The thalamus is a heterogeneous structure crucial for corticocortical communication, affective-perceptual integration, motor preparation, and memory-related functions. Posttraumatic stress disorder (PTSD) is characterized by various symptoms that likely relate to thalamic functions. Group-level and individual differential structural covariance (SC) analyses were conducted on intrathalamic, thalamocortical, and thalamosubcortical volumetric networks by segmenting structural MRI data from 2,784 subjects (PTSD n = 1,306; controls n = 1,478) into 25 thalamic nuclei per hemisphere. We found that PTSD was associated with stronger intrathalamic and thalamocortical network strength and stronger SC between the limbic thalamus and the somatomotor and auditory thalamus. PTSD severity was related to specific regional alterations in the intrathalamic network involving the lateral pulvinar. Comorbid depression severity positively correlated with global intrathalamic alterations, while avoidance symptoms positively correlated with global thalamosubcortical alterations. Hyperarousal symptoms related to altered SC in the thalamocortical network between the reuniens, central medial, paratenial, centromedian, and limitans-suprageniculate nuclei and lateral cortical regions spanning the occipital, temporal, and orbitofrontal cortices. Differential associations between avoidance, hyperarousal, and comorbid depression symptoms and thalamic SC in PTSD suggest that specific thalamic covariance patterns may be involved in unique facets of PTSD symptomatology.

The long-term neurobiological and psychological effects of war-related stress on civilians remain understudied. This study focuses on survivors of the war in the former Yugoslavia (G1) who now reside in the Czech Republic and on the children of survivors (G2) who were born after the conflict. Participants from G1, G2, and a control group (CG) with no war experience underwent structural MRI, answered a semi-structured interview, and completed psychological questionnaires (PTGI, PCL-5, SWSL, MSPSS, Brief-COPE). Voxel-based morphometry was used to assess brain volume differences. Compared to CG, G1 showed reduced grey matter volume in regions associated with PTSD and autobiographical memory, including Crus II, parahippocampal gyrus, middle temporal gyrus, and fusiform gyrus. Psychologically, G1 reported higher PTSD symptoms, lower life satisfaction, and greater post-traumatic growth. G2 showed no structural brain changes but scored higher on post-traumatic growth than CG, with no significant differences in other psychological measures. The findings suggest long-lasting neuroanatomical and psychological effects of war stress in directly exposed individuals (G1). Although G2 showed no brain alterations, the increased post-traumatic growth may indicate subtle adaptation effects of growing up in a post-war environment, but not necessarily only in a maladaptive sense.

Objective: Studies investigating resting-state functional connectivity of the amygdala and hippocampus have produced inconsistent findings. The authors' objective was to conduct the largest systematic comparison of alterations in functional connectivity of the amygdala and hippocampus in individuals with posttraumatic stress disorder (PTSD) using a multicohort mega-analysis with uniform processing steps and parameters across all cohorts. Methods: Resting-state functional MRI data from 1,017 PTSD patients and 1,702 control participants from 32 international sites were centrally preprocessed with HALFpipe and analyzed using the Image-Based Meta- and Mega-Analysis (IBMMA) package for neuroimaging processing. Group-level seed-based whole-brain analyses were completed for the right and left amygdala and hippocampus. Additional correlation analyses were conducted between PTSD norm-severity scores and resting-state functional connectivity (rs-FC). Results: Compared to control participants, individuals with PTSD showed stronger rs-FC between the left amygdala seed and right hippocampus and amygdala and the left and right lingual gyri. Greater PTSD total norm-severity scores were significantly associated with rs-FC between the left amygdala and right hippocampus/amygdala and rs-FC between the right amygdala and left hippocampus/amygdala. Conclusions: Greater connectivity between subcortical threat centers involved in fear processing, memory, and extinction learning characterizes the resting state in PTSD. Future directions include investigating how different interventions, such as brain stimulation, neurofeedback, and psychotherapy, might modulate the aberrant neural networks in PTSD.

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 successfully analyzed a large-n dataset of several thousand participants and revealed findings in brain regions that some traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.

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. We analyzed data from the ENIGMA-PTSD dataset (n = 2,814) and the Human Connectome Project – Young Adult (HCP-YA) dataset (n = 890) to investigate whether structural covariance of early visual cortex is associated with either PTSD symptoms or perceived stress. Structural covariance was derived from a multimodal pattern previously identified in recent trauma survivors, and participant loadings on the profile were included in linear mixed effects models to evaluate associations with stress. Early visual cortex covariance loadings were negatively associated with PTSD symptoms in the ENIGMA-PTSD dataset. The relationship persisted when accounting for prior childhood maltreatment; supporting PTSD symptom specificity, no relationship was observed with depressive symptoms and no association was observed between loadings and perceived stress measures in the HCP-YA dataset. Structural covariance of early visual cortex was robustly associated with PTSD symptoms across an international, heterogeneous sample of trauma survivors. Future studies should aim to identify specific mechanisms that underlie structural alterations in the visual cortex to better understand posttrauma psychopathology.

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 that the 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-naïve individuals to determine whether such a neural signature is a robust marker of vulnerability. METHODS:We analyzed data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-PTSD dataset (N = 2814) and the HCP-YA (Human Connectome Project-Young Adult) dataset (N = 890) to investigate whether the structural covariance of the early visual cortex is associated with either PTSD symptoms or perceived stress. Structural covariance was derived from a multimodal pattern previously identified in recent trauma survivors, and participant loadings on the profile were included in linear mixed effects models to evaluate associations with stress. RESULTS:Early visual cortex covariance loadings were negatively associated with PTSD symptoms in the ENIGMA-PTSD dataset. The relationship persisted when accounting for prior childhood maltreatment; supporting PTSD symptom specificity, no relationship was observed with depressive symptoms, and no association was observed between loadings and perceived stress measures in the HCP-YA dataset. CONCLUSIONS:The structural covariance of early visual cortex was robustly associated with PTSD symptoms across an international, heterogeneous sample of trauma survivors. Future studies should aim to identify specific mechanisms that underlie structural alterations in the visual cortex to better understand posttrauma psychopathology.

Objective: The aim of this work was to study the differences at the whole-brain level between self-paced and cued movement processing in Parkinson's disease (PD). Methods: High density electroencephalogram (HD-EEG) was recorded during the performance of self-paced movements (Bereitschaftspotential - BP) and visually cued movements (VMT) in PD patients (n = 38) and in a group of healthy controls (HC, n = 23). Oscillatory changes in the alpha, beta, and gamma frequencies were evaluated and correlated to the clinical scales- MDS-UPDRS and Freezing of Gait Questionnaire (FOGQ). Results: The main difference in the alpha range was an activation in the basal ganglia area during VMT performance as compared to BP performance; this activation was present only in HC. The most important finding was observed in the high beta range: a higher activation of the right postcentral area during BP performance in PD subjects as compared to HC, correlating to the severity of FOG. Moreover, PD patients had lower gamma activation of the right frontal areas. Conclusion: A simplification of motor circuits and a hyperactivation of the right somatosensory cortex were observed in PD subjects. Significance: Future studies should be focused on this area to confirm or disprove its role in FOG.

BACKGROUND:Music-based neuromodulation has garnered interest as a potential therapeutic approach for drug-resistant epilepsy. This study expands on prior research by examining the effects of different musical features on interictal epileptiform discharges (IEDs) within intracerebral EEG (iEEG). METHODS:Twenty-five patients with drug-resistant epilepsy undergoing presurgical iEEG evaluation participated in the study. Over 2 days, patients listened to various musical compositions characterized by distinct acoustic properties. EEG measurements were recorded before and after each listening session to evaluate IED changes. RESULTS:The study identified individualized patterns in IED reduction, with certain acoustic properties showing consistent effects across musical genres. Mozart's "Piano Concerto No. 27" K 595c globally reduced IEDs by 28% while listening to music (p = 0.0191) and 19% in the postmusic resting state (p = 0.0111); relaxation music increased IEDs by 55% (p = 0.0197). Based on the acoustic analysis of individuals, we identified compositions that significantly reduced IEDs, with reductions ranging from 32% to 44% (p = 0.0001). In contrast, compositions with differing acoustic properties did not result in significant changes in IEDs. These results suggest that specific acoustic properties, rather than genre, primarily influence IEDs. CONCLUSIONS:The findings suggest that specific acoustic properties can influence brain activity in a reproducible manner at the individual level, modulating IEDs based on personalized testing and selection across a spectrum of musical genres. These results suggest the potential for music-based neuromodulation as a personalized therapeutic approach in epilepsy management, emphasizing the importance of acoustic features over musical genre. Further research is needed to explore individual aspects of music-based interventions.

Background:Cortical gyrification involves the formation of folds in the cerebral cortex, coinciding with key neurodevelopmental processes. Its strong correlation with increased cortical surface area and decreased cortical thickness may improve cortical signaling efficiency by decreasing cortico-cortical distance. Differences in brain structure have been found in posttraumatic stress disorder (PTSD), yet few small studies have examined cortical gyrification. Methods:Gyrification was quantified using FreeSurfer's Local Gyrification Index (lGI), derived from 3-dimensional T1-weighted volumetric brain magnetic resonance imaging in 1876 participants (PTSD n = 789, control n = 1087) across 24 sites from the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta-Analysis and Psychiatric Genomics Consortium) PTSD working group. Using a region of interest-based approach, we fitted a linear mixed-effects model with age (mean = 35.6, SD = 9.23, range = 8-95), sex (female = 967 [52%], male = 909 [48%]), pial surface area, PTSD, and random site effects to test associations between PTSD diagnosis/severity and regional lGI. We examined moderating effects of depression, childhood trauma, age, and sex. Results:PTSD diagnosis and severity were both associated with lower lGI for the right medial orbitofrontal and right rostral anterior cingulate cortices. The interaction of PTSD and age was associated with lower lGI for the rostral middle frontal cortex bilaterally. Contrasting comorbid PTSD and major depressive disorder with the PTSD-only group showed that comorbidity was associated with lower lGI in the left inferior and medial temporal cortices. Conclusions:Lower lGI, which is associated with impaired signaling efficiency, was observed in the PTSD group compared with the control group for the ventromedial prefrontal cortex, a region that has been strongly implicated in associative fear learning and extinction. It is possible that PTSD accelerates the typical age-associated decline in lGI of the rostral middle frontal cortices.

BACKGROUND:Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are associated with alterations in the functional connectome, specifically in canonical resting-state networks including the default mode network (DMN), central executive network (CEN), and salience network (SN). Comorbid PTSD+TBI is linked to worse functional outcomes, but little is known about effects on the functional connectome. METHODS:We investigated brain phenotypes from resting-state functional magnetic resonance imaging associated with PTSD (n = 326), mTBI (n = 448), and comorbid PTSD+mTBI (n = 289) in military veterans and civilians (N = 1526) from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-TBI and ENIGMA-PTSD studies. We examined static functional connectivity (FC) and dynamic functional connectivity (DFC), which we quantified both as variability in FC (VFC) over time and as dwell time in recurring FC states identified through clustering. Analysis of covariance was followed by post hoc linear regression analysis to test main and interaction effects of diagnosis on FC metrics. RESULTS:We found a significant (false discovery rate-corrected p < .05) interaction of diagnosis × age on VFC. Older participants with comorbid PTSD+mTBI had greater VFC within the SN, between the SN and CEN, and between the SN and DMN than older control participants. Compared with control participants, comorbid participants had significantly greater dwell time in an externally focused state. Participants in the comorbid and mTBI groups had greater dwell time in a moderate-connectivity transition state than control participants. CONCLUSIONS:DFC related to the SN revealed distinct brain network patterns across diagnostic groups, with participants with comorbid PTSD+mTBI showing age- and anxiety-related effects. Older comorbid participants had heightened hypervigilance and reduced network segregation. PTSD and anxiety may synergistically worsen network instability, while mTBI reflects more rigid, disconnected states, highlighting DFC as a sensitive marker of neuropsychiatric comorbidity.

PURPOSE:The aim of this study was to develop a simple, robust, and easy-to-use calibration procedure for correcting misalignments in rosette MRI k-space sampling, with the objective of producing images with minimal artifacts. METHODS:Quick automatic calibration scans were proposed for the beginning of the measurement to collect information on the time course of the rosette acquisition trajectory. A two-parameter model was devised to match the measured time-varying readout gradient delays and approximate the actual rosette sampling trajectory. The proposed calibration approach was implemented, and performance assessment was conducted on both phantoms and human subjects. RESULTS:The fidelity of phantom and in vivo images exhibited significant improvement compared with uncorrected rosette data. The two-parameter calibration approach also demonstrated enhanced precision and reliability, as evidenced by quantitative T 2 * $$ {\mathrm{T}}_2^{\ast } $$ relaxometry analyses. CONCLUSION:Adequate correction of data sampling is a crucial step in rosette MRI. The presented experimental results underscore the robustness, ease of implementation, and suitability for routine experimental use of the proposed two-parameter rosette trajectory calibration approach.

Beta hypersynchrony was recently introduced into clinical practice in Parkinson’s disease (PD) to identify the best stimulation contacts and for adaptive deep brain stimulation (aDBS) sensing. However, many other oscillopathies accompany the disease, and beta power sensing may not be optimal for all patients. The aim of this work was to study the potential clinical usefulness of beta power phase-amplitude coupling (PAC) with high frequency oscillations (HFOs). Subthalamic nucleus (STN) local field potentials (LFPs) from externalized DBS electrodes were recorded and analyzed in PD patients (n = 19). Beta power and HFOs were evaluated in a resting-state condition; PAC was then studied and compared with the electrode contact positions, structural connectivity, and medication state. Beta-HFO PAC (mainly in the 200–500 Hz range) was observed in all subjects. PAC was detectable more specifically in the motor part of the STN compared to beta power and HFOs. Moreover, the presence of PAC better corresponds to the stimulation setup based on the clinical effect. PAC is also sensitive to the laterality of symptoms and dopaminergic therapy, where the greater PAC cluster reflects the more affected side and medication “off” state. Coupling between beta power and HFOs is known to be a correlate of the PD “off” state. Beta-HFO PAC seems to be more sensitive than beta power itself and could be more helpful in the selection of the best clinical stimulation contact and probably also as a potential future input signal for aDBS.

In addition to the loss of life, Russian aggression against Ukraine, which began in February 2022, also brings interpersonal losses resulting from the need to emigrate. Parallel to the fighting men, women bear most of the burden of caring for the family. Using in-depth interviews supplemented by questions about adverse childhood experiences and administration of The Centrality of Events Scale and the PTSD Checklist - PCL-5 with 43 Ukrainian women (18-60 years old), we analyzed adaptation to the situation of emigration and the association of their war and earlier experiences with the level of traumatization. Women were interviewed shortly after emigration to the Czech Republic (3-42 week afterward). High levels of adverse childhood experiences and post-traumatic stress symptoms were found. The war was perceived as a currently negative central event associated with traumatic stress symptoms, and 79% of the sample expressed the opinion that the war had changed them. The results of this study suggest an intertwining of previous life experiences with the current need and ability to adapt.

The aim of this work was to study the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on the subnetwork of subcortical and cortical motor regions and on the whole brain connectivity using the functional connectivity analysis in Parkinson's disease (PD). The high-density source space EEG was acquired and analyzed in 43 PD subjects in DBS on and DBS off stimulation states (off medication) during a cognitive-motor task. Increased high gamma band (50-100 Hz) connectivity within subcortical regions and between subcortical and cortical motor regions was significantly associated with the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III improvement after DBS. Whole brain neural correlates of cognitive performance were also detected in the high gamma (50-100 Hz) band. A whole brain multifrequency connectivity profile was found to classify optimal and suboptimal responders to DBS with a positive predictive value of 0.77, negative predictive value of 0.55, specificity of 0.73, and sensitivity of 0.60. Specific connectivity patterns related to PD, motor symptoms improvement after DBS, and therapy responsiveness predictive connectivity profiles were uncovered.

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.