Sponheim, S. | Search bioRxiv

bioRxiv2023

Neural underpinnings of comorbid posttraumatic stress and excessive alcohol use: Opposing effects on loss-related mediofrontal theta in combat veterans

ObjectiveOver half of US military veterans with posttraumatic stress disorder (PTSD) use alcohol heavily, potentially to cope with their symptoms. This study investigated the neural underpinnings of PTSD symptoms and heavy drinking in veterans. We focused on brain responses to salient outcomes within predictive coding theory. This framework suggests the brain generates prediction errors (PEs) when outcomes deviate from expectations. Alcohol use might provide negative reinforcement by reducing the salience of negatively-valenced PEs and dampening experiences like loss. MethodsWe analyzed electroencephalography (EEG) responses to unpredictable gain/loss feedback in veterans of Operations Enduring and Iraqi Freedom. We used time-frequency principal components analysis of event-related potentials to isolate neural responses indicative of PEs, identifying mediofrontal theta linked to losses (feedback-related negativity, FRN) and central delta associated with gains (reward positivity, RewP). ResultsIntrusive reexperiencing symptoms of PTSD were associated with intensified mediofrontal theta signaling during losses, suggesting heightened negative PE sensitivity. Conversely, increased hazardous alcohol use was associated with reduced theta responses, implying a dampening of these negative PEs. The separate delta-RewP component showed associations with alcohol use but not PTSD symptoms. ConclusionsFindings suggest a common neural component of PTSD and hazardous alcohol use involving altered PE processing. We suggest that reexperiencing enhances the intensity of salient negative PEs, while chronic alcohol use may reduce their intensity, thereby providing negative reinforcement by muting emotional disruption from reexperienced trauma. Modifying the mediofrontal theta response could address the intertwined nature of PTSD symptoms and alcohol use, providing new avenues for treatment.

neuroscience↗

bioRxiv2023

Connectome architecture shapes large-scale cortical reorganization in schizophrenia: a worldwide ENIGMA study

While schizophrenia is considered a prototypical network disorder characterized by widespread brain-morphological alterations, it still remains unclear whether distributed structural alterations robustly reflect underlying network layout. Here, we tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2,439 adults with schizophrenia and 2,867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n=207), we evaluated structural alterations of schizophrenia against two network susceptibility models: i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; ii) epicenter mapping, which identify regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Schizophrenia-related structural alterations co-localized with interconnected functional and structural hubs and harbored temporo-paralimbic and frontal epicenters. Findings were robust across sites and related to individual symptom profiles. We observed localized unique epicenters for first-episode psychosis and early stages, and transmodal epicenters that were shared across first-episode to chronic stages. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, yielding insights in pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work contributes to recognizing potentially common pathways to better understand macroscale structural alterations, and inter-individual variability in schizophrenia.

neuroscience↗