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.

Moral wounds run deep: exaggerated midbrain functional network connectivity across the default mode network in posttraumatic stress disorder.

BACKGROUND: A moral injury occurs when a deeply held moral code has been violated, and it can lead to the development of symptoms of posttraumatic stress disorder (PTSD). However, the neural correlates that differentiate moral injury and PTSD remain largely unknown. Intrinsic connectivity networks such as the default mode network (DMN) appear to be altered in people with PTSD who have experienced moral injury. However, brainstem, midbrain and cerebellar systems are rarely integrated into the intrinsic connectivity networks; this is a critical oversight, because these systems display marked differences in people with PTSD and are thought to underlie strong moral emotions such as shame, guilt and betrayal. METHODS: We conducted an independent component analysis on data generated during script-driven memory recall of moral injury in participants with military- or law enforcement-related PTSD (n = 28), participants with civilian-related PTSD (n = 28) and healthy controls exposed to a potentially morally injurious event (n = 18). We conducted group-wise comparisons of functional network connectivity differences across a DMN-correlated independent component, with a particular focus on brainstem, midbrain and cerebellar systems. RESULTS: We found stronger functional network connectivity in the midbrain periaqueductal grey (t 71 = 4.95, p FDR = 0.028, k = 39) and cerebellar lobule IX (t 71 = 4.44, p FDR = 0.046, k = 49) in participants with civilian-related PTSD as compared to healthy controls. We also found a trend toward stronger functional network connectivity in the midbrain periaqueductal grey (t 71 = 4.22, p FDR = 0.076, k = 60) in participants with military- or law enforcement-related PTSD as compared to healthy controls. LIMITATIONS: The significant clusters were large, but resolution is generally lower for subcortical structures. CONCLUSION: In PTSD, the DMN appears to be biased toward lower-level, midbrain systems, which may drive toxic shame and related moral emotions that are common in PTSD, highlighting the depth at which moral injuries are represented neurobiologically.

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 (ß = 0.127, p < 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 (ß = 0.566, p < 0.0001), which was in turn associated with greater alcohol-related problems (ß = 0.184, p < 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.

Care aides' perceptions of caring for residents with a history of psychological trauma in Western Canadian care homes.

OBJECTIVE: To explore care aide perceptions of caring for residents who aides perceived had past psychological trauma. METHODS: Through cognitive interviews, we developed a definition of trauma for four survey questions about caring for residents with psychological trauma. We added these questions to our routine care aide survey in 91 care homes in Western Canada (September 2019 to February 2020). We asked if care aides perceived that they were caring for residents with trauma, how often, types of trauma experienced, and what indication led them to perceive a resident had experienced trauma. We analyzed data using content analysis (open-ended questions) and regression analyses (closed-ended questions). RESULTS: Three thousand seven hundred and sixty five care aides responded (70% response rate) to the survey, and 53% perceived caring for one or more residents with a history of psychological trauma in the previous 2 weeks. Within six categories of traumatic events, abuse (35%) and war exposure (26%) were most common. Most common indications of trauma reported by care aides (five categories) were reliving the experience or having intrusive symptoms (28%) and avoidant behaviors (24%). Care aides were more likely to report caring for a resident who they perceived had experienced past psychological trauma if they were younger, spoke English as their first language, self-reported experiencing more aggression from residents, or who worked in not-for-profit homes. CONCLUSIONS: This preliminary study supports the need for further study of care aides' perceptions and experiences of caring for residents with past trauma, and the effects of caring for these residents on quality of work life.

Examining the 4-D Model in Persons Enrolled in the Top DD Internet Intervention.

The 4-dimensional (4-D) model of trauma-related dissociation differentiates between dissociative experiences involving trauma-related altered states of consciousness and symptoms of distress that do not appear to involve alterations in normal waking consciousness across four phenomenological dimensions (i.e., our experience of time, thought, body, and emotions). The current study evaluated hypotheses associated with the 4-D model using analyses of variance and correlation analyses in individuals with a primary diagnosis of a trauma-related dissociative disorder who were participating in the TOP DD internet study involving a combination of in-person psychotherapy and an online psychoeducational program (n = 111). Intrusive memories of traumatic events were more frequently endorsed than flashbacks, but emotional numbing was more frequently endorsed than other forms of affect dysregulation. Negative thoughts and emotion dysregulation were more strongly intercorrelated than were voice hearing and emotional numbing. Distress symptoms were more strongly associated with PTSD symptoms and difficulties in emotion regulation, whereas experiences of depersonalization were more strongly associated with dissociative self-states. Greater reduction in distress symptoms was also seen in comparison with trauma-related altered states of consciousness over the course of the combined psychotherapy and internet-based psychoeducational intervention. Overall, results continue to suggest that measures of distress and dissociative experiences can be distinguished by measures of symptom frequency, co-occurrence, and convergence with other measures of distress vs. dissociation albeit that results varied across the four phenomenological dimensions that were surveyed.

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis.

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.

Altered basal forebrain BOLD signal variability at rest in posttraumatic stress disorder: A potential candidate vulnerability mechanism for neurodegeneration in PTSD.

Individuals with posttraumatic stress disorder (PTSD) are at increased risk for the development of various forms of dementia. Nevertheless, the neuropathological link between PTSD and neurodegeneration remains unclear. Degeneration of the human basal forebrain constitutes a pathological hallmark of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. In this seed-based resting-state (rs-)fMRI study identifying as outcome measure the temporal BOLD signal fluctuation magnitude, a seed-to-voxel analyses assessed temporal correlations between the average BOLD signal within a bilateral whole basal forebrain region-of-interest and each whole-brain voxel among individuals with PTSD (n = 65), its dissociative subtype (PTSD+DS) (n = 38) and healthy controls (n = 46). We found that compared both with the PTSD and healthy controls groups, the PTSD+DS group exhibited increased BOLD signal variability within two nuclei of the seed region, specifically in its extended amygdaloid region: the nucleus accumbens and the sublenticular extended amygdala. This finding is provocative, because it mimics staging models of neurodegenerative diseases reporting allocation of neuropathology in early disease stages circumscribed to the basal forebrain. Here, underlying candidate etiopathogenetic mechanisms are neurovascular uncoupling, decreased connectivity in local- and large-scale neural networks, or disrupted mesolimbic dopaminergic circuitry, acting indirectly upon the basal forebrain cholinergic pathways. These abnormalities may underpin reward-related deficits representing a putative link between persistent traumatic memory in PTSD and anterograde memory deficits in neurodegeneration. Observed alterations of the basal forebrain in the dissociative subtype of PTSD point towards the urgent need for further exploration of this region as a potential candidate vulnerability mechanism for neurodegeneration in PTSD.

Shame on the brain: Neural correlates of moral injury event recall in posttraumatic stress disorder.

BACKGROUND: Moral injury (MI) is consistently associated with adverse mental health outcomes, including the development of posttraumatic stress disorder (PTSD) and suicidality. METHODS: We investigated neural activation patterns associated with MI event recall using functional magnetic resonance imaging in participants with military and public safety-related PTSD, relative to civilian MI-exposed controls. RESULTS: MI recall in the PTSD as compared to control group was associated with increased neural activation among salience network nodes involved in viscerosensory processing and hyperarousal (right posterior insula, dorsal anterior cingulate cortex; dACC), regions involved in defensive responding (left postcentral gyrus), and areas responsible for top-down cognitive control of emotions (left dorsolateral prefrontal cortex; dlPFC). Within the PTSD group, measures of state and trait shame correlated negatively with activity among default mode network regions associated with self-related processing and moral cognition (dorsomedial prefrontal cortex; dmPFC) and salience network regions associated with viscerosensory processing (left posterior insula), respectively. CONCLUSIONS: These findings suggest that MI event processing is altered in military and public safety-related PTSD, relative to MI-exposed controls. Here, it appears probable that as individuals with PTSD recall their MI event, they experience a surge of blame-related processing of bodily sensations within salience network regions, including the right posterior insula and the dACC, which in turn, prompt regulatory strategies at the level of the left dlPFC aimed at increasing cognitive control and inhibiting emotional affect. These results are consistent with previous findings showing enhanced sensory processing and altered top-down control in PTSD samples during autobiographical memory recall.

Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist).

Neurofeedback has begun to attract the attention and scrutiny of the scientific and medical mainstream. Here, neurofeedback researchers present a consensus-derived checklist that aims to improve the reporting and experimental design standards in the field.

The neural correlates of trauma-related autobiographical memory in posttraumatic stress disorder: A meta-analysis.

BACKGROUND: Autobiographical memory (AM) refers to memories of events that are personally relevant and are remembered from one's own past. The AM network is a distributed brain network comprised largely by prefrontal medial and posteromedial cortical brain regions, which together facilitate AM. Autobiographical memories with high arousal and negatively valenced emotional states are thought to be retrieved more readily and re-experienced more vividly. This is critical in the case of trauma-related AMs, which are related to altered phenomenological experiences as well as aberrations to the underlying neural systems in posttraumatic stress disorder (PTSD). Critically, these alterations to the AM network have not been explored recently and have never been analyzed with consideration to the different processes of AM, them being retrieval and re-experiencing. METHODS: We conducted a series of effect-size signed differential mapping meta-analyses across twenty-eight studies investigating the neural correlates of trauma-related AMs in participants with PTSD as compared with controls. Studies included either trauma-related scripts or trauma-related materials (i.e., sounds, images, pictures) implemented to evoke the recollection of a trauma-related memory. RESULTS: The meta-analyses revealed that control and PTSD participants displayed greater common brain activation of prefrontal medial and posteromedial cortices, respectively. Whereby the prefrontal medial cortices are suggested to facilitate retrieval monitoring, the posteromedial cortices are thought to enable the visual imagery processes of AM. CONCLUSIONS: Taken together, reduced common activation of prefrontal cortices may be interpreted as a bias toward greater re-experiencing, where the more salient elements of the traumatic memory are relived as opposed to retrieved in a controlled manner in PTSD.

The effects of trauma on brain and body: A unifying role for the midbrain periaqueductal gray.

Post-traumatic stress disorder (PTSD), a diagnosis that may follow the experience of trauma, has multiple symptomatic phenotypes. Generally, individuals with PTSD display symptoms of hyperarousal and of hyperemotionality in the presence of fearful stimuli. A subset of individuals with PTSD; however, elicit dissociative symptomatology (i.e., depersonalization, derealization) in the wake of a perceived threat. This pattern of response characterizes the dissociative subtype of the disorder, which is often associated with emotional numbing and hypoarousal. Both symptomatic phenotypes exhibit attentional threat biases, where threat stimuli are processed preferentially leading to a hypervigilant state that is thought to promote defensive behaviors during threat processing. Accordingly, PTSD and its dissociative subtype are thought to differ in their proclivity to elicit active (i.e., fight, flight) versus passive (i.e., tonic immobility, emotional shutdown) defensive responses, which are characterized by the increased and the decreased expression of the sympathetic nervous system, respectively. Moreover, active and passive defenses are accompanied by primarily endocannabinoid- and opioid-mediated analgesics, respectively. Through critical review of the literature, we apply the defense cascade model to better understand the pathological presentation of defensive responses in PTSD with a focus on the functioning of lower-level midbrain and extended brainstem systems.

Machine learning multivariate pattern analysis predicts classification of posttraumatic stress disorder and its dissociative subtype: a multimodal neuroimaging approach.

BACKGROUND: The field of psychiatry would benefit significantly from developing objective biomarkers that could facilitate the early identification of heterogeneous subtypes of illness. Critically, although machine learning pattern recognition methods have been applied recently to predict many psychiatric disorders, these techniques have not been utilized to predict subtypes of posttraumatic stress disorder (PTSD), including the dissociative subtype of PTSD (PTSD + DS). METHODS: Using Multiclass Gaussian Process Classification within PRoNTo, we examined the classification accuracy of: (i) the mean amplitude of low-frequency fluctuations (mALFF; reflecting spontaneous neural activity during rest); and (ii) seed-based amygdala complex functional connectivity within 181 participants [PTSD (n = 81); PTSD + DS (n = 49); and age-matched healthy trauma-unexposed controls (n = 51)]. We also computed mass-univariate analyses in order to observe regional group differences [false-discovery-rate (FDR)-cluster corrected p < 0.05, k = 20]. RESULTS: We found that extracted features could predict accurately the classification of PTSD, PTSD + DS, and healthy controls, using both resting-state mALFF (91.63% balanced accuracy, p < 0.001) and amygdala complex connectivity maps (85.00% balanced accuracy, p < 0.001). These results were replicated using independent machine learning algorithms/cross-validation procedures. Moreover, areas weighted as being most important for group classification also displayed significant group differences at the univariate level. Here, whereas the PTSD + DS group displayed increased activation within emotion regulation regions, the PTSD group showed increased activation within the amygdala, globus pallidus, and motor/somatosensory regions. CONCLUSION: The current study has significant implications for advancing machine learning applications within the field of psychiatry, as well as for developing objective biomarkers indicative of diagnostic heterogeneity.

An Online Educational Program for Individuals With Dissociative Disorders and Their Clinicians: 1-Year and 2-Year Follow-Up.

Individuals with dissociative disorders (DDs) are underrecognized, underserved, and often severely psychiatrically ill, characterized by marked dissociative and posttraumatic stress disorder (PTSD) symptoms with significant disability. Patients with DD have high rates of nonsuicidal self-injury (NSSI) and suicide attempts. Despite this, there is a dearth of training about DDs. We report the outcome of a web-based psychoeducational intervention for an international sample of 111 patients diagnosed with dissociative identity disorder (DID) or other complex DDs. The Treatment of Patients with Dissociative Disorders Network (TOP DD Network) program was designed to investigate whether, over the course of a web-based psychoeducational program, DD patients would exhibit improved functioning and decreased symptoms, including among patients typically excluded from treatment studies for safety reasons. Using video, written, and behavioral practice exercises, the TOP DD Network program provided therapists and patients with education about DDs as well as skills for improving emotion regulation, managing safety issues, and decreasing symptoms. Participation was associated with reductions in dissociation and PTSD symptoms, improved emotion regulation, and higher adaptive capacities, with overall sample |d|s = 0.44-0.90, as well as reduced NSSI. The improvements in NSSI among the most self-injurious patients were particularly striking. Although all patient groups showed significant improvements, individuals with higher levels of dissociation demonstrated greater and faster improvement compared to those lower in dissociation |d|s = 0.54-1.04 vs. |d|s  = 0.24-0.75, respectively. These findings support dissemination of DD treatment training and initiation of treatment studies with randomized controlled designs.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Un programa educativo online para personas con trastornos disociativos y sus médicos: Seguimiento de uno y dos años INTERVENCIÓN ONLINE PARA TRASTORNOS DISOCIATIVOS Las personas con trastornos disociativos (TDs) se encuentran sub-reconocidas, con pocos servicios y, a menudo, con enfermedades psiquiátricas graves, caracterizadas por marcados síntomas disociativos y de trastorno de estrés postraumático (TEPT) con discapacidad significativa. Los pacientes con TD tienen altas tasas de autolesión no suicida (ALNS) e intentos de suicidio. A pesar de esto, hay una escasez de entrenamiento sobre los TDs. Reportamos el resultado de una intervención psicoeducativa basado en la web para una muestra internacional de 111 pacientes diagnosticados con trastorno de identidad disociativa (TID) u otros TDs complejos. El programa de la Red de Tratamiento de Pacientes con Trastornos Disociativos (TOP DD Network, en su denominación en inglés) se diseñó para investigar si, en el transcurso de un programa psicoeducativo basado en la web, los pacientes con TD exhibirían un mejor funcionamiento y reducción de síntomas, incluso en los pacientes que generalmente han sido excluidos de los estudios de tratamiento por razones de seguridad. Mediante el uso de videos, ejercicios de escritura y prácticas conductuales, el programa TOP DD Network brindó a los terapeutas y los pacientes educación sobre los TDs y las habilidades para mejorar la regulación de las emociones, manejar los problemas de seguridad, y disminuir los síntomas. La participación se asoció con reducciones en los síntomas de disociación y de TEPT, mejor regulación de las emociones y mayores capacidades de adaptación, muestra total ds = .44-.90, así como reducción de ALNS. Las mejoras en ALNS entre los pacientes más auto-agresivos fueron particularmente sorprendentes. Aunque todos los grupos de pacientes mostraron mejoras significativas, los individuos con niveles más altos de disociación demostraron una mejoría mayor y más rápida en comparación con los más bajos en disociación |d|s = .54-1.04 vs. |d|s = .24-.75, respectivamente. Estos hallazgos apoyan la diseminación de la capacitación en el tratamiento del TD y el inicio de estudios de tratamiento con diseños controlados aleatorios.

The Dissociative Subtype of PTSD Interview (DSP-I): Development and Psychometric Properties.

The inclusion of the dissociative subtype of post-traumatic stress disorder (PTSD-DS) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reflects the importance of assessing PTSD-DS. We developed the Dissociative Subtype of PTSD Interview (DSP-I). This clinician-administered instrument assesses the presence and severity of PTSD-DS (i.e., symptoms of depersonalization or derealization) and contains a supplementary checklist that enables assessment and differentiation of other trauma-related dissociative symptoms (i.e., blanking out, emotional numbing, alterations in sensory perception, amnesia, and identity confusion). The psychometric properties were tested in 131 treatment-seeking individuals with PTSD and histories of multiple trauma, 17.6 % of whom met criteria for PTSD-DS in accordance with the DSP-I. The checklist was tested in 275 treatment-seeking individuals. Results showed the DSP-I to have high internal consistency, good convergent validity with PTSD-DS items of the CAPS-5, and good divergent validity with scales of somatization, anxiety and depression. The depersonalization and derealization scales were highly associated. Moreover, the DSP-I accounted for an additional variance in PTSD severity scores of 8% over and above the CAPS-5 and number of traumatic experiences. The dissociative experiences of the checklist were more strongly associated with scales of overall distress, somatization, depression, and anxiety than scales of depersonalization and derealization. In conclusion, the DSP-I appears to be a clinically relevant and psychometrically sound instrument that is valuable for use in clinical and research settings.

The cerebellum after trauma: Resting-state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype.

The cerebellum plays a key role not only in motor function but also in affect and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Accordingly, we compared seed-based resting-state functional connectivity of the anterior cerebellum (lobule IV-V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD + DS; n = 37), and non-trauma-exposed healthy controls (HC; n = 47). Here, we observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in somatosensory processing, multisensory integration, and bodily self-consciousness (temporo-parietal junction, postcentral gyrus, and superior parietal lobule) in PTSD + DS as compared to PTSD and HC. Moreover, the PTSD + DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation (ventromedial prefrontal and orbito-frontal cortex, subgenual anterior cingulum) as compared to PTSD. By contrast, PTSD showed increased functional connectivity of the anterior cerebellum with cortical areas associated with visual processing (fusiform gyrus), interoceptive awareness (posterior insula), memory retrieval, and contextual processing (hippocampus) as compared to HC. Finally, we observed decreased functional connectivity between the posterior cerebellum and prefrontal regions involved in emotion regulation, in PTSD as compared to HC. These findings not only highlight the crucial role of each cerebellar region examined in the psychopathology of PTSD but also reveal unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD versus PTSD.

Resting-state functional connectivity of the bed nucleus of the stria terminalis in post-traumatic stress disorder and its dissociative subtype.

The bed nucleus of the stria terminals (BNST) is a subcortical structure involved in anticipatory and sustained reactivity to threat and is thus essential to the understanding of anxiety and stress responses. Although chronic stress and anxiety represent a hallmark of post-traumatic stress disorder (PTSD), to date, few studies have examined the functional connectivity of the BNST in PTSD. Here, we used resting state functional Magnetic Resonance Imaging (fMRI) to investigate the functional connectivity of the BNST in PTSD (n = 70), its dissociative subtype (PTSD + DS) (n = 41), and healthy controls (n = 50). In comparison to controls, PTSD showed increased functional connectivity of the BNST with regions of the reward system (ventral and dorsal striatum), possibly underlying stress-induced reward-seeking behaviors in PTSD. By contrast, comparing PTSD + DS to controls, we observed increased functional connectivity of the BNST with the claustrum, a brain region implicated in consciousness and a primary site of kappa-opioid receptors, which are critical to the dynorphin-mediated dysphoric stress response. Moreover, PTSD + DS showed increased functional connectivity of the BNST with brain regions involved in attention and salience detection (anterior insula and caudate nucleus) as compared to PTSD and controls. Finally, BNST functional connectivity positively correlated with default-mode network regions as a function of state identity dissociation, suggesting a role of BNST networks in the disruption of self-relevant processing characterizing the dissociative subtype. These findings represent an important first step in elucidating the role of the BNST in aberrant functional networks underlying PTSD and its dissociative subtype.

Superior colliculus resting state networks in post-traumatic stress disorder and its dissociative subtype.

OBJECTIVES: The innate alarm system (IAS) models the neurocircuitry involved in threat processing in posttraumatic stress disorder (PTSD). Here, we investigate a primary subcortical structure of the IAS model, the superior colliculus (SC), where the SC is thought to contribute to the mechanisms underlying threat-detection in PTSD. Critically, the functional connectivity between the SC and other nodes of the IAS remains unexplored. EXPERIMENTAL DESIGN: We conducted a resting-state fMRI study to investigate the functional architecture of the IAS, focusing on connectivity of the SC in PTSD (n = 67), its dissociative subtype (n = 41), and healthy controls (n = 50) using region-of-interest seed-based analysis. PRINCIPAL OBSERVATIONS: We observed group-specific resting state functional connectivity between the SC for both PTSD and its dissociative subtype, indicative of dedicated IAS collicular pathways in each group of patients. When comparing PTSD to its dissociative subtype, we observed increased resting state functional connectivity between the left SC and the right dorsolateral prefrontal cortex (DLPFC) in PTSD. The DLPFC is involved in modulation of emotional processes associated with active defensive responses characterising PTSD. Moreover, when comparing PTSD to its dissociative subtype, increased resting state functional connectivity was observed between the right SC and the right temporoparietal junction in the dissociative subtype. The temporoparietal junction is involved in depersonalization responses associated with passive defensive responses typical of the dissociative subtype. CONCLUSIONS: Our findings suggest that unique resting state functional connectivity of the SC parallels the unique symptom profile and defensive responses observed in PTSD and its dissociative subtype. Hum Brain Mapp 39:563-574, 2018. © 2017 Wiley Periodicals, Inc.

Resting-state pulvinar-posterior parietal decoupling in PTSD and its dissociative subtype.

Key evidence points toward alterations in the neurocircuitry of large-scale networks among patients with posttraumatic stress disorder (PTSD). The pulvinar is a thalamic region displaying reciprocal connectivity with the cortex and has been shown to modulate alpha synchrony to facilitate network communication. During rest, the pulvinar displays functional connectivity with the posterior parietal cortex (PPC), a heteromodal network of brain areas underlying multisensory integration and socioaffective functions that are shown at deficit in PTSD. Accordingly, this study seeks to reveal the resting-state functional connectivity (rsFC) patterns of individuals with PTSD, its dissociative subtype (PTSD + DS) and healthy controls. A whole-brain rsFC analysis was conducted using SPM12 and PickAtlas. Connectivity was analyzed for the left and right pulvinar across groups of individuals with PTSD (n = 81), PTSD + DS (n = 49), and controls (n = 51). As compared to PTSD, controls displayed significantly greater pulvinar rsFC with the superior parietal lobule and precuneus. Moreover, as compared to PTSD + DS, controls showed increased pulvinar connectivity with the superior parietal lobule, inferior parietal lobule and the precuneus. PTSD groups did not display stronger connectivity with any region as compared to controls. Last, PTSD had greater rsFC in the supramarginal gyrus relative to PTSD + DS. Reduced connectivity between the pulvinar and PPC may explain impairments to autobiographical memory, self-referential processing, and socioaffective domains in PTSD and PTSD + DS even at "rest." Critically, these alterations appear to be exacerbated in individuals with PTSD + DS, which may have important implications for treatment.

Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis.

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

Mindfulness-based treatments for posttraumatic stress disorder: a review of the treatment literature and neurobiological evidence.

Mindfulness-based treatments for posttraumatic stress disorder (PTSD) have emerged as promising adjunctive or alternative intervention approaches. A scoping review of the literature on PTSD treatment studies, including approaches such as mindfulness-based stress reduction, mindfulness-based cognitive therapy and metta mindfulness, reveals low attrition with medium to large effect sizes. We review the convergence between neurobiological models of PTSD and neuroimaging findings in the mindfulness literature, where mindfulness interventions may target emotional under- and overmodulation, both of which are critical features of PTSD symptomatology. Recent emerging work indicates that mindfulness-based treatments may also be effective in restoring connectivity between large-scale brain networks among individuals with PTSD, including connectivity between the default mode network and the central executive and salience networks. Future directions, including further identification of the neurobiological mechanisms of mindfulness interventions in patients with PTSD and direct comparison of these interventions to first-line treatments for PTSD are discussed.