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. CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptInterpretation-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.Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor functions in patients with Parkinson disease (PD). 1,2 However, growing evidence suggests that STN-DBS also causes executive inhibitory deficits and impulsive behavior under high-conflict conditions. [3][4][5][6][7] Abnormal basal ganglia activity in PD produces a series of downstream effects affecting thalamic and cortical areas. 8 Within the basal ganglia, the STN plays a major role in motor control, and operating as a relay, influences response suppression by inhibiting thalamocortical programs. The fact that a large part of the STN receives motor inputs from the primary motor cortex (M1), the premotor cortex (PMC), the supplementary motor area (SMA), and the pre-SMA strongly supports its important motor contribution. 9,10 However, the STN also receives several projections from the anterior cingulate cortex (ACC) and inferior frontal cortex (IFC), as well as the medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex, accounting for a more cognitive aspect of motor control. 10,11 Within this framework, Frank and colleagues have proposed a neurocomputational model 7,12 in which the STN provides a dynamic "hold your horses" signal temporarily preventing the execution of any response in face of high-conflict decisions. According to their model, the STN would...

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease?

“…The possibility of induction of new onset ICD by STN-DBS has been already reported [22], even if other studies demonstrated an improvement of pre-existing ICD after DBS [23]. The central position of the STN within the basal ganglia thalamo-cortical associative and limbic circuits could explain its role in promoting the onset of ICD in some patients [24]; STN-DBS can indeed interfere with the response inhibition pattern, leading to an increase of impulsivity [25]. This finding further supports the necessity of a psychiatric surveillance of the patients after STN-DBS.…”

“…In addition to total score (items 18-31), specific subscores were taken into account: bradykinesia (items 19,[23][24][25][26]31), tremor (items 20-21), rigidity (item 22), speech (item 18), gait (item 29), postural stability (item 30) and axial score (items 18, 27-30).…”

Dianas quirúrgicas en el tratamiento de enfermedades psiquiátricas. Desde el movimiento a las emociones

“…Otros autores, por el contrario, han referido la aparición de ICD en pacientes tratados con DBS a pesar de la reducción de agonistas DA 49,72,104 . Por último en otros estudios realizados, la estimulación del núcleo subtalámico en pacientes jóvenes, aumentaría el riesgo de desarrollar ICD y en este contexto, no únicamente existiría un incremento en presentar un cuadro de impulsividad, sino también un mayor riesgo de suicidio 12,55,98,103,104,119 .…”

The subthalamic nucleus modulates the early phase of probabilistic classification learning

“…Early studies on patients with idiopathic Parkinson's disease (iPD) have demonstrated that the subthalamic nucleus (STN) influences learning and attentional processes, which can either be improved or impaired depending on the task (Jahanshahi et al 2000). More recently, the STN was suggested as relay in the decision making process by providing an inhibitory signal to prevent premature execution of responses in conflicting decisions (Mink 1996;Aron and Poldrack 2006;Frank et al 2007;Thobois et al 2007;Ballanger et al 2009 (Frank 2006) are critical in the early phase of skill acquisition. In particular, STN activity was predicted in Frank's model to increase during trial repetitions '25-60' during early decision making repetitions (Frank 2006).…”

“…In particular, STN activity was predicted in Frank's model to increase during trial repetitions '25-60' during early decision making repetitions (Frank 2006). However, the experimental paradigms used in healthy subjects and iPD patients with subthalamic nucleus deep brain stimulation (STN-DBS) were independent of the learning process and included a well-trained probabilistic selection task (Frank et al 2007), a random number generation task (Thobois et al 2007) and a Go/NoGo task (Aron and Poldrack 2006;Ballanger et al 2009). …”