Most recent paper

Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Aug 13:S2451-9022(25)00248-4. doi: 10.1016/j.bpsc.2025.07.013. Online ahead of print.

ABSTRACT

BACKGROUND: Negative symptom severity predicts functional outcome and quality of life in people with psychosis. However, negative symptoms are poorly responsive to medication, and existing literature has not converged on their neurobiological basis. Previous work in small schizophrenia samples has observed that lower cerebellar-dorsolateral prefrontal cortex (DLPFC) connectivity is associated with higher negative symptom severity and that increasing cerebellar-DLPFC connectivity with neuromodulation reduces negative symptoms. We extended this finding by testing associations between cerebellar-DLPFC connectivity, negative symptoms, and cognitive performance in a large sample of individuals with psychosis.

METHODS: Individuals with psychosis spectrum disorders (n=260) underwent resting-state fMRI and clinical characterization using the Positive and Negative Symptoms Scale and the Screen for Cognitive Impairment in Psychiatry. Using a previously identified cerebellar region as a seed, we measured connectivity to the DLPFC and regressed connectivity against negative symptom severity, covarying for age, sex, and scanner. We then tested if cognitive performance indirectly affected the relationship between connectivity and negative symptom severity.

RESULTS: Across the psychosis spectrum, higher cerebellar-DLPFC connectivity was associated with lower negative symptom severity (r=-0.17, p=.007). This connectivity-negative symptoms relationship was not affected by psychosis subtype or duration of illness. Better delayed verbal learning was associated with higher cerebellar-DLPFC connectivity (r=.13, p=.034) and had a significant indirect effect on the relationship between connectivity and negative symptoms.

CONCLUSIONS: Our results extend relationships between cerebellar-DLPFC connectivity, negative symptom severity, and cognitive performance across the psychosis spectrum. Larger neuromodulation studies should test if increasing cerebellar-DLPFC connectivity reduces negative symptoms in psychotic disorders.

PMID:40816655 | DOI:10.1016/j.bpsc.2025.07.013

Brain Stimul. 2025 Aug 13;18(5):1539-1550. doi: 10.1016/j.brs.2025.08.003. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory cranial-cervical dystonia (CCD or Meige syndrome). However, clinical responses vary substantially across individuals, likely due to differences in electrode placement and modulation of target neural circuits.

METHODS: We retrospectively analyzed 51 patients with CCD treated with STN-DBS at a single center. Pre- and postoperative imaging was used to reconstruct electrode locations and model patient-specific electric fields. We then performed (i) voxel-wise sweet spot mapping to identify optimal stimulation sites, (ii) fiber filtering using normative tractography to determine white matter pathways associated with clinical improvement, and (iii) network mapping based on resting-state fMRI to identify functional connectivity patterns predictive of DBS response.

RESULTS: Voxel-wise correlation analysis revealed that the optimal stimulation localized to the STN motor subregion (R = 0.52, p < 0.001). Normative structural connectivity analysis showed that symptom improvement correlated strongly with modulation of fibers projecting to the cranial and cervical regions of sensorimotor cortex (R = 0.52, p < 0.001) and sensorimotor-associated basal ganglia pathways (R = 0.62, p < 0.001). Functional network mapping further revealed connectivity to the sensorimotor cortex as significantly associated with clinical improvement (R = 0.43, p = 0.002).

CONCLUSION: These findings inform refinement of STN targeting strategies in DBS for CCD. The involvement of cranial and cervical sensorimotor regions highlights the importance of symptom-based dystonia classification for individualized neuromodulation approaches.

PMID:40816470 | DOI:10.1016/j.brs.2025.08.003

J Affect Disord. 2025 Aug 13:120063. doi: 10.1016/j.jad.2025.120063. Online ahead of print.

ABSTRACT

BACKGROUND: Studies have demonstrated an association between cognitive decline and body mass index (BMI). However, the neural mechanisms that underlie this association remain unclear. This study aimed to investigate the relationship between BMI, cognitive function, and brain structural-functional connectivity (SC-FC) coupling.

METHODS: This study included 490 healthy subjects undergoing resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) scans and cognitive function tests. Structural connectivity (SC) was constructed using DTI, and functional connectivity (FC) was constructed using rs-fMRI. The SC-FC coupling was constructed using Spearman's correlation between the SC and FC. Linear regression analyses were conducted to investigate the associations of BMI and SC-FC with cognitive function. Finally, mediation analysis was performed to test whether SC-FC coupling mediated the relationship between BMI and cognitive function.

RESULTS: BMI was positively correlated with Fluency, TMT-A, and WMS-III-SS, while showing negative associations with BACS-SC, BVMT-R, and NAB-Mazes (all p < 0.05). Higher BMI was linked to increased SC-FC in the right caudal hippocampus (cHipp; β = 0.19) and middle temporal gyrus (MTG; β = 0.19). Mediation analyses showed that the positive effect of BMI on the right cHipp SC-FC mediated its negative impact on Fluency (45.43 % mediated); the influence of BMI on right cHipp SC-FC mediated poorer performance on NAB-Mazes (85.25 % mediated); and the positive effect of BMI on right MTG SC-FC enhanced NAB-Mazes performance (69.12 % mediated).

CONCLUSIONS: BMI influences cognitive function through its effects on brain SC-FC coupling, with distinct regional SC-FC patterns mediating both detrimental and beneficial cognitive outcomes.

PMID:40816371 | DOI:10.1016/j.jad.2025.120063

Psychiatry Res Neuroimaging. 2025 Aug 10;352:112046. doi: 10.1016/j.pscychresns.2025.112046. Online ahead of print.

ABSTRACT

BACKGROUND: Emerging evidence suggests that alcohol use disrupts large-scale brain network interactions, particularly within the triple network model-comprising the Salience Network (SN), Default Mode Network (DMN), and Frontoparietal Network (FPN). However, few studies have examined how these connectivity alterations vary across the full spectrum of alcohol consumption, especially using ultra-high-field imaging and data-driven approaches. This study leverages 7 Tesla resting-state fMRI and multivariate pattern analysis (MVPA) to characterize distinct brain connectivity patterns across heavy, moderate, and non-drinking adults, aiming to identify neural signatures that differentiate alcohol use severity levels.

METHODS: We analyzed resting-state functional connectivity data from 69 adults (Mean age - 28.96; SD - 3.49; Range: 22-36) [41M, 28F] drawn from the Human Connectome Project. Participants were stratified into three matched groups (n=23 each): heavy alcohol users (HA), moderate users (MA), and non-users (NA). Alcohol consumption was quantified using the Achenbach Self-Report (ASR) and the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Functional connectivity within and between the SN, DMN, and FPN was assessed using both traditional seed-based analyses and MVPA. Between-group differences (HA vs. MA, HA vs. NA, MA vs. NA) were evaluated using Bonferroni corrected statistical tests.

RESULTS: Compared to non-users, alcohol users showed widespread increases in both intra- and inter-network functional coupling. The most striking differences emerged between HA and MA groups, with MVPA revealing unique hyperconnectivity signatures that distinguished these subgroups. Notably, HA individuals demonstrated reduced connectivity between the superior lateral occipital cortex and the precuneus, and hypoconnectivity between the orbitofrontal cortex and language-related regions. No significant sex differences were observed.

CONCLUSIONS: This study provides the first evidence from 7T MRI and MVPA that distinct functional connectivity profiles can discriminate levels of alcohol use severity in adults. The observed triple network hyperconnectivity-particularly between heavy and moderate users-may reflect early neurofunctional reorganization or compensatory mechanisms preceding the onset of alcohol use disorder. These findings advance the search for neurobiological markers of risk and resilience along the continuum of alcohol use and underscore the utility of high-field neuroimaging coupled with machine learning in addiction neuroscience.

PMID:40816048 | DOI:10.1016/j.pscychresns.2025.112046

Neuroimage Clin. 2025 Aug 6;48:103862. doi: 10.1016/j.nicl.2025.103862. Online ahead of print.

ABSTRACT

BACKGROUND: High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) serves as an effective treatment for major depression and other psychiatric disorders. Despite its growing clinical application, the neural mechanisms by which prefrontal rTMS exerts its therapeutic effects remain incompletely understood. To address this gap, we investigated the immediate blood-oxygen-level-dependent (BOLD) activity during 600 stimuli of left DLPFC 10 Hz rTMS in healthy individuals using interleaved TMS-fMRI.

METHODS: In a crossover design, 17 healthy subjects received 10 Hz rTMS (60 trains with 9-second intertrain intervals) over the left DLPFC at 40 % and 80 % of their resting motor threshold (rMT) inside the MR scanner.

RESULTS: 10 Hz rTMS over the left DLPFC elicited BOLD responses in prefrontal regions, cingulate cortex, insula, striatum, thalamus, as well as auditory and somatosensory areas. Notably, our findings revealed that 10 Hz rTMS effects were lateralized towards the contralateral (right) DLPFC. Dose-response effects between 40 % vs. 80 % rMT were exclusively observed in the hippocampus.

CONCLUSIONS: The 10 Hz rTMS protocol used in this study induced distinct target engagement and propagation patterns in the prefrontal cortex. These patterns differ from our previous interleaved TMS-fMRI findings using 600 stimuli of left DLPFC intermittent theta burst stimulation (iTBS) at the same intensities. Thus, interleaved TMS-fMRI emerges as a valuable method for comparing clinical prefrontal rTMS protocols regarding their immediate effect on brain circuits in order to differentiate their action mechanisms and to potentially inform clinical applications.

PMID:40816029 | PMC:PMC12362399 | DOI:10.1016/j.nicl.2025.103862