Search

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 6 h of high-frequency bilateral VMPFC DBS daily to 8 9-week old C57Bl/6 mice for 5 days. 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.

Ventromedial prefrontal cortex (vmPFC) forms a core region of larger brain circuits that assign value to sensory inputs and interfaces motivational and cognitive dominated brain processes. This network function of the vmPFC could be realized by synchronizing local activity at time scales that are shared by connected brain areas, but it is unknown whether vmPFC circuitry engages in functionally specific synchronization. Here, we recorded in human subcallosal vmPFC while subjects engaged in an emotion tracking task that required the assignment of positive or negative affective value to ambiguous (happy-sad) facial expressions. We found that vmPFC engages in low beta-band (15-20 Hz) coherent activation just before subjects subjectively judged ambiguous facial expressions as conveying negative valence ('sad') information, but not before positive valence ('happy') judgments. The predictive beta coherence emerged particularly for conflicting rather than pure emotional facial cues and dissipated slowly after the choice was made. These results suggest that 15-20 Hz coherent activity within vmPFC marks a functional signature of a valuation process that informs categorical affective choices. We hypothesize that coherent beta band activation signifies functional interactions to anatomical vmPFC projection targets, raising the possibility that dysfunctional biases in affective valuation and an enhanced decision conflict in clinical depression could be indexed by alterations of beta coherent network activation.