Transcranial direct current stimulation and lesions hierarchically reorganize brain network dynamics with biological annotations

Mapping human brain function based on neuromodulation and lesions could reorganize brain network dynamics and uncover causal relationships with behaviors or symptoms. However, the principles of reorganization, neural mechanisms, and clinical implications underlying brain network dynamics in response to such modulations remain unclear. Here, we leveraged large-scale fMRI data and perturbation approaches to modulate brain network dynamics, investigating their associations with multi-level micro-architectural profiles including neurotransmitter receptors and transporters, cell types, laminar differentiation, microstructure, cortical expansion, and metabolism. We found that neuromodulation and lesions modulating the prefrontal and motor cortices led to distinct and opposing reorganizations in the topographic distribution of network dynamics along the sensorimotor-association hierarchy. Moreover, we observed a predominant co-localization between the reorganizations and micro-architectural properties, particularly neurotransmitter profiles. Behavioral analyses showed that the network dynamics of bilateral motor regions were associated with the motor functions of patients with lesions. These findings offer insights into the hierarchical reorganizational principle, cortical plasticity, and neurobiological basis underlying network dynamics, and potentially guide the development of alternative treatment approaches for complex brain disorders.