Deep brain stimulation of the subcallosal cingulate white matter (SCC25 DBS) is an emerging interventional strategy for treatment resistant depression (TRD). Close clinical monitoring and systematic long-term follow-up has provided additional perspectives on the time course, trajectory and sustainability of DBS-mediated effects. Implementation of refined techniques for surgical targeting and emerging clues as to which patients are most likely to benefit. Chronic electrophysiological monitoring further enables the characterization of this chronology at the neural level. To extend this progress, our team is working on three complementary projects: (1) Biomarkers using quantitative brain and behavior readouts of treatment response; (2) Imaging TRD phenotypes using structural and functional imaging to improve DBS patient selection; (3) Develop a non-human primate model of putative structural and synaptic plasticity induced by chronic SCC DBS using combined multimodal imaging and histological methods.
Study 1. Ongoing characterization of electrophysiological and behavior changes in TRD during DBS of the SCC. These studies initiated at Emory have now been expanded with NIH support for additional studies. 10 subjects have been implanted and data collection and analysis in ongoing from the Emory cohort. New NIH sponsored studies at ISMMS will commence in late 2019, complemented by continued support from HDRF for quantitative readouts of emotions and movement.
Study 2. Human imaging studies are examining depression progression to characterize the evolution of structural and functional network abnormalities at different levels of treatment resistance. New analyses of hippocampal volume and cortical thickness are underway with preliminary results demonstrating new and unexpected findings in subsets of TRD patients. Results of these new structural findings will be assessed in combination with diffusion (white matter) and functional connectivity (resting state fMRI) analyses in the same patients. Across the different imaging modalities, there is clear evidence of differential abnormalities in grey matter volumes, and white matter integrity and functional connectivity in MDD groups at different stages of chronicity and treatment resistance. Further we have identified gender differences in the pattern of hippocampal change with progressive treatment resistance and a correlation in women with inflammation—thus linking our findings with those of the DTF more broadly. Models that evaluate the interactions among these identified structural and functional change patterns will be developed in year 3, including expansion of an ongoing collaboration with Conor Liston.
Study 3. New studies in non-human primate (NHP) will examine structural and functional underpinnings of SCC DBS at the macrostructural and cellular level. We hypothesize that chronic SCC DBS will leads to permanent changes in connectivity at the structural and functional levels, and that these changes are driven by oligodendrocyte proliferation and increased myelination in the stimulated pathways. Unique structural and functional imaging studies will be supplemented by post-mortem histological examination of cellular changes in white matter.