Deconstructing dissociation: a triple network model of trauma-related dissociation and its subtypes.

Trauma-related pathological dissociation is characterized by disruptions in one's sense of self, perceptual, and affective experience. Dissociation and its trauma-related antecedents disproportionately impact women. However, despite the gender-related prevalence and high individual and societal costs, dissociation remains widely underappreciated in clinical practice. Moreover, dissociation lacks a synthesized neurobiological model across its subtypes. Leveraging the Triple Network Model of psychopathology, we sought to parse heterogeneity in dissociative experience by examining functional connectivity of three core neurocognitive networks as related to: (1) the dimensional dissociation subtypes of depersonalization/derealization and partially-dissociated intrusions; and, (2) the diagnostic category of dissociative identity disorder (DID). Participants were 91 women with and without: a history of childhood trauma, current posttraumatic stress disorder (PTSD), and varied levels of dissociation. Participants provided clinical data about dissociation, PTSD symptoms, childhood maltreatment history, and completed a resting-state functional magnetic resonance imaging scan. We used a novel statistical approach to assess both overlapping and unique contributions of dissociation subtypes. Covarying for age, childhood maltreatment and PTSD severity, we found dissociation was linked to hyperconnectivity within central executive (CEN), default (DN), and salience networks (SN), and decreased connectivity of CEN and SN with other areas. Moreover, we isolated unique connectivity markers associated with depersonalization/derealization in CEN and DN, to partially-dissociated intrusions in CEN, and to DID in CEN. This suggests dissociation subtypes have robust functional connectivity signatures that may serve as targets for PTSD/DID treatment engagement. Our findings underscore dissociation assessment as crucial in clinical care, in particular, to reduce gender-related health disparities.

Cortical thickness in default mode network hubs correlates with clinical features of dissociative seizures.

BACKGROUND: Dissociative seizures (DS) are a common subtype of functional neurological disorder (FND) with an incompletely understood pathophysiology. Here, gray matter variations and their relationship to clinical features were investigated. METHODS: Forty-eight patients with DS without neurological comorbidities and 43 matched clinical control patients with syncope with structural brain MRIs were identified retrospectively. FreeSurfer-based cortical thickness and FSL FIRST-based subcortical volumes were used for quantitative analyses, and all findings were age and sex adjusted, and corrected for multiple comparisons. RESULTS: Groups were not statistically different in cortical thickness or subcortical volumes. For patients with DS, illness duration was inversely correlated with cortical thickness of left-sided anterior and posterior cortical midline structures (perigenual/dorsal anterior cingulate cortex, superior parietal cortex, precuneus), and clusters at the left temporoparietal junction (supramarginal gyrus, postcentral gyrus, superior temporal gyrus), left postcentral gyrus, and right pericalcarine cortex. Dissociative seizure duration was inversely correlated with cortical thickness in the left perigenual anterior cingulate cortex, superior/middle frontal gyri, precentral gyrus and lateral occipital cortex, along with the right isthmus-cingulate and posterior-cingulate, middle temporal gyrus, and precuneus. Seizure frequency did not show any significant correlations. CONCLUSIONS: In patients with DS, illness duration inversely correlated with cortical thickness of left-sided default mode network cortical hubs, while seizure duration correlated with left frontopolar and right posteromedial areas, among others. Etiological factors contributing to neuroanatomical variations in areas related to self-referential processing in patients with DS require more research inquiry.

Social and emotion dimensional organizations in the abstract semantic space: the neuropsychological evidence.

An essential aspect of human cognition is supported by a rich reservoir of abstract concepts without tangible external referents (e.g., "honor", "relationship", "direction"). While decades of research showed that the neural organization of conceptual knowledge referring to concrete words respects domains of evolutionary salience and sensorimotor attributes, the organization principles of abstract word meanings are poorly understood. Here, we provide neuropsychological evidence for a domain (sociality) and attribute (emotion) structure in abstract word processing. Testing 34 brain-damaged patients on a word-semantic judgment task, we observed double dissociations between social and nonsocial words and a single dissociation of sparing of emotional (relative to non-emotional) words. The lesion profiles of patients with specific dissociations suggest potential neural correlates positively or negatively associated with each dimension. These results unravel a general domain-attribute architecture of word meanings and highlight the roles of the social domain and the emotional attribute in the non-object semantic space.

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.

Absence of negative associations of insular and medial frontal gray matter volume with dissociative symptoms in schizophrenia.

BACKGROUND: Dissociative symptoms have been constantly found in schizophrenia (SCZ). Traumatic experience seems to relate to dissociative symptoms and brain volume alterations in SCZ. The current study aimed to clarify the inter-relations of dissociative symptoms, traumatic experience, and brain volume in SCZ. METHODS: We employed voxel-based morphometry to compare the distributions of gray matter volumes (GMV) in 37 SCZ patients and 26 healthy volunteers (HV). All participants underwent T1-weighted images on a 1.5 T MRI system. Traumatic experience was examined by the Brief Betrayal Trauma Survey. Pathological and non-pathological dissociation were measured by the Dissociative Symptoms Scale and the Dissociative Experiences Scale, respectively. RESULTS: A GMV reduction was found in SCZ patients in the right thalamus. Importantly, a significant group by pathological dissociation interaction was observed in the medial frontal cortex (MFC), bilateral anterior insular area, and precuneus. A negative correlation between MFC/insular GMV and pathological dissociation was observed in HV; higher non-pathological dissociation and smaller volume in MFC/insula were associated with pathological dissociation. In contrast, higher traumatic experience, higher non-pathological dissociation, and larger volume in MFC/insula were associated with pathological dissociation in SCZ. CONCLUSION: The negative association between MFC/insula GMV and pathological dissociation in HV was not observed in SCZ patients. The absent negative association in SCZ suggests a unique neural underpinning in SCZ with dissociative pathology, in which medial frontal and temporal regions play crucial roles.

The dissociative subtype of posttraumatic stress disorder is associated with subcortical white matter network alterations.

Posttraumatic stress disorder (PTSD) is characterized by intrusions, avoidance, and hyperarousal while patients of the dissociative subtype (PTSD-D) experience additional dissociative symptoms. A neurobiological model proposes hyper-inhibition of limbic structures mediated by prefrontal cortices to underlie dissociation in PTSD. Here, we tested whether functional alterations in fronto-limbic circuits are underpinned by white matter network abnormalities on a network level. 23 women with PTSD-D and 19 women with classic PTSD participated. We employed deterministic diffusion tractography and graph theoretical analyses. Mean fractional anisotropy (FA) was chosen as a network weight and group differences assessed using network-based statistics. No significant white matter network alterations comprising both frontal and limbic structures in PTSD-D relative to classic PTSD were found. A subsequent whole brain exploratory analysis revealed relative FA alterations in PTSD-D in two subcortical networks, comprising connections between the left amygdala, hippocampus, and thalamus as well as links between the left ventral diencephalon, putamen, and pallidum, respectively. Dissociative symptom severity in the PTSD-D group correlated with FA values within both networks. Our findings suggest fronto-limbic inhibition in PTSD-D may present a dynamic neural process, which is not hard-wired via white matter tracts. Our exploratory results point towards altered fiber tract communication in a limbic-thalamic circuit, which may underlie (a) an initial strong emotional reaction to trauma reminders before conscious regulatory processes are enabled and (b) deficits in early sensory processing. In addition, aberrant structural connectivity in low-level motor regions may present neural correlates for dissociation as a passive threat-response.

Deep posteromedial cortical rhythm in dissociation.

Advanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide dynamical patterns give rise to complex behavioural states1-12. Dissociation is an altered behavioural state in which the integrity of experience is disrupted, resulting in reproducible cognitive phenomena including the dissociation of stimulus detection from stimulus-related affective responses. Dissociation can occur as a result of trauma, epilepsy or dissociative drug use13,14, but despite its substantial basic and clinical importance, the underlying neurophysiology of this state is unknown. Here we establish such a dissociation-like state in mice, induced by precisely-dosed administration of ketamine or phencyclidine. Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1-3-Hz rhythm in layer 5 neurons of the retrosplenial cortex. Electrophysiological recording with four simultaneously deployed high-density probes revealed rhythmic coupling of the retrosplenial cortex with anatomically connected components of thalamus circuitry, but uncoupling from most other brain regions was observed-including a notable inverse correlation with frontally projecting thalamic nuclei. In testing for causal significance, we found that rhythmic optogenetic activation of retrosplenial cortex layer 5 neurons recapitulated dissociation-like behavioural effects. Local retrosplenial hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1) pacemakers were required for systemic ketamine to induce this rhythm and to elicit dissociation-like behavioural effects. In a patient with focal epilepsy, simultaneous intracranial stereoencephalography recordings from across the brain revealed a similarly localized rhythm in the homologous deep posteromedial cortex that was temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation of this region elicited dissociative experiences. These results identify the molecular, cellular and physiological properties of a conserved deep posteromedial cortical rhythm that underlies states of dissociation.

Structural and functional brain alterations in psychiatric patients with dissociative experiences: A systematic review of magnetic resonance imaging studies.

INTRODUCTION: There is currently no general agreement on how to best conceptualize dissociative symptoms and whether they share similar neural underpinnings across dissociative disorders. Neuroimaging data could help elucidate these questions. OBJECTIVES: The objective of this review is to summarize empirical evidence for neural aberrations observed in patients suffering from dissociative symptoms. METHODS: A systematic literature review was conducted including patient cohorts diagnosed with primary dissociative disorders, post-traumatic stress disorder (PTSD), or borderline personality disorder. RESULTS: Results from MRI studies reporting structural (gray matter and white matter) and functional (during resting-state and task-related activation) brain aberrations were extracted and integrated. In total, 33 articles were included of which 10 pertained to voxel-based morphology, 2 to diffusion tensor imaging, 10 to resting-state fMRI, and 11 to task-related fMRI. Overall findings indicated aberrations spread across diverse brain regions, especially in the temporal and frontal cortices. Patients with dissociative identity disorder and with dissociative PTSD showed more overlap in brain activation than each group showed with depersonalization/derealization disorder. CONCLUSION: In conjunction, the results indicate that dissociative processing cannot be localized to a few distinctive brain regions but rather corresponds to differential neural signatures depending on the symptom constellation.

Dissociation as a disorder of integration - On the footsteps of Pierre Janet.

At the end of the 19th century Pierre Janet described dissociation as an altered state of consciousness manifested in disrupted integration of psychological functions. Clinically, such disruption comprises compartmentalization symptoms like amnesia, detachment symptoms like depersonalization/derealization, and structural dissociation of personality with changes in the sense of self. The exact neuronal mechanisms leading to these different symptoms remain unclear. We here suggest to put Janet's original account of dissociation as disrupted integration of psychological functions into a novel context, that is, a neuronal context as related to current brain imaging. This requires a combined theoretical and empirical approach on data supporting such neuronal reframing of Janet. For that, we here review (i) past and (ii) recent psychological and neuronal views on dissociation together with neuroscientific theories of integration, which (iii) are supported and complemented by preliminary fMRI data. We propose three neuronal mechanisms of dynamic integration operating at different levels of the brain's spontaneous activity - temporo-spatial binding on the regional level, temporo-spatial synchronization on the network level, and temporo-spatial globalization on the global level. These neuronal mechanisms, in turn, may be related to different symptomatic manifestation of dissociation operating at different levels, e.g., compartmentalization, detachment, and structural, which, as we suggest, can all be traced to disrupted integration of neuronal and psychological functions as originally envisioned by Janet.

Spontaneous Resolution of Dorsal Midbrain Syndrome Caused by a Pineal Cyst.

BACKGROUND: Pineal lesions are common causes of dorsal midbrain syndrome and typically require surgical intervention in symptomatic patients. We describe a unique case of spontaneous resolution of dorsal midbrain syndrome resulting from a pineal gland cyst. CASE DESCRIPTION: A 23-year-old woman developed a supranuclear upgaze palsy, convergence-retraction nystagmus, and light-near dissociation from a pineal gland cyst (1.0 × 1.3 × 1.2 cm) with mild mass effect on the posterior surface of the tectum. Seven days after symptom onset, she had complete, spontaneous resolution of her symptoms, and examination returned to normal. Repeat magnetic resonance imaging demonstrated an unchanged pineal cyst with new T2/fluid attenuated inversion recovery hyperintensity along the mesial surface of the left thalamus. CONCLUSIONS: Dorsal midbrain syndrome resulting from a pineal cyst may spontaneously improve even without a significant change in lesion size. This suggests that observation may be an appropriate initial management strategy.

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting-state functional connectivity and its predictive validity using machine learning.

Individuals with post-traumatic stress disorder (PTSD) typically experience states of reliving and hypervigilance; however, the dissociative subtype of PTSD (PTSD+DS) presents with additional symptoms of depersonalization and derealization. Although the insula is critical to emotion processing, its association with these contrasting symptom profiles is yet to be fully delineated. Accordingly, we investigated insula subregion resting-state functional connectivity patterns among individuals with PTSD, PTSD+DS, and healthy controls. Using SPM12 and PRONTO software, we implemented a seed-based resting-state functional connectivity approach, along with multiclass Gaussian process classification machine learning, respectively, in order to evaluate unique patterns and the predictive validity of insula subregion connectivity among individuals with PTSD (n = 84), PTSD+DS (n = 49), and age-matched healthy controls (n = 51). As compared to PTSD and PTSD+DS, healthy controls showed increased right anterior and posterior insula connectivity with frontal lobe structures. By contrast, PTSD showed increased bilateral posterior insula connectivity with subcortical structures, including the periaqueductal gray. Strikingly, as compared to PTSD and controls, PTSD+DS showed increased bilateral anterior and posterior insula connectivity with posterior cortices, including the left lingual gyrus and the left precuneus. Moreover, machine learning analyses were able to classify PTSD, PTSD+DS, and controls using insula subregion connectivity patterns with 80.4% balanced accuracy (p < .01). These findings suggest a neurobiological distinction between PTSD and its dissociative subtype with regard to insula subregion functional connectivity patterns. Furthermore, machine learning algorithms were able to utilize insula resting-state connectivity patterns to discriminate between participant groups with high predictive accuracy.

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia.

BACKGROUND: Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood. METHODS: We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS. RESULTS: In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy. CONCLUSION: This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

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.

Developmental abnormalities of the brain exposed to childhood maltreatment detected by diffusion tensor imaging.

Objective: This study aimed to investigate brain developmental alterations in individuals exposed to childhood maltreatment (CM) with dissociative experiences and motor coordination symptoms using diffusion tensor imaging on a 3Tesla (3T) magnetic resonance (MR) system. Methods: Five individuals exposed to CM who manifest behavioral and developmental problems with dissociative experiences and motor coordination symptoms (age range: 14-18 years; all female), as well as seven age- and gender-matched normal control individuals, participated in the study using a 3T MR system. Diffusion characteristics, as indexed by fractional anisotropy (FA), were assessed for cerebral white matter structures. A preliminary whole brain analysis was performed complementary to an anatomically guided region of interest (ROI) analysis. Results: In individuals exposed to CM, scattered decreases in FA were detected in multiple brain regions over the frontoparietal and temporal areas in the whole brain map. ROI analysis subsequently identified significant decreases in FA (p < 0.05) in the right parietal white matter area as well as in the right prefrontal, bilateral premotor, bilateral orbitofrontal, and temporal white matter areas in CM-exposed individuals compared to that in controls. Conclusion: The observed altered diffusion characteristics indicate attendant developmental abnormalities within the white matter structures, which are associated with the observed clinical and behavioral patterns including dissociative experiences and coordination symptoms in individuals exposed to CM. The study provides objective evidence regarding the effects of CM on brain microstructure.

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.

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.

Cortical thickness alterations linked to somatoform and psychological dissociation in functional neurological disorders.

BACKGROUND: Links between dissociation and functional neurological disorder (FND)/conversion disorder are well-established, yet the pathophysiology of dissociation remains poorly understood. This MRI study investigated structural alterations associated with somatoform and psychological dissociation in FND. We hypothesized that multimodal, paralimbic cingulo-insular regions would relate to the severity of somatoform dissociation in patients with FND. METHODS: FreeSurfer cortical thickness and subcortical volumetric analyses were performed in 26 patients with motor FND and 27 matched healthy controls. Patients with high dissociation as measured by the Somatoform Dissociation Questionnaire-20 (SDQ) or Dissociative Experiences Scale (DES) were compared to controls in stratified analyses. Within-group analyses were also performed with SDQ and DES scores in patients with FND. All cortical thickness analyses were whole-brain corrected at the cluster-wise level. RESULTS: Patients with FND and high somatoform dissociation (SDQ > 35) showed reduced left caudal anterior cingulate cortex (ACC) cortical thickness compared to controls. In within-group analyses, SDQ scores inversely correlated with left caudal ACC cortical thickness in patients with FND. Depersonalization/derealization scores positively correlated with right lateral occipital cortical thickness. Both within-group findings remained statistically significant controlling for trait anxiety/depression, borderline personality disorder and post-traumatic stress disorder, adverse life events, and motor FND subtypes in post-hoc analyses. CONCLUSION: Using complementary between-group and within-group analyses, an inverse association between somatoform dissociation and left caudal ACC cortical thickness was observed in patients with FND. A positive relationship was also appreciated between depersonalization/derealization severity and cortical thickness in visual association areas. These findings advance our neuropathobiological understanding of dissociation in FND. Hum Brain Mapp 39:428-439, 2018. © 2017 Wiley Periodicals, Inc.

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.

Sensory overload and imbalance: Resting-state vestibular connectivity in PTSD and its dissociative subtype.

BACKGROUND: The vestibular system integrates multisensory information to monitor one's bodily orientation in space, and is influenced by interoceptive awareness. Post-traumatic stress disorder (PTSD) involves typically alterations in interoceptive and bodily self-awareness evidenced by symptoms of hyperarousal, as well as of emotional detachment, including emotional numbing, depersonalization, and derealization. These alterations may disrupt vestibular multisensory integration between the brainstem (vestibular nuclei) and key vestibular cortical regions (parieto-insular vestibular cortex, prefrontal cortex). Accordingly, this study examined functional connectivity of the vestibular system in PTSD and its dissociative subtype. METHODS: Using resting-state fMRI data in SPM12 and PickAtlas, a seed-based analysis was employed to examine vestibular nuclei functional connectivity differences among PTSD (n = 60), PTSD dissociative subtype (PTSD + DS, n = 41) and healthy controls (n = 40). RESULTS: Increased vestibular nuclei functional connectivity with the parieto-insular vestibular cortex and the dorsolateral prefrontal cortex (dlPFC) was observed in PTSD and in controls as compared to PTSD + DS, and greater connectivity with the posterior insula was observed in controls as compared to PTSD. Interestingly, whereas PTSD symptom severity correlated negatively with dlPFC connectivity, clinical measures of depersonalization/derealization correlated negatively with right supramarginal gyrus connectivity. DISCUSSION: Taken together, decreased vestibular nuclei functional connectivity with key cortical vestibular regions in the PTSD + DS as compared to PTSD group, and its negative correlations with PTSD and dissociative symptoms, suggest that dysregulation of vestibular multisensory integration may contribute to the unique symptom profiles of each group. Further research examining disruption of vestibular system neural circuitry in PTSD and its dissociative subtype will be critical in capturing the neurophenomenology of PTSD symptoms and in identifying psychotherapeutic techniques that target dysfunction related to the vestibular system.

Dynamic causal modeling in PTSD and its dissociative subtype: Bottom-up versus top-down processing within fear and emotion regulation circuitry.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with decreased top-down emotion modulation from medial prefrontal cortex (mPFC) regions, a pathophysiology accompanied by hyperarousal and hyperactivation of the amygdala. By contrast, PTSD patients with the dissociative subtype (PTSD + DS) often exhibit increased mPFC top-down modulation and decreased amygdala activation associated with emotional detachment and hypoarousal. Crucially, PTSD and PTSD + DS display distinct functional connectivity within the PFC, amygdala complexes, and the periaqueductal gray (PAG), a region related to defensive responses/emotional coping. However, differences in directed connectivity between these regions have not been established in PTSD, PTSD + DS, or controls. METHODS: To examine directed (effective) connectivity among these nodes, as well as group differences, we conducted resting-state stochastic dynamic causal modeling (sDCM) pairwise analyses of coupling between the ventromedial (vm)PFC, the bilateral basolateral and centromedial (CMA) amygdala complexes, and the PAG, in 155 participants (PTSD [n = 62]; PTSD + DS [n = 41]; age-matched healthy trauma-unexposed controls [n = 52]). RESULTS: PTSD was characterized by a pattern of predominant bottom-up connectivity from the amygdala to the vmPFC and from the PAG to the vmPFC and amygdala. Conversely, PTSD + DS exhibited predominant top-down connectivity between all node pairs (from the vmPFC to the amygdala and PAG, and from the amygdala to the PAG). Interestingly, the PTSD + DS group displayed the strongest intrinsic inhibitory connections within the vmPFC. CONCLUSIONS: These results suggest the contrasting symptom profiles of PTSD and its dissociative subtype (hyper- vs. hypo-emotionality, respectively) may be driven by complementary changes in directed connectivity corresponding to bottom-up defensive fear processing versus enhanced top-down regulation. Hum Brain Mapp 38:5551-5561, 2017. © 2017 Wiley Periodicals, Inc.