Brain tissue is composed of neurons and glia. Myelinated axons comprise the white matter and the cell bodies, dendrites, and synapses comprise the gray matter (Kandel et al., 2021). Synaptic plasticity is the activity-dependent change in the size and number of synaptic contacts that result in the brain’s ability to adapt and change in response to experience, called neuroplasticity (Kandel et al., 2021; Pittenger and Duman, 2008). Neuroplasticity can result in measurable anatomical changes such as changes in cortical thickness and/or the amount of gray matter.

Neuroplasticity is thought to be disrupted or impaired in mental health disorders such as anxiety, depression, post-traumatic stress disorder (PTSD), and substance use disorders (Appelbaum et al., 2023; Fuchs et al., 2004) and is associated with reduced density of dendrites and synapses in the cortex (Pittenger and Duman, 2008). That is, the brain’s capacity to reshape its structure and rewire its connections by strengthening or weakening synaptic transmission is impaired.

These data, along with long-term data about the timing and the efficacy of traditional antidepressants, have fundamentally changed our understanding of the causes of depression. The monoamine theory of depression posits that depression is due to depletion of serotonin, norepinephrine, and/or dopamine in the central nervous system. The theory is consistent with the fact that antidepressants elevate the levels of these neurotransmitters. However, the length of time it takes to see antidepressant effects and the lack of evidence of a primary dysfunction of a specific monoamine system in patients with major depressive disorders suggest that traditional antidepressants may work by supporting neuroplasticity rather than reversing monoamine depletion (Artin et al., 2021). The neuroplasticity theory of depression is supported by data that indicate that the treatment response to classic antidepressants, ketamine, and serotonergic psychedelics may be mediated by changes in neuroplasticity resulting from in increased density of dendrites and synaptic connections (Artin et al., 2021; Hess and Gould, 2023; Pittenger and Duman, 2008; Vargas et al., 2023; Wang et al., 2022).

The neuroplasticity theory of depression provides a plausible framework for the effects of art therapy on depression (Dunphy et al., 2018; Jiang et al., 2020; Kaimal et al., 2018). Creativity is associated with changes in functional connectivity and the expression of genes linked to synaptic plasticity (Orwig et al., 2021). Serotoninergic psychedelic use is associated with increased spontaneous creative insights that are accompanied by changes in the connectivity of the default mode network (Mason et al., 2021).

Creativity training and artistic training appear to result in neuroplastic changes in organization, activity, and connectivity in frontal, emotional, and sensory circuits (Schlegel et al., 2015; Sun et al., 2016, 2020), while depression and PTSD are both associated with dysfunctional plasticity and synaptic loss in prefrontal circuits associated with cognition, emotion, and memory (Appelbaum et al., 2023). If neuroplasticity is mechanism that links healing and creativity, then interventions that increase creative engagement might be effective in alleviating depression. The challenge will be in testing whether art therapy results in neuroplastic changes that correlate with reduced symptoms of depression and whether those effects are specific to the art therapy interventions.

In the 1990s, researchers at the Università degli Studi di Parma, discovered neurons in the frontal and premotor cortex of macaque monkeys that fired when the monkey performed a movement and when it observed the same movement by another monkey or a human (Kilner and Lemon, 2013). There is evidence that mirror neurons exist in homologous regions of human brains (de la Rosa et al., 2016; Iacoboni and Dapretto, 2006; Kilner and Lemon, 2013), and these systems are involved in movement recognition, selection of movement, and imitation (Iacoboni and Dapretto, 2006; Mukamel et al., 2010). A recent study showed populations of neurons in mouse hypothalamus are active during aggressive behavior and when seeing aggressive behavior of other mice. External activation of those neurons resulted in aggressive behavior, providing direct evidence of mirror neuron systems in social behaviors (Yang et al., 2023).

In humans, mirror systems are thought to transform sensory observations of others’ actions to an internal visceromotor representation of the action goal, such as reaching for a piece of food, to support planning and control of behavior (Rizzolatti and Sinigaglia, 2016). There are correlational and indirect data that that mirror systems underlie the ability to infer the intentions of and emotions of others based on one’s own internal experiences (Heyes and Catmur, 2022; Napolitano, 2021), that motor resonance to stimuli representing social connection positively correlates with empathy scores (Guidali et al., 2023), and that mirror systems support social interaction and learning during childhood development (Dickerson et al., 2017). However, mirror neurons also respond to non-natural movements of inanimate objects (Napolitano, 2021), and the direct evidence that mirror systems are involved in higher level cognitive or empathetic processes is limited (Heyes and Catmur, 2022).

The process of art making is integral to the art therapy process. It is likely that mirror systems are activated when art therapists observe clients’ making art. In fact, it is tempting to speculate that activation of mirror systems may be related to the psychodynamic concept of countertransference. This speculation underscores that caveat that any inferences we make about client behavior, cognition and emotions, even if we frame them as based on mirror systems, still arise from our own internal visceromotor representations, which are based on our own learning, experiences and emotions. Further, positing a mirror neuron system to underlie therapeutic relationship does not change the fact that that mirror systems do not fully explain relational phenomena such as behavioral synchrony and entrainment (Denworth, 2023; Wheatley et al., 2012; Wohltjen et al., 2023), phenomena that may also be important in building therapeutic relationships.

The central nervous system (CNS) receives information about the internal state of the body from the vagus nerve of the parasympathetic nervous system (Breit et al., 2018). The vagus nerve is a mixed nerve, with motor neurons that of the convey parasympathetic motor output to internal organs (~10–20%) and sensory neurons that convey information about the internal state of the body to the brain (~80–90%) (Breit et al., 2018; Paciorek and Skora, 2020). The motor outputs are responsible for the “rest and digest” functions that counterbalance sympathetic “fight or flight” responses. The vagal sensory neurons project to a wide range of brain regions, including brainstem nuclei, the insula, the thalamus, hippocampus, amygdala (Breit et al., 2018; Engelen et al., 2023). Vagal sensory projections give rise to interoception, knowledge about the internal state of the body. Interoception that can occur at several levels. The non-conscious level is associated with homeostatic and allostatic mechanisms and with the sense of self and body ownership. The preconscious level is thought to influence cognition, affective processing, and decision-making. The conscious level includes direct awareness of the body, along with metacognitive awareness of body processes and emotions (Engelen et al., 2023).

Interoception can include sensations such as heartbeat awareness, pain and temperature signals as well as hunger and satiety signals (Breit et al., 2018) that can affect behavior on preconscious or conscious levels, and might presumably be reflected in the art process. Information about and responses to the internal condition of the body can be influenced by gut microbiome. The brain-gut axis can influence regulation of the stress response, immune function, digestion, and heart rate (Palacios-García and Parada, 2020) as well as brain systems involved in mood and anxiety disorders, PTSD, substance use disorders, and eating disorders (Breit et al., 2018; Engelen et al., 2023; Palacios-García and Parada, 2020).

Parasympathetic activity is referred to as vagal tone. Higher vagal tone is thought to be adaptive. It is indirectly measured by heart rate variability (HRV) which is thought to determine relative contributions of the parasympathetic motor system to control of heart rate (Laborde et al., 2017). HRV refers to how much variability occurs in the interval between heartbeats. For example, two individuals may each have a resting heart rate of 60 beats per minute. The individual with one beat exactly every second would have low HRV, while the individual with an interval between beats that varies in a range of a beat every 0.75–1.25 s would have a higher HRV. While there are more than 70 variables that can be considered in measuring HRV, in general, higher HRV is associated with more relative parasympathetic input, greater vagal tone, lower stress levels, and potentially better cognitive and emotional regulation (Laborde et al., 2017).

These data suggest that art therapy interventions that focus on interoceptive processes might be possible therapeutic targets. The activation of central and peripheral systems in art making could plausibly interact with the three levels of interoception, with the potential of using HRV as an outcome measure.

The first direct evidence of the role of the brain in human behavior was from the loss of specific functions after brain injuries or strokes, demonstrating that a specific region was necessary for a specific function. The early localization of function data led to the first understanding of functional roles of brain regions. For example, the removal of Henry Mollasion’s temporal lobe as a treatment for otherwise intractable epilepsy led to the understanding the different brain regions are necessary for retention of explicit and procedural memories (Baro and Priftis, 2023). Another example is the post-mortem brain damage in patients with aphasia studied by Paul Broca in the 19th century. These studies led to an eponymously named anatomical region, Broca’s area, thought to be necessary for language production (Rutten, 2022). In part because brain function in living humans can now be measured noninvasively by techniques such as electroencephalography (EEG), positron emission tomography (PET), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI) (Konopka et al., 2024), these localization of function studies have given way to the understanding that complex cognition and behavior are associated with the activity of multiple cortical and subcortical brain regions organized into complex bilateral networks (Koban et al., 2021). Single brain structures may be necessary for a given function, but they are not sufficient by themselves.

Paul MacLean’s Triune Brain Theory emphasized the hierarchical function of three key brain regions that were said to reflect evolutionary steps from reptiles to early mammals and to late mammals (MacLean, 1982). MacLean’s theory was based in part on Paul Broca’s work showing an evolutionarily conserved anatomical region around the edge of the brain stem, and used the term “limbic” to describe this region (Ploog, 2003). The protoreptilian brain included parts of the midbrain, diencephalon, and basal ganglia and was said to be responsible for instinctive, species-typical, and routine behaviors. The paleomammalian brain represented the transition from retile to mammals and included the limbic system, and was said to be responsible for maternal care, vocal communication, and play. Finally, the neomammalian brain comprised the neocortex and thalamus, and was thought to be the basis of sensory, cognitive, and linguistic processes (Ploog, 2003).

This theory has been discredited because the assumption that each “newer” region was anatomically layered upon the “older” regions reflects an incorrect understanding of evolution (Cesario et al., 2020). In the triune brain formulation, reptilian brains would not have limbic or neocortical regions. However, brain structures are evolutionarily conserved from reptiles to mammals. Instead, the homologous structures differ in size and proportion (Cesario et al., 2020). Steffen’s Adaptive Brain Theory is a more recent alternative evolutionary theory that posits interdependent networks that support adaptation, survival, and reproduction (Steffen et al., 2022). In this conceptualization, the integration of interoceptive and exteroceptive information enables optimal adaptation to continuously changing internal and external environments.

While the triune brain theory has been used to explain and normalize behaviors and emotional responses, the conceptualization of a part of the brain as independently instinctual has the potential to cause harm or impede therapeutic progress. Ascribing behavior related to the autonomic nervous system as controlled by the “reptilian-brain” implies that one has no choice about the “instinctive” behavior. It implies judgments about the behaviors or the person, and in some cases, individuals may use this language to avoid uncomfortable change.

The evolutionary perspective that humans have integrated functions that are adaptive for fast survival responses is important but is better served by an approach that identifies specific structures associated with cognition, behavior, and emotion in context. Using language related to adaptive responses is more consistent with meeting treatment goals around improving coping skills and creating behavioral change.

One of the most pernicious myths associated with human creativity is that the “right brain” is exclusively associated with creativity and the “left brain” is exclusively associated with analytical skills. While there are important structural and functional asymmetries (Esteves et al., 2020; Khalil and Demarin, 2023), unless you are a sleeping dolphin (Mascetti, 2021), both hemispheres are active and communicating all the time. The corpus callosum in healthy humans has ~100 million myelinated axons (Goldstein et al., 2023). Severing those connections to treat intractable epilepsy resulted in disconnection syndromes and communication impairments that were overgeneralized in popular culture.

While high creativity is associated with more interhemispheric connectivity (Khalil and Demarin, 2023), data indicate that art-making or creativity can enhance or change connections between neurons in many brain regions (Khalil and Demarin, 2023; Orwig et al., 2021; Schlegel et al., 2015; Sun et al., 2016). Further, creative cognition requires integration of regions and networks across both hemispheres (Patil et al., 2021). The artificial separation of analytic and creative skills, or of science and art, implies that people are only capable of one or the other. This approach can subtly undermine an individual’s sense of capability and self-efficacy, rather than supporting an integrated frame of healing through artmaking and creativity.