Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup.

Background: Identifying robust neural signatures of posttraumatic stress disorder (PTSD) symptoms is important to facilitate precision psychiatry and help in understanding and treatment of the disorder. Emergent research suggests structural covariance of early visual regions is associated with later PTSD development. However, large-scale analyses are needed - in heterogeneous samples of trauma-exposed and trauma naive individuals - to determine if such a neural signature is a robust marker of vulnerability.

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

Background: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

Methods: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD  = 1309; controls  = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool).

Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis.

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA produced stronger effect sizes and revealed findings in brain regions that traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage.

Associations between PACAP levels and psychophysiological indicators of fear and arousal in adults with posttraumatic stress symptoms.

Posttraumatic stress disorder (PTSD) is associated with heightened fear responding and decreased fear regulation, as demonstrated with psychophysiological measures (e.g., autonomic function) and circulating biomarkers of stress, such as pituitary adenylate cyclase-activating polypeptide (PACAP).

Connectometry reveals differing associations of cortisol and PACAP with dorsal cingulum microstructure in posttraumatic stress.

Posttraumatic stress disorder (PTSD) has been associated with altered arousal regulation and dysfunction of the hypothalamic-pituitary-adrenal axis, including changes in circulating cortisol and pituitary adenylate cyclaseactivating polypeptide (PACAP). Both stress-related hormones affect extended amygdala to medial prefrontal cortex (mPFC) circuit functioning, but it is unclear whether they relate to white matter microstructure connecting these regions. We examined this question in 139 trauma-exposed adults (81 female; ages 19-54) who completed the Clinician-Administered PTSD Scale, a blood draw, and diffusion magnetic resonance imaging.

Traumatic stress alters neural reactivity to visual stimulation.

Traumatic stress is a precursor to the development of posttraumatic stress disorder (PTSD). Emergent research suggests visual processing regions may be relevant to PTSD development; however, no previous research to date has investigated the potential effects of trauma exposure on neural reactivity to non-affective visual stimulation. In the present study, 24 recently trauma-exposed (RTE) and 16 without recent exposure to trauma (NRTE) individuals completed functional magnetic resonance imaging during alternating blocks of flickering checkerboard presentations and attention/rest with an attentional check.

Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup.

Background: Identifying robust neural signatures of posttraumatic stress disorder (PTSD) symptoms is important to facilitate precision psychiatry and help in understanding and treatment of the disorder. Emergent research suggests structural covariance of early visual regions is associated with later PTSD development. However, large-scale analyses are needed - in heterogeneous samples of trauma-exposed and trauma naive individuals - to determine if such a neural signature is a robust - and potentially a pretrauma - marker of vulnerability.

Intrinsic Functional Connectivity of Right Dorsolateral Prefrontal Cortex and Hippocampus Subregions Relates to Emotional and Sensory-Perceptual Properties of Intrusive Trauma Memories.

Background: Trauma-related intrusive memories (TR-IMs) are core symptoms of posttraumatic stress disorder (PTSD). Prior research links reexperiencing symptoms with resting-state functional coupling between the right dorsolateral prefrontal cortex (dlPFC) and right hippocampus (HPC). However, prior work has not examined whether this negative coupling relates to TR-IMs or has differentiated between the anterior and posterior HPC (aHPC/pHPC).

Multimodal associations between posterior hippocampus glutamate metabolism, visual cortex connectivity, and intrusive trauma reexperiencing symptoms.

Objective: Hippocampal dysfunction is implicated in posttraumatic stress disorder (PTSD), particularly intrusive reexperiencing symptoms, and may be mediated by glutamatergic excitotoxicity. Markers of glutamate dysfunction (higher glutamate to N-acetyl aspartate levels; Glu/NAA) in the hippocampus (HPC) have been linked to reexperiencing symptoms. However, the HPC demonstrates heterogeneity along its anterior-posterior axis, with different functional connectivity patterns and PTSD symptom associations, motivating investigations into glutamate metabolism in anterior and posterior HPC subregions (a/pHPC).

Aberrant neural event segmentation during a continuous social narrative in trauma-exposed older adolescents and young adults.

Post-traumatic stress and major depressive disorders are associated with "overgeneral" autobiographical memory, or impaired recall of specific life events. Interpersonal trauma exposure, a risk factor for both conditions, may influence how symptomatic trauma-exposed (TE) individuals segment everyday events. The ability to parse experience into units (event segmentation) supports memory.

Intrinsic functional connectivity of right dorsolateral prefrontal cortex and hippocampus subregions relates to emotional and sensory-perceptual properties of intrusive trauma memories.

Background: Trauma-related intrusive memories (TR-IMs), unwanted and vivid, are core symptoms of posttraumatic stress disorder (PTSD). Prior research links voluntary TR-IM suppression to inhibitory control of the right dorsolateral prefrontal cortex (dlPFC) over the hippocampus (HPC). However, the potential relevance of tonic resting-state inhibition has not been examined, nor has the functional differentiation of the anterior and posterior hippocampus (aHPC/HPC).

Neural and behavioral markers of inhibitory control predict symptom improvement during internet-delivered cognitive behavioral therapy for depression.

Poor inhibitory control contributes to deficits in emotion regulation, which are often targeted by treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT). Brain regions that contribute to inhibitory control and emotion regulation overlap; thus, inhibitory control might relate to response to CBT. In this study, we examined whether baseline inhibitory control and resting state functional connectivity (rsFC) within overlapping emotion regulation-inhibitory control regions predicted treatment response to internet-based CBT (iCBT).

Affective Visual Circuit Dysfunction in Trauma and Stress-Related Disorders.

Posttraumatic stress disorder (PTSD) is widely recognized as involving disruption of core neurocircuitry that underlies processing, regulation, and response to threat. In particular, the prefrontal cortex-hippocampal-amygdala circuit is a major contributor to posttraumatic dysfunction. However, the functioning of core threat neurocircuitry is partially dependent on sensorial inputs, and previous research has demonstrated that dense, reciprocal connections exist between threat circuits and the ventral visual stream.

Ecological Momentary Assessments of Trauma-Related Intrusive Memories: Potential Clinical Utility.

As the global prevalence of trauma rises, there is a growing need for accessible and scalable treatments for trauma-related disorders like posttraumatic stress disorder (PTSD). Trauma-related intrusive memories (TR-IMs) are a central PTSD symptom and a target of exposure-based therapies, gold-standard treatments that are effective but resource-intensive. This study examined whether a brief ecological momentary assessment (EMA) protocol assessing the phenomenology of TR-IMs could reduce intrusion symptoms in trauma-exposed adults.

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder.

Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus.

Spatiotemporal dynamics of hippocampal-cortical networks underlying the unique phenomenological properties of trauma-related intrusive memories.

Trauma-related intrusive memories (TR-IMs) possess unique phenomenological properties that contribute to adverse post-traumatic outcomes, positioning them as critical intervention targets. However, transdiagnostic treatments for TR-IMs are scarce, as their underlying mechanisms have been investigated separate from their unique phenomenological properties. Extant models of more general episodic memory highlight dynamic hippocampal-cortical interactions that vary along the anterior-posterior axis of the hippocampus (HPC) to support different cognitive-affective and sensory-perceptual features of memory.

Trauma-related intrusive memories and anterior hippocampus structural covariance: an ecological momentary assessment study in posttraumatic stress disorder.

Trauma-related intrusive memories (TR-IMs) are hallmark symptoms of posttraumatic stress disorder (PTSD), but their neural correlates remain partly unknown. Given its role in autobiographical memory, the hippocampus may play a critical role in TR-IM neurophysiology. The anterior and posterior hippocampi are known to have partially distinct functions, including during retrieval of autobiographical memories.

Unconditioned response to a naturally aversive stimulus is associated with sensitized defensive responding and self-reported fearful traits in a PTSD sample.

Unconditioned responding (UCR) to a naturally aversive stimulus is associated with defensive responding to a conditioned threat cue (CS+) and a conditioned safety cue (CS-) in trauma-exposed individuals during fear acquisition. However, the relationships of UCR with defensive responses during extinction training, posttraumatic stress disorder (PTSD) symptom severity, and fearful traits in trauma-exposed individuals are not known. In a sample of 100 trauma-exposed adults with a continuum of PTSD severity, we recorded startle responses and skin conductance responses (SCR) during fear acquisition and extinction training using a 140 psi, 250-ms air blast to the larynx as the unconditioned stimulus.

Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder.

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus.

Predicting Fear Extinction in Posttraumatic Stress Disorder.

Fear extinction is the basis of exposure therapies for posttraumatic stress disorder (PTSD), but half of patients do not improve. Predicting fear extinction in individuals with PTSD may inform personalized exposure therapy development. The participants were 125 trauma-exposed adults (96 female) with a range of PTSD symptoms.

Anhedonia and Delay Discounting: Differing Patterns of Brain-Behavior Relationships in Healthy Control Participants Versus Individuals With Posttraumatic Stress Disorder.

Background: Anhedonia may contribute to individual differences in delay discounting (DD). In prior work, we found that higher anhedonia was associated with shallower DD in healthy control (HC) participants but steeper DD in individuals with posttraumatic stress disorder (PTSD). In this study, we aimed to directly compare the relationship between anhedonia and DD across groups and to identify functional brain correlates of this interaction.

Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder.

The pituitary adenylate cyclase-activating polypeptide (PACAP) system is implicated in posttraumatic stress disorder (PTSD) and related amygdala-mediated arousal and threat reactivity. PTSD is characterized by increased amygdala reactivity to threat and, more recently, aberrant intrinsic connectivity of the amygdala with large-scale resting state networks, specifically the default mode network (DMN). While the influence of PACAP on amygdala reactivity has been described, its association with intrinsic amygdala connectivity remains unknown.