Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism

Frank, Michael J.; Samanta, Johan; Moustafa, Ahmed A.; Sherman, Scott J.

doi:10.1126/science.1146157

Cited by 986 publications

(1,025 citation statements)

References 34 publications

(67 reference statements)

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“…This suggests that the inhibition of normal behaviour related to obsessions and compulsions on the one hand and impulsivity on the other might be on opposite sides of a behavioural spectrum. STN DBS in PD induces cognitive impulsivity, but at the same time improves cognitive flexibility [40,49] and speeds up decisions under high-conflict conditions [107], so we propose that cognitive-behavioural disinhibition might help in improving the incapacity to make a decision because of permanent doubt, which is a core feature of OCD. Although OCD seems as an area of high potential application of DBS, clinical trials are needed to reach conclusions regarding the best anatomical target site for this condition.…”

Section: Obsessive-compulsive Disordermentioning

confidence: 93%

Deep brain stimulation in Parkinson disease—what went wrong?

Krack

Hariz

2010

Nat Rev Neurol

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Section: Obsessive-compulsive Disordermentioning

confidence: 93%

Deep brain stimulation in Parkinson disease—what went wrong?

Krack

Hariz

2010

Nat Rev Neurol

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“…Worsening of dyskinesia or dystonia can appear during initial DBS programming sessions, but these symptoms decline after several hours of continuous stimulation. 160 Deep brain stimulation can generate cognitive side effects as well, including mood changes, 161 depression, 162 decreased working memory performance, 163,164 impulsivity, 165 and hallucinations. 166 One explanation for the emergence of such cognitive side effects is that suprathreshold currents spread into nonmotor regions within the basal ganglia and thalamocortical networks.…”

Section: What To Avoid: Targets That Lead To Undesirable Side Effectsmentioning

confidence: 99%

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

et al. 2008

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Summary:Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.

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“…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).…”

Section: Introductionmentioning

confidence: 99%

“…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). …”

Section: Introductionmentioning

confidence: 99%

The subthalamic nucleus modulates the early phase of probabilistic classification learning

et al. 2014

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Previous models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. Thirteen idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, and medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high-probability patterns, and more differentiated strategy analyses were used. The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high-probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention toward unacquainted content. The STN might play a role in balancing the short-term success against strategy optimization for improved long-term outcome. AbstractPrevious models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. 13 idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high probability patterns, and more differentiated strategy analyses were used.The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention towards unacquainted content.The STN might play a role in balancing the short-term success against strategy optimi...

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Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism

Cited by 986 publications

References 34 publications

Deep brain stimulation in Parkinson disease—what went wrong?

Deep brain stimulation in Parkinson disease—what went wrong?

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

The subthalamic nucleus modulates the early phase of probabilistic classification learning

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