Neuroimaging & Brain Connectivity

Structural, functional and diffusion MRI of psychiatric illness, including brain-age modelling of progressive change across the course of schizophrenia and mood disorders.

         Identifying key brain pathology in bipolar and unipolar depression using a region-specific brain aging trajectories approach: Insights from the Taiwan Aging and Mental Illness Cohort          Investigating sex-related differences in brain structure and function in bipolar I disorder using multimodal MRI          Investigating brain aging trajectory deviations in different brain regions of individuals with schizophrenia using multimodal magnetic resonance imaging and brain-age prediction: a multicenter study   

25 publications

2026

Assessing glymphatic function in schizophrenia and mood disorders: Insights from a diffusion tensor image along the perivascular space (DTI-ALPS) and neuroanatomical correlations

Zhu JD, Liao DL, Lin CP, Yang AC, Tsai HJ, … Tsai SJ (9 authors). Psychiatry and clinical neurosciences80(3):215-223.

doi:10.1111/pcn.70016

These findings support its potential as an indirect biomarker of neurobiological alterations.

2025

Cognitive impairment and associated white matter organization abnormalities across the illness course of schizophrenia

Shen CL, Tsai SJ, Lin CP, Yang AC. European archives of psychiatry and clinical neuroscience.

PDF doi:10.1007/s00406-025-02161-2

Our findings suggested active cognitive rehabilitation to patients with schizophrenia throughout the course of illness may be warranted.

Senior author

Identifying key brain pathology in bipolar and unipolar depression using a region-specific brain aging trajectories approach: Insights from the Taiwan Aging and Mental Illness Cohort

Zhu JD, Chi IJ, Hsu HY, Tsai SJ, Yang AC. Psychological medicine55:e253.

Full text · PMC doi:10.1017/S0033291725101517

These findings highlight the potential of brain aging trajectories as biomarkers for BD and MDD, offering insights into distinct and overlapping neuroanatomical changes.

Senior authorHigh impact

2024

Exploring timescale-specific functional brain networks and their associations with aging and cognitive performance in a healthy cohort without dementia

Tsai WX, Tsai SJ, Lin CP, Huang NE, Yang AC. NeuroImage289:120540.

doi:10.1016/j.neuroimage.2024.120540

These results underscore the importance of exploring timescales of BOLD signals when constructing FBN and highlight the relevance of specific intrinsic FBNs to aging and cognitive performance.

Senior authorHigh impact

Investigating sex-related differences in brain structure and function in bipolar I disorder using multimodal MRI

Lee MY, Zhu JD, Tsai HJ, Tsai SJ, Yang AC. BMC psychiatry24(1):855.

Full text · PMC doi:10.1186/s12888-024-06228-7

Our findings revealed a noteworthy sex-by-diagnosis interaction, with male individuals with bipolar I disorder displaying larger gray matter volume and altered functional connectivity in the limbic system compared to female individuals with bipolar I disorder and healthy participants.

Senior author

2023

Exploring the role of hub and network dysfunction in brain connectomes of schizophrenia using functional magnetic resonance imaging

Chan YE, Tsai SJ, Chern Y, Yang AC. Frontiers in psychiatry14:1305359.

Full text · PMC doi:10.3389/fpsyt.2023.1305359

Pair-wise brain regions with significantly different functional connectivity among the two groups were identified and further analyzed for their concurrent ratio of connectomic differences with another solitary brain region (single-FC dysfunction) or dynamically interconnected brain network (network-FC dysfunction).

Senior author

Investigating brain aging trajectory deviations in different brain regions of individuals with schizophrenia using multimodal magnetic resonance imaging and brain-age prediction: a multicenter study

Zhu JD, Wu YF, Tsai SJ, Lin CP, Yang AC. Translational psychiatry13(1):82.

Full text · PMC doi:10.1038/s41398-023-02379-5

Our findings provided more insights into schizophrenia neuropathology.

Senior authorHigh impact

Right-side frontal-central cortical hyperactivation before the treatment predicts outcomes of antidepressant and electroconvulsive therapy responsivity in major depressive disorder

Tsai HJ, Yang WC, Tsai SJ, Lin CH, Yang AC. Journal of psychiatric research161:377-385.

doi:10.1016/j.jpsychires.2023.03.023

Our findings indicated that pre-treatment, right-side cortical hyperactivation is associated with poor outcomes of antidepressant-based or ECT-based treatment in major depression.

Senior author

2021

Differential Patterns of Gyral and Sulcal Morphological Changes During Normal Aging Process

Lin HY, Huang CC, Chou KH, Yang AC, Lo CZ, … Lin CP (7 authors). Frontiers in aging neuroscience13:625931.

Full text · PMC doi:10.3389/fnagi.2021.625931

Our findings show that comparing to gyri, the sulcal thinning is the most prominent pattern during the aging process, and the gyrification of pial and white matter surfaces were also affected differently, which implies the vulnerability of functional segregation during aging.

2020

Age-related changes in the association of resting-state fMRI signal variability and global functional connectivity in non-demented healthy people

Xie W, Peng CK, Shen J, Lin CP, Tsai SJ, … Yang AC (8 authors). Psychiatry research291:113257.

doi:10.1016/j.psychres.2020.113257

Research suggests that the aging relates to variability of resting-state fMRI (rs-fMRI) signal and the functional connectivity.

Senior author

Beyond the disconnectivity hypothesis of schizophrenia

Rolls ET, Cheng W, Gilson M, Gong W, Deco G, … Feng J (11 authors). Cerebral cortex (New York, N.Y. : 1991)30(3):1213-1233.

doi:10.1093/cercor/bhz161

To go beyond the disconnectivity hypothesis of schizophrenia, directed (effective) connectivity was measured between 94 brain regions, to provide evidence on the source of the changes in schizophrenia and a mechanistic model.

High impact

Functional, Anatomical, and Morphological Networks Highlight the Role of Basal Ganglia-Thalamus-Cortex Circuits in Schizophrenia

Zhao W, Guo S, Linli Z, Yang AC, Lin CP, Tsai SJ. Schizophrenia bulletin46(2):422-431.

Full text · PMC doi:10.1093/schbul/sbz062

These findings provide direct evidence for the disconnection hypothesis of schizophrenia, suggesting that abnormalities in the basal ganglia-thalamus-cortex circuit can be used as a biomarker of schizophrenia.

High impact

Topographic diversity of structural connectivity in schizophrenia

Ruan H, Luo Q, Palaniyappan L, Lu W, Huang CC, … Feng J (11 authors). Schizophrenia research215:181-189.

doi:10.1016/j.schres.2019.10.034

These findings suggest a highly individualized pattern of structural dysconnectivity underlies the heterogeneity of schizophrenia, but these disruptions likely converge on an emergent common pathway to generate the clinical phenotype of the disorder.

Transdiagnostic and Illness-Specific Functional Dysconnectivity Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Huang CC, Luo Q, Palaniyappan L, Yang AC, Hung CC, … Robbins TW (13 authors). Biological psychiatry. Cognitive neuroscience and neuroimaging5(5):542-553.

doi:10.1016/j.bpsc.2020.01.010

These findings suggest that prominent psychiatric disorders share common impairments, possibly linked to perception and motor output, as well as unique dysconnectivity profiles that hypothetically mediate the more distinctive features of the disorder-specific psychopathology.

High impact

2019

A powerful and efficient multivariate approach for voxel-level connectome-wide association studies

Gong W, Cheng F, Rolls ET, Lo CZ, Huang CC, … Feng J (9 authors). NeuroImage188:628-641.

doi:10.1016/j.neuroimage.2018.12.032

To demonstrate the utility of sKPCR for real data analysis, we have also compared sKPCR with the above methods based on the identification of voxel-wise differences between schizophrenic patients and healthy controls in four independent rsfMRI datasets.

High impact

2018

Callosal and subcortical white matter alterations in schizophrenia: A diffusion tensor imaging study at multiple levels

Zhao W, Guo S, He N, Yang AC, Lin CP, Tsai SJ. NeuroImage. Clinical20:594-602.

Full text · PMC doi:10.1016/j.nicl.2018.08.027

We replicated these findings using an automated anatomical labeling atlas to define the network node.

Effective Connectivity in Depression

Rolls ET, Cheng W, Gilson M, Qiu J, Hu Z, … Feng J (16 authors). Biological psychiatry. Cognitive neuroscience and neuroimaging3(2):187-197.

doi:10.1016/j.bpsc.2017.10.004

Moreover, we show how the approach can be used to measure the differences in effective connectivity between different groups of individuals, using as an example effective connectivity in the healthy brain and in individuals with depression.

High impact

Frequency and amplitude modulation of resting-state fMRI signals and their functional relevance in normal aging

Yang AC, Tsai SJ, Lin CP, Peng CK, Huang NE. Neurobiology of aging70:59-69.

doi:10.1016/j.neurobiolaging.2018.06.007

These findings indicate that resting-state fMRI signal modulations are dynamic during the normal aging process.

First author

Functional brain lateralization in schizophrenia based on the variability of resting-state fMRI signal

Xie W, Peng CK, Huang CC, Lin CP, Tsai SJ, Yang AC. Progress in neuro-psychopharmacology & biological psychiatry86:114-121.

doi:10.1016/j.pnpbp.2018.05.020

These results provide further evidence that abnormal variability and lateralization exist in schizophrenia patients, and abnormality in fusiform, lingual and inferior temporal could have potential help to identify the dysfunctional brain lateralization in schizophrenia.

Senior authorHigh impact

Functional connectivity of the human amygdala in health and in depression

Cheng W, Rolls ET, Qiu J, Xie X, Lyu W, … Feng J (14 authors). Social cognitive and affective neuroscience13(6):557-568.

Full text · PMC doi:10.1093/scan/nsy032

To analyse the functioning of the amygdala in depression, we performed the first voxel-level resting state functional-connectivity neuroimaging analysis of depression of voxels in the amygdala with all other voxels in the brain, with 336 patients with major depressive disorder and 350 controls.

Increased functional connectivity of the posterior cingulate cortex with the lateral orbitofrontal cortex in depression

Cheng W, Rolls ET, Qiu J, Xie X, Wei D, … Feng J (13 authors). Translational psychiatry8(1):90.

Full text · PMC doi:10.1038/s41398-018-0139-1

To analyze the functioning of the posterior cingulate cortex (PCC) in depression, we performed the first fully voxel-level resting state functional-connectivity neuroimaging analysis of depression of the PCC, with 336 patients with major depressive disorder and 350 controls.

High impact

Nonlinear pattern of the emergence of white matter hyperintensity in healthy Han Chinese: an adult lifespan study

Huang CC, Yang AC, Chou KH, Liu ME, Fang SC, … Lin CP (8 authors). Neurobiology of aging67:99-107.

doi:10.1016/j.neurobiolaging.2018.03.012

Our findings support that the changes in WMH volume in the healthy population follow a nonlinear pattern with age, especially in PVWMH.

2016

Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression

Cheng W, Rolls ET, Qiu J, Liu W, Tang Y, … Feng J (17 authors). Brain : a journal of neurology139(Pt 12):3296-3309.

doi:10.1093/brain/aww255

The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects.

High impact

The Association of Aging with White Matter Integrity and Functional Connectivity Hubs

Yang AC, Tsai SJ, Liu ME, Huang CC, Lin CP. Frontiers in aging neuroscience8:143.

Full text · PMC doi:10.3389/fnagi.2016.00143

These results support the compensatory hypothesis of neurocognitive aging theory and reveal the DTI-fMRI relationship associated with normal aging.

First author

2015

Functional Connectivity Density Mapping of Depressive Symptoms and Loneliness in Non-Demented Elderly Male

Lan CC, Tsai SJ, Huang CC, Wang YH, Chen TR, … Yang AC (9 authors). Frontiers in aging neuroscience7:251.

Full text · PMC doi:10.3389/fnagi.2015.00251

Loneliness is associated with FCD changes in bilateral lingual gyri that are known to be important in social cognition.

Senior author