Deep brain stimulation induces white matter remodeling and functional changes to brain-wide networks

Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant neurological and psychiatric disorders. Despite this, little is known about the anatomical and functional mechanisms that underlie this therapy. We targeted DBS to white matter adjacent to the subcallosal anterior cingulate cortex (SCC-DBS) in macaques, modeling the approach proven effective for depression in humans. SCC-DBS caused a selective increase in fractional anisotropy, linked to white matter microstructure, in the cingulum bundle. At the cellular level, this was associated with an increase in both myelinated oligodendrocytes and the degree of myelination in the mid-cingulum bundle. SCC-DBS also altered brain-wide functional connectivity, changing interactions between the SCC and multiple brain networks, most notably the default mode network that has been implicated in depression. Overall, our data indicate that white matter remodeling as well as selective changes in multiple brain networks may contribute to DBS's therapeutic efficacy.