The Neural Circuitry of Sensory Processing in Post-traumatic Stress Disorder

Background: Traumatic experiences can have severe emotional and psychological consequences, which may affect the capacity to process both internal and external sensory information. Such aberrations may have cascading effects in individuals with post-traumatic stress disorder (PTSD), where alterations in sensory processing may hinder the capacity for higher-order executive functions, including emotion regulation. Delineating the neural circuitry of subcortical and cortical structures thought to be central to sensory processing is therefore critical to the study of PTSD and may help to develop an understanding of the neurobiological mechanisms underlying this often debilitating disorder. Methods: Various neuroimaging approaches were employed to investigate sensory processing in PTSD, its dissociative subtype, and healthy controls. First, resting-state connectivity patterns of subcortical brainstem structures linked to interoceptive and exteroceptive sensory processing, including the periaqueductal gray and the vestibular nuclei, were examined (chapters 2 and 3). In addition, given that the insula is critical for relaying exteroceptive and interoceptive sensory information to other neurocognitive networks in the brain, resting-state whole brain seed-based connectivity patterns of different insula subregions were investigated (chapter 4). Furthermore, machine learning analyses were used to assess the utility of insula subregion resting-state connectivity patterns as a diagnostic predictor for classifying PTSD, its dissociative subtype, and healthy controls. Finally, a task-based paradigm using oculomotor stimuli with simultaneous traumatic autobiographical memory recall was employed to examine cortical brain structures involved in the convergence of exteroceptive and interoceptive sensory information (chapter 5). Results and Discussion: As compared to controls, widespread periaqueductal gray connectivity was observed with cortical structures associated with emotional reactivity and defensive responding in PTSD and its dissociative subtype at rest. In addition, as compared to controls, decreased vestibular nuclei connectivity with cortical structures essential to exteroceptive sensory processing and multisensory integration was observed in individuals with the PTSD dissociative subtype. Moreover, PTSD showed limited cortical insula subregion resting-state connectivity with frontal lobe structures involved in the central executive network, which may be associated with impairment of higher-order executive functions, including emotion regulation, in PTSD. Finally, exposure to simultaneous exteroceptive and interoceptive sensory stimuli through oculomotor eye movements performed simultaneous to traumatic memory recall engaged the dorsal attentional network and default-mode frontoparietal networks that have been demonstrated to work in tandem to facilitate connectivity with structures in the central executive network, including the dorsolateral and dorsomedial prefrontal cortex, necessary for multisensory integration and emotion regulation. This effect was greater in individuals with PTSD and may provide a neurobiological account for how oculomotion may influence the frontoparietal cortical representation of traumatic memories. Overall, the findings of this dissertation reveal that individuals with PTSD experience aberrations in the neural circuitry necessary for processing both interoceptive and exteroceptive sensory information. We hypothesize that these observed alterations in interoceptive and exteroceptive neural processing may underlie, in part, the emotion dysregulation and maladaptive responses to chronic stress, including hypervigilance and dissociative symptoms, observed in PTSD and its dissociative subtype

Increased top-down control of emotions during symptom provocation working memory tasks following a RCT of alpha-down neurofeedback in PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been found to be associated with emotion under-modulation from the prefrontal cortex and a breakdown of the top-down control of cognition and emotion. Novel adjunct therapies such as neurofeedback (NFB) have been shown to normalize aberrant neural circuits that underlie PTSD psychopathology at rest. However, little evidence exists for NFB-linked neural improvements under emotionally relevant cognitive load. The current study sought to address this gap by examining the effects of alpha-down NFB in the context of an emotional n-back task. METHODS: We conducted a 20-week double-blind randomized, sham-controlled trial of alpha-down NFB and collected neuroimaging data before and after the NFB protocol. Participants performed an emotional 1-back and 2-back working memory task, with interleaved trauma-neutral and trauma-relevant cues in the fMRI scanner. Data from 35 participants with a primary diagnosis of PTSD were analyzed in this study (n = 18 in the experimental group undergoing alpha-down NFB, n = 17 in the sham-control group). RESULTS: Firstly, within-group analyses showed clinically significant reductions in PTSD symptom severity scores at the post-intervention timepoint and 3-month follow-up for the experimental group, and not for the sham-control group. The neuroimaging analyses revealed that alpha-down NFB enhanced engagement of top-down cognitive and emotional control centers, such as the dorsolateral prefrontal cortex (dlPFC), and improved integration of the anterior and posterior parts of the default mode network (DMN). Finally, our results also indicate that increased alpha-down NFB performance correlated with increased activity in brain regions involved in top-down control and bodily consciousness/embodied processing of self (TPJ and posterior insula). CONCLUSION: This is the first study to provide mechanistic insights into how NFB may normalize dysfunctional brain activity and connectivity in PTSD under cognitive load with simultaneous symptom provocation, adding to a growing body of evidence supporting the therapeutic neuromodulatory effects of NFB. This preliminary study highlights the benefits of alpha-down NFB training as an adjunctive therapy for PTSD and warrants further investigation into its therapeutic effects on cognitive and emotion control in those with PTSD

Public safety personnel feedback from a remote trial of Goal Management Training for post-traumatic stress during Covid-19

Purpose: This paper explores participants’ perspectives on the acceptability, utility, and perceived therapeutic effects of a virtual group cognitive remediation program, Goal Management Training (GMT)™, during the COVID-19 pandemic. The advantages and drawbacks of these groups are considered as part of an online research study protocol exploring cognitive remediation among first responders (police, firefighters, paramedics, emergency dispatchers, corrections and parole officers, and nurses) who have been impacted by trauma. Methods: We qualitatively examined the results of an anonymous participant feedback survey collected from 20 first responders who took part in the first round of our online therapy groups. A thematic analysis approach was taken to highlight key themes and recommendations. Results: Survey results indicated that participants found our online protocol effective in terms of group facilitation, the utility of online platforms, and perceived therapeutic effects. Further, some participants preferred participating online versus attending in-person groups. Conclusion: This early data suggests that providing virtual options for research and treatment among trauma-impacted public safety personnel may increase accessibility and overall participation among this population

“I can't tell whether it's my hand”: a pilot study of the neurophenomenology of body representation during the rubber hand illusion in trauma-related disorders

Background: Early traumatic experiences are thought to be causal factors in the development of trauma-related dissociative experiences, including depersonalization and derealization. The rubber hand illusion (RHI), a well-known paradigm that measures multi-sensorial integration of a rubber hand into one's own body representation, has been used to investigate alterations in the experience of body ownership and of body representation. Critically, however, it has never been studied in individuals with trauma-related disorders. Objective: To investigate body representation distortions occurring in trauma-related disorders in response to the RHI. Method: The RHI was administered to three individuals with the dissociative subtype of posttraumatic stress disorder (PTSD), and subjective, behavioral, cardiovascular and skin conductance responses were recorded. Results: Participants’ subjective experiences of the RHI were differentiated and complex. The illusion was induced following both synchronous and asynchronous brushing and variably evoked subjective distress, depersonalization and derealization experiences, tonic immobility, increased physiological arousal and flashbacks. Conclusions: The present findings point towards the RHI as a strong provocation stimulus that elicits individual patterns of symptom presentation, including experiences of distress and dissociation, in individuals with trauma-related disorders, including the dissociative subtype of PTSD. Highlights of the article

Overlapping frontoparietal networks in response to oculomotion and traumatic autobiographical memory retrieval: implications for eye movement desensitization and reprocessing

Background: Oculomotor movements have been shown to aid in the retrieval of episodic memories, serving as sensory cues that engage frontoparietal brain regions to reconstruct visuospatial details of a memory. Frontoparietal brain regions not only are involved in oculomotion, but also mediate, in part, the retrieval of autobiographical episodic memories and assist in emotion regulation. Objective: We sought to investigate how oculomotion influences retrieval of traumatic memories by examining patterns of frontoparietal brain activation during autobiographical memory retrieval in post-traumatic stress disorder (PTSD) and in healthy controls. Method: Thirty-nine participants (controls, n = 19; PTSD, n = 20) recollected both neutral and traumatic/stressful autobiographical memories while cued simultaneously by horizontal and vertical oculomotor stimuli. The frontal (FEF) and supplementary (SEF) eye fields were used as seed regions for psychophysiological interaction analyses in SPM12. Results: As compared to controls, upon retrieval of a traumatic/stressful memory while also performing simultaneous horizontal eye movements, PTSD showed: i) increased SEF and FEF connectivity with the right dorsolateral prefrontal cortex, ii) increased SEF connectivity with the right dorsomedial prefrontal cortex, and iii) increased SEF connectivity with the right anterior insula. By contrast, as compared to PTSD, upon retrieval of a traumatic/stressful memory while also performing simultaneous horizontal eye movements, controls showed: i) increased FEF connectivity with the right posterior insula and ii) increased SEF connectivity with the precuneus. Conclusions: These findings provide a neurobiological account for how oculomotion may influence the frontoparietal cortical representation of traumatic memories. Implications for eye movement desensitization and reprocessing are discussed

A randomized controlled trial of Deep Brain Reorienting: a neuroscientifically guided treatment for post-traumatic stress disorder

Background: Advanced neuroscientific insights surrounding post-traumatic stress disorder (PTSD) and its associated symptomatology should beget psychotherapeutic treatments that integrate these insights into practice. Deep Brain Reorienting (DBR) is a neuroscientifically-guided psychotherapeutic intervention that targets the brainstem-level neurophysiological sequence that transpired during a traumatic event. Given that contemporary treatments have non-response rates of up to 50% and high drop-out rates of >18%, DBR is investigated as a putative candidate for effective treatment of some individuals with PTSD. Objective: To conduct an interim evaluation of the effectiveness of an eight-session clinical trial of videoconference-based DBR versus waitlist (WL) control for individuals with PTSD. Method: Fifty-four individuals with PTSD were randomly assigned to DBR (N = 29) or WL (N = 25). At baseline, post-treatment, and three-month follow-up, participants’ PTSD symptom severity was assessed using the Clinician Administered PTSD Scale (CAPS-5). This is an interim analysis of a clinical trial registered with the U. S. National Institute of Health (NCT04317820). Results: Significant between-group differences in CAPS-total and all subscale scores (re-experiencing, avoidance, negative alterations in cognitions/mood, alterations in arousal/reactivity) were found at post-treatment (CAPS-total: Cohen’s d = 1.17) and 3-month-follow-up (3MFU) (CAPS-total: Cohen’s d = 1.18). Significant decreases in CAPS-total and all subscale scores were observed within the DBR group pre – to post-treatment (36.6% CAPS-total reduction) and pre-treatment to 3MFU (48.6% CAPS-total reduction), whereas no significant decreases occurred in the WL group. After DBR, 48.3% at post-treatment and 52.0% at 3MFU no longer met PTSD criteria. Attrition was minimal with one participant not completing treatment; eight participants were lost to 3MFU. Conclusions: These findings provide emerging evidence for the effectiveness of DBR as a well-tolerated treatment that is based on theoretical advances highlighting alterations to subcortical mechanisms in PTSD and associated symptomatology. Additional research utilizing larger sample sizes, neuroimaging data, and comparisons or adjacencies with other psychotherapeutic approaches is warranted. Trial registration: ClinicalTrials.gov identifier: NCT04317820.

Data_Sheet_1_Altered Sense of Body Ownership and Agency in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Rubber Hand Illusion Study.DOCX

<p>Traumatic experiences have been linked to the development of altered states of consciousness affecting bodily perception, including alterations in body ownership and in sense of agency, the conscious experience of the body as one's own and under voluntary control. Severe psychological trauma and prolonged distress may lead to posttraumatic stress disorder (PTSD). Together, symptoms of derealization and, related specifically to the sense of body ownership and agency, of depersonalization (where parts of the body or the entire body itself is perceived as detached and out of control), constitute the dissociative subtype (PTSD+DS). In this study, we explored the Rubber Hand Illusion, an experimental paradigm utilized to manipulate sense of body ownership in PTSD (n = 4) and PTSD+DS (n = 6) as compared to healthy controls (n = 7). Perceived finger location and self-report questionnaires were used as behavioral and subjective measures of the illusion, respectively. In addition, the correlation between the illusion's effect and sense of agency as a continuous feeling of controlling one's own body movements was explored. Here, a lower illusion effect was observed in the PTSD as compared to the control group after synchronous stimulation for both the proprioceptive drift and subjectively perceived illusion. Moreover, by both proprioceptive drift and by subjective ratings, the PTSD+DS group showed a response characterized by high variance, ranging from a very strong to a very weak effect of the illusion. Finally, sense of agency showed a trend toward a negative correlation with the strength of the illusion as subjectively perceived by participants with PTSD and PTSD+DS. These findings suggest individuals with PTSD may, at times, maintain a rigid representation of the body as an avoidance strategy, with top-down cognitive processes weakening the impact of manipulation of body ownership. By contrast, the response elicited in PTSD+DS appeared to be driven by either an increased vulnerability to manipulation of embodiment or by a dominant top-down cognitive representation of the body, with disruption of multisensory integration processes likely in both cases. Taken together, these findings further our understanding of bodily consciousness in PTSD and its dissociative subtype and highlight the supportive role played by sense of agency for the maintenance of body ownership.</p

Altered Sense of Body Ownership and Agency in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Rubber Hand Illusion Study

Traumatic experiences have been linked to the development of altered states of consciousness affecting bodily perception, including alterations in body ownership and in sense of agency, the conscious experience of the body as one's own and under voluntary control. Severe psychological trauma and prolonged distress may lead to posttraumatic stress disorder (PTSD). Together, symptoms of derealization and, related specifically to the sense of body ownership and agency, of depersonalization (where parts of the body or the entire body itself is perceived as detached and out of control), constitute the dissociative subtype (PTSD+DS). In this study, we explored the Rubber Hand Illusion, an experimental paradigm utilized to manipulate sense of body ownership in PTSD (n = 4) and PTSD+DS (n = 6) as compared to healthy controls (n = 7). Perceived finger location and self-report questionnaires were used as behavioral and subjective measures of the illusion, respectively. In addition, the correlation between the illusion's effect and sense of agency as a continuous feeling of controlling one's own body movements was explored. Here, a lower illusion effect was observed in the PTSD as compared to the control group after synchronous stimulation for both the proprioceptive drift and subjectively perceived illusion. Moreover, by both proprioceptive drift and by subjective ratings, the PTSD+DS group showed a response characterized by high variance, ranging from a very strong to a very weak effect of the illusion. Finally, sense of agency showed a trend toward a negative correlation with the strength of the illusion as subjectively perceived by participants with PTSD and PTSD+DS. These findings suggest individuals with PTSD may, at times, maintain a rigid representation of the body as an avoidance strategy, with top-down cognitive processes weakening the impact of manipulation of body ownership. By contrast, the response elicited in PTSD+DS appeared to be driven by either an increased vulnerability to manipulation of embodiment or by a dominant top-down cognitive representation of the body, with disruption of multisensory integration processes likely in both cases. Taken together, these findings further our understanding of bodily consciousness in PTSD and its dissociative subtype and highlight the supportive role played by sense of agency for the maintenance of body ownership