Capturing Brain Response Patterns to Subcallosal Cingulate Deep Brain Stimulation Using Cycling fMRI: A...

BackgroundDeep brain stimulation targeting the subcallosal cingulate (SCC-DBS) is a promising therapy for treatment-resistant depression. However, the lack of a consistent, rapid behavioural response to SCC-DBS complicates the selection of optimal stimulation settings following implantation, requiring a prolonged and burdensome trial-and-error process. Immediate biomarkers of effective stimulation could overcome this problem.MethodsIn this proof-of-concept study, three patients with SCC-DBS implants were scanned at 3 T using a block-design paradigm in which stimulation alternated between "ON" and "OFF" states in 30-s cycles during a single 6.5-min acquisition. Scans were performed using participants' clinically optimized parameters. Blood-oxygen-level-dependent (BOLD) response maps were generated by contrasting DBS-ON and DBS-OFF conditions, and exploratory correlations with clinical outcome-indexed by percentage reduction in Hamilton Depression Rating Scale scores at 12 months-were also assessed.ResultsContrasting stimulation settings enabled the identification of regional BOLD signal changes associated with DBS, revealing consistent hemodynamic changes in several brain regions during active stimulation. Specifically, the precuneus, posterior cingulate cortex, middle frontal gyrus, and frontal pole exhibited decreased BOLD responses during active DBS, while the occipital cortex, middle temporal gyrus, inferior parietal lobule, and superior frontal gyrus showed increased BOLD responses. Exploratory analysis further suggested a potential correlation between precuneus BOLD signal change and clinical improvement (R = -0.98, p_permute = 0.09).ConclusionThese findings speak to the utility of block-design fMRI with cycling DBS stimulation as a tool to identify objective, brain-based biomarkers of effective SCC-DBS, potentially expediting stimulation parameter selection and therapeutic optimization.