Resting-state functional connectivity modulates the BOLD activation induced by nucleus accumbens stimulation in the swine brain.

Shinho Cho,Hang Joon Jo,Myung‐Ho In,Irena Balzekas,Jan T Hachmann,Hoon‐Ki Min,Lindsey G Andres‐Beck,Kendall H Lee

doi:10.1002/brb3.1431

Abstract

IntroductionWhile the clinical efficacy of deep brain stimulation (DBS) the treatment of motor‐related symptoms is well established, the mechanism of action of the resulting cognitive and behavioral effects has been elusive.MethodsBy combining functional magnetic resonance imaging (fMRI) and DBS, we investigated the pattern of blood‐oxygenation‐level‐dependent (BOLD) signal changes induced by stimulating the nucleus accumbens in a large animal model.ResultsWe found that diffused BOLD activation across multiple functional networks, including the prefrontal, limbic, and thalamic regions during the stimulation, resulted in a significant change in inter‐regional functional connectivity. More importantly, the magnitude of the modulation was closely related to the strength of the inter‐regional resting‐state functional connectivity.ConclusionsNucleus accumbens stimulation affects the functional activity in networks that underlie cognition and behavior. Our study provides an insight into the nature of the functional connectivity, which mediates activation effect via brain networks.

Highlights

While deep brain stimulation (DBS) is an established therapy for essential tremor (Benabid, et al, 1991), Parkinson’s disease (PD) (Benabid, 2003; Group, 2001), and dystonia (Coubes, et al, 2004), the recent use of DBS is expanding into the realm of neuropsychiatric disorders, i.e., obsessive-compulsive disorder (OCD) (Greenberg, et al, 2010; Greenberg, et al, 2006; Mallet, et al, 2008), treatment-refractory depression (TRD) (Denys, et al, 2010; Mayberg, et al, 2005; Schlaepfer, et al, 2008), addiction (Kuhn, et al, 2009; Kuhn, et al, 2007), and Tourette’s syndrome (TS) (Houeto, et al, 2005; Servello, et al, 2008)
Sine DBS action is thought to alter functional coupling and regularize abnormal brain signals, previous studies have suggested that stimulating near the stimulation locus (NAc) influenced neural signaling between the ventral striatum and the prefrontal cortex (Figee, et al, 2013), resulted in attenuating pathological hyperactivity
BOLD activation was found in the ipsilateral NAc, indicating the current spread near the DBS electrode tip likely evoked the direct neuromodulatory effect (McIntyre, et al, 2004)

Summary

INTRODUCTION

While deep brain stimulation (DBS) is an established therapy for essential tremor (Benabid, et al, 1991), Parkinson’s disease (PD) (Benabid, 2003; Group, 2001), and dystonia (Coubes, et al, 2004), the recent use of DBS is expanding into the realm of neuropsychiatric disorders, i.e., obsessive-compulsive disorder (OCD) (Greenberg, et al, 2010; Greenberg, et al., 2006; Mallet, et al, 2008), treatment-refractory depression (TRD) (Denys, et al, 2010; Mayberg, et al, 2005; Schlaepfer, et al, 2008), addiction (Kuhn, et al, 2009; Kuhn, et al, 2007), and Tourette’s syndrome (TS) (Houeto, et al, 2005; Servello, et al, 2008). Cumulative results suggest that abnormal functional couplings between brain regions may be associated with neuropsychiatric diseases, i.e., cortico-striato-thalamo-cortical (CSTC) circuit and orbitofrontal cortex (OFC) (Greenberg, et al, 2010; Greenberg, et al, 2006; Rauch, et al, 1994; Volkow, et al., 2007). It remains unclear how DBS alters the functional coupling in potentially diseaserelated brain networks, and what biological mechanism supports the DBS effect A large animal model in our study presumably better recapitulates human brain anatomy (Van Gompel, et al, 2011) than small animal models (Albaugh, et al, 2016), our findings should be assumed to be general in nature, in terms of understanding the therapeutic effects of human DBS

MATERIALS AND METHODS

RESULTS

DISCUSSION