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The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered. To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl's gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls. Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl's gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl's gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03). These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological agents for treating obsessive-compulsive disorder (OCD). However, because nearly half of patients show insufficient SSRI responses, serotonergic dysfunction in heterogeneous OCD patients should be investigated for precision medicine. We aimed to determine whether functional connectivity (FC) of the raphe nucleus (RN), the major source of most serotonergic neurons, was altered in OCD patients and could predict the SSRI response. A total of 102 medication-free OCD patients and 101 matched healthy control (HC) subjects participated in resting-state functional magnetic resonance imaging. Among them, 54 OCD patients were treated with SSRIs for 16 weeks, resulting in 26 responders and 28 nonresponders. Seed-based whole brain FC with the RN as a seed region was compared between the OCD and HC groups, as well as between SSRI responders and nonresponders. FC cluster values showing significant group differences were used to investigate factors correlated with symptomatic severity before treatment and predictive of SSRI response. Compared to HCs, OCD patients exhibited significantly larger FC between the RN and temporal cortices including the middle temporal gyrus (MTG), paracingulate gyrus, amygdala, hippocampus, putamen, thalamus, and brain stem. Greater RN-left MTG FC was positively correlated with OC symptom severity at baseline. In addition, larger FC of the RN-left MTG was also found in SSRI nonresponders compared to responders, which was a significant predictor of SSRI response after 16 weeks. The FC of RN may reflect the neurobiological underpinning of OCD and could aid future precision medicine as a differential brain-based biomarker.

The striatum and its cortical circuits play central roles in the pathophysiology of obsessive-compulsive disorder (OCD). The striatum is subdivided by cortical connections and functions; however, the anatomical aberrations in different cortico-striatal connections and coexisting microstructural anomalies in striatal subregions of OCD patients are poorly understood. Thus, we aimed to elucidate the aberrations in cortico-striatal white matter (WM) connectivity and the associated subregional microstructure of the striatum in patients with OCD. From diffusion tensor/kurtosis imaging of 107 unmedicated OCD patients and 110 matched healthy controls (HCs), we calculated the cortico-striatal WM connectivity and segmented the striatum using probabilistic tractography. For the segmented striatal subregions, we measured average diffusion kurtosis values, which represent microstructural complexity. Connectivity and mean kurtosis values in each cortical target and associated striatal subregions were compared between groups. We identified significantly reduced orbitofrontal WM connectivity with its associated striatal subregion in patients with OCD compared to that in HCs. However, OCD patients exhibited significantly increased caudal-motor and parietal connectivity with the associated striatal subregions. The mean kurtosis values of the striatal subregions connected to the caudal-motor and parietal cortex were significantly decreased in OCD patients. Our results highlighted contrasting patterns of striatal WM connections with the orbitofrontal and caudal-motor/parietal cortices, thus supporting the cortico-striatal circuitry imbalance model of OCD. We suggest that aberrations in WM connections and the microstructure of their downstream regions in the caudal-motor-/parietal-striatal circuits may underlie OCD pathophysiology and further provide potential neuromodulation targets for the treatment of OCD.

Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = −0.39, p = 0.034) and right (R = −0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.

While recent studies have explored the maintenance of the effect of meditation on stress resilience, the underlying neural mechanisms have not yet been investigated. The present study conducted a highly controlled residential study of a 4-day meditation intervention to investigate the brain functional changes and long-term effects of meditation on mindfulness and resilience. Thirty participants in meditation practice and 17 participants in a relaxation retreat (control group) underwent magnetic resonance imaging scans at baseline and post-intervention and completed the Cognitive and Affective Mindfulness Scale (CAMS) and Resilience Quotient Test (RQT) at baseline, post-intervention, and the 3-month follow-up. All participants showed increased CAMS and RQT scores post-intervention, but only the meditation group sustained the enhancement after 3 months. Resting-state functional connectivity (rsFC) between the left rostral anterior cingulate cortex (rACC) and the dorsomedial prefrontal cortex (dmPFC), precuneus, and angular gyrus was significantly increased post-intervention in the meditation group compared with the relaxation group. The changes in rACC-dmPFC rsFC mediated the relationship between the changes in the CAMS and RQT scores and correlated with the changes in the RQT score both immediately and at 3 months post-intervention. Our findings suggest that increased rACC-dmPFC rsFC meditation causes an immediate enhancement in resilience that is sustained. Since resilience is known to be associated with the preventative effect of various psychiatric disorders, the improvement in stress-related neural mechanisms may be beneficial to individuals at high clinical risk.

Increasing evidence indicates that multiple structures in the brain are associated with intelligence and cognitive function at the network level. The association between the grey matter (GM) structural network and intelligence and cognition is not well understood. We applied a multivariate approach to identify the pattern of GM and link the structural network to intelligence and cognitive functions. Structural magnetic resonance imaging was acquired from 92 healthy individuals. Source-based morphometry analysis was applied to the imaging data to extract GM structural covariance. We assessed the intelligence, verbal fluency, processing speed, and executive functioning of the participants and further investigated the correlations of the GM structural networks with intelligence and cognitive functions. Six GM structural networks were identified. The cerebello-parietal component and the frontal component were significantly associated with intelligence. The parietal and frontal regions were each distinctively associated with intelligence by maintaining structural networks with the cerebellum and the temporal region, respectively. The cerebellar component was associated with visuomotor ability. Our results support the parieto-frontal integration theory of intelligence by demonstrating how each core region for intelligence works in concert with other regions. In addition, we revealed how the cerebellum is associated with intelligence and cognitive functions.

The study of brain differences across Eastern and Western populations provides vital insights for understanding potential cultural and genetic influences on cognition and mental health. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter (WM) connectivity and brain tissue microstructure across different populations. However, a comprehensive investigation into WM fiber tracts between Eastern and Western populations is challenged due to the lack of a cross-population WM atlas and the large site-specific variability of dMRI data. This study presents a dMRI tractography atlas, namely the East-West WM Atlas , for concurrent WM mapping between Eastern and Western populations and creates a large, harmonized dMRI dataset (n=306) based on the Human Connectome Project and the Chinese Human Connectome Project. The curated WM atlas, as well as subject-specific data including the harmonized dMRI data, the whole brain tractography data, and parcellated WM fiber tracts and their diffusion measures, are publicly released. This resource is a valuable addition to facilitating the exploration of brain commonalities and differences across diverse cultural backgrounds.

Psychotic symptoms typically emerge in adolescence. Age-associated thalamocortical connectivity differences in psychosis remain unclear. We analyzed diffusion-weighted imaging data from 1254 participants 8–23 years old (typically developing (TD):N = 626, psychosis-spectrum (PS): N = 329, other psychopathology (OP): N = 299) from the Philadelphia Neurodevelopmental Cohort. We modeled thalamocortical tracts using deterministic fiber tractography, extracted Q-Space Diffeomorphic Reconstruction (QSDR) and diffusion tensor imaging (DTI) measures, and then used generalized additive models to determine group and age-associated thalamocortical connectivity differences. Compared to other groups, PS exhibited thalamocortical reductions in QSDR global fractional anisotropy (GFA, p-values range = 3.0 × 10–6–0.05) and DTI fractional anisotropy (FA, p-values range = 4.2 × 10–4–0.03). Compared to TD, PS exhibited shallower thalamus-prefrontal age-associated increases in GFA and FA during mid-childhood, but steeper age-associated increases during adolescence. TD and OP exhibited decreases in thalamus-frontal mean and radial diffusivities during adolescence; PS did not. Altered developmental trajectories of thalamocortical connectivity may contribute to the disruptions observed in adults with psychosis.

While remission from clinical high risk (CHR) for psychosis is a favorable outcome, it is not well characterized over time. To examine remission incidence, prevalence, and stability, and their association with demographic, clinical, medication, and cognitive variables, comparing 2 commonly used definitions. This cohort study examined data from individuals aged 12 to 30 years at CHR in the North American Prodromal Longitudinal Study 3, collected from 9 sites across the US from February 2015 to November 2018. Statistical analyses were conducted between January 2023 and May 2025. CHR status using 2 definitions: (1) a symptoms-only definition based on the positive symptoms from the Scale of Prodromal Symptoms and (2) a symptoms-and-function definition based on positive symptoms and the modified Global Assessment of Functioning. The primary outcomes were remission incidence, prevalence, and stability for 7 follow-up visits over 2 years. Associations of remission with age, sex at birth, race, antipsychotic and antidepressant medication, history of trauma, and cognitive performance were determined using mixed-effects logistic regression. The sample included 692 individuals (mean [SD] age, 18.7 [4.1] years; 319 female [46%]) at baseline, with 614 completing at least 1 follow-up. For the symptoms-only definition, 7% (95% CI, 5%-10%) met remission criteria after 2 months, 34% (95% CI, 31%-38%) met remission criteria at least once during the study, and 26% (95% CI, 22%-29%) met criteria at their last visit. The symptoms-and-function definition was associated with a lower remission incidence and prevalence, with 4% (95%CI, 2%-5%) meeting remission criteria after 2 months, 21% (95% CI, 18%-24%) meeting criteria at least once, and 15% (95% CI, 13%-18%) meeting criteria at their last visit. Under the symptoms-only definition, 83 of 153 individuals at CHR with at least 1 follow-up after remission (54%; 95% CI, 46%-62%) were stable remitters. Under the symptoms-and-function definition, 43 of 91 individuals (47%; 95% CI, 37%-58%) were stable remitters. The chance of staying in remission rose drastically once a person had more than 1 previous recorded remission visit. Higher functioning was associated with higher likelihood of remission (current score for symptoms only: OR, 1.04; 95% CI, 1.01-1.08; current score for symptoms and function: OR, 1.08; 95% CI, 1.02-1.14). More symptoms at baseline was associated with a lower likelihood of remission (general symptoms for symptoms only: OR, 0.77; 95% CI, 0.70-0.84; general symptoms for symptoms and function: OR, 0.80; 95% CI, 0.69-0.92). These findings suggest that CHR status is a dynamic state and that vulnerability can persist even after functional remission. Hence, continued follow-up and facilitated reengagement with clinical services after remission are essential.

Background 22q11.2 Deletion Syndrome (22q11DS) is considered to be a promising cohort to explore biomarkers of schizophrenia risk based on a 30 % probability of developing schizophrenia in adulthood. In this study, we investigated abnormalities in the microstructure of white matter in adolescents with 22q11DS and their specificity to prodromal symptoms of schizophrenia. Methods Diffusion Magnetic Resonance Imaging (dMRI) data were acquired from 50 subjects with 22q11DS (9 with and 41 without prodromal psychotic symptoms), and 47 matched healthy controls (mean age 18 +/−2 years). DMRI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and compared between groups using the Tract Based Spatial Statistics (TBSS) method. Additionally, correlations between dMRI measures and scores on positive symptoms were performed. Results Reductions in MD, AD and RD (but not FA) were found in the corpus callosum (CC), left and right superior longitudinal fasciculus (SLF), and left and right corona radiata in the entire 22q11DS group. In addition, the 22q11DS subgroup with prodromal symptoms showed reductions in AD and MD, but no changes in RD when compared to the non-prodromal subgroup, in CC, right SLF, right corona radiata and right internal capsule. Finally, AD values in these tracts correlated with the scores on the psychosis subscale. Conclusion Microstructural abnormalities in brain white matter are present in adolescent subjects with prodromal psychotic symptoms .