Transcriptomic and Macroscopic Architectures of Multimodal Covariance Network Reveal Molecular–Structural–Functional Co-alterations
Lin Jiang,
Yueheng Peng,
Runyang He,
Qingqing Yang,
Chanlin Yi,
Yuqin Li,
Bin Zhu,
Yajing Si,
Tao Zhang,
Bharat B. Biswal,
Dezhong Yao,
Lan Xiong,
Fali Li,
Peng Xu
Affiliations
Lin Jiang
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Yueheng Peng
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Runyang He
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Qingqing Yang
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Chanlin Yi
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Yuqin Li
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Bin Zhu
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Yajing Si
School of Psychology,
Xinxiang Medical University, Xinxiang 453003, China.
Tao Zhang
School of Science,
Xihua University, Chengdu 610039, China.
Bharat B. Biswal
Department of Biomedical Engineering,
New Jersey Institute of Technology, Newark, NJ, USA.
Dezhong Yao
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Lan Xiong
Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
Fali Li
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Peng Xu
The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation,
University of Electronic Science and Technology of China, Chengdu 611731, China.
Human cognition is usually underpinned by intrinsic structure and functional neural co-activation in spatially distributed brain regions. Owing to lacking an effective approach to quantifying the covarying of structure and functional responses, how the structural–functional circuits interact and how genes encode the relationships, to deepen our knowledge of human cognition and disease, are still unclear. Here, we propose a multimodal covariance network (MCN) construction approach to capture interregional covarying of the structural skeleton and transient functional activities for a single individual. We further explored the potential association between brain-wide gene expression patterns and structural–functional covarying in individuals involved in a gambling task and individuals with major depression disorder (MDD), adopting multimodal data from a publicly available human brain transcriptomic atlas and 2 independent cohorts. MCN analysis showed a replicable cortical structural–functional fine map in healthy individuals, and the expression of cognition- and disease phenotype-related genes was found to be spatially correlated with the corresponding MCN differences. Further analysis of cell type-specific signature genes suggests that the excitatory and inhibitory neuron transcriptomic changes could account for most of the observed correlation with task-evoked MCN differences. In contrast, changes in MCN of MDD patients were enriched for biological processes related to synapse function and neuroinflammation in astrocytes, microglia, and neurons, suggesting its promising application in developing targeted therapies for MDD patients. Collectively, these findings confirmed the correlations of MCN-related differences with brain-wide gene expression patterns, which captured genetically validated structural–functional differences at the cellular level in specific cognitive processes and psychiatric patients.
