Deep brain stimulation of the ventromedial prefrontal cortex causes reorganization of neuronal processes and vasculature.

TitleDeep brain stimulation of the ventromedial prefrontal cortex causes reorganization of neuronal processes and vasculature.
Publication TypeJournal Article
Year of Publication2016
AuthorsM Chakravarty M, Hamani C, Martinez-Canabal A, Ellegood J, Laliberté C, Nobrega JN, Sankar T, Lozano AM, Frankland PW, Lerch JP
JournalNeuroimage
Volume125
Pagination422-7
Date Published2016 Jan 15
ISSN1095-9572
KeywordsAnimals, Brain, Deep Brain Stimulation, Image Processing, Computer-Assisted, Immunohistochemistry, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL
Abstract

BACKGROUND: Chronic high-frequency electrical deep brain stimulation (DBS) of the subcallosal cingulate region is currently being investigated clinically as a therapy for treatment of refractory depression. Experimental DBS of the homologous region, the ventromedial prefrontal cortex (VMPFC), in rodent models has previously demonstrated anti-depressant-like effects. Our goal was to determine if structural remodeling accompanies the alterations of brain function previously observed as a result of chronic DBS.METHODS: Here we applied 6h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5days. We investigated the "micro-lesion" effect by using a sham stimulation group (8 mice) and a control group (8 mice with a hole drilled into the skull only). Whole brain anatomy was investigated post-mortem using high-resolution magnetic resonance imaging and areas demonstrating volumetric expansion were further investigated using histology and immunohistochemistry.RESULTS: The DBS group demonstrated bilateral increases in whole hippocampus and the left thalamus volume compared to both sham and control groups. Local hippocampal and thalamic volume increases were also observed at the voxel-level; however these increases were observed in both DBS and sham groups. Follow-up immunohistochemistry in the hippocampus revealed DBS increased blood vessel size and synaptic density relative to the control group whereas the sham group demonstrated increased astrocyte size.CONCLUSIONS: Our work demonstrates that DBS not only works by altering function with neural circuits, but also by structurally altering circuits at the cellular level. Neuroplastic alterations may play a role in mediating the clinical efficacy of DBS therapy.

DOI10.1016/j.neuroimage.2015.10.049
Alternate JournalNeuroimage
PubMed ID26525655
Grant List / / Canadian Institutes of Health Research / Canada