High-Frequency Deep Brain Stimulation of the Nucleus Accumbens Region Suppresses Neuronal Activity and Selectively Modulates Afferent Drive in Rat Orbitofrontal CortexIn Vivo

Abstract

High-frequency deep-brain stimulation (DBS) of the nucleus accumbens (NAc) region is an effective therapeutic avenue for patients with treatment-resistant obsessive-compulsive disorder (OCD). Imaging studies suggest that DBS acts by suppressing the aberrant metabolism in the orbitofrontal cortex (OFC) that is a hallmark of OCD; however, little is known about the mechanisms by which this occurs. We examined the effects of 30 min NAc DBS at 130 Hz on spontaneously active OFC neurons and local field potentials (LFPs) in addition to evoked responses elicited by single-pulse stimulation of the NAc or mediodorsal thalamus (MD) in urethane-anesthetized rats. NAc DBS reduced the mean firing rate of OFC neurons, although neurons receiving monosynaptic input from MD were less affected and some putative interneurons were excited by DBS. Single-pulse stimulation of the NAc produced a robust inhibition in OFC neurons that was attenuated after DBS, whereas excitatory responses were unchanged. In contrast, after DBS inhibitory responses evoked from MD were unchanged, whereas excitatory responses were enhanced. NAc-evoked LFP responses were potentiated after DBS, whereas MD-evoked LFP responses were unchanged. NAc DBS also enhanced OFC spontaneous LFP oscillatory activity in the slow (0.5-4 Hz) frequency band. These results suggest that DBS of the NAc region may alleviate OCD symptoms by reducing activity in subsets of OFC neurons, potentially by driving recurrent inhibition though antidromic activation of corticostriatal axon collaterals. Moreover, selective potentiation of input to these inhibitory circuits may also contribute to the therapeutic effects produced by DBS in OCD patients.

Neuroelectric Signatures of Reward Learning and Decision-Making in the Human Nucleus Accumbens

“…That is, although it is clear that DBS to this region alleviates symptoms of depression (Schlaepfer et al, 2008), the mechanism of this improvement remains unknown. For example, it is possible that DBS-driven overstimulation of nucleus accumbens target or afferent regions (McIntyre et al, 2004;McCracken and Grace, 2007) drives the efficacy of this procedure. Consistent with this 'network modulation' idea, DBS to other brain regions such as the subgenual cingulate is also effective at alleviating depression symptoms (Mayberg et al, 2005).…”

Advanced research on deep brain stimulation in treating mental disorders (Review)

“…Many scholars conclude that the influence of DBS on the neurological network is more complicated than simply damaged surgery and that DBS therapy may affect the neuronal somas and the two-way activation function of axons (21,22). Previous studies have reported that various neurotransmitters, including glutamic acid and dopamine, are released following DBS (23,24).…”

Deep brain stimulation: from neurology to psychiatry?

“…Other possible mechanisms of action for high-frequency DBS include local neuronal inhibition with concomitant activation of surrounding fibres, thus resulting in increased synaptic output [73] and activation of afferent axon terminals (e.g. the cortical inputs in the case of STN or NAcc HFS [73,74]; for a review, see [75]). The functional outcome of these complex putative mechanisms of action is uncertain and is probably variable, depending on the specific anatomophysiological arrangements of each target region.…”