Effects Of Subthalamic Nucleus Stimulation Research Articles

Selective Activation of Subthalamic Nucleus Output Quantitatively Scales Movements.

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatments of Parkinsonian motor symptoms. According to the dominant model, the STN output can suppress movement by enhancing inhibitory basal ganglia (BG) output via the indirect pathway, and disrupting STN output using DBS can restore movement in Parkinson's patients. But the mechanisms underlying STN DBS remain poorly understood, as previous studies usually relied on electrical stimulation, which cannot selectively target STN output neurons. Here, we selectively stimulated STN projection neurons using optogenetics and quantified behavior in male and female mice using 3D motion capture. STN stimulation resulted in movements with short latencies (10-15 ms). A single pulse of light was sufficient to generate movement, and there was a highly linear relationship between stimulation frequency and kinematic measures. Unilateral stimulation caused movement in the ipsiversive direction (toward the side of stimulation) and quantitatively determined head yaw and head roll, while stimulation of either STN raises the head (pitch). Bilateral stimulation does not cause turning but raised the head twice as high as unilateral stimulation of either STN. Optogenetic stimulation increased the firing rate of STN neurons in a frequency-dependent manner, and the increased firing is responsible for stimulation-induced movements. Finally, stimulation of the STN's projection to the brainstem mesencephalic locomotor region was sufficient to reproduce the behavioral effects of STN stimulation. These results question the common assumption that the STN suppresses movement, and instead suggest that STN output can precisely specify action parameters via direct projections to the brainstem.SIGNIFICANCE STATEMENT Our results question the common assumption that the subthalamic nucleus (STN) suppresses movement, and instead suggest that STN output can precisely specify action parameters via direct projections to the brainstem.

Non-motor effects of subthalamic nucleus stimulation in Parkinson patients.

The current white matter connectivity analyses of the subthalamic region have focused on the motor effects of deep brain stimulation. We investigate white matter connectivity associated with the stimulation-induced non-motor acute clinical effects in three domains: mood changes, dizziness, and sweating. We performed whole-brain probabilistic tractography seeded from the domain-specific stimulation volumes. The resultant connectivity maps were statistically compared across patients. The cortical voxels associated with each non-motor domain were compared with stimulation-induced motor improvements in a multivariate model. The resulting voxel maps were thresholded for false discovery (FDR q < 0.05) and clustered using a multimodal atlas. We also performed a group-level parcellation of stimulation volumes to identify the local pathways associated with each non-motor domain. The non-motor effects were rarely observed during stimulation titration: from 1100 acute clinical effects, mood change was observed in 14, dizziness in 23, and sweating in 20. Distinct cortical clusters were associated with each domain; notably, mood change was associated with voxels in the salience network and dizziness with voxels in the visual association cortex. The subthalamic parcellation yielded a mediolateral gradient, with the motor parcel being lateral and the non-motor parcels medial. We also observed an anteroposterior organization in the medial non-motor clusters with mood changes being anterior, followed posteriorly by dizziness, and sweating. We interpret these findings based on the literature and foresee these to be useful in guiding DBS programming.

Sex-specific effects of subthalamic nucleus stimulation on pain in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is known to reduce motor symptoms of Parkinson's disease (PD). The effects of DBS on various nonmotor symptoms often differ from patient to patient. The factors that determine whether or not a patient will respond to treatment have not been elucidated. Here, the authors evaluated sex differences in pain relief after DBS for PD. The authors prospectively evaluated 20 patients preoperatively and postoperatively after bilateral STN DBS with the validated numeric rating scale (NRS), Revised Oswestry Disability Index for low-back pain (RODI), and King's Parkinson's Disease Pain Scale (KPDPS) and assessed the impact of sex as a biological variable. The cohort consisted of 6 female and 14 male patients with a mean duration of 11.8 ± 2.0 months since DBS surgery. Females were significantly older (p = 0.02). Covariate analysis, however, showed no effect of age, stimulation settings, or other confounding variables. KPDPS total scores statistically significantly improved only among males (p < 0.001). Males improved more than females in musculoskeletal and chronic subsets of the KPDPS (p = 0.03 and p = 0.01, respectively). RODI scores significantly improved in males but not in females (p = 0.03 and p = 0.30, respectively). Regarding the NRS score, the improvements seen in both sexes in NRS were not significant. Although it is well recognized that pain complaints in PD are different between men and women, this study is unique in that it examines the sex-specific DBS effects on this symptom. Considering sex as a biological variable may have important implications for DBS pain outcome studies moving forward.

Subthalamic Nucleus Stimulation Modulates Motor Epileptic Activity in Humans.

Pharmaco-refractory focal motor epileptic seizures pose a significant challenge. Deep brain stimulation (DBS) is a recently recognized therapeutic option for the treatment of refractory epilepsy. To identify the specific target for focal motor seizures, we evaluate the modulatory effects of the subthalamic nucleus (STN) stimulation because of the critical role of STN in cortico-subcortical motor processing. Seven patients with epilepsy with refractory seizures who underwent chronic stereoelectroencephalography (SEEG) monitoring were studied in presurgical evaluation. Seizure onset zone was hypothesized to be partially involved in the motor areas in 6 patients. For each patient, one electrode was temporally implanted into the STN that was ipsilateral to the seizure onset zone. The cortical-subcortical seizure propagation was systemically evaluated. The simultaneously electrophysiological responses over distributed cortical areas to STN stimulation at varied frequencies were quantitatively assessed. We observed the consistent downstream propagation of seizures from the motor cortex toward the ipsilateral STN and remarkable cortical responses on motor cortex to single-pulse STN stimulation. Furthermore, we showed frequency-dependent upstream modulatory effect of STN stimulation on motor cortex specifically. In contrast to the enhanced effects of low frequency stimulation, high-frequency stimulation of the STN can significantly reduce interictal spikes, high-frequency oscillations over motor cortex disclosing effective connections to the STN. This result showed that the STN is not only engaged in as a propagation network of focal motor seizures but STN stimulation can profoundly modulate the epileptic activity of motor cortex in humans, suggesting a mechanism-based alternative for patients suffering from refractory focal motor seizures. ANN NEUROL 2020;88:283-296.

Sex differences in the short-term and long-term effects of subthalamic nucleus stimulation in Parkinson's disease

ObjectiveTo assess the influence of sex on the short-term and long-term effects of subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) MethodsWe evaluated 48 male and 52 female PD patients enrolled in our prospective DBS registry who received bilateral STN-DBS between 2005 and 2013 and had 5-year follow-up data. Motor function, dyskinesia duration/disability, activities of daily living, health-related quality of life (HRQoL), cognitive function, and depression severity were investigated at baseline and at the 1- and 5-year follow-up visits. HRQoL was assessed using the 36-Item Short Form Health Survey (SF-36), which consists of physical-component summary (PCS) and mental-component summary scores. ResultsNone of the changes from baseline to the 1- or 5-year follow-up in clinical outcomes differed between the men and women except for the SF-36 PCS scores. Compared with the baseline, there was an improvement in the PCS scores in both men (p < 0.001) and women (p = 0.001) at the 1-year follow-up; however, a trend toward greater improvement in men was observed (p = 0.061). At the 5-year follow-up, STN-DBS improved the PCS scores in men (p < 0.001) but not in women (p=0.409) compared with the baseline, and there was a significant difference between the groups (p = 0.002). ConclusionsOur data suggest that STN-DBS induce a similar degree of short-term and long-term effects on motor function, cognitive and depressive symptoms, and functional status between male and female PD patients. Nevertheless, physical HRQoL seemed to improve to a greater extent in men, and this sex difference was more prominent with long-term observation.

Reduction of Side Effects by Segmented Electrodes in Case of Subthalamic Nucleus Deep Brain Stimulation in Parkinson Disease: A Case Report.

Patients suffering treatment resistant Parkinson´s disease (PD) are potential candidates for deep brain stimulation (DBS). Commonly most implanted electrodes have a cylindrical shape with quadripolar electrode contacts and generate a symmetrical stimulation field around the lead. To reduce side effects through activation of neighboring fibers a new electrode design with segmented contacts was developed and enables a better adaption of the field of stimulation as well as a multi-target stimulation to improve therapeutic benefits. We report about a 51-year-old male patient with a 15-year history of treatment-refractory PD, who was implanted with bilateral segmented electrodes in the subthalamic nucleus (STN) with St. Jude Medical Infinity™ DBS System (Abbott/St. Jude Medical, Saint Paul, Minnesota, USA). Despite a clear mood-enhancing effect, stimulation with ring electrodes caused motor side effects including rigor and speech disorder. With segmented electrodes an effective and gentle stimulation was achieved. The stimulation of the anterior segments in the central position of the electrode in the STN showed no side-effects and allowed a reduction of initial symptoms in an low stimulation amplitude. Despite precise preoperatively planning and intraoperative trial stimulation, side effects of STN stimulation are very common. The application of segmented electrodes permits more options to reduce side effects rather than using ring electrodes. Studies with larger samples sizes are needed to establish the optional DBS electrode.

Effects of subthalamic nucleus stimulation and levodopa on decision-making in Parkinson's disease.

Parkinson's disease (PD) is frequently associated with behavioral disorders, particularly within the spectrum of motivated behaviors such as apathy or impulsivity. Both pharmacological and neurosurgical treatments have an impact on these impairments. However, there still is controversy as to whether subthalamic nucleus deep brain stimulation (STN-DBS) can cause or reduce impulsive behaviors. We aimed to identify the influence of functional surgery on decision-making processes in PD. We studied 13 PD patients and 13 healthy controls. The experimental task involved squeezing a dynamometer with variable force to obtain rewards of various values under four conditions: without treatment, with l-dopa or subthalamic stimulation alone, and with both l-dopa and subthalamic stimulation. Statistical analyses consisted of generalized linear mixed models including treatment condition, reward value, level of effort, and their interactions. We analyzed acceptance rate (the percentage of accepted trials), decision time, and force applied. Comparatively to controls, patients without treatment exhibited lower acceptance rate and force applied. Patients under l-dopa alone did not exhibit increased acceptance rate. With subthalamic stimulation, either with or without added l-dopa, all measures were improved so that patients' behaviors were undistinguishable from healthy controls'. Our study shows that l-dopa administration does not fully restore cost-benefit decision-making processes, whereas STN-DBS fully normalizes patients' behaviors. These findings suggest that dopamine is partly involved in cost-benefit valuation, and that STN-DBS can have a beneficial effect on motivated behaviors in PD and may improve certain forms of impulsive behaviors. © 2019 International Parkinson and Movement Disorder Society.

High frequency stimulation of the subthalamic nucleus: linking mood and motor effects at the level of the basal ganglia and 5-HT system

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a neurosurgical procedure commonly used for the management of severe movement disability in advanced Parkinson’s disease (PD), but some patients experience debilitating psychiatric effects that have an uknown neural origin. Here we use animal models to uncover effects of DBS of the STN on the lateral habenula nucleus (LHb), a fast emerging controller of motivational and emotive behaviours, and a major source of input to 5-HT neurons in the dorsal raphe nucleus (DRN). STN stimulation at clinical parameters, consistently modulated the firing of the majority of LHb neurons tested. LHb neurons projecting to the DRN were identified using antidromic activation, and were also modulated by STN stimulation. Juxtacellular labelling confirmed that STN-responsive neurons were LHb glutamatergic neurons. We identified a behavioural correlate of the neurophysiological effects of STN stimulation. Thus, STN stimulation induced a behaviourally selective decrease in food and sucrose intake, consistent with a reduced motivational state. Moreover, the use of neurotoxic lesions demonstrated that these STN-evoked responses were dependent on both the LHb and 5 HT. Collectively, the present data demonstrate that DBS of the STN influences the LHb and its pathway to the midbrain 5-HT system to generate decreases in motivational outputs. Thus, the impact of the STN on a major controller of motivational and emotive behaviours offers an unexpected route by which STN stimulation might evoke psychiatric effects in patients with PD.

Deep Brain Stimulation and Sleep-Wake Disturbances in Parkinson Disease: A Review.

Sleep-wake disturbances are common non-motor manifestations in Parkinson Disease (PD). Complex pathophysiological changes secondary to neurodegeneration in combination with motor symptoms and dopaminergic medications contribute to development of sleep-wake disturbances. The management of sleep complaints in PD is important as this symptom can affect daily activities and impair quality of life. Deep brain stimulation (DBS) is an effective adjunctive therapy for management of motor symptoms in PD. However, its effect on non-motor symptoms including sleep-wake disturbances is not widely understood. In this article, we reviewed studies assessing the effect of DBS at various therapeutic targets on sleep-wake disturbances. Of the studies examining the role of DBS in sleep-wake disturbances, the effect of subthalamic nucleus stimulation is most widely studied and has shown improvement in sleep quality, sleep efficiency, and sleep duration. Although, studies investigating changes in sleep with stimulation of thalamus, globus pallidus interna, and pedunculopontine nucleus are limited, they support the potential for modulation of sleep-wake centers with DBS at these sites. The mechanism by which DBS at different anatomical targets affects sleep-wake disturbances in PD is unclear and may involves multiple factors, including improved motor symptoms, medication adjustment, and direct modulation of sleep-wake centers.

Subthalamic nucleus deep brain stimulation protects neurons by activating autophagy via PP2A inactivation in a rat model of Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for alleviating disability in patients with moderate to severe Parkinson's disease (PD). Preclinical studies have shown that stimulation of the rat STN can protect against nigral dopaminergic neuron loss. However, the underlying mechanism is unclear. To investigate the molecular basis of the neuroprotective effects of STN stimulation, a rat model of PD was established by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the striatum. PD rats were subjected to DBS of the STN (STN-DBS) and the effects on motor symptoms and number of nigral tyrosine hydroxylase-positive (TH+) neurons was examined. We found that STN-DBS improved movement disorder and mitigated the loss of TH+ neurons induced by 6-OHDA. Furthermore, STN-DBS blocked protein phosphatase (PP)2A activation induced by 6-OHDA and led to the phosphorylation of B cell lymphoma (Bcl)-2, thereby increasing its activity. This induced its disassociation from Beclin1, a positive regulator of autophagy, leading to autophagy and inhibition of apoptosis. These findings demonstrate for the first time that STN-DBS could exert neuroprotective effects against 6-OHDA-induced cell injury in PD by inducing autophagy via PP2A inactivation and dissociation of the Bcl-2/Beclin1 complex, thereby providing a molecular basis of STN-DBS neuroprotection for PD.

An investigation into the effects and prognostic factors of cognitive decline following subthalamic nucleus stimulation in patients with Parkinson’s disease

We retrospectively investigated the effects of subthalamic nucleus stimulation (STN-DBS) on new postoperative onset of cognitive decline and prognostic factors for advanced Parkinson’s disease (PD). We studied 39 PD patients who had received bilateral STN-DBS. Clinical symptoms, cognitive function, psychiatric function, and health-related quality of life (HRQOL) were assessed before and six months after surgery. Based on the results of neuropsychological examinations six months after the surgery, the subjects were divided into those with and those without cognitive decline. We compared pre- and post-operative assessments between the two groups. Prognostic factors were investigated using multiple logistic regression analyses. Seven patients had cognitive decline six months after the operation (17.9%); they were significantly older than those without cognitive decline. Preoperative neuropsychological examinations revealed impairments in language and executive function. No differences were found in clinical symptoms. Patients with cognitive decline had significantly worse apathy scale scores. The HRQOL revealed significant declines in the Mental Component Summary (MCS), vitality, and mental health (MH) domains. Postoperative comparisons revealed novel significant differences in activities of daily living in the “on” and “off” states and in daytime drowsiness. Preoperative differences seen in the MCS and vitality indices were no longer present. Word fluency, and apathy scale and MH scores were independent preoperative prognostic factors for cognitive decline. New postoperative onset of cognitive decline due to STN-DBS affected activities of daily living and psychiatric function. Preoperative non-motor symptoms may be prognostic factors for new onset of cognitive decline.

Effect of subthalamic nucleus deep brain stimulation on balance in Parkinson’s disease: A static posturographic analysis

BackgroundThe effect of subthalamic deep brain stimulation on balance in Parkinson’s disease remains unclear. ObjectiveTo evaluate the effect of subthalamic nucleus stimulation on balance in Parkinson’s disease using posturography. Methods16 patients (9 women) who underwent subthalamic deep brain stimulation [mean age 59.6 years (46–70); mean disease duration 15.6 years (7–25); mean duration of subthalamic stimulation 32.1 months (3.0–69.6)] and 13 healthy age-matched controls were evaluated using a static posturography analysis. Patients were assessed under four conditions: 1) off medication/off stimulation; 2) off medication/on stimulation; 3) on medication/off stimulation and 4) on medication/on stimulation in ten experimental paradigms, some reproducing common situations of daily living. The displacement of the centre of pressure was analyzed using 14 posturographic parameters. The Mann-Whitney test was used to compare patients with controls. The Wilcoxon signed rank test was used to compare patients under different clinical conditions. ResultsPatients off medication/off stimulation showed larger and more rapid displacements of the centre of pressure than controls in most paradigms (p<0.05), particularly when performing a dual task. Subthalamic stimulation alone reduced the lateral excursion and anterior-posterior velocity of the centre of pressure in quite stance paradigms (p<0.05). Subthalamic stimulation combined with antiparkinsonian medication did not induce statistically significant changes in posturagraphic measures in any experimental paradigm. ConclusionsAlthough subthalamic stimulation alone may induce some positive effect on balance, subthalamic stimulation in addition to antiparkinsonian medication, which is the usual treatment in clinical practice, did not modify balance as assessed by static posturography in patients with Parkinson’s disease.

High-frequency stimulation of the subthalamic nucleus modulates neuronal activity in the lateral habenula nucleus.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is often used to treat movement disability in advanced Parkinson's disease, but some patients experience debilitating psychiatric effects including depression. Interestingly, HFS of the STN modulates 5-HT neurons in the dorsal raphe nucleus (DRN) which are linked to depression, but the neural substrate of this effect is unknown. Here, we tested the effect of STN stimulation on neuronal activity in the lateral habenula nucleus (LHb), an important source of input to DRN 5-HT neurons and also a key controller of emotive behaviours. LHb neurons were monitored in anaesthetized rats using single-unit extracellular recording, and localization within the LHb was confirmed by juxtacellular labelling. HFS of the STN (130Hz) evoked rapid changes in the firing rate of the majority of LHb neurons tested (38 of 68). Some LHb neurons (19/68) were activated by HFS, while others (19/68), distinguished by a higher basal firing rate, were inhibited. LHb neurons that project to the DRN were identified using antidromic activation and collision testing (n=17 neurons). Some of these neurons (5/17) were also excited by HFS of the STN, and others (7/17) were inhibited although this was only a statistical trend. In summary, HFS of the STN modulated the firing of LHb neurons, including those projecting to the DRN. The data identify that the STN impacts on the LHb-DRN pathway. Moreover, this pathway may be part of the circuitry mediating the psychiatric effects of STN stimulation experienced by patients with Parkinson's disease.

Subthalamic nucleus stimulation effects on single and combined task performance in Parkinson's disease patients: a PET study.

Subthalamic nucleus deep brain stimulation (STN-DBS) represents one of the most efficacious treatments for Parkinson's disease, along with L-dopa therapy. The objective of the present work was to identify the cerebral networks associated with hand movement and speech production tasks performed alone and simultaneously, as well as the effects of STN-DBS on these profiles. Clinical, behavioral, and neuroimaging (oxygen 15-labeled water and Positron Emission Tomography) investigations were used to study single and combined performances of unilateral hand movements and speech production in 11 unmedicated individuals with PD, both off and on STN-DBS. Specifically, a flexible factorial design with the tasks (hand movement, speech production, combined task) and the STN-DBS conditions (off, on) as main factors was chosen for brain activation statistical analysis, using a Family-Wise Error corrected p-value at the cluster level of at least 10 contiguous voxels. Increased activation of fronto-parietal and cingulate areas was observed under STN-DBS for hand movement in single and combined tasks, respectively, reflecting a partial restoration of cortico-sub-cortical connections. The lack of results for speech production for both off and on STN-DBS could illustrate its relatively poor response to the treatment. STN-DBS tended to restore the additive function capacity that can be achieved when performing the combined task. We confirmed with original neuroimaging data that speech is much less responsive to STN-DBS than any other motor function and we concluded that speech outcomes following STN-DBS can be different from those observed pre-operatively following L-dopa administration.

Effect of Subthalamic Nucleus Stimulation on Pedunculopontine Nucleus Neural Activity

Background: The pedunculopontine nucleus has recently been proposed as an alternative target for deep brain stimulation for the treatment of medically intractable Parkinson's disease. The suggested indication for pedunculopontine nucleus deep brain stimulation is severe and medically intractable axial symptoms such as gait and postural impairment. Objective: Our goal in this study was to describe the effects of subthalamic nucleus stimulation on pedunculopontine nucleus electrophysiological activity. Methods: Fourteen male Wistar rats were divided into a sham stimulation group and an experimental group. In both groups, electrodes were implanted bilaterally into the subthalamic nucleus and into the right pedunculopontine nucleus. Microelectrode recordings were carried out in both groups prior to and during subthalamic nucleus stimulation. Results: Subthalamic nucleus stimulation produced no clear inhibition of neuronal firing in the pedunculopontine nucleus. However, we found that stimulation of the subthalamic nucleus at 60 Hz produces some entrainment of pedunculopontine nucleus neuronal firing and a shift of subthalamic nucleus firing patterns to more tonic and random patterns. These results are consistent with the effects of deep brain stimulation on neuronal activity in the subthalamic nucleus and globus pallidus internus. Conclusion: The result of this study provides additional evidence to improve our understanding of the mechanism of subthalamic nucleus-deep brain stimulation, and its physiological consequences.

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

The subthalamic nucleus (STN) is proposed to modulate response thresholds and speed–accuracy trade-offs. In situations of conflict, the STN is considered to raise response thresholds, allowing time for the accumulation of information to occur before a response is selected. Conversely, speed pressure is thought to reduce the activity of the STN and lower response thresholds, resulting in fast, errorful responses. In Parkinson’s disease (PD), subthalamic nucleus deep brain stimulation (STN-DBS) reduces the activity of the nucleus and improves motor symptoms. We predicted that the combined effects of STN stimulation and speed pressure would lower STN activity and lead to fast, errorful responses, hence resulting in impulsive action. We used the motion discrimination ‘moving-dots’ task to assess speed–accuracy trade-offs, under both speed and accuracy instructions. We assessed 12 patients with PD and bilateral STN-DBS and 12 age-matched healthy controls. Participants completed the task twice, and the patients completed it once with STN-DBS on and once with STN-DBS off, with order counterbalanced. We found that STN stimulation was associated with significantly faster reaction times but more errors under speed instructions. Application of the drift diffusion model showed that stimulation resulted in lower response thresholds when acting under speed pressure. These findings support the involvement of the STN in the modulation of speed–accuracy trade-offs and establish for the first time that speed pressure alone, even in the absence of conflict, can result in STN stimulation inducing impulsive action in PD.

The influence of weakness on posture control: A simulation study

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Spotlight on the August 4 Issue

#### Notable in Neurology This issue features articles discussing physician response to a medication alert system in inpatients with levodopa-treated diseases and the effects of subthalamic nucleus stimulation on motor cortex plasticity in Parkinson disease. Another featured article focuses on the characteristic features and progression of abnormalities on MRI for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. ### Aerobic training and postexercise protein in facioscapulohumeral muscular dystrophy: RCT study![Graphic][1]</img>![Graphic][2]</img> The authors found that regular endurance training safely improved fitness, walking speed, and self-assessed health in patients with newly diagnosed facioscapulohumeral muscular dystrophy. Postexercise … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif

Effects of subthalamic nucleus stimulation on motor cortex plasticity in Parkinson disease.

We hypothesized that subthalamic nucleus (STN) deep brain stimulation (DBS) will improve long-term potentiation (LTP)-like plasticity in motor cortex in Parkinson disease (PD). We studied 8 patients with PD treated with STN-DBS and 9 age-matched healthy controls. Patients with PD were studied in 4 sessions in medication (Med) OFF/stimulator (Stim) OFF, Med-OFF/Stim-ON, Med-ON/Stim-OFF, and Med-ON/Stim-ON states in random order. Motor evoked potential amplitude and cortical silent period duration were measured at baseline before paired associated stimulation (PAS) and at 3 different time intervals (T0, T30, T60) up to 60 minutes after PAS in the abductor pollicis brevis and abductor digiti minimi muscles. Motor evoked potential size significantly increased after PAS in controls (+67.7% of baseline at T30) and in patients in the Med-ON/Stim-ON condition (+55.8% of baseline at T30), but not in patients in the Med-OFF/Stim-OFF (-0.4% of baseline at T30), Med-OFF/Stim-ON (+10.3% of baseline at T30), and Med-ON/Stim-OFF conditions (+17.3% of baseline at T30). Cortical silent period duration increased after PAS in controls but not in patients in all test conditions. Our findings suggest that STN-DBS together with dopaminergic medications restore LTP-like plasticity in motor cortex in PD. Restoration of cortical plasticity may be one of the mechanisms of how STN-DBS produces clinical benefit.

Subthalamic nucleus stimulation and spontaneous language production in Parkinson’s disease: A double laterality problem

BackgroundAsymmetric degeneration of dopaminergic neurons, are characteristic for Parkinson’s disease (PD). Despite the lateralized representation of language, the correlation of asymmetric degeneration of nigrostriatal networks in PD with language performance has scarcely been examined. Objective/hypothesisThe laterality of dopamine depletion influences language deficits in PD and thus modulates the effects of subthalamic nucleus (STN) stimulation on language production. MethodsThe spontaneous language production of patients with predominant dopamine depletion of the left (PD-left) and right (PD-right) hemisphere was compared in four stimulation conditions. ResultsPD-right made comparatively more verb inflection errors than PD-left. Bilateral STN stimulation improves spontaneous language production only for PD-left. ConclusionsThe laterality of dopamine depletion influences spontaneous language production and the effect of STN stimulation on linguistic functions. However, it is probably only one of the many variables influencing the effect of STN stimulation on language production.