Farnaz Delavari

: The human claustrum is a small, irregular, and complexly positioned structure, yet it carries long range projections to most cortical regions responsible for executive functioning. Prior structural MRI research has largely relied on global volume as the metric of its morphology. Such measures may obscure regionally specific morphological changes relevant to developmental and pathological variation. We therefore addressed this limitation by applying longitudinal surface-based morphometry to 874 scans from 440 individuals aged 5–35 years, comparing typical development with 22q11.2 deletion syndrome (22q11DS), a genetic condition characterized by brain dysmaturation, and assessing associations with working memory performance. Our data show a significant age-related volumetric decline that is reduced in 22q11DS left claustra, while surface deformation and thickness analyses revealed spatial patterns unique to hemisphere, group, and developmental age. In controls, the claustrum surface deformed with age in clustered zones along a dorsoventral gradient, and the dorsal-anterior zone thinned across development while the ventral zone thickened. 22q11DS claustra showed less age-related deformation than controls, whose claustrum surface changes associated with verbal working memory. This structural correlate was statistically equivalent to zero in carriers, consistent with a disrupted claustral development to the working memory vulnerability of the syndrome. These findings show the value of surface-based morphometry over volume alone, highlight dysmaturation and regionally organized claustrum shape variation, and suggest that disrupted structural organization is accompanied by a weaker claustrum-working memory association.

Background and Clinical Significance: Bow Hunter’s syndrome is an uncommon cause of vertebrobasilar insufficiency caused by dynamic vertebral artery narrowing during head rotation or extension. It is classically described at the atlantoaxial level, whereas subaxial compression is less recognised. Thyroid cartilage-related vertebral artery compression is particularly rare and may mimic vertebral artery dissection on static imaging. This case highlights the need to distinguish anatomical conflict from clinically causal haemodynamic compression. Case Presentation: A 51-year-old man with vascular risk factors and a well-anticoagulated mechanical aortic valve presented with three transient ischaemic attacks within two hours, including left-hand paraesthesia, right hemianopia, transient aphasia, and right-hand paraesthesia. Symptoms occurred spontaneously, without clear relation to head or neck movement or trauma. Doppler ultrasound showed normal carotid and vertebral flow. CT angiography demonstrated focal stenosis of the right vertebral artery at the V1–V2 junction caused by an osteocartilaginous “pincer” between the right thyroid cartilage ala and the C5 transverse process. The axial appearance mimicked vertebral artery dissection, but multiplanar CTA and contrast-enhanced MRA supported external indentation without mural haematoma, intimal flap, pseudoaneurysm, or double lumen. Perfusion CT showed no focal hypoperfusion, and diffusion-weighted MRI showed no acute infarct. Because symptoms were not positional and competing embolic risk factors were present, conservative management was chosen. Conclusions: Thyroid cartilage-related subaxial vertebral artery compression is a rare diagnostic pitfall. Static imaging may suggest dissection or Bow Hunter’s syndrome, but causality should not be inferred without compatible symptoms, exclusion of alternative mechanisms, and, when needed, dynamic confirmation.

Magnetic resonance spectroscopic imaging (MRSI) enables non-invasive mapping of neu-rometabolites levels across the human brain. Although spectral fitting and metabolite quan-tification are increasingly supported by mature software tools, the downstream processing of quantified metabolite maps remains heterogeneous across laboratories. Here, we introduce MRSIPrep, an open-source, modular, and reproducible post-quantification framework for whole-brain MRSI. MRSIPrep standardizes quality control, tissue correction, spatial nor- malization, atlas projection, and derivative generation from quantified metabolite maps and associated quality metrics. The framework produces voxelwise, regional, and connectomics-ready outputs together with automated quality-control reports. We describe the architecture of MRSIPrep and demonstrate its utility for reproducible MRSI analysis across datasets,acquisition protocols, and downstream applications.

The brain’s ability to regulate blood flow is fundamental to both its function and development. In the context of neurodevelopmental disorders such as schizophrenia, understanding the complex interactions between cerebrovascular health and brain function is crucial for unraveling the pathophysiology of psychosis. This study investigates the developmental trajectory of cerebrovascular reactivity (CVR) in 22q11 deletion syndrome (22q11.2DS) compared to healthy controls, and its association with psychosis susceptibility. Using one of the largest longitudinal data-set of resting-state fMRI, we mapped for the first time voxel-level CVR across development. We found an early reduction in CVR in 22q11.2DS, and in particular in those who later developed positive psychotic symptoms (PPS + ). These reductions were evident within the anterior cingulate cortex, frontal lobes, and globi pallidi (GP). We propose that the pattern of CVR alterations presenting early during childhood is possibly linked to altered blood-brain barrier integrity or permeability, potentially involving endothelial or tight-junction dysfunction; however, BBB integrity was not directly measured in this study. A decrease in CVR during childhood and within the frontal regions and GP was predictive of subsequent development of positive psychotic symptoms), which often occurs during adolescence in 22q11.2DS patients. These findings suggest that cerebrovascular health is critical for normal brain development, particularly in regions like the striatum, which are vulnerable to vascular damage due to their anatomical features. These results underline the potential of CVR as an early biomarker for psychosis vulnerability, emphasizing the need for targeted interventions to mitigate neurodevelopmental disruptions of cerebrovascular health in 22q11.2DS.

Emotion dysregulation (ED) is a core transdiagnostic feature of several psychiatric disorders, including borderline personality disorder, bipolar disorder, and attention-deficit/hyperactivity disorder. These ED disorders (EDD) exhibit overlapping clinical presentations, shared heritability, and common neurobiological substrates. This study used a transdiagnostic framework to identify early and multimodal markers of vulnerability, particularly in high-risk populations such as the offspring of EDD patients (EDDoff). A total of 237 participants (97 EDD patients, 67 EDDoff, 73 healthy controls; 139 females in total) completed a multimodal assessment including clinical evaluations, diffusion and functional MRI, and immune and neurotrophic serum biomarkers. Dimensionality reduction was performed using principal component analysis (PCA), and exploratory random forest (RF) models were trained for group classification and symptoms prediction. PCA on the full multimodal dataset yielded eight components, two of which significantly differed between groups, one reflecting high ED and altered hippocampal dynamic functional connectivity (dFC), for which EDDoff showed an intermediate phenotype, and another driven by systemic inflammation, increased in EDD patients only. Modality-specific PCA identified significant inter-modality correlations, including reduced white matter integrity with increasing immune dysregulation, and positive correlations between hippocampal dFC and both ED symptoms and inflammation ( p _adj = < 0.01 for all correlations). A RF classifier achieved a balanced accuracy of 80.3% in distinguishing controls from EDD/EDDoff individuals. Multimodal non-clinical features predicted ED symptoms ( p < 0.01). This study identifies a specific, clinically relevant, transdiagnostic and multimodal signature of vulnerability to ED, spanning behavioral, neural, and immune systems. This multimodal profile may inform future early intervention strategies targeting at-risk populations, such as EDDoff.

Autism is characterized by social-communicative difficulties, with sex differences in symptom presentation. Social functioning is inherently dynamic, however, many neuroimaging studies rely on static, time-averaged approaches that obscure time-varying network interactions, potentially limiting our ability to capture the dynamic processes underlying social cognition. The fusiform gyrus (FFG), central to face and social perception, shows differences in functional connectivity in autism, yet is rarely examined dynamically or as a spatially heterogeneous structure. Here, we investigate the dynamic functional connectivity of FFG subregions in terms of their large-scale network configurations as a function of diagnosis and sex. We applied micro co-activation patterns analysis (µCAPs) to resting-state fMRI data from 286 autistic individuals (208:78 males:females) and 228 non-autistic individuals (146:82 males:females), aged 6–30 years, from the EU-AIMS LEAP dataset. µCAPs were identified using k-means clustering with FFG as the seed, and connectopic mapping positioned each µCAP along the principal connectivity gradient. We quantified µCAPs occurrence and further examined dwell time, transition probabilities, and spatial extent, along with associations with social functioning. Six µCAPs mapped onto distinct FFG subregions along a posterior-anterior axis. A significant sex-by-diagnosis interaction emerged for a default mode network (DMN)-related µCAP. Non-autistic females exhibited significantly more frequent occurrences, longer dwell times and distinct transition dynamics compared to males, while no sex difference was observed in autism. The spatial extent of this µCAP showed a reversal of typical sex effects. Autism is associated with an attenuation and reversal of typical sex differences in the functional configuration and spatial extent of FFG-DMN coupling, indicating that neural signatures of social-cognitive functions are sex-specific and dynamic. These findings suggest that sex is a neurobiologically meaningful dimension of heterogeneity in autism, expressed in dynamic network organization.

Sex differences in brain disorders span age at onset, symptom profiles, disease course and treatment response, and may partly reflect underlying differences in cellular metabolism. Indeed, in vivo evidence of sex-related neurometabolic variation remains sparse, with heterogenous and conflicting findings. Using fast high-resolution whole-brain three-dimensional magnetic resonance spectroscopic imaging, we mapped five brain metabolites in three independent cohorts of healthy participants (total n = 114). In a discovery sample of adolescents scanned at 3 Tesla (3T) (n = 61), males showed higher total N-acetylaspartate (tNAA) across widespread gray matter regions. Regional analyses further revealed opposing sex patterns with a complementary higher total creatine (tCr) observed in females, motivating examination of their ratio as an integrative metabolic index. The tNAA/tCr ratio was consistently higher in males in the discovery sample and this finding was replicated across two independent young-adult samples (3T, n = 26; 7T, n = 27), with a widespread gray and white matter distribution. This tNAA/tCr ratio may link neuronal mitochondrial metabolism with cellular energy buffering, positioning it as a potential index of bioenergetic balance relevant for conditions showing both sex differences and altered neurometabolism, notably multiple sclerosis, Alzheimer disease, and psychosis. Together, these findings reveal a reproducible, distributed metabolic sexual dimorphism in the human brain, and underscore the importance of accounting for sex-specific neurometabolic profiles in studies of brain health and disease.

The hippocampus and amygdala form a tightly integrated circuit supporting memory-emotion integration and stress regulation, critically implicated in psychosis development. However, the maturation of the hippocampus-amygdala (HIP-AMY) complex as a functional unit remains poorly understood. 22q11.2 deletion syndrome (22q11DS), with increased risk of schizophrenia, provides a valuable model to study its neurodevelopmental trajectories. A prospective longitudinal cohort of 133 individuals with 22q11DS and 150 healthy controls (HC) underwent neuroimaging and psychiatric assessments approximately every three years. Resting-state fMRI data were analysed using a data-driven clustering approach to identify transient states of dynamic functional connectivity linked to the activation of specific ensembles of HIP-AMY nuclei. State occurrences over age were compared between 22q11DS and HC and between 22q11DS individuals with and without positive psychotic symptoms (PPS+ and PPS−). Seven HIP-AMY states were identified, three showing significant and one trend-level age-by-diagnosis interaction. Importantly, the occurrence of a CA3-centromedial amygdala driven state showing co-activation of limbic and thalamo-striatal salience hubs decreased over age in HC, but remained elevated in 22q11DS. This divergence was reflected within 22q11DS, with PPS− showing a decrease and PPS+ a modest increase. The persistence of this pattern over development may provide a dynamic signature of emergence of psychosis.