Dissociation by Network Integration.

Dissociation is a disconnection between a person’s thoughts, memories, feelings, actions, and sense of self (1). Dissociative symptoms are associated with intrusions into awareness, cognition, and behavior, with accompanying deficits in continuity of subjective experience (2). Multiple lines of evidence support a powerful relationship between dissociation and trauma, particularly early-life trauma and childhood maltreatment, and dissociation constitutes a distinct subtype of posttraumatic stress disorder (PTSD) (3). Given the complexity of the underlying psychological phenomena, it has been a challenge to determine the neurobiological signatures of trauma-related dissociation. A study reported in this issue by Lebois et al. (4) has addressed this gap in our knowledge and uncovered a potential brain circuit mechanism underlying individual differences in dissociative symptoms in adults with early-life trauma and PTSD. Previous studies of trauma-related dissociation have focused on emotion centers in the brain and have reported that among patients with PTSD, individuals with dissociative symptoms exhibit greater amygdala functional connectivity (“synchronization”) with prefrontal cortex regions involved in emotion regulation, including the middle and medial frontal gyrus as well as the default mode network (DMN) (5). A related study focusing on the periaqueductal gray, a brainstem nucleus involved in autonomic control and modulation of pain, found that dissociative, compared with nondissociative, PTSD patients exhibited greater functional connectivity with multiple parietal cortex regions (6). Although the brain areas examined and the targets differ across the two studies, a common pattern that emerges here is one of hyperconnected subcortical-cortical pathways. While these studies capture dysfunction in emotion-related circuits associated with PTSD, what has been missing is a broader examination of brain networks associated with trauma-related dissociations. Lebois and colleagues used a dimensional approach to investigate continuous measures of trauma-related dissociation using the Multidimensional Inventory of Dissociation (7) in a group of 65 women with histories of childhood abuse and current PTSD. Functional connectivity analysis was applied to resting-state functional MRI (fMRI) scans to investigate network dysfunction. The authors examined seven canonical brain networks, including the DMN, the frontoparietal network (FPN), and the dorsal and ventral attention networks, and used connectivity measures with a cross-validation procedure to predict dissociation scores in a subset of individuals within the cohort. Internetwork connectivity measures predicted symptom scores reasonably well, with a correlation between predicted and actual scores of about 0.5. Connections that contributed most prominently to the estimation of dissociation scores involved the DMN and FPN. Furthermore, the most predictive links showed crossnetwork hyperconnectivity between the DMN and FPN, indicating that greater synchronization between these networks was associated with more severe dissociative symptoms. The FPN and DMN serve different roles in human cognition. The FPN or “central executive” network, anchored in the dorsolateral prefrontal cortex and posterior parietal cortex, is critical for active maintenance andmanipulation of information inworkingmemory (8). TheDMNis anchored in anatomically distinct regions within the medial posterior cingulate cortex, ventromedial prefrontal cortex, medial temporal lobe, andangulargyrus (8, 9). Incontrast to theFPN, the DMN is typically suppressed during focused attention to external stimuli and is involved incognitiveprocesses that are internally focused, such as self-referential processing, recall of autobiographical events, rumination, and mind wandering. Both networks are fundamental to human cognition, and their dynamic interactions are critical for regulating adaptive goal-directed behaviors (10). Moreover, tasks involving autobiographical planning coactivate the DMN and FPN, indicating a role in internally focused goal-directed cognition (11). In this context, hyperconnectivity between the DMN and FPN in individuals with high levels of dissociation points to maladaptive integration and regulation of selfrelevant internal mental processes. An intriguing technical aspect of the Lebois et al. study is that the predictive signatures of trauma-related dissociations were significant only when homologous cortical regions were defined individually for each participant, but not when a canonical whole brain atlas was used. The authors employed a brain connectivity analysis approach in which cortical functional boundaries were defined at the individual level, prior to assessing connectivity between regions. This approach has demonstrated substantial improvements in the sensitivity and specificity of connectivity-based symptom prediction in other clinical domains, including schizophrenia Given the complexity of the underlying psychological phenomena, it has been a challenge to determine the neurobiological signatures of trauma-related dissociation.