High frequency unilateral deep brain stimulation of the nucleus accumbens induces alterations in local field potential oscillations in regions both ipsilateral and contralateral to stimulation in awake, freely moving animals

2012-12-06T15:04:35Z (GMT) by Samuel Ewing Anthony Grace
<p>Deep brain stimulation (DBS) of the nucleus accumbens has been shown to be an effective treatment for patients with treatment refactory obsessive-compulsive disorder (OCD). Stimulation of this region has also demonstrated benefit in patients with treatment resistant depression and has been proposed for the treatment of the positive symptoms associated with schizophrenia. Despite its increasing application in the clinic, the mechanism by which DBS of the nucleus accumbens affects its therapeutic benefit remains poorly understood. Using combined stimulation and recording techniques, we examined how 24 hours of DBS affected rhythmic brain activity in freely moving rats. Local field potential (LFP) recording electrodes were fabricated and implanted, bilaterally, into the orbitofrontal cortex, prelimbic cortex, mediodorsal thalamus, and ventral subiculum. Bipolar concentric stimulating electrodes were fabricated and implanted, bilaterally, into the nucleus accumbens - one pole was used to record the LFP in the post stimulation period. Following recovery, rats were stimulated with square, monophasic, constant current 90µs duration pulses at a frequency of 130Hz delivered at an amplitude of 90µA using a custom made stimulation device. LFPs were recorded from all regions, both ipsilateral and contralateral to stimulation, before and immediately after stimulation. LFPs were collected from animals in their home cages following short-term (1 and 3 hours) and extended (24 and 48 hours) DBS.<br>Signals were processed to remove movement artifacts and analyzed to determine stimulation-induced changes in spectral power within regions, and coherence between regions.<br>Increases in spectral power, particularly in high frequency bandwidths (beta and gamma), were found in both the orbital and prelimbic cortices both ipsilateral and contralateral to stimulation. The magnitude of these increases was greater after long-term DBS compared to short-term stimulation. In addition a significant increase was seen in the gamma band in the nucleus accumbens contralateral to the stimulation site, whereas no such increase was seen in the stimulated accumbens. These findings support and extend previous reports from this lab implicating activation of the frontal cortices as a consequence of stimulation of the nucleus accumbens. In awake animals this activation is seen in higher bandwidths. Furthermore unilateral stimulation of the accumbens is seen to significantly modulate LFPs in the contralateral accumbens. These data further support the contention that DBS induces active changes in brain circuits rather than replicating a lesion.</p>