Potential therapeutic mechanism of deep brain stimulation of the nucleus accumbens in obsessive-compulsive disorder

Abstract

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) (NAc-DBS) is an effective solution to refractory obsessive-compulsive disorder (OCD). However, evidence for the neurobiological mechanisms of OCD and the effect of NAc-DBS is still lacking. One hypothesis is that the electrophysiological activities in the NAc are modulated by DBS, and another hypothesis is that the activities of neurotransmitters in the NAc are influenced by DBS. To investigate these potential alterations, rats with quinpirole (QNP)- induced OCD were treated with DBS of the core part of NAc. Then, extracellular spikes (SPK) and local field potentials (LFP) in the NAc were recorded, and the levels of relevant neurotransmitters and related proteins were measured. Analysis of SPK revealed that the firing rate was decreased and the firing pattern was changed after NAc-DBS, and analysis of LFP showed that overall power spectral density (PSD) levels were reduced after NAc-DBS. Additionally, we found that the relative powers of the theta band, alpha band and beta band were increased in OCD status, while the relative powers of the delta band and gamma band were decreased. This pathological pattern of power distribution was reformed by NAc-DBS. Furthermore, we found that the local levels of monoamines [dopamine (DA) and serotonin (5-HT)] and amino acids [glutamate (Glu) and gamma-aminobutyric acid (GABA)] in the NAc were increased in OCD status, and that the expression of the two types of DA receptors in the NAc exhibited an opposite change. These abnormalities could be reversed by NAc-DBS. These findings provide a more comprehensive understanding about the function of the NAc in the pathophysiology of OCD and provide more detailed evidence for the potential effect of NAc-DBS.

Neural oscillations in the ventral striatum reveal differences between the encoding of palatable food and ethanol consumption

“…During instrumental behaviors (e.g., pressing levers for reward) or during food reward receipt there is evidence for increased striatal low frequency power (Donnelly et al, 2014; Gruber et al, 2009); however, in our experiment, the rats are not performing a task or receiving a reward per se, suggesting that there may be an intrinsic difference between these instrumental behaviors and outcomes and naturalistic feeding behavior as represented by low frequency striatal oscillations. There is also some evidence that increased dopamine signaling correlates with decreased delta power in the nucleus accumbens (Shi et al, 2022; Zhang et al, 2021), suggesting that there may actually be decreased dopamine signaling SF consumption which is characterized in part by decreased delta power. High gamma power has also been shown to correlate with behavior during a spatial task with transient increases in power upon reward receipt followed by a marked, and longer lasting, decline in power (van der Meer & Redish, 2009).…”

Dopamine Release Dynamics in the Nucleus Accumbens Are Modulated by the Timing of Electrical Stimulation Pulses When Applied to the Medial Forebrain Bundle and Medial Prefrontal Cortex

“…The NAc is involved in motivation, error-driven learning, and encoding unpredicted reward . The NAc is also implicated in many diseases such as addiction and depression, and a few DBS studies have targeted the NAc to treat obsessive compulsive disorder, , depression, ,, and addiction. , Furthermore, dopaminergic release in the NAc is modulated by the timing of the neural activity or stimulation . The primary accumbal afferent dopaminergic connections are projections from the ventral tegmental area (VTA).…”