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The Journal of Neuroscience, November 14, 2007, 27(46):12601-12610; doi:10.1523/JNEUROSCI.3750-07.2007

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

Clinton B. McCracken and Anthony A. Grace

Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Correspondence should be addressed to Dr. Clinton B. McCracken, Department of Neuroscience, A210 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260. Email: cbm12{at}pitt.edu

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.

Key words: electrical stimulation; nucleus accumbens; prefrontal; thalamus; electrophysiology; obsessive–compulsive

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Received June 26, 2007; revised Sept. 21, 2007; accepted Sept. 22, 2007.

Correspondence should be addressed to Dr. Clinton B. McCracken, Department of Neuroscience, A210 Langley Hall, University of Pittsburgh, Pittsburgh, PA 15260. Email: cbm12{at}pitt.edu

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