Addiction in Parkinson's disease: Impact of subthalamic nucleus deep brain stimulation

In Parkinson's disease, dopamine dysregulation syndrome (DDS) is characterized by severe dopamine addiction and behavioral disorders such as manic psychosis, hypersexuality, pathological gambling, and mood swings. Here, we describe the case of 2 young parkinsonian patients suffering from disabling motor fluctuations and dyskinesia associated with severe DDS. In addition to alleviating the motor disability in both patients, subthalamic nucleus (STN) deep brain stimulation greatly reduced the behavioral disorders as well as completely abolished the addiction to dopaminergic treatment. Dopaminergic addiction in patients with Parkinson's disease, therefore, does not constitute an obstacle to high‐frequency STN stimulation, and this treatment may even cure the addiction. © 2005 Movement Disorder Society     

Conflict-dependent dynamic of subthalamic nucleus oscillations during moral decisions

Although lesional, neuroimaging, and brain stimulation studies have provided an insight into the neural mechanisms of judgement and decision-making, all these works focused on the cerebral cortex, without investigating the role of subcortical structures such as the basal ganglia. Besides being an effective therapeutic tool, deep brain stimulation (DBS) allows local field potential (LFP) recordings through the stimulation electrodes thus providing a physiological “window” on human subcortical structures. In this study we assessed whether subthalamic nucleus LFP oscillations are modulated by processing of moral conflictual, moral nonconflictual, and neutral statements. To do so, in 16 patients with Parkinson's disease (8 men) bilaterally implanted with subthalamic nucleus (STN) electrodes for DBS, we recorded STN LFPs 4 days after surgery during a moral decision task. During the task, recordings from the STN showed changes in LFP oscillations. Whereas the 14–30 Hz band (beta) changed during the movement executed to perform the task, the 5–13 Hz band (low-frequency) changed when subjects evaluated the content of statements. Low-frequency band power increased significantly more during conflictual than during nonconflictual or neutral sentences. We conclude that STN responds specifically to conflictual moral stimuli, and could be involved in conflictual decisions of all kinds, not only those for moral judgment. LFP oscillations provide novel direct evidence that the neural processing of conflictual decision-making spreads beyond the cortex to the basal ganglia and encompasses a specific subcortical conflict-dependent component.     

Coordinated reset has sustained aftereffects in Parkinsonian monkeys

Coordinated reset neuromodulation consists of the application of consecutive brief high‐frequency pulse trains through the different contacts of the stimulation electrode. In theoretical studies, by achieving unlearning of abnormal connectivity between neurons, coordinated reset neuromodulation reduces pathological synchronization, a hallmark feature of Parkinson's disease pathophysiology. Here we show that coordinated reset neuromodulation of the subthalamic nucleus has both acute and sustained long‐lasting aftereffects on motor function in parkinsonian nonhuman primates. Long‐lasting aftereffects were not observed with classical deep brain stimulation. These observations encourage further development of coordinated reset neuromodulation for treating motor symptoms in Parkinson disease patients. ANN NEUROL 2012;72:816–820     

Modulation of subthalamic alpha activity to emotional stimuli correlates with depressive symptoms in Parkinson's disease1

Background : Deep brain stimulation of the subthalamic nucleus is an effective treatment for patients with advanced Parkinson's disease. However, affective side effects following subthalamic deep brain stimulation have been reported. Here, we aim to elucidate the influence of affective state on emotional processing as indexed by local field potential activity and to identify neurophysiological markers in patients at risk of developing depressive symptoms during subthalamic deep brain stimulation. Methods : Subthalamic local field potentials were directly recorded via electrodes implanted for deep brain stimulation in 12 Parkinson's disease patients while viewing emotionally salient and neutral pictures. Parkinson's disease patients were assessed for depressive symptoms using the Beck depression inventory at the time of operation and 3 months after continuous subthalamic nucleus deep brain stimulation. Results : We found a significant event‐related desynchronization in the local alpha frequency band (8–12 Hz) for emotionally arousing but not neutral pictures. The the event‐related desynchronization (ERD) in the alpha frequency band was reduced for pleasant stimuli in patients with mild to moderate depressive symptoms compared with patients without depression. The alpha‐ERD to unpleasant stimuli showed the opposite pattern. Consistently, the index of event‐related alpha desynchronization (alpha ERD for pleasant stimuli minus alpha ERD for unpleasant stimuli) correlated with the Beck depression inventory at the time of the recordings and at 3 months after continuous deep brain stimulation. The alpha ERD to unpleasant pictures correlated significantly with the Beck depression inventory score at 3 months after chronic deep brain stimulation. Discusion : In conclusion, we found mood‐congruent stimulus processing in the subthalamic nucleus of Parkinson's disease patients. Electrophysiological markers such as event‐related desynchronization of subthalamic alpha activity reflect state‐dependent emotional processing and may potentially be used to predict depressive mood disturbances in Parkinson's disease patients with chronic subthalamic deep brain stimulation at an early stage. © 2011 Movement Disorder Society     

Conflict-dependent dynamic of subthalamic nucleus oscillations during moral decisions

Although lesional, neuroimaging, and brain stimulation studies have provided an insight into the neural mechanisms of judgement and decision-making, all these works focused on the cerebral cortex, without investigating the role of subcortical structures such as the basal ganglia. Besides being an effective therapeutic tool, deep brain stimulation (DBS) allows local field potential (LFP) recordings through the stimulation electrodes thus providing a physiological "window" on human subcortical structures. In this study we assessed whether subthalamic nucleus LFP oscillations are modulated by processing of moral conflictual, moral nonconflictual, and neutral statements. To do so, in 16 patients with Parkinson's disease (8 men) bilaterally implanted with subthalamic nucleus (STN) electrodes for DBS, we recorded STN LFPs 4 days after surgery during a moral decision task. During the task, recordings from the STN showed changes in LFP oscillations. Whereas the 14--30 Hz band (beta) changed during the movement executed to perform the task, the 5--13 Hz band (low-frequency) changed when subjects evaluated the content of statements. Low-frequency band power increased significantly more during conflictual than during nonconflictual or neutral sentences. We conclude that STN responds specifically to conflictual moral stimuli, and could be involved in conflictual decisions of all kinds, not only those for moral judgment. LFP oscillations provide novel direct evidence that the neural processing of conflictual decision-making spreads beyond the cortex to the basal ganglia and encompasses a specific subcortical conflict-dependent component.     

High‐frequency oscillations in Parkinson's disease: Spatial distribution and clinical relevance

The pathophysiology of Parkinson's disease (PD) has been related to excessive beta band oscillations in the basal ganglia. Recent recordings from the subthalamic nucleus of PD patients showed that beta oscillations show strong cross‐frequency coupling with high‐frequency oscillations (>200 Hz). However, little is known about the characteristics and functional properties of these oscillations. We studied the spatial distribution of high‐frequency oscillations and their relation to PD motor symptoms. We included 10 PD patients in medication OFF who underwent implantation of deep brain stimulation (DBS) electrodes. Intraoperative five‐channel microelectrode recordings were performed at 9 to 10 recording sites within the subthalamic nucleus and its immediate surroundings. We found a focal spatial distribution of high‐frequency oscillations with highest power 2 mm below the dorsolateral border of the subthalamic nucleus. Within the subthalamic nucleus, power peaked slightly anterior to the DBS target site. In addition, contralateral akinesia/rigidity scores were negatively correlated with high‐frequency oscillation power. Our results demonstrate a focal origin of high‐frequency oscillations within the subthalamic nucleus and provide further evidence for their functional association with motor state. © 2014 International Parkinson and Movement Disorder Society     

Parkinson's Disease and pathological gambling: Results from a functional MRI study

Seven patients with a diagnosis of Parkinson's disease (PD) and pathological gambling (PG) and 7 PD patients without PG were investigated by functional MRI and a block‐design experiment with gambling‐related visual cues alternating with neutral stimuli and rest periods. Compared with PD/non‐PG, in PD/PG patients, several areas of increased cue‐related blood oxygen level dependent (BOLD)‐response were observed including bilateral anterior cingulate cortex, medial and superior frontal gyri, and precuneus, right inferior parietal lobule, and ventral striatum. The over activation of cingulate cortex and ventral striatum in PD/PG patients after the craving task is similar to that reported in addicted patients, whereas the activation of the parietal structures is probably related to the attentional network. © 2010 Movement Disorder Society.     

Interaction of synchronized dynamics in cortex and basal ganglia in Parkinson's disease

Parkinson's disease pathophysiology is marked by increased oscillatory and synchronous activity in the beta frequency band in cortical and basal ganglia circuits. This study explores the functional connections between synchronized dynamics of cortical areas and synchronized dynamics of subcortical areas in Parkinson's disease. We simultaneously recorded neuronal units (spikes) and local field potentials (LFP) from subthalamic nucleus (STN) and electroencephalograms (EEGs) from the scalp in parkinsonian patients, and analysed the correlation between the time courses of the spike–LFP synchronization and inter‐electrode EEG synchronization. We found the (non‐invasively obtained) time course of the synchrony strength between EEG electrodes and the (invasively obtained) time course of the synchrony between spiking units and LFP in STN to be weakly, but significantly, correlated with each other. This correlation is largest for the bilateral motor EEG synchronization, followed by bilateral frontal EEG synchronization. Our observations suggest that there may be multiple functional modes by which the cortical and basal ganglia circuits interact with each other in Parkinson's disease: not only may synchronization be observed between some areas in cortex and the basal ganglia, but also synchronization within cortex and within basal ganglia may be related, suggesting potentially a more global functional interaction. More coherent dynamics in one brain region may modulate or activate the dynamics of another brain region in a more powerful way, causing correlations between changes in synchrony strength in the two regions.     

Subthalamic nucleus neuronal firing rate increases with Parkinson's disease progression

Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic cells in the central nervous system, in particular the substantia nigra, resulting in an unrelenting loss of motor and nonmotor function. Animal models of Parkinson's disease reveal hyperactive neurons in the subthalamic nucleus that have increased firing rates and bursting activity compared with controls. Although subthalamic nucleus activity has been characterized in patients with advanced‐stage Parkinson's disease, it has not been described in patients with early‐stage Parkinson's disease. Here we present the results of subthalamic nucleus neuronal recordings from patients with early‐stage Parkinson's disease (Hoehn and Yahr stage II) enrolled in an ongoing clinical trial compared with recordings from age‐ and sex‐matched patients with advanced Parkinson's disease. Subthalamic nucleus neurons had a significantly lower firing rate in early versus advanced Parkinson's disease (28.7 vs 36.3 Hz; P < .01). The overall activity of the subthalamic nucleus was also significantly lower in early versus late Parkinson's disease, as measured by background neuronal noise (12.4 vs 14.0 mV; P < .05). No significant difference was identified between groups in the bursting or variability of neuronal firing in the subthalamic nucleus, as measured by a burst index or the interspike interval coefficient of variability. The results suggest that neuronal firing in the subthalamic nucleus increases with Parkinson's disease progression. © 2011 Movement Disorder Society     

Subthalamic nucleus stimulation selectively improves motor and visual memory performance in Parkinson's disease

Although the treatment of Parkinson's disease via subthalamic stimulation yields remarkable improvements in motor symptoms, its effects on memory function are less clear. In this context, we previously demonstrated dissociable effects of levodopa therapy on parkinsonian performance in spatial and nonspatial visual working memory. Here we used the same protocol with an additional, purely motor task to investigate visual memory and motor performance in 2 groups of patients with Parkinson's disease with or without subthalamic stimulation. In each stimulation condition, subjects performed a simple motor task and 3 successive cognitive tasks: 1 conditional color‐response association task and 2 visual (spatial and nonspatial) working memory tasks. The Parkinson's groups were compared with a control group of age‐matched healthy subjects. Our principal results demonstrated that (1) in the motor task, stimulated patients were significantly improved with respect to nonstimulated patients and did not differ significantly from healthy controls, and (2) in the cognitive tasks, stimulated patients were significantly improved with respect to nonstimulated patients, but both remained significantly impaired when compared with healthy controls. These results demonstrate selective effects of subthalamic stimulation on parkinsonian disorders of motor and visual memory functions, with clear motor improvement for stimulated patients and a partial improvement for their visual memory processing. © 2011 Movement Disorder Society     

Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease

Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS‐exacerbated dysarthria. We use the unilateral, 6‐hydroxydopamine (6‐OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism‐associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism‐associated changes in each of these metrics, the subthalamic stimulated 6‐OHDA rat is a good model of DBS‐induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. © 2015 Wiley Periodicals, Inc.     

The rhythm of the executive gate of speech: subthalamic low‐frequency oscillations increase during verbal generation

We investigated neurophysiological mechanisms of subthalamic nucleus involvement in verbal fluency through a verbal generation task. The subthalamic nucleus is thought to act as a behavioural go/no‐go instance by means of oscillatory communication in the theta band with the prefrontal cortex. Because subthalamic alpha‐theta frequency stimulation has been shown to exert beneficial effects on verbal fluency in Parkinson′s disease, we hypothesized that an alpha‐theta oscillatory network involving the subthalamic nucleus underlies verbal generation task performance as a gating instance for speech execution. Postoperative subthalamic local field potential recordings were performed during a verbal generation compared to a control task. Time‐frequency analysis revealed a significant alpha‐theta power increase and enhanced alpha‐theta coherence between the subthalamic nucleus and the frontal surface EEG during the verbal generation task. Beta and gamma oscillations were not significantly modulated by the task. Power increase significantly correlated with verbal generation performance. Our results provide experimental evidence for local alpha‐theta oscillatory activity in the subthalamic nucleus and coherence to frontal associative areas as a neurophysiological mechanism underlying a verbal generation task. Thus, verbal fluency improvement during subthalamic alpha‐theta stimulation in Parkinson′s disease is likely due to an enhancement of alpha‐theta oscillatory network activity. Alpha‐theta oscillations can be interpreted as the rhythmic gating signature in a speech executing subthalamic‐prefrontal network.     

Deep brain stimulation of the subthalamic nucleus transiently enhances loss-chasing behaviour in patients with Parkinson's disease

Dopaminergic treatments are associated with impulse control disorders such as pathological gambling in a subset of patients with Parkinson's Disease. While deep brain stimulation of the subthalamic nucleus has been reported to reduce symptoms of impulse control disorders in some Parkinson's Disease patients, little is known about its specific effects on gambling behaviour. In this experiment, we investigated the effects of deep brain stimulation of the subthalamic nucleus on one of the central features of pathological gambling: the tendency to chase losses. Loss-chasing is associated with impaired control over gambling behaviour and it is one of the most salient features of pathological gambling as it presents in the clinic. Twenty two patients with advanced idiopathic Parkinson's Disease and chronically implanted subthalamic nucleus electrodes for deep brain stimulation completed a simple laboratory model of loss-chasing behaviour twice: once with and once without stimulation. Exploratory analysis indicated that deep brain stimulation of the subthalamic nucleus increased the value of losses chased by patients with Parkinson's Disease when shifting from off- to on-stimulation. These effects were not attributable to changes in state affect or to the motor impairments produced by the withdrawal of deep brain stimulation of the subthalamic nucleus. The effects of the stimulation on the value of losses chased were more pronounced in female than in male patients and reduced in patients taking dopamine receptor agonists. Collectively, these results suggest that deep brain stimulation of the subthalamic nucleus can transiently alter the evaluation of accumulated losses during gambling episodes in idiopathic Parkinson's Disease.     

Decreased neuronal activity in reward circuitry of pathological gamblers during processing of personal relevant stimuli

Pathological gamblers impress by an increasing preoccupation with gambling, which leads to the neglect of stimuli, interests, and behaviors that were once of high personal relevance. Neurobiologically dysfunctions in reward circuitry underlay pathological gambling. To explore the association of both findings, we investigated 16 unmedicated pathological gamblers using an fMRI paradigm that included two different tasks: the evaluation of personal relevance and a reward task that served as a functional localizer. Pathological gamblers revealed diminished deactivation during monetary loss events in some of our core reward regions, the left nucleus accumbens and the left putamen. Moreover, while pathological gamblers viewed stimuli of high personal relevance, we found decreased neuronal activity in all of our core reward regions, including the bilateral nucleus accumbens and the left ventral putamen cortex as compared to healthy controls. We demonstrated for the first time altered neuronal activity in reward circuitry during personal relevance in pathological gamblers. Our findings may provide new insights into the neurobiological basis of pathological gamblers' preoccupation by gambling. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Subthalamic–Cortical Network Reorganization during Parkinson's Tremor

Tremor, a common and often primary symptom of Parkinson''s disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from 10 patients (9 male, 1 female) performing a naturalistic visual–motor task. From this task, we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state.SIGNIFICANCE STATEMENT Tremor is a common symptom of Parkinson''s disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello–thalamic–cortical circuits, it is unknown how these structures functionally interact to produce tremor. In this article, we analyzed intracranial recordings from the subthalamic nucleus and sensorimotor cortex in patients with PD undergoing deep brain stimulation surgery. Using an intraoperative task, we examined tremor in two separate dynamic contexts: when tremor first emerged, and when tremor was sustained. We believe that these findings reconcile several models of Parkinson''s tremor, while describing the short-timescale dynamics of subcortical–cortical interactions during tremor for the first time. These findings may describe a framework for developing proactive and responsive neurostimulation models for specifically treating tremor.     

Beta activity in the subthalamic nucleus during sleep in patients with Parkinson's disease

The recordings of local field potentials in the subthalamic nucleus in patients with Parkinson's disease (PD), carried out through the stimulators implanted to treat the motor symptoms of the disease, show a prominent basal (“off”) activity in the beta range, which is attenuated after dopaminergic therapy. A recent study described improvement of parkinsonian features during rapid eyes movements (REM) sleep. We describe, for the first time, the changes in activity of the subthlamic nucleus (STN) during different sleep stages in Parkinson's disease with special interest in the beta band. Ten patients with PD treated with deep brain stimulation of the STN were studied. Subthalamic local field potentials (LFPs) were recorded through the stimulation electrodes during wakefulness (“off” medication) and different sleep stages. In Stage 2 and slow‐wave sleep, a significant decrease of beta activity was recorded. During REM sleep, beta power values were similar to wakefulness values or even higher. These findings indicate that STN activity is modulated and modified during different sleep stages. The increased beta activity during REM sleep is a new but unexpected finding, which requires further analysis. © 2008 Movement Disorder Society     

Deep brain stimulation of the subthalamic nucleus improves sense of well‐being in parkinson's disease

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of Parkinson's disease. Although a range of psychiatric and behavioral problems have been documented following deep brain stimulation, the short‐term effects of subthalamic nucleus stimulation on patients' mood have only been investigated in a few studies. Our aim was to compare self‐reported mood in Parkinson's patients with deep brain stimulation of the subthalamic nucleus ON versus OFF. Twenty‐three Parkinson's patients with bilateral deep brain stimulation of the subthalamic nucleus and 11 unoperated Parkinson's patients completed a mood visual analogue scale twice. Operated patients were tested with deep brain stimulation of the subthalamic nucleus both ON and OFF. All were assessed on medication. The operated Parkinson's group reported feeling significantly better coordinated, stronger, and more contented with deep brain stimulation ON compared to OFF. Fourteen of the 16 mood scales changed in a positive direction when deep brain stimulation of the subthalamic nucleus was ON. When changes in motor scores were taken into account, the operated patients still reported feeling better‐coordinated, but also less gregarious with stimulation ON. Unoperated Parkinson's patients showed no differences on any of these measures between their 2 ratings. Short‐term changes in deep brain stimulation of the subthalamic nucleus have a small and mostly positive effect on mood, which may be partly related to improvements in motor symptoms. The implications for day‐to‐day management of patients with deep brain stimulation of the subthalamic nucleus are discussed. © 2012 Movement Disorder Society     

Pathological Gambling in Parkinson's disease: Autonomic measures supporting impaired decision‐making

According to the somatic marker hypothesis, autonomic measures and arousal modulation can reveal a difference in subgroups of patients developing impaired decision‐making because of addictions. Previously, pathological gambling (PG) and Parkinson's disease (PD) have been associated with differential arousal levels during gambling behavior. However, no research considered the specific autonomic responses of Parkinson's disease patients with pathological gambling and with a previous history of gambling. Thus, this study investigated skin conductance responses (SCRs), skin conductance level (SCL) and heart rate (HR) during the Iowa Gambling Task (IGT) in two groups of PD patients with gambling disorder, active (PD Gamblers; n = 14) or remitted (PD Non‐Gamblers; n = 13) and a control group of patients with Parkinson's disease only (n = 13). Anticipatory autonomic responses to disadvantageous decks and advantageous decks during the Iowa Gambling Task were measured for each participant. The PD Gamblers group performed worse than the PD Non‐Gamblers and the control groups at the IGT task and exhibited lower SCRs, SCL, and HR during the decision‐making processing of cards belonging to disadvantageous decks. The role of autonomic and behavioral measures was considered.     

Disruption of dopaminergic transmission remodels tripartite synapse morphology and astrocytic calcium activity within substantia nigra pars reticulata

The substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia circuitry particularly sensitive to pathological dopamine depletion. Indeed, hyperactivity of SNr neurons is known to be responsible for some motor disorders characteristic of Parkinson's disease. The neuronal processing of basal ganglia dysfunction is well understood but, paradoxically, the role of astrocytes in the regulation of SNr activity has rarely been considered. We thus investigated the influence of the disruption of dopaminergic transmission on plastic changes at tripartite glutamatergic synapses in the rat SNr and on astrocyte calcium activity. In 6‐hydroxydopamine‐lesioned rats, we observed structural plastic changes of tripartite glutamatergic synapses and perisynaptic astrocytic processes. These findings suggest that subthalamonigral synapses undergo morphological changes that accompany the pathophysiological processes of Parkinson's disease. The pharmacological blockade of dopaminergic transmission (with sulpiride and SCH‐23390) increased astrocyte calcium excitability, synchrony and gap junction coupling within the SNr, suggesting a functional adaptation of astrocytes to dopamine transmission disruption in this output nucleus. This hyperactivity is partly reversed by subthalamic nucleus high‐frequency stimulation which has emerged as an efficient symptomatic treatment for Parkinson's disease. Therefore, our results demonstrate structural and functional reshaping of neuronal and glial elements highlighting a functional plasticity of neuroglial interactions when dopamine transmission is disrupted. GLIA 2015;63:673–683     

Speed effects of deep brain stimulation for Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) accelerates reaction time (RT) in patients with Parkinson's disease (PD), particularly in tasks in which decisions on the response side have to be made. This might indicate that DBS speeds up both motor and nonmotor operations. Therefore, we studied the extent to which modifications of different processing streams could explain changes of RT under subthalamic DBS. Ten PD patients on‐DBS and off‐DBS and 10 healthy subjects performed a choice‐response task (CRT), requiring either right or left finger button presses. At the same time, EEG recordings were performed, so that RTs could be assessed together with lateralized readiness potentials (LRP), indicative of movement preparation. Additionally, an oddball task (OT) was run, in which right finger responses to target stimuli were recorded along with cognitive P300 responses. Generally, PD patients off‐DBS had longer RTs than controls. Subthalamic DBS accelerated RT only in CRT. This could largely be explained by analog shortenings of LRP. No DBS‐dependent changes were identified in OT, neither on the level of RT nor on the level of P300 latencies. It follows that RT accelerations under DBS of the STN are predominantly due to effects on the timing of motor instead of nonmotor processes. This starting point explains why DBS gains of response speed are low in tasks in which reactions are initiated from an advanced level of movement preparation (as in OT), and high whenever motor responses have to be raised from scratch (as in CRT). © 2010 Movement Disorder Society