Local Fields in Human Subthalamic Nucleus Track the Lead-up to Impulsive Choices.

John M Pearson,Dennis A Turner,Shivanand P Lad,Michael L Platt,Patrick T Hickey

doi:10.3389/fnins.2017.00646

Abstract

The ability to adaptively minimize not only motor but cognitive symptoms of neurological diseases, such as Parkinson's Disease (PD) and obsessive-compulsive disorder (OCD), is a primary goal of next-generation deep brain stimulation (DBS) devices. On the basis of studies demonstrating a link between beta-band synchronization and severity of motor symptoms in PD, the minimization of beta band activity has been proposed as a potential training target for closed-loop DBS. At present, no comparable signal is known for the impulsive side effects of PD, though multiple studies have implicated theta band activity within the subthalamic nucleus (STN), the site of DBS treatment, in processes of conflict monitoring and countermanding. Here, we address this challenge by recording from multiple independent channels within the STN in a self-paced decision task to test whether these signals carry information sufficient to predict stopping behavior on a trial-by-trial basis. As in previous studies, we found that local field potentials (LFPs) exhibited modulations preceding self-initiated movements, with power ramping across multiple frequencies during the deliberation period. In addition, signals showed phasic changes in power around the time of decision. However, a prospective model that attempted to use these signals to predict decision times showed effects of risk level did not improve with the addition of LFPs as regressors. These findings suggest information tracking the lead-up to impulsive choices is distributed across multiple frequency scales in STN, though current techniques may not possess sufficient signal-to-noise ratios to predict—and thus curb—impulsive behavior on a moment-to-moment basis.

Highlights

The well-attested success of deep brain stimulation (DBS) in ameliorating the symptoms of neurological disorders, such as Parkinson’s Disease (PD) and essential tremor has brought with it an intense interest in DBS as a treatment modality for other conditions, including obsessive-compulsive disorder (OCD) and treatment-resistant depression (JohansenBerg et al, 2008; Malone et al, 2009; de Koning et al, 2011; Figee et al, 2013)
By recording directly from humans undergoing invasive brain surgery, we have demonstrated the presence of single units within the basal ganglia that increase firing over the course of the decision process, but that population measures like the local field potential exhibit ramping activity during the process of deliberation
The most prevalent single unit response was to elapsed time in the trial, suggesting that subthalamic nucleus (STN) plays a role in stopping behavior, and encodes critical information related to upcoming choice during more prolonged deliberative processes

Summary

Introduction

The well-attested success of deep brain stimulation (DBS) in ameliorating the symptoms of neurological disorders, such as Parkinson’s Disease (PD) and essential tremor has brought with it an intense interest in DBS as a treatment modality for other conditions, including obsessive-compulsive disorder (OCD) and treatment-resistant depression (JohansenBerg et al, 2008; Malone et al, 2009; de Koning et al, 2011; Figee et al, 2013). Studies have shown that oscillations in the theta band (4–8 Hz) play a key role in mediating the influence of frontal cortical areas on decisions in the basal ganglia and likely represent cognitive, top-down aspects of the decision process (Frank et al, 2007; Ballanger et al, 2009; Cavanagh et al, 2011; Zavala et al, 2014, 2015) This complements an extensive literature on the role of beta band oscillations (13–30 Hz) in the pathophysiology of Parkinson’s Disease, where it is known that such oscillations are suppressed by dopaminergic medication and effective DBS stimulation (Levy et al, 2002; Bronte-Stewart et al, 2009; Jenkinson and Brown, 2011; Whitmer et al, 2012). Power at these frequencies is reduced prior to voluntary movement, suggesting that such suppression is necessary for movement initiation (Jenkinson and Brown, 2011; Brittain et al, 2012)

Methods

Results

Conclusion