Neuroimaging studies have reported that chronic pain may be associated with brain functional changes and related molecular mechanisms. However, there are few studies in anterior shoulder pain (ASP). Thus, we aimed to assess the possible brain functional changes and their associations with neurotransmitter receptor maps in ASP patients. Resting-state functional magnetic resonance imaging data were obtained from 27 ASP patients and 20 healthy controls (HCs). Regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) methods were used to examine altered brain functions. JuSpace toolbox was employed for evaluating the spatial correlations between ReHo and fALFF changes and neurotransmitter receptor maps. Regression analysis was conducted to explore the associations between neuroimaging findings and clinical characteristics in ASP patients. Furthermore, we investigated reliable biomarkers to distinguish ASP patients from HCs using receiver operating characteristic (ROC) curve analysis. ASP patients had abnormal ReHo/fALFF in the middle temporal gyrus, putamen, caudate, pallidum, precentral gyrus, medial prefrontal cortex, precuneus, posterior cingulate cortex and inferior temporal gyrus. ReHo/fALFF alterations in ASP patients were associated with the serotonin, dopamine, GABA, choline, glutamate and norepinephrine neurotransmitter systems. Visual analog scale was positively correlated with ReHo in the right insula. Moreover, ROC analysis showed higher classification accuracy in the middle temporal gyrus, precentral gyrus and putamen. Our study investigated abnormal brain function and associated neurotransmitter receptor maps in ASP patients, which may contribute to improving our understanding of the pathophysiological mechanisms in ASP.
Metabolic health and socioeconomic environments may jointly shape neurodevelopment during adolescence, a sensitive period of brain maturation. This cross-sectional study investigated overall and neighborhood socioeconomic deprivation moderated associations between glycemic control and brain structure in youth. Data were analyzed from 705 healthy 10–13-year-olds participating in the Adolescent Brain and Cognitive Development (ABCD) Study® across 21 sites in the United States. Glycemic control was assessed using hemoglobin A1c (HbA1c), brain structure was evaluated via magnetic resonance imaging (MRI), and neighborhood deprivation was measured with the Area Deprivation Index (ADI). Mixed-effects models examined associations between HbA1c and brain structural measures while controlling for sociodemographic covariates, with additional analyses stratified by ADI tertiles. Higher HbA1c was associated with lower mean cortical thickness and smaller total cortical gray matter volume. Each one percent increase in HbA1c corresponded to a 0.024 mm reduction in mean cortical thickness and a 9,611 mm3 reduction in total cortical gray matter volume. Regionally, higher HbA1c was associated with thinner cortex and smaller gray matter volumes primarily within frontal, cingulate and occipital areas. Exploratory analysis found that higher HbA1c was associated with lower total cortical gray matter volume among youth living in medium and high ADI neighborhoods, but not low ADI neighborhoods, whereas higher HbA1c was associated with lower mean cortical thickness only among youth living in high ADI neighborhoods. These findings highlight the interplay between metabolic health and neighborhood deprivation, supporting a model in which socioeconomic disadvantage may magnify the neurodevelopmental impact of metabolic variation, even within the non-diabetic range.
Hypertension is a major modifiable vascular risk factor for cognitive decline. However, how regional gray matter (GM) alterations differ according to hypertension duration remains incompletely understood. We hypothesized that different brain regions would exhibit heterogeneous GMV profiles across hypertension-duration groups and that regional GMV alterations would be associated with cognitive performance. Structural MRI and cognitive data were obtained from 487 participants with hypertension and 165 normotensive controls. Participants with hypertension were stratified by disease duration (≤ 4, 5–11, and ≥ 12 years). Voxel-based morphometric analysis was used to identify whole-brain GMV alterations across groups. Regional associations with hypertension duration and cognitive performance were subsequently examined, adjusting for age, sex, total intracranial volume, and, where appropriate, education. Regression models further assessed whether GMV–cognition associations differed across hypertension-duration groups. Three cross-sectional duration-related GMV patterns were identified: early and relatively stable alterations, duration-sensitive alterations, and intermediate-to-long-duration alterations. Longer hypertension duration was associated with lower GMV in the right rectus, left middle temporal, and left angular gyri, and higher GMV in the bilateral putamen and right insula after FDR correction. Only greater left thalamic GMV remained associated with higher MoCA scores after correction. Interaction analyses suggested duration-group differences in GMV–cognition associations in the right insula and right precuneus. Hypertension was associated with heterogeneous, region-specific GMV alteration across duration groups rather than a uniform cumulative atrophy pattern. The direction and cognitive relevance of these alterations varied across regions, highlighting the importance of considering hypertension duration when evaluating brain structural alterations. Longitudinal studies are needed to clarify their temporal evolution.
Hippocampal hyperactivity, detected with mnemonic similarity task (MST) fMRI, is both a promising marker of risk and a probable driver of degeneration in Alzheimer’s disease (AD). However, implementation of such fMRI in interventional research is limited by long scan times and the absence of a framework for identifying prospective participants with hyperactivity who could be targeted with therapeutic approaches aimed at reducing this activity. We used multi-echo fMRI during the MST, an episodic memory task previously shown to engage hippocampal subfields CA3 and dentate gyrus (DG), to characterize activity profiles in 33 cognitively normal older adults. We compared MST-related CA3 and DG activation and behavioural performance across subsets of eight task runs. Behavioural and activation effects were equivalent for the first set of four runs (Runs-A) and the second set (Runs-B), suggesting that robust data can be obtained with four runs. Left and right CA3 + DG activation did not differ. We provide an exemplar framework for the derivation of a threshold for single-participant classification of elevated hippocampal activation as an indicator of AD risk in cognitively normal older individuals. Scalable ( 22 min) multi-echo MST fMRI robustly captures hippocampal activation and provides a framework for individual-level characterization of hippocampal function in cognitively normal older adults. This enables individualized detection of elevated hippocampal activation as a modifiable risk factor and may guide enrolment into prevention trials targeting preclinical AD.
To investigate hippocampal subfield volumes and resting-state functional connectivity (rsFC) in patients with axial spondyloarthritis (axSpA), and to assess their clinical relevance. In this cross-sectional study, 39 patients with axSpA and 41 healthy controls (HCs) underwent 3-T structural T1-weighted and resting-state functional MRI. Hippocampal subfields were segmented using FreeSurfer, and seed-based rsFC maps were computed for 12 subfields per hemisphere. Group differences were assessed with general linear models (FDR-corrected) for volumes and permutation-based family-wise error correction with threshold-free cluster enhancement for rsFC. Partial correlations adjusted for age, sex, and education tested associations between rsFC and clinical parameters (FDR-corrected). No hippocampal subfield volume differed significantly between groups after FDR correction, although patients with axSpA showed nominally larger right CA4 and bilateral GC-ML-DG volumes. Increased rsFC between the left presubiculum and left precentral gyrus/supplementary motor area (PreCG/SMA) was observed in patients relative to HCs (permutation-based FWER-corrected p < 0.05). Presubiculum–PreCG/SMA rsFC was negatively associated with overall back pain (partial r = -0.52, p = 0.001, FDR-corrected q = 0.028), the only association surviving FDR correction across all clinical parameters. No significant associations were observed with inflammatory markers or disease activity indices. axSpA is associated with hippocampal-motor cortical connectivity, with increased presubiculum–PreCG/SMA rsFC linked to lower back pain severity, whereas hippocampal subfield volumes are largely preserved. These findings support reconceptualizing axSpA as a systemic disease with measurable central nervous system involvement and pain-related network reorganization. Clinical trials register number: ChiCTR2500111024 (October 23th 2025).
