Load-Dependent Interference of Deep Brain Stimulation of the Subthalamic Nucleus with Switching from Automatic to Controlled Processing During Random Number Generation in Parkinson’s Disease

Abstract

Background: Deep brain stimulation of the subthalamic nucleus (STN DBS) ameliorates the motor symptoms of Parkinson’s disease (PD). However, some aspects of executive control are impaired with STN DBS.Objective: We tested the prediction that (i) STN DBS interferes with switching from automatic to controlled processing during fast-paced random number generation (RNG) (ii) STN DBS-induced cognitive control changes are load-dependent.Methods: Fifteen PD patients with bilateral STN DBS performed paced-RNG, under three levels of cognitive load synchronised with a pacing stimulus presented at 1, 0.5 and 0.33 Hz (faster rates require greater cognitive control), with DBS on or off. Measures of output randomness were calculated. Countscore 1 (CS1) indicates habitual counting in steps of one (CS1). Countscore 2 (CS2) indicates a more controlled strategy of counting in twos.Results: The fastest rate was associated with an increased CS1 score with STN DBS on compared to off. At the slowest rate, patients had higher CS2 scores with DBS off than on, such that the differences between CS1 and CS2 scores disappeared.Conclusions: We provide evidence for a load-dependent effect of STN DBS on paced RNG in PD. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load. These findings are consistent with the proposal that the STN implements a switch signal from the medial frontal cortex which enables a shift from automatic to controlled processing.

In Parkinson’s disease on a probabilistic Go/NoGo task deep brain stimulation of the subthalamic nucleus only interferes with withholding of the most prepotent responses

“…The finding that the discriminability with STN stimulation was lowest on the block with the highest Go probability means that STN-DBS interfered with action restraint on trials when the Go response was most prepotent. Therefore, the results of our study and those of Hershey et al ( 2004 ) and Williams et al ( 2015 ) indicate that the effect of STN-DBS on performance of attention-demanding tasks requiring the ability to withhold prepotent responses is load-dependent. For example, Williams et al ( 2015 ) found that STN-DBS differentially impaired inhibition of habitual counting responses (count score 1) during paced RNG in a load-dependent fashion only at the fastest rate of 1 Hz, but not at the slower rates of 0.33 and 0.5 Hz.…”

“…STN-DBS does not affect global cognitive functioning in PD (Krack et al 2003 ; Follett et al 2010 ; Williams et al 2011 ; Rothlind et al 2014 ), and only isolated deficits in verbal fluency have been documented following surgery (Parsons et al 2006 ). However, there is evidence that executive control of action becomes worse with STN-DBS in PD (Frank et al 2007 ; Jahanshahi 2013 ; Jahanshahi et al 2015 ; Williams et al 2015 ). This was shown with various tasks of executive function, such as the Stroop (Jahanshahi et al 2000 ; Brittain et al 2012 ), fast-paced random number generation (Thobois et al 2007 ; Anzak et al 2011 ), the stop signal task (Ray et al 2012 ; Obeso et al 2014 ), the Go/NoGo task (Hershey et al 2004 , 2010 ; Kühn et al 2004 ; Ballanger et al 2009 ), the Simon interference task (Wylie et al 2010 ); and on tasks requiring decision-making under conflict (Frank et al 2007 ; Cavanagh et al 2011 ; Coulthard et al 2012 ; Zaghloul et al 2012 ).…”

“…This was not observed for the 50 % Go task (low demand on cognitive control). More recently, using a paced random number generation (RNG) task at different rates, with faster rates requiring a higher level of executive control, Williams et al ( 2015 ) showed that STN-DBS differentially impaired inhibition of habitual counting responses during paced RNG in a load-dependent fashion and only at the fastest rate of 1 Hz. Patients could switch to more controlled RNG strategies during conditions of low cognitive load at slower rates only when the STN stimulators were off, but when STN stimulation was on, they engaged in more automatic habitual counting under increased cognitive load at the fastest rate.…”

“…In the light of the results of Hershey et al ( 2004 ) and Williams et al ( 2015 ), the first aim of the study was to investigate the effect of STN-DBS on action restraint as a function of the prepotency of the Go response. We compared tasks with three different levels of prepotency of the Go response (probabilistic Go/NoGo reaction time (RT) task—pGNG—with 80, 50 and 20 % Go stimuli).…”

Subthalamic nucleus deep brain stimulation induces impulsive action when patients with Parkinson’s disease act under speed pressure

“…The comparison of the results of the two studies raises interesting questions about the effect of STN-DBS in relation to task difficulty, which may have implications for theories of STN function. As previously noted (Jahanshahi 2013 ), to date, the STN-DBS-induced deficits in executive and inhibitory control have been mainly observed in conditions of high demand for cognitive control (Hershey et al 2004 ; Williams et al 2015 ) or motivational salience (Frank et al 2007 ). The interaction of STN-DBS with task difficulty is an issue of theoretical and clinical interest that is worth addressing in future studies.…”