Stimulation of the subthalamic nucleus and impulsivity: release your horses

Abstract

Objective: In Parkinson disease (PD) patients, deep brain stimulation (DBS) of the subthalamic nucleus (STN) may contribute to certain impulsive behavior during high-conflict decisions. A neurocomputational model of the basal ganglia has recently been proposed that suggests this behavioral aspect may be related to the role played by the STN in relaying a "hold your horses" signal intended to allow more time to settle on the best option. The aim of the present study was 2-fold: 1) to extend these observations by providing evidence that the STN may influence and prevent the execution of any response even during low-conflict decisions; and 2) to identify the neural correlates of this effect.

Methods: We measured regional cerebral blood flow during a Go/NoGo and a control (Go) task to study the motor improvement and response inhibition deficits associated with STN-DBS in patients with PD.

Results: Although it improved Unified Parkinson Disease Rating Scale motor ratings and induced a global decrease in reaction time during task performance, STN-DBS impaired response inhibition, as revealed by an increase in commission errors in NoGo trials. These behavioral effects were accompanied by changes in synaptic activity consisting of a reduced activation in the cortical networks responsible for reactive and proactive response inhibition.

Interpretation: The present results suggest that although it improves motor functions in PD patients, modulation of STN hyperactivity with DBS may tend at the same time to favor the appearance of impulsive behavior by acting on the gating mechanism involved in response initiation.

Fig 1

Schematic representation of the approximate location of the electrode contacts used for stimulation during the study over a series of 4 axial sections of the Schaltenbrand & Wahren atlas (A = anterior; M = medial; P = posterior; L = lateral). Numbers on the graphs represent millimeters from the midcommissural point (MCP). Negative values are inferior to the midcommissural point. A.aq = Annulus aquaeductus; Aq = Aquaductus mesencephali; B.cj = Brachium conjuctivum; B.co.i = Brachium colliculi inferioris; Co.s = Colliculi superioris; Cp.i.p = Internal capsula lenticular fascicularis; G.m = corpus geniculatum mediale; H1/H2 = forel’s field; Hpth = hypothalamus; L.1 = lemniscus lateralis; L.m = lemniscus medialis; P.m = medial pallidus; Pp.d = nucleus peripeduncularis; Pu.ig = nucleus pulvinaris intergeniculartus; Q = fasciculus Q; Ra.pr1 = preliminiscal radiation; Ru = red nucleus; Sth = subthalamic nucleus; Tmth = mammillo-thalamic tract; T.t.c = central tegmental tract; v.ci = nucleus ventrocaudalis internus; v.c.pc.e = ventrocaudalis parvocellularis externus; v.c.pc.i = ventrocaudalis parvocellularis internus; v.por = nucleus ventralis portae; z.i. = zona incerta.

Fig 2

(A) Variations of reaction time as a function of the experimental condition. (B) Percentage of commission error (CE) during the Go/NoGo (GNG) task as a function of the stimulation condition (subthalamic nucleus deep brain stimulation, STN-DBS). *Statistically significant effect.

Fig 3

Statistical parametric maps of brain regions showing common significant changes with subthalamic nucleus (STN) stimulation during both Go and Go/NoGo tasks at a statistical threshold of p < 0.001 (uncorrected) at the single-voxel level. Areas of increased regional cerebral blood flow (rCBF) with STN stimulation involving the ventral anterior cingulate cortex (ACC) are in yellow. Areas of decreased rCBF during STN stimulation involving the left motor and premotor areas, the medial dorsal ACC, posterior cingulate cortex, and pre–supplementary motor area are in blue. These areas are superimposed on sagittal (right column) and coronal (left column) sections of a single subject’s brain magnetic resonance imaging from SPM2. R = right; L = left.