Dissociative symptomatology mediates the relation between posttraumatic stress disorder severity and alcohol-related problems

Background: Up to 50% of individuals with posttraumatic stress disorder (PTSD) endorse problematic alcohol use. Typically, these individuals present with more complex and often more severe PTSD symptoms than those who do not report problematic alcohol use. Emerging literature suggests that heightened symptoms of dissociation are likewise associated with greater PTSD symptom severity. Despite this knowledge, the role of dissociation in the relation between PTSD severity and alcohol-related problems has yet to be examined. Here, we explore the mediating role of dissociative symptomatology on the association between PTSD severity and alcohol-related problems within a PTSD treatment-seeking sample. Methods: Structural equation modeling was used to test the mediating role of dissociative symptomatology between PTSD severity and alcohol-related problems. Participants [N = 334; mean age (SD) = 44.29 (9.77), 50% female] were drawn from a clinical intake battery database for PTSD in-patient treatment services at Homewood Health Care, Guelph, ON, Canada. A subset of battery measures assessing PTSD severity, dissociative symptomatology, and alcohol-related problems were submitted to analysis. Results: A significant positive association emerged between PTSD severity and alcohol-related problems (β = 0.127, p \u3c 0.05) in the absence of dissociative symptomatology. Critically, however, when added to this model, dissociative symptomatology (six unique facets of dissociation assessed by the Multiscale Dissociation Inventory) mediated the relation between PTSD severity and alcohol-related problems. Specifically, greater PTSD severity was associated with greater dissociative symptomatology (β = 0.566, p \u3c 0.0001), which was in turn associated with greater alcohol-related problems (β = 0.184, p \u3c 0.05). Conclusions: These results suggest that dissociative symptomatology plays a key role in explaining the relation between PTSD severity and alcohol-related problems. Future studies should examine the impact of targeting dissociative symptomatology specifically in treating individuals with PTSD who endorse alcohol-related problems

Restoring large-scale brain networks in PTSD and related disorders: a proposal for neuroscientifically-informed treatment interventions

Background: Three intrinsic connectivity networks in the brain, namely the central executive, salience, and default mode networks, have been identified as crucial to the understanding of higher cognitive functioning, and the functioning of these networks has been suggested to be impaired in psychopathology, including posttraumatic stress disorder (PTSD). Objective: 1) To describe three main large-scale networks of the human brain; 2) to discuss the functioning of these neural networks in PTSD and related symptoms; and 3) to offer hypotheses for neuroscientificallyinformed interventions based on treating the abnormalities observed in these neural networks in PTSD and related disorders. Methods: Literature relevant to this commentary was reviewed. Results: Increasing evidence for altered functioning of the central executive, salience, and default mode networks in PTSD has been demonstrated. We suggest that each network is associated with specific clinical symptoms observed in PTSD, including cognitive dysfunction (central executive network), increased and decreased arousal/interoception (salience network), and an altered sense of self (default mode network). Specific testable neuroscientifically-informed treatments aimed to restore each of these neural networks and related clinical dysfunction are proposed. Conclusions: Neuroscientifically-informed treatment interventions will be essential to future research agendas aimed at targeting specific PTSD and related symptoms

The Vestibulocerebellum and the Shattered Self: a Resting-State Functional Connectivity Study in Posttraumatic Stress Disorder and Its Dissociative Subtype

The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting responses. Despite growing evidence of vestibular and oculomotor impairments in the aftermath of traumatic stress, little is known about the effects of chronic psychological trauma on vestibulocerebellar functioning. Here, we investigated alterations in functional connectivity of the flocculus at rest among individuals with post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS) as compared to healthy controls. Forty-four healthy controls, 57 PTSD, and 32 PTSD + DS underwent 6-min resting-state MRI scans. Seed-based functional connectivity analyses using the right and left flocculi as seeds were performed. These analyses revealed that, as compared to controls, PTSD and PTSD + DS showed decreased resting-state functional connectivity of the left flocculus with cortical regions involved in bodily self-consciousness, including the temporo-parietal junction, the supramarginal and angular gyri, and the superior parietal lobule. Moreover, as compared to controls, the PTSD + DS group showed decreased functional connectivity of the left flocculus with the medial prefrontal cortex, the precuneus, and the mid/posterior cingulum, key regions of the default mode network. Critically, when comparing PTSD + DS to PTSD, we observed increased functional connectivity of the right flocculus with the right anterior hippocampus, a region affected frequently by early life trauma. Taken together, our findings point toward the crucial role of the flocculus in the neurocircuitry underlying a coherent and embodied self, which can be compromised in PTSD and PTSD + DS

Contrasting Associations Between Heart Rate Variability and Brainstem-Limbic Connectivity in Posttraumatic Stress Disorder and Its Dissociative Subtype: A Pilot Study

Background: Increasing evidence points toward the need to extend the neurobiological conceptualization of posttraumatic stress disorder (PTSD) to include evolutionarily conserved neurocircuitries centered on the brainstem and the midbrain. The reticular activating system (RAS) helps to shape the arousal state of the brain, acting as a bridge between brain and body. To modulate arousal, the RAS is closely tied to the autonomic nervous system (ANS). Individuals with PTSD often reveal altered arousal patterns, ranging from hyper- to blunted arousal states, as well as altered functional connectivity profiles of key arousal-related brain structures that receive direct projections from the RAS. Accordingly, the present study aims to explore resting state functional connectivity of the RAS and its interaction with the ANS in participants with PTSD and its dissociative subtype. Methods: Individuals with PTSD (n = 57), its dissociative subtype (PTSD + DS, n = 32) and healthy controls (n = 40) underwent a 6-min resting functional magnetic resonance imaging and pulse data recording. Resting state functional connectivity (rsFC) of a central node of the RAS – the pedunculopontine nuclei (PPN) – was investigated along with its relation to ANS functioning as indexed by heart rate variability (HRV). HRV is a prominent marker indexing the flexibility of an organism to react adaptively to environmental needs, with higher HRV representing greater effective adaptation. Results: Both PTSD and PTSD + DS demonstrated reduced HRV as compared to controls. HRV measures were then correlated with rsFC of the PPN. Critically, participants with PTSD and participants with PTSD + DS displayed inverse correlations between HRV and rsFC between the PPN and key limbic structures, including the amygdala. Whereas participants with PTSD displayed a positive relationship between HRV and PPN rsFC with the amygdala, participants with PTSD + DS demonstrated a negative relationship between HRV and PPN rsFC with the amygdala. Conclusion: The present exploratory investigation reveals contrasting patterns of arousal-related circuitry among participants with PTSD and PTSD + DS, providing a neurobiological lens to interpret hyper- and more blunted arousal states in PTSD and PTSD + DS, respectively

A Pilot Randomized Controlled Trial of Goal Management Training in Canadian Military Members, Veterans, and Public Safety Personnel Experiencing Post-Traumatic Stress Symptoms

Post-traumatic stress disorder (PTSD) is a severe psychiatric illness that disproportionately affects military personnel, veterans, and public safety personnel (PSP). Evidence demonstrates that PTSD is significantly associated with difficulties with emotion regulation (ER) and difficulties with cognitive functioning, including difficulties with attention, working memory, and executive functioning. A wide body of evidence suggests a dynamic interplay among cognitive dysfunction, difficulties with ER, and symptoms of PTSD, where numerous studies have identified overlapping patterns of alterations in activation among neuroanatomical regions and neural circuitry. Little work has examined interventions that may target these symptoms collectively. The primary objective of this pilot randomized controlled trial (RCT) with a parallel experimental design was to assess the effectiveness of goal management training (GMT), a cognitive remediation intervention, in reducing difficulties with cognitive functioning, and to determine its effects on PTSD symptoms and symptoms associated with PTSD, including difficulties with ER, dissociation, and functioning among military personnel, veterans, and PSP. Forty-two military personnel, veterans, and PSP between the ages of 18 and 70 with symptoms of PTSD were recruited across Ontario, Canada between October 2017 and August 2019. Participants were randomized to either the waitlist (WL) (n = 18) or the GMT (n = 22) condition. Participants in both conditions received self-report measures and a comprehensive neuropsychological assessment at baseline, post-intervention, and 3-month follow-up. Following their completion of the 3-month follow-up, participants in the WL condition were given the opportunity to participate in GMT. Assessors and participants were blind to intervention allocation during the initial assessment. A series of 2 (time) × 2 (group) ANOVAs were conducted to assess the differences between the WL and GMT conditions from pre-to post-intervention for the self-report and neuropsychological measures. The results demonstrated significant improvements in measures of executive functioning (e.g., verbal fluency, planning, impulsivity, cognitive shifting, and discrimination of targets) and trending improvements in short-term declarative memory for participants in the GMT condition. Participants in the GMT condition also demonstrated significant improvements from pre-to post-testing in measures of subjective cognition, functioning, PTSD symptom severity, difficulties with ER, dissociative symptom severity, and depression and anxiety symptoms. No adverse effects were reported as a result of participating in GMT. The results of this pilot RCT show promise that GMT may be a useful intervention to improve symptoms of cognitive dysfunction, symptoms of PTSD, and symptoms associated with PTSD within military personnel, veterans, and PSP. Future work is needed to address the small sample size and the durability of these findings

Back to the Basics: Resting State Functional Connectivity of the Reticular Activation System in PTSD and its Dissociative Subtype.

BACKGROUND: Brainstem and midbrain neuronal circuits that control innate, reflexive responses and arousal are increasingly recognized as central to the neurobiological framework of post-traumatic stress disorder (PTSD). The reticular activation system represents a fundamental neuronal circuit that plays a critical role not only in generating arousal but also in coordinating innate, reflexive responding. Accordingly, the present investigation aims to characterize the resting state functional connectivity of the reticular activation system in PTSD and its dissociative subtype. METHODS: We investigated patterns of resting state functional connectivity of a central node of the reticular activation system, namely, the pedunculopontine nuclei, among individuals with PTSD (n = 77), its dissociative subtype (PTSD+DS; n = 48), and healthy controls (n = 51). RESULTS: Participants with PTSD and PTSD+DS were characterized by within-group pedunculopontine nuclei resting state functional connectivity to brain regions involved in innate threat processing and arousal modulation (i.e., midbrain, amygdala, ventromedial prefrontal cortex). Critically, this pattern was most pronounced in individuals with PTSD+DS, as compared to both control and PTSD groups. As compared to participants with PTSD and controls, individuals with PTSD+DS showed enhanced pedunculopontine nuclei resting state functional connectivity to the amygdala and the parahippocampal gyrus as well as to the anterior cingulate and the ventromedial prefrontal cortex. No group differences emerged between PTSD and control groups. In individuals with PTSD+DS, state derealization/depersonalization was associated with reduced resting state functional connectivity between the left pedunculopontine nuclei and the anterior nucleus of the thalamus. Altered connectivity in these regions may restrict the thalamo-cortical transmission necessary to integrate internal and external signals at a cortical level and underlie, in part, experiences of depersonalization and derealization. CONCLUSIONS: The present findings extend the current neurobiological model of PTSD and provide emerging evidence for the need to incorporate brainstem structures, including the reticular activation system, into current conceptualizations of PTSD and its dissociative subtype

The Threatful Self: Midbrain Functional Connectivity to Cortical Midline and Parietal Regions During Subliminal Trauma-Related Processing in PTSD.

BACKGROUND: The innate alarm system consists of a subcortical network of interconnected midbrain, lower brainstem, and thalamic nuclei, which together mediate the detection of evolutionarily-relevant stimuli. The periaqueductal gray is a midbrain structure innervated by the innate alarm system that coordinates the expression of defensive states following threat detection. In participants with post-traumatic stress disorder, the periaqueductal gray displays overactivation during the subliminal presentation of trauma-related stimuli as well as altered resting-state functional connectivity. Aberrant functional connectivity is also reported in post-traumatic stress disorder for the default-mode network, a large-scale brain network recruited during self-referential processing and autobiographical memory. Here, research lacks investigation on the extent to which functional interactions are displayed between the midbrain and the large-scale cortical networks in post-traumatic stress disorder. METHODS: Using a subliminal threat presentation paradigm, we investigated psycho-physiological interactions during functional neuroimaging in participants with post-traumatic stress disorder (n = 26) and healthy control subjects (n = 20). Functional connectivity of the periaqueductal gray was investigated across the whole-brain of each participant during subliminal exposure to trauma-related and neutral word stimuli. RESULTS: As compared to controls during subliminal threat presentation, the post-traumatic stress disorder group showed significantly greater periaqueductal gray functional connectivity with regions of the default-mode network (i.e., angular gyrus, precuneus, superior frontal gyrus). Moreover, multiple regression analyses revealed that the functional connectivity between the periaqueductal gray and the regions of the default-mode network correlated positively to symptoms of avoidance and state dissociation in post-traumatic stress disorder. CONCLUSION: Given that the periaqueductal gray engages the expression of defensive states, stronger midbrain functional coupling with the default-mode network may have clinical implications to self-referential and trauma-related processing in participants with post-traumatic stress disorder

The hijacked self: Disrupted functional connectivity between the periaqueductal gray and the default mode network in posttraumatic stress disorder using dynamic causal modeling.

Self-related processes define assorted self-relevant or social-cognitive functions that allow us to gather insight and to draw inferences related to our own mental conditions. Self-related processes are mediated by the default mode network (DMN), which, critically, shows altered functionality in individuals with posttraumatic stress disorder (PTSD). In PTSD, the midbrain periaqueductal gray (PAG) demonstrates stronger functional connectivity with the DMN [i.e., precuneus (PCN), medial prefrontal cortex (mPFC)] as compared to healthy individuals during subliminal, trauma-related stimulus processing. Here, we analyzed the directed functional connectivity between the PAG and the PCN, as well as between the PAG and the mPFC to more explicitly characterize the functional connectivity we have observed previously on the corresponding sample and paradigm. We evaluated three models varying with regard to context-dependent modulatory directions (i.e., bi-directional, bottom-up, top-down) among individuals with PTSD (n = 26) and healthy participants (n = 20), where Bayesian model selection was used to identify the most optimal model for each group. We then compared the effective connectivity strength for each parameter across the models and between our groups using Bayesian model averaging. Bi-directional models were found to be favoured across both groups. In PTSD, we revealed the PAG to show stronger excitatory effective connectivity to the PCN, as well as to the mPFC as compared to controls. In PTSD, we further demonstrated that PAG-mediated effective connectivity to the PCN, as well as to the mPFC were modulated more strongly during subliminal, trauma-related stimulus conditions as compared to controls. Clinical disturbances towards self-related processes are reported widely by participants with PTSD during trauma-related stimulus processing, where altered functional connectivity directed by the PAG to the DMN may elucidate experiential links between self- and trauma-related processing in traumatized individuals

Large-scale functional hyperconnectivity patterns in trauma-related dissociation: an rs-fMRI study of PTSD and its dissociative subtype

The dissociative subtype of post-traumatic stress disorder (PTSD) is a distinct PTSD phenotype characterized by trauma-related dissociation, alongside unique patterns of functional connectivity. However, disparate findings across multiple scales of investigation have highlighted the need for a cohesive understanding of dissociative neurobiology. We took a step towards this goal by conducting one of the broadest region of interest (ROI)-to-ROI analyses performed on a PTSD population to date. In this retrospective study, we investigated resting-state functional MRI data collected from a total of 192 participants, 134 of whom were diagnosed with PTSD. Small functional connectivity differences (maximum effect size 0.27) were found between participants with PTSD and controls in the temporal regions and the right frontoparietal network. Participants with the dissociative subtype showed a markedly different pattern of widespread functional hyperconnectivity compared with controls (maximum effect size 0.46), spanning subcortical regions, sensorimotor and other intrinsic connectivity networks. Furthermore, analysis of latent dimensions underlying both ROI-to-ROI brain results and a range of behavioral and clinical measures identified three clinically relevant latent dimensions—two linked to dissociation and one linked to PTSD symptoms. These results advance our understanding of dissociative neurobiology, characterizing it as a divergence from normative small-world organization. These patterns of hyperconnectivity are thought to serve a compensatory function to preserve global brain functioning in participants experiencing trauma-related dissociation