Anatomical and Functional Connectivity of Critical Deep Brain Structures and Their Potential Clinical Application in Brain Stimulation

Subcortical structures, such as the hippocampus, amygdala, and nucleus accumbens (NAcc), play crucial roles in human cognitive, memory, and emotional processing, chronic pain pathophysiology, and are implicated in various psychiatric and neurological diseases. Interventions modulating the activities of these deep brain structures hold promise for improving clinical outcomes. Recently, non-invasive brain stimulation (NIBS) has been applied to modulate brain activity and has demonstrated its potential for treating psychiatric and neurological disorders. However, modulating the above deep brain structures using NIBS may be challenging due to the nature of these stimulations. This study attempts to identify brain surface regions as source targets for NIBS to reach these deep brain structures by integrating functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). We used resting-state functional connectivity (rsFC) and probabilistic tractography (PTG) analysis to identify brain surface stimulation targets that are functionally and structurally connected to the hippocampus, amygdala, and NAcc in 119 healthy participants. Our results showed that the medial prefrontal cortex (mPFC) is functionally and anatomically connected to all three subcortical regions, while the precuneus is connected to the hippocampus and amygdala. The mPFC and precuneus, two key hubs of the default mode network (DMN), as well as other cortical areas distributed at the prefrontal cortex and the parietal, temporal, and occipital lobes, were identified as potential locations for NIBS to modulate the function of these deep structures. The findings may provide new insights into the NIBS target selections for treating psychiatric and neurological disorders and chronic pain.