Response to Deep Brain Stimulation in Three Brain Targets with Implications in Mental Disorders: A PET Study in Rats

Objective To investigate metabolic changes in brain networks by deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) and dorsomedial thalamus (DM) using positron emission tomography (PET) in naive rats. Methods 43 male Wistar rats underwent stereotactic surgery and concentric bipolar platinum-iridium electrodes were bilaterally implanted into one of the three brain sites. [F-18]-fluoro-2-deoxyglucose-PET ((18)FDG-PET) and computed tomography (CT) scans were performed at the 7th (without DBS) and 9th day (with DBS) after surgery. Stimulation period matched tracer uptake period. Images were acquired with a small-animal PET-CT scanner. Differences in glucose uptake between groups were assessed with Statistical Parametric Mapping. Results DBS induced site-specific metabolic changes, although a common increased metabolic activity in the piriform cortex was found for the three brain targets. mPFC-DBS increased metabolic activity in the striatum, temporal and amygdala, and reduced it in the cerebellum, brainstem (BS) and periaqueductal gray matter (PAG). NAcc-DBS increased metabolic activity in the subiculum and olfactory bulb, and decreased it in the BS, PAG, septum and hypothalamus. DM-DBS increased metabolic activity in the striatum, NAcc and thalamus and decreased it in the temporal and cingulate cortex. Conclusions DBS induced significant changes in (18)FDG uptake in brain regions associated with the basal ganglia-thalamo-cortical circuitry. Stimulation of mPFC, NAcc and DM induced different patterns of (18)FDG uptake despite interacting with the same circuitries. This may have important implications to DBS research suggesting individualized target selection according to specific neural modulatory requirements.