STN-DBS Increases Proactive but Not Retroactive Interference During Verbal Learning in PD.

BACKGROUND: Proactive interference (PI) refers to the interference of previously learned materials with new learning and reflects the failure of inhibitory processes in memory. Retroactive interference (RI) refers to the unfavorable effect of new learning on the later recall of previously learned information. Although subthalamic nucleus deep brain stimulation (STN-DBS) does not affect global cognition in Parkinson's disease (PD), it has negative effects on specific aspects of cognition, including verbal fluency and executive inhibitory control of action.To this end, we set to test the acute effect of STN-DBS on PI and RI during verbal learning. METHODS: Twenty PD patients with STN-DBS were tested on the California Verbal Learning Test-II using an ON/OFF stimulation design. RESULTS: The results showed that stimulation increased PI ON stimulation (P = 0.012) but had no effect on RI (P = 0.816). CONCLUSIONS: Our results extend the role of STN to the inhibitory control that is required during memory encoding or recall for prevention of PI. © 2020 International Parkinson and Movement Disorder Society.

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 evidence on the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on action restraint on Go/NoGO reaction time (RT) tasks in Parkinson's disease (PD) is inconsistent; with some studies reporting no effect and others finding that STN stimulation interferes with withholding of responses and results in more commission errors relative to STN-DBS off. We used a task in which the probability of Go stimuli varied from 100% (simple RT task) to 80, 50 and 20% (probabilistic Go/NoGo RT task), thus altering the prepotency of the response and the difficulty in withholding it on NoGo trials. Twenty PD patients with STN-DBS, ten unoperated PD patients and ten healthy controls participated in the study. All participants were tested twice; the order of on versus off stimulation for STN-DBS PD patients was counterbalanced. Both STN-DBS and unoperated PD patients were tested on medication. The results indicated that STN-DBS selectively decreased discriminability when the response was most prepotent (high--80%, as compared to low Go probability trials--50 and 20%). Movement times were faster with STN stimulation than with DBS off across different Go probability levels. There was neither an overall nor a selective effect of STN-DBS on RTs depending on the level of Go probability. Furthermore, compared to healthy controls, both STN-DBS and unoperated PD patients were more prone to making anticipatory errors; which was not influenced by STN stimulation. The results provide evidence for 'load-dependent' effects of STN stimulation on action restraint as a function of the prepotency of the Go response.

Problem solving, impulse control and planning in patients with early- and late-stage Huntington's disease.

Sub-domains of executive functions, including problems with planning, accuracy, impulsivity, and inhibition, are core features of Huntington's disease. It is known that the decline of cognitive function in Huntington's disease is related to the anatomical progression of pathology in the basal ganglia. However, it remains to be determined whether the severity of executive dysfunction depends on the stage of the disease. To examine the severity of sub-domains of executive dysfunction in early- and late-stage Huntington's disease, we studied performance in the Tower of London task of two groups of Huntington's disease patients (Group 1: early, n = 23, and Group 2: late stage, n = 29), as well as a third group of age, education, and IQ matched healthy controls (n = 34). During the task, we measured the total number of problems solved, total planning time, and total number of breaks taken. One aspect of executive function indexed by the number of solved problems seems to progress in the course of the disease. Late-stage Huntington's disease patients scored significantly worse than early-stage patients and controls, and early-stage patients scored significantly worse than controls on this measure of accuracy. In contrast, late- and early-stage HD patients did not differ in terms of planning time and number of breaks. Early- and late-stage HD pathology has a different impact on executive sub-domains. While accuracy differs between early- and late-stage HD patients, other domains like planning time and number of breaks do not. Striatal degeneration, which is a characteristic feature of the disease, might not affect all aspects of executive function in HD.

The subthalamic nucleus and inhibitory control: impact of subthalamotomy in Parkinson's disease.

The aim of our study was to investigate two inter-related hypotheses about the role of the subthalamic nucleus. First that the subthalamic nucleus plays a role in adjusting response thresholds and speed-accuracy trade-offs and second that it is involved in reactive and proactive inhibition and conflict resolution. These were addressed by comparing the performance of 10 patients with Parkinson's disease treated with right subthalamotomy and 12 patients with left subthalamotomy, to 14 unoperated patients with Parkinson's disease and 23 age-matched healthy control participants on a conditional stop signal task and applying the drift diffusion model. Unilateral subthalamotomy significantly improved Parkinson's disease motor signs. Patients with right subthalamotomy had significantly faster Go reaction times with their contra-lesional hand than the unoperated patients and did not differ from the control participants, indicating their speed of response initiation was 'normalized'. However, operated patients made significantly more discrimination errors than unoperated patients and controls, suggesting that subthalamotomy influenced speed-accuracy trade-offs. This was confirmed by the drift diffusion model, revealing that while the unoperated patients had significantly lower drift rate and higher response thresholds than the control participants, the response thresholds for the operated groups did not differ from the controls and the patients with right subthalamotomy had a significantly higher drift rate than unoperated patients and similar to that of controls. The drift diffusion model further established that unlike the control participants, operated patients failed to show context-dependent strategic modulation of response thresholds. The patients with right subthalamotomy could not engage in late phase, fast inhibition of the response and showed minimal proactive inhibition when tested with the contra-lesional hand. These results provide strong evidence that the subthalamic nucleus is involved in response inhibition, in modulating the rate of information accumulation and the response threshold and influencing the balance between speed and accuracy of performance. Accordingly, the subthalamic nucleus can be considered a key component of the cerebral inhibitory network.

Probabilistic classification learning with corrective feedback is associated with in vivo striatal dopamine release in the ventral striatum, while learning without feedback is not.

The basal ganglia (BG) mediate certain types of procedural learning, such as probabilistic classification learning on the 'weather prediction task' (WPT). Patients with Parkinson's disease (PD), who have BG dysfunction, are impaired at WPT-learning, but it remains unclear what component of the WPT is important for learning to occur. We tested the hypothesis that learning through processing of corrective feedback is the essential component and is associated with release of striatal dopamine. We employed two WPT paradigms, either involving learning via processing of corrective feedback (FB) or in a paired associate manner (PA). To test the prediction that learning on the FB but not PA paradigm would be associated with dopamine release in the striatum, we used serial (11) C-raclopride (RAC) positron emission tomography (PET), to investigate striatal dopamine release during FB and PA WPT-learning in healthy individuals. Two groups, FB, (n = 7) and PA (n = 8), underwent RAC PET twice, once while performing the WPT and once during a control task. Based on a region-of-interest approach, striatal RAC-binding potentials reduced by 13-17% in the right ventral striatum when performing the FB compared to control task, indicating release of synaptic dopamine. In contrast, right ventral striatal RAC binding non-significantly increased by 9% during the PA task. While differences between the FB and PA versions of the WPT in effort and decision-making is also relevant, we conclude striatal dopamine is released during FB-based WPT-learning, implicating the striatum and its dopamine connections in mediating learning with FB.

Selective executive dysfunction but intact risky decision-making in early Huntington's disease.

Executive dysfunction, including problems with decision-making, inhibition of prepotent responses, and verbal fluency, are main features of Huntington's disease (HD). The decline of executive function in HD is related to the anatomical progression of HD pathology in the basal ganglia, where the earliest changes of neuronal cell death are seen in the dorsolateral caudate. To examine the specific pattern of executive dysfunction in early HD, 18 patients with early HD were assessed on: (1) the Iowa Gambling Task to measure risky decision making, (2) the Stroop test to measure inhibition of prepotent responses, and (3) the verbal fluency test to measure internally guided word search and production, necessitating suppression of retrieval/production of inappropriate words and monitoring of the output. Patients with early HD were significantly impaired on the Stroop and verbal fluency tests relative to controls. However, Iowa Gambling Task performance was comparable across the 2 groups. This pattern of selective executive dysfunction in early HD probably reflects the fact that inhibitory processing involved in both the Stroop and verbal fluency tests recruits the dorsolateral caudate and its cortical connections, which are dysfunctional in early HD, whereas risky decision-making during the Iowa Gambling Task recruits the ventromedial caudate and its connections, which remain spared early on in the disease. The current results demonstrate that the deterioration of executive functioning in HD is variable and that some types of executive processing might already be impaired in early HD, whereas others remain intact.

Bilateral stimulation of the subthalamic nucleus has differential effects on reactive and proactive inhibition and conflict-induced slowing in Parkinson's disease.

It has been proposed that the subthalamic nucleus (STN) mediates response inhibition and conflict resolution through the fronto-basal ganglia pathways. Our aim was to compare the effects of deep brain stimulation (DBS) of the STN on reactive and proactive inhibition and conflict resolution in Parkinson's disease using a single task. We used the conditional Stop signal reaction time task that provides the Stop signal reaction time (SSRT) as a measure of reactive inhibition, the response delay effect (RDE) as a measure of proactive inhibition and conflict-induced slowing (CIS) as a measure of conflict resolution. DBS of the STN significantly prolonged SSRT relative to stimulation off. However, while the RDE measure of proactive inhibition was not significantly altered by DBS of the STN, relative to healthy controls, RDE was significantly lower with DBS off but not DBS on. DBS of the STN did not alter the mean CIS but produced a significant differential effect on the slowest and fastest RTs on conflict trials, further prolonging the slowest RTs on the conflict trials relative to DBS off and to controls. These results are the first demonstration, using a single task in the same patient sample, that DBS of the STN produces differential effects on reactive and proactive inhibition and on conflict resolution, suggesting that these effects are likely to be mediated through the impact of STN stimulation on different fronto-basal ganglia pathways: hyperdirect, direct and indirect.

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.

Levodopa medication does not influence motor inhibition or conflict resolution in a conditional stop-signal task in Parkinson's disease.

Evidence from animal, clinical, and imaging studies suggests that the basal ganglia and their frontal connections mediate motor inhibition, but the role of dopamine remains unclear. The aim of our study was to investigate, for the first time, whether levodopa medication influences motor inhibition and conflict resolution on the conditional stop-signal reaction time task in patients with Parkinson's disease (PD) tested on or off their medication. Sixteen PD patients and 17 healthy controls performed the conditional stop-signal reaction time (SSRT) task, which requires inhibition of responses when a stop signal is presented on "critical" trials. Additionally, on "non-critical" trials, participants are instructed to ignore the stop signal and respond, thus generating conflict between motor inhibition and initiation; and conflict-induced slowing (CIS) on these "non-critical" trials. Levodopa medication did not significantly influence response initiation, inhibition (SSRT) or the measure of conflict resolution (CIS). Compared to healthy controls, PD patients showed significantly worse response initiation and inhibition both on and off their levodopa medication. Our results suggest that motor inhibition or conflict-induced slowing on the conditional stop-signal RT task are not altered by dopamine replacement in PD. This conclusion is consistent with evidence from animal studies and clinical pharmacological investigations suggesting a role for noradrenaline in motor inhibition and impulsivity.

Deficits in inhibitory control and conflict resolution on cognitive and motor tasks in Parkinson's disease.

Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinson's disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.

Impaired ideomotor limb apraxia in cortical and subcortical dementia: a comparison of Alzheimer's and Huntington's disease.

BACKGROUND: Although ideomotor limb apraxia is often considered to occur only in dementia with cortical involvement like Alzheimer's disease (AD), it is also frequently seen in dementia with subcortical degeneration like Huntington's disease (HD). METHODS: To assess the occurrence of ideomotor limb apraxia, 46 patients with HD (27 men) and 37 patients with AD (16 men), matched for cognitive performance, were assessed with an apraxia test battery containing tests of the imitation of meaningless hand and finger gestures, the performance of meaningful gestures and of pantomimic movements. RESULTS: There was a high frequency of ideomotor limb apraxia in both AD and HD patients. For the assessment of hands' imitation 13.5% of the AD patients and 41.3% of the HD patients were apraxic, for fingers' imitation 21.6% (AD) and 41.3% (HD) were apraxic, for gestures 27.0% (AD) and 32.6% (HD), and for the assessment of pantomimic movements 24.3% (AD) and 52.2% (HD) showed apraxia. In the AD patients, disease severity was related to the occurrence of apraxia. CONCLUSIONS: Ideomotor limb apraxia is a common sign in both groups of patients, occurring in a high percentage. For particular neuropsychological deficits, including ideomotor limb apraxia, a division of dementia in a subcortical and cortical subtype seems to be clinically not meaningful.

The contribution of primary motor cortex is essential for probabilistic implicit sequence learning: evidence from theta burst magnetic stimulation.

Theta burst transcranial magnetic stimulation (TBS) is considered to produce plastic changes in human motor cortex. Here, we examined the inhibitory and excitatory effects of TBS on implicit sequence learning using a probabilistic serial reaction time paradigm. We investigated the involvement of several cortical regions associated with implicit sequence learning by examining probabilistic sequence learning in five age- and IQ-matched groups of healthy participants following continuous inhibitory TBS over primary motor cortex (M1); or the supplementary motor area (SMA) or dorsolateral prefrontal cortex (DLPFC) or following intermittent excitatory TBS of M1; or after sham TBS. Relative to sham TBS, probabilistic sequence learning was abolished by inhibitory TBS over M1, demonstrating that this region is critical for implicit motor sequence learning. Sequence learning was not significantly affected by inhibitory TBS over the SMA, DLPFC or excitatory TBS over M1. These results demonstrate that the M1 mediates implicit sequence learning.

Abnormal explicit but normal implicit sequence learning in premanifest and early Huntington's disease.

Learning may occur with or without awareness, as explicit (intentional) or implicit (incidental) learning. The caudate nucleus and the putamen, which are affected early in Huntington's disease (HD), are thought to be essential for motor sequence learning. However, the results of existing studies are inconsistent concerning presence/absence of deficits in implicit and explicit motor sequence learning in HD. We assessed implicit and explicit motor sequence learning using sequences of equivalent structure in 15 individuals with a positive HD genetic test (7 premanifest; 8 early stage disease) and 11 matched controls. The HD group showed evidence of normal implicit motor sequence learning, whereas explicit motor sequence learning was impaired in manifest and premanifest HD gene carriers, with progressive decline with progressive disease. Explicit sequence learning may be a useful cognitive biomarker for HD progression.

Dissociable effects of subthalamic nucleus deep brain stimulation surgery and acute stimulation on verbal fluency in Parkinson's disease.

OBJECT: Verbal fluency (VF) is the cognitive test which shows the most consistent and persistent post-operative decline after subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD). However, the reasons are not completely understood, and the debate has focused on two hypotheses: a surgical effect or an acute STN-DBS effect. METHODS: We recruited 3 PD samples: (1) a group assessed before and after STN-DBS surgery (2) a group assessed On vs. Off STN-DBS and (3) an unoperated PD control group. All groups performed letter, category and switching category VF tasks. The total number of correct words generated were noted and measures of clustering and switching were also obtained. RESULTS: We found a significant effect of STN-DBS surgery on all VF tasks which was associated with a post-operative decline in the total number of words generated, and a reduction of phonemic switching during the letter and category VF tasks, and a reduction of semantic clustering for category VF. By contrast to the effects of surgery, acute On vs. Off stimulation did not influence the number of words generated on any of the VF tasks. Acute stimulation only produced two effects on the category VF task: increased semantic cluster size and decreased number of semantic switches when STN-DBS was switched On. CONCLUSIONS: This study differentiates between the effects of STN-DBS surgery and acute stimulation on VF performance. Our findings indicate that the STN-DBS effect on VF are a surgical and not an acute STN stimulation effect.

The effect of feedback on non-motor probabilistic classification learning in Parkinson's disease.

It has been proposed that procedural learning is mediated by the striatum and, it has been reported that patients with Parkinson's disease (PD) are impaired on the weather prediction task (WPT) which involves probabilistic classification learning with corrective feedback (FB). However, PD patients were not impaired on probabilistic classification learning when it was performed without corrective feedback, in a paired associate (PA) manner; suggesting that the striatum is involved in learning with feedback rather than procedural learning per se. In Experiment 1 we studied FB- and PA-based learning in PD patients and controls and, as an improvement on previous methods, used a more powerful repeated measures design and more equivalent test phases during FB and PA conditions (including altering the FB condition to remove time limits on responding). All participants (16 PD patients, H&Y I-III and 14 matched-controls) completed the WPT under both FB and PA conditions. In contrast to previous results, in Experiment 1 we did not find a selective impairment in the PD group on the FB version of the WPT relative to controls. In Experiment 2 we used a between groups design and studied learning with corrective FB in 11 PD patients (H&Y I.5-IV) and 13 matched controls on a more standard version of the WPT similar to that used in previous studies. With such a between groups design for comparison of FB and PA learning on the WPT in PD, we observed impaired learning in PD patients relative to controls across both the FB and PA versions of the WPT. Most importantly, in Experiment 2 we also failed to find a selective impairment on the FB version of the WPT coupled with normal learning on the PA version in PD patients relative to controls. Our results do not support the proposal that the striatum plays a specific role in probabilistic classification learning with feedback.

Patients with Parkinson's disease learn to control complex systems via procedural as well as non-procedural learning.

The striatum is considered to mediate some forms of procedural learning. Complex dynamic control (CDC) tasks involve an individual having to make a series of sequential decisions to achieve a specific outcome (e.g. learning to operate and control a car), and they involve procedural learning. The aim of this study was to test the hypothesis that patients with Parkinson's disease who have striatal dysfunction, are impaired on CDC tasks only when learning involves procedural learning. 26 patients with Parkinson's disease (PD) and 26 age-matched controls performed two CDC tasks, one in which training was observation-based (non-procedural), and a second in which training was action-based (procedural). Both groups were able to control the system to a specific criterion equally well, regardless of the training condition. However, when reporting their knowledge of the underlying structure of the system, both groups showed poorer accuracy when learning took place through observation-based compared with action-based training. Moreover, the controls' accuracy in reporting the underlying structure of the systems was superior to that of PD patients. The findings suggest that the striatal dysfunction in Parkinson's disease is not associated with impairment of procedural learning, regardless of whether the task involved procedural learning or not. It is possible that the learning and performance on CDC tasks are mediated by perceptual priming mechanisms in the neocortex.

STN stimulation alters pallidal-frontal coupling during response selection under competition.

To investigate the effects of bilateral subthalamic nucleus (STN) stimulation on patterns of brain activation during random number generation (RNG), a task that requires suppression of habitual counting and response selection under competition. We used H(2)(15)O positron emission tomography to investigate the changes of regional cerebral blood flow (rCBF) induced by bilateral STN stimulation during a RNG task, in six patients with Parkinson's disease. Paced RNG at 1 Hz was compared with a control counting task. Both tasks were performed off medication with deep brain stimulation on and off. Subthalamic nucleus stimulation had a negative effect on performance of fast-paced RNG, leading to reduced randomness and increased habitual counting. Subthalamic nucleus stimulation also induced a reduction of rCBF in the left dorsal frontal gyrus, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior and right anterior cingulate, and an increase of rCBF in the right internal globus pallidum (GPi) during RNG. Stimulation of the STN significantly altered pallidal coupling with frontal and temporal areas compared with when the stimulators were off. In conclusion, during RNG: (i) STN stimulation activates its output neurons to the GPi; (ii) STN stimulation induces increased inhibition of a prefrontal-cingulate network. This is the first direct evidence that STN stimulation significantly alters pallidal coupling with prefrontal, cingulate, and temporal cortices during performance of a task that requires response selection under competition.

The striatum and probabilistic implicit sequence learning.

The distinction between implicit (unconscious) and explicit (conscious) learning is controversial. Some argue that explicit learning is dependent on the medial temporal lobes, whereas implicit learning is mediated by the basal ganglia and others propose that all learning is explicit. The purpose of the present study was to investigate the involvement of the basal ganglia in implicit learning by examining learning of a probabilistic sequence of targets, in patients with Parkinson's disease (PD) and controls. Following learning, we assessed participants' awareness of the sequence structure by asking them to generate or withhold sequence consistent responses (process dissociation procedure) and to perform a recognition test in which measures of priming and recognition were obtained concurrently. Although the PD group demonstrated evidence of probabilistic sequence learning in this study, learning was significantly attenuated compared to controls. Residual learning in the PD group was genuinely implicit in nature because (a) PD patients were not able to control the expression of their acquired knowledge, and (b) their knowledge supported subsequent priming of sequence-consistent responses but recognition ratings were at chance. In contrast, following learning controls were capable of above chance recognition indicating that their sequential knowledge was acquired in a more explicit way. The results support the view that (i) the basal ganglia contribute to probabilistic implicit sequence learning (ii) that such learning can occur implicitly without explicit knowledge in PD patients.

Motor cortex inhibition by TMS reduces cognitive non-motor procedural learning when immediate incentives are present.

Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the primary motor area (M1) impairs motor sequence-learning, but not basic motor function. It is unknown if this is specific for motor forms of procedural learning or a more general effect. To investigate, we tested the effect of M1-inhibition on the weather prediction task (WPT), a learning task with minimal motor learning component. In the WPT, participants learn arbitrary, probabilistic, associations between sets of meaningless cues and fictional outcomes. In our "Feedback" (FB) condition, they received monetary rewards/punishments during learning. In the "paired associate" (PA) condition they learned the same information by passive observation of associations. The observational and feedback learning conditions were matched for their non-learning-specific motor demands. In each of two FB or PA sessions, we delivered Real (inhibitory) or Sham continuous theta-burst (cTBS) to the left-M1, before 150 training-trials. We then tested learning with 42 trials without feedback immediately after learning and again 1-h after cTBS. Compared to Sham, Real cTBS reduced performance during FB-learning, when learning was immediately reinforced, but not when knowledge was tested after PA learning. Furthermore, when FB-based memory was tested after learning without immediate incentive, there was no effect of TMS compared to post-PA test performance, showing the TMS effect operated only in the presence of incentive and feedback. We conclude that M1 is a node in a network underlying feedback-driven procedural learning and inhibitory rTMS there results in decreased network efficiency.

Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition.

BACKGROUND: Stopping an ongoing motor response or resolving conflict induced by conflicting stimuli are associated with activation of a right-lateralized network of inferior frontal gyrus (IFG), pre-supplementary motor area (pre-SMA) and subthalamic nucleus (STN). However, the roles of the right IFG and pre-SMA in stopping a movement and in conflict resolution remain unclear. We used continuous theta burst stimulation (cTBS) to examine the involvement of the right IFG and pre-SMA in inhibition and conflict resolution using the conditional stop signal task. METHODS: We measured stop signal reaction time (SSRT, measure of reactive inhibition), response delay effect (RDE, measure of proactive action restraint) and conflict induced slowing (CIS, measure of conflict resolution). RESULTS: Stimulation over the pre-SMA resulted in significantly shorter SSRTs (improved inhibition) compared to sham cTBS. This effect was not observed for CIS, RDE, or any other measures. cTBS over the right IFG had no effect on SSRT, CIS, RDE or on any other measure. CONCLUSIONS: The improvement of SSRT with cTBS over the pre-SMA suggests its critical contribution to stopping ongoing movements.