Zang YF papers

Biol Psychiatry. 2026 Aug 17:S0006-3223(26)01470-8. doi: 10.1016/j.biopsych.2026.07.025. Online ahead of print.

ABSTRACT

BACKGROUND: Response to repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder (MDD) varies substantially. Normative modeling of functional connectivity can disentangle disease-related pathophysiology from demographic variability, potentially refining personalized targeting.

METHODS: We constructed a normative model of subgenual anterior cingulate cortex (sgACC)-dorsolateral prefrontal cortex (DLPFC) functional connectivity using exclusively healthy controls (HCs; DIRECT dataset, n = 1,313). Individual Z-score maps were generated for 1,583 MDD patients; the DLPFC voxel with the most negative Z-score defined the functional connectivity normative deviation (FCND)-guided target. Clinical utility was tested in two independent rTMS cohorts (active: n=39, sham: n=23; accelerated iTBS: n=15) by correlating Euclidean distance from the stimulation site to the FCND target with improvement. We explored whether Z-score normalization statistically mediated this relationship.

RESULTS: In the DIRECT dataset, patients with MDD showed significantly more negative values for the most negative Z-score (Min Z-score) than HCs, and this Min Z-score correlated negatively with depressive symptom severity, as measured by the 17-item Hamilton Depression Rating Scale. In the YT active group, shorter distance to the FCND-guided target was associated with greater clinical improvement, while no association was observed in the sham group. This association was also significant in the aiTBS dataset. Exploratory mediation analysis revealed an indirect effect statistically consistent with the hypothesis that distance influences improvement through Z-score normalization in the active group, with a directionally consistent trend in the iTBS dataset.

CONCLUSION: The FCND-guided target framework provides a personalized, mechanism-informed strategy for precision neuromodulation in MDD.

PMID:42607914 | DOI:10.1016/j.biopsych.2026.07.025

Neuroimage. 2026 Aug 7:122160. doi: 10.1016/j.neuroimage.2026.122160. Online ahead of print.

ABSTRACT

Functional magnetic resonance imaging (fMRI) is the most commonly used technique for non-invasive exploration of human cognition and neuroscience. Conventional T2*-weighted single-echo resting-state fMRI (SE-rfMRI) is limited by signal loss in regions prone to susceptibility artifacts and inseparable confounding from non-neuronal baseline (i.e., initial signal intensity S0) fluctuations. While multi-echo optimally combined rfMRI (ME-OC) effectively mitigates signal loss, confounding from S0 fluctuations remains unaddressed. Here, we leverage quantitative T2* fluctuation from ME-rfMRI to derive intrinsic functional metrics that are biophysically cleaner and more robust. Across both cortical and subcortical brain regions, we systematically evaluated the test-retest reliability and functional validity of two key local metrics, amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo), derived from our proposed method against those from conventional SE-rfMRI and ME-OC. In subcortical regions, T2*-derived metrics showed the highest mean ICCs among the three signal representations for both ALFF (ICC = 0.67, 0.66, and 0.54) and ReHo (ICC = 0.73, 0.67, and 0.63) for T2* fluctuation, ME-OC, and SE-rfMRI, respectively. A similar regionally selective pattern was observed in cortical areas susceptible to magnetic field inhomogeneities, including the orbitofrontal cortex (ALFF ICC = 0.87, 0.75, and 0.82), insula (0.83, 0.61, and 0.71), and temporal pole (0.80, 0.73, and 0.79) for T2* fluctuation, ME-OC, and SE-rfMRI, respectively. In terms of functional validity, ALFF from T2* fluctuation uniquely revealed significant condition-related differences in the right putamen, inferior frontal gyrus, and suborbital sulcus, which both ME-OC and SE-rfMRI failed to detect. Together, our findings suggest that quantitative T2*-derived metrics may provide a reliable and more biophysically specific characterization of intrinsic fMRI signal fluctuations, particularly in subcortical and susceptibility-prone cortical regions, and may complement conventional approaches in future research applications.

PMID:42567430 | DOI:10.1016/j.neuroimage.2026.122160

Biomed Environ Sci. 2026 Jun 20;39(6):641-651. doi: 10.3967/bes2026.044.

ABSTRACT

OBJECTIVE: Dyslipidemia has been linked to increased arterial stiffness. However, few studies have comprehensively assessed the cumulative effects of lipid profiles on arterial stiffness.

METHODS: Based on the initial recruitment of 7,134 participants from the China-PAR cohort, we finally included 6,717 participants with up to four repeated lipid measurements between baseline (1998-2008) and the most recent follow-up (2018-2020). Cumulative exposure to total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and remnant cholesterol (RC) was estimated using the area under the curve method. Arterial stiffness was measured in 2018-2020 using the arterial pressure-volume index (API) and the arterial velocity-pulse index (AVI), which reflect the stiffness of peripheral and central arteries, respectively.

RESULTS: Participants (mean age: 51.4 ± 10.3 years) included 2,598 men (38.68%), with a mean cumulative lipid exposure duration of 14.02 years. Cumulative TG, HDL-C, and RC were significantly associated with API levels, with adjusted β s (95% confidence intervals [ CIs]) of 2.31 (1.53, 3.08), -1.14 (-2.24, -0.04), and 2.39 (1.52, 3.25), respectively, for the highest quartile compared with the lowest quartile. Restricted cubic splines showed nonlinear associations of cumulative TG and RC with API and a linear association for HDL-C (all P < 0.05). For AVI, only cumulative HDL-C showed a significant inverse association, with an adjusted β (95% CI) of -1.16 (-2.12, -0.21) for the highest quartile, and a nonlinear association was observed ( P < 0.05).

CONCLUSION: Long-term cumulative TG and RC were associated with increased peripheral arterial stiffness but not central arterial stiffness, and cumulative HDL-C was negatively associated with both peripheral and central arterial stiffness. These findings underscore the importance of long-term TG and RC control along with maintaining adequate HDL-C levels.

PMID:42417233 | DOI:10.3967/bes2026.044