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

Abstract

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 naïve 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. [18F]-fluoro-2-deoxy-glucose-PET (18FDG-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 18FDG uptake in brain regions associated with the basal ganglia-thalamo-cortical circuitry. Stimulation of mPFC, NAcc and DM induced different patterns of 18FDG 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.

Fig 1. Correct electrode location verification.

Sagittal, coronal and axial views of a CT scan registered to the MR template of an animal to verify the correct electrode location. Only animals with electrodes placed correctly in the respective target were included in the study.

Fig 2. Brain glucose metabolism during DBS in the three brain targets. Effects depend on stimulation target.

Colored PET overlays on MR reference indicate increased 18FDG uptake (hot colors) or decreased (cold colors). AA: amygdala; BS: brainstem, Cb: cerebellum, CC: cingulate cortex, Hypoth: hypothalamus, NAcc: nucleus accumbens, PAG: periaqueductal gray matter, Pir C: piriform cortex, Sub: subiculum hippocampal, Str: striatum, Temp C: temporal cortex, Th: thalamus.