The Embodied-Enactive-Interactive Brain: Bridging Neuroscience and Creative Arts Therapies.

The recognition and incorporation of evidence-based neuroscientific concepts into creative arts therapeutic knowledge and practice seem valuable and advantageous for the purpose of integration and professional development. Moreover, exhilarating insights from the field of neuroscience coincide with the nature, conceptualization, goals, and methods of Creative Arts Therapies (CATs), enabling comprehensive understandings of the clinical landscape, from a translational perspective. This paper contextualizes and discusses dynamic brain functions that have been suggested to lie at the heart of intra- and inter-personal processes. Touching upon fundamental aspects of the self and self-other interaction, the state-of-the-art neuroscientific-informed views will shed light on mechanisms of the embodied, predictive and relational brain. The conceptual analysis introduces and interweaves the following contemporary perspectives of brain function: firstly, the grounding of mental activity in the lived, bodily experience will be delineated; secondly, the enactive account of internal models, or generative predictive representations, shaped by experience, will be defined and extensively deliberated; and thirdly, the interpersonal simulation and synchronization mechanisms that support empathy and mentalization will be thoroughly considered. Throughout the paper, the cross-talks between the brain and the body, within the brain through functionally connected neural networks and in the context of agent-environment dynamics, will be addressed. These communicative patterns will be elaborated on to unfold psychophysiological linkage, as well as psychopathological shifts, concluding with the neuroplastic change associated with the formulation of CATs. The manuscript suggests an integrative view of the brain-body-mind in contexts relevant to the therapeutic potential of the expressive creative arts and the main avenues by which neuroscience may ground, enlighten and enrich the clinical psychotherapeutic practice.

The autism-mutated ADNP plays a key role in stress response.

Activity-dependent neuroprotective protein (ADNP), discovered and first characterized in our laboratory (IG), is vital for mammalian brain formation and presents one of the leading genes mutated de novo causing an autistic syndrome, namely the ADNP syndrome. Furthermore, a unique mouse model of Adnp-haploinsufficiency was developed in the laboratory (IG), with mice exhibiting cognitive and social deficiencies. ADNP is regulated by vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP). In this respect, PACAP was independently identified as a sexual divergent master regulator of the stress response. Here, we sought to determine the impact of the Adnp genotype and the efficacy of PACAP pre-treatment when subjecting Adnp+/- mice to stressful conditions. Significant sex differences were observed with Adnp+/- males being more susceptible to stress in the object and social recognition tests, and the females more susceptible in the open field and elevated plus maze tests. Splenic Adnp expression and plasma cortisol levels in mice were correlated with cognition (male mice) and anxiety-related behavior. These findings were further translated to humans, with observed correlations between ADNP expression and stress/cortisol content in a young men cohort. Altogether, our current results may establish ADNP as a marker of stress response.

Moving Along and Beyond the Spectrum: Creative Group Therapy for Children With Autism.

Group therapy for autism confronts the core of the syndrome. Non-directed dynamic approaches, in which moment-to-moment spontaneous expressions drive the content of group sessions, are even more intricate. The implementation of nonverbal creative techniques holds the key to self-expression and self-other exploration, promoting communication and play. This manuscript offers an integrative conceptual model and a case report regarding such mind-body therapeutic perspective. The creative arts intervention is presented via a small group of young minimally verbal children with autism, deprived of communicative language, offering an interdisciplinary perspective to delineate group challenges and rationale, process, and outcomes. Vignettes are provided to illustrate the group development. A thorough discussion follows, addressing three intertwining axes: firstly, the implications of nonverbal creative means are considered; secondly, the psychophysiological processes set in motion through sensory-motor experiences are deliberated; and thirdly, the emergence of "moments of meeting" and spontaneously generated playful group activities are enlightened.

Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study.

OBJECTIVES: Implicit regulation of emotions involves medial-prefrontal cortex (mPFC) regions exerting regulatory control over limbic structures. Diminished regulation relates to aberrant mPFC functionality and psychopathology. Establishing means of modulating mPFC functionality could benefit research on emotion and its dysregulation. Here, we tested the capacity of transcranial direct current stimulation (tDCS) targeting mPFC to modulate subjective emotional states by facilitating implicit emotion regulation. MATERIALS AND METHODS: Stimulation was applied concurrently with functional magnetic resonance imaging to validate its neurobehavioral effect. Sixteen participants were each scanned twice, counterbalancing active and sham tDCS application, while undergoing negative mood induction (clips featuring negative vs. neutral contents). Effects of stimulation on emotional experience were assessed using subjective and neural measures. RESULTS: Subjectively, active stimulation led to significant reduction in reported intensity of experienced emotions to negatively valenced (p = 0.005) clips but not to neutral clips (p > 0.99). Active stimulation further mitigated a rise in stress levels from pre- to post-induction (sham: p = 0.004; active: p = 0.15). Neurally, stimulation increased activation in mPFC regions associated with implicit emotion regulation (ventromedial-prefrontal cortex; subgenual anterior-cingulate cortex, sgACC), and in ventral striatum, a core limbic structure (all ps < 0.05). Stimulation also altered functional connectivity (assessed using whole-brain psycho-physiological interaction) between these regions, and with additional limbic regions. Stimulation-induced sgACC activation correlated with reported emotion intensity and depressive symptoms (rs > 0.64, ps < 0.018), suggesting individual differences in stimulation responsivity. CONCLUSIONS: Results of this study indicate the potential capacity of tDCS to facilitate brain activation in mPFC regions underlying implicit regulation of emotion and accordingly modulate subjective emotional experiences.

A large-scale perspective on stress-induced alterations in resting-state networks.

Stress is known to induce large-scale neural modulations. However, its neural effect once the stressor is removed and how it relates to subjective experience are not fully understood. Here we used a statistically sound data-driven approach to investigate alterations in large-scale resting-state functional connectivity (rsFC) induced by acute social stress. We compared rsfMRI profiles of 57 healthy male subjects before and after stress induction. Using a parcellation-based univariate statistical analysis, we identified a large-scale rsFC change, involving 490 parcel-pairs. Aiming to characterize this change, we employed statistical enrichment analysis, identifying anatomic structures that were significantly interconnected by these pairs. This analysis revealed strengthening of thalamo-cortical connectivity and weakening of cross-hemispheral parieto-temporal connectivity. These alterations were further found to be associated with change in subjective stress reports. Integrating report-based information on stress sustainment 20 minutes post induction, revealed a single significant rsFC change between the right amygdala and the precuneus, which inversely correlated with the level of subjective recovery. Our study demonstrates the value of enrichment analysis for exploring large-scale network reorganization patterns, and provides new insight on stress-induced neural modulations and their relation to subjective experience.

Neuro-Epigenetic Indications of Acute Stress Response in Humans: The Case of MicroRNA-29c.

Stress research has progressively become more integrative in nature, seeking to unfold crucial relations between the different phenotypic levels of stress manifestations. This study sought to unravel stress-induced variations in expression of human microRNAs sampled in peripheral blood mononuclear cells and further assess their relationship with neuronal and psychological indices. We obtained blood samples from 49 healthy male participants before and three hours after performing a social stress task, while undergoing functional magnetic resonance imaging (fMRI). A seed-based functional connectivity (FC) analysis was conducted for the ventro-medial prefrontal cortex (vmPFC), a key area of stress regulation. Out of hundreds of microRNAs, a specific increase was identified in microRNA-29c (miR-29c) expression, corresponding with both the experience of sustained stress via self-reports, and alterations in vmPFC functional connectivity. Explicitly, miR-29c expression levels corresponded with both increased connectivity of the vmPFC with the anterior insula (aIns), and decreased connectivity of the vmPFC with the left dorso-lateral prefrontal cortex (dlPFC). Our findings further revealed that miR-29c mediates an indirect path linking enhanced vmPFC-aIns connectivity during stress with subsequent experiences of sustained stress. The correlative patterns of miR-29c expression and vmPFC FC, along with the mediating effects on subjective stress sustainment and the presumed localization of miR-29c in astrocytes, together point to an intriguing assumption; miR-29c may serve as a biomarker in the blood for stress-induced functional neural alterations reflecting regulatory processes. Such a multi-level model may hold the key for future personalized intervention in stress psychopathology.

Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity.

Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a 'recovery' pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies.