="ref11">Ciucci et al., 2008</xref>; <xref ref-type="bibr" rid="ref36">Kitashima et al., 2013</xref>; <xref ref-type="bibr" rid="ref50">Lengerer et al., 2012</xref>; <xref ref-type="bibr" rid="ref10">Cebi et al., 2024</xref>). This parallel responsiveness suggests that dopaminergic manifestations of oropharyngeal dysphagia, particularly pharyngeal bradykinesia, may share common underlying pathophysiological mechanisms that can be modulated either through dopamine replacement therapy or through direct basal ganglia deep brain stimulation. Nevertheless, the impact of levodopa on swallowing remains variable, with some studies reporting no clinically meaningful effects (<xref ref-type="bibr" rid="ref62">Nascimento et al., 2020</xref>) or mixed results across different swallowing parameters (<xref ref-type="bibr" rid="ref52">Lim et al., 2008</xref>). Discordance between subjective and instrumental swallowing outcomes was observed following DBS. Participant-reported improvement were not always supported by instrumental findings (<xref ref-type="bibr" rid="ref41">Kulneff et al., 2013</xref>), and conversely, deterioration on instrumental assessments was partly not reflected in subjective reports (<xref ref-type="bibr" rid="ref84">Troche et al., 2014</xref>). Such discrepancies between subjective and instrumental evaluations have previously been documented in PD (<xref ref-type="bibr" rid="ref65">Pflug et al., 2018</xref>; <xref ref-type="bibr" rid="ref67">Rangwala et al., 2025</xref>; <xref ref-type="bibr" rid="ref59">Monteiro et al., 2014</xref>; <xref ref-type="bibr" rid="ref35">Kalf et al., 2012</xref>; <xref ref-type="bibr" rid="ref63">Nienstedt et al., 2019</xref>) and are therefore not unique to the DBS setting. Nevertheless, <xref ref-type="bibr" rid="ref99">Yu et al. (2020)</xref> suggested a DBS-specific explanation: overall motor improvement after DBS may enhance general patient satisfaction, thereby positively biasing perceptions of swallowing function. Additionally, the choice of statistical analysis for rating scales can affect detection of subtle, yet clinically meaningful, treatment effects. The PAS was the most common measurement tool of swallowing safety across studies, but how the measured values were handled in the statistical analysis varied: some studies used group-level scores only, collapsed categories (e.g., &#x201C;safe&#x201D; [PAS 1&#x2013;2] vs. &#x201C;unsafe&#x201D; [PAS 3&#x2013;8]), or pooled results across consistencies. Essential swallowing protocol details such as consistency types, swallows per consistency, or statistical handling of multiple swallows were often not reported. Such discrepancies can limit statistical power (<xref ref-type="bibr" rid="ref5">Borders and Brates, 2020</xref>). A recent simulation study (<xref ref-type="bibr" rid="ref6">Borders et al., 2025</xref>) modeled hypothetical OD intervention trials in PD and demonstrated that using only the worst PAS score or collapsing scores into categories significantly reduces statistical power and introduces bias in effect size estimates. Whereas multilevel models accounting for multiple swallows per participant were more sensitive and accurate in detecting group-level changes over time. These insights are relevant to DBS studies, where mild or variable improvements across stimulation modalities or consistencies may be obscured by summary scoring.</p>
</sec>
<sec id="sec20">
<label>4</label>
<title>Future directions</title>
<p>Despite increasing research on the effects of DBS on swallowing function in PD, several important questions remain unanswered. The heterogeneity of study designs, the choice of outcomes and outcome measures, and incomplete reporting of relevant parameters hinder the aggregation of findings. In addition, major gaps in knowledge, including the influence of stimulation settings and anatomical targets, emphasize the need for well-designed, hypothesis-driven studies.</p>
<p>The impact of stimulation settings (frequency, amplitude, pulse width) on swallowing function remains critical but understudied, as most investigations treat these as fixed parameters rather than variables of interest. This may be due to several practical constraints. Systematically varying stimulation parameters increases the study design&#x2019;s complexity, requiring longer observation periods and larger sample sizes. Ethical considerations may limit experimental manipulation in patients who may risk symptom exacerbation due to parameter changes. Moreover, the multitude of different parameters -encompassing voltage, frequency, pulse width, lead configuration, stimulation directionality- creates a combinatorial challenge difficult to address within a clinical study. Cross-over study designs may enable within-subject comparisons while minimizing risks of prolonged suboptimal stimulation. Additionally, technical limitations such as battery life constraints and programming complexity may impact study designs including frequent parameter adjustments in research protocols. However, the availability of rechargeable pulse generators has alleviated concerns about battery depletion associated with programming exploration (<xref ref-type="bibr" rid="ref69">Rizzi et al., 2015</xref>). Overcoming these barriers is particularly important for understanding parameter-specific effects on swallowing function. Limited evidence suggests that individual parameters may differentially influence swallowing physiology, potentially enhancing safety and efficiency or causing adverse outcomes. Future research should systematically evaluate how stimulation settings modulate swallowing function and incorporate swallowing outcomes into DBS programming to account for interindividual variability and optimize therapeutic benefit. In terms of outcome measurement, FEES is particularly well suited for real-time optimization of stimulation, with its ability to provide repeated and radiation-free assessments during programming. With recent technological advances, understanding the role of stimulation parameters is essential not only for improving conventional DBS but also for informing the development of adaptive DBS (aDBS). Unlike traditional open-loop DBS, which delivers continuous stimulation irrespective of physiological state, aDBS adjusts stimulation in real time according to dynamic biomarkers such as local field potentials, thereby offering a more individualized approach that may improve both motor and non-motor outcomes. A recent international Delphi expert consensus (<xref ref-type="bibr" rid="ref27">Guidetti et al., 2025</xref>) emphasized the importance of systematically evaluating the effects of aDBS on non-motor symptoms, including swallowing. However, weak correlations between patient&#x2019;s subjective perception and objective diagnostic findings complicate symptom-driven aDBS algorithms. Integrating easily detectable real-time biomarkers such as speech-based metrics or acoustic features of swallowing, supported by advances in digital health and wearable sensors (<xref ref-type="bibr" rid="ref48">Labeit et al., 2023</xref>; <xref ref-type="bibr" rid="ref97">Xu et al., 2025</xref>), may enable continuous monitoring to enhance aDBS precision for targeting OD. However, stronger correlations with OD must be established before reliable clinical application is possible.</p>
<p>Another important factor in assessing DBS effects on swallowing function is outcome measurement selection. Future studies should address prior limitations, such as solely relying on the swallowing-related items of the UPDRS, which lacks sensitivity for OD. Current OD research is expanding beyond traditional safety-focused scales to also include swallowing efficiency measures and detailed phenotypic/biomechanical characterization (<xref ref-type="bibr" rid="ref87">Warnecke et al., 2021</xref>). This may have clinical implications, as distinct OD phenotypes are likely to respond differently to specific stimulation settings.</p>
<p>To better understand how DBS parameters affect swallowing, short-term within-subject studies comparing DBS-on versus -off across stimulation settings are needed. Sensitive tools such as the Visual Analysis of Swallowing Efficiency and Safety (VASES) (<xref ref-type="bibr" rid="ref14">Curtis et al., 2022</xref>) or the FEES-Levodopa-test (<xref ref-type="bibr" rid="ref90">Warnecke et al., 2016</xref>) could detect setting-dependent differences. Validated outcome measures for classic motor symptoms in the oropharynx (tremor, rigidity, bradykinesia, freezing) are also essential, yet currently remain only provisional or partly lack quantitative scoring. Further refinement and validation of such oropharyngeal motor symptom scores that allow quantification may lead to progress in characterizing DBS but also dopaminergic PD-treatment effects. Since pharyngeal bradykinesia-related OD manifestations partly seem to respond to both levodopa (<xref ref-type="bibr" rid="ref46">Labeit et al., 2020b</xref>; <xref ref-type="bibr" rid="ref89">Warnecke et al., 2022</xref>) and DBS, future studies should compare both DBS-off/on and levodopa-off/&#x2212;on states within the same participants to better characterize these potentially overlapping and synergistic therapeutic mechanisms. Comprehensive insight into parameter effects will support prospective interventional trials with long-term follow-up to capture disease progression, DBS adaptations, and potential remodeling effects of OD. The recently validated DIGEST-FEES tool (<xref ref-type="bibr" rid="ref47">Labeit et al., 2024</xref>) may be particularly suited for assessing clinically relevant long-term DBS effects on OD in PD.</p>
</sec>
<sec id="sec21">
<label>5</label>
<title>Limitations</title>
<p>This review has several limitations. Screening and data extraction were conducted by a single reviewer, no standardized reporting framework was applied, and heterogeneity in study design, outcome measures, electrode placement, and stimulation parameters precluded quantitative synthesis. However, as a narrative review, this work does not aim for systematic synthesis but rather is designed to synthesize emerging and limited evidence.</p>
</sec>
<sec sec-type="conclusions" id="sec22">
<label>6</label>
<title>Conclusion</title>
<p>OD is a prevalent and relevant complication in PD, yet its role in the context of DBS has received limited attention. Evidence from available studies indicates that DBS may influence swallowing outcomes, but effects vary across stimulation targets, parameters, and OD phenotypes. Importantly, patient-reported outcome measures partly contrast with instrumental measures, underscoring the complexity of assessing treatment effects in this domain.</p>
<p>These discrepancies highlight the need for methodologically rigorous, adequately powered, and hypothesis-driven studies that incorporate standardized instrumental assessments, refined phenotyping of OD, and systematic exploration of stimulation parameters. Future research should consider swallowing outcomes in DBS programming. Moreover, advances in adaptive DBS offer an opportunity to personalize stimulation based on physiological biomarkers, although their integration into swallowing-related outcomes will require validation of robust, sensitive, and clinically meaningful markers.</p>
<p>Although current evidence does not support firm clinical recommendations, swallowing function may warrant consideration during DBS programming in patients with PD. When feasible, instrumental assessment with FEES and the use of sensitive outcome measures (e.g., VASES, DIGEST-FEES, or the FEES-levodopa test) may help identify stimulation-related effects and support individualized clinical decision-making.</p>
<p>In summary, while DBS has clear benefits for motor symptoms in PD, its effects on swallowing remain uncertain. Addressing this gap through carefully designed studies is essential to optimize DBS therapy, improve the management of OD, and ultimately enhance quality of life and safety for patients with PD.</p>
</sec>
</body>
<back>
<sec sec-type="author-contributions" id="sec23">
<title>Author contributions</title>
<p>JH: Investigation, Writing &#x2013; original draft, Conceptualization. BB: Writing &#x2013; review &#x0026; editing, Visualization. CH: Writing &#x2013; review &#x0026; editing. CJH: Writing &#x2013; review &#x0026; editing. IC: Writing &#x2013; review &#x0026; editing. SS-K: Writing &#x2013; review &#x0026; editing. AS: Writing &#x2013; review &#x0026; editing. TW: Writing &#x2013; review &#x0026; editing, Conceptualization. BL: Investigation, Supervision, Writing &#x2013; review &#x0026; editing, Conceptualization.</p>
</sec>
<sec sec-type="COI-statement" id="sec24">
<title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
<p>The author(s) declared that TW, AS were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.</p>
</sec>
<sec sec-type="ai-statement" id="sec25">
<title>Generative AI statement</title>
<p>The author(s) declared that Generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="disclaimer" id="sec26">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec27">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fnagi.2025.1734432/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fnagi.2025.1734432/full#supplementary-material</ext-link></p>
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<fn-group>
<fn fn-type="custom" custom-type="edited-by" id="fn0002">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2927536/overview">Liane Kaufmann</ext-link>, Ernst von Bergmann Clinic, Germany</p>
</fn>
<fn fn-type="custom" custom-type="reviewed-by" id="fn0003">
<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3167821/overview">Rabab Rangwala</ext-link>, University of California, San Francisco, United States</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3267969/overview">May Smith-Hublou</ext-link>, University of Florida, United States</p>
</fn>
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