Search

Deep brain stimulation of the subthalamic nucleus is effective to alleviate motor symptoms in advanced Parkinson's disease. Using a novel conditioning paradigm, it has been shown that deep brain stimulation pulses from electrodes in the subthalamic nucleus modulate corticospinal excitability as determined with transcranial magnetic stimulation applied to the motor cortex. The mechanism of action is unclear.To investigate the effects of subthalamic nucleus and dorsal premotor cortex conditioning on corticospinal excitability as a function of interstimulus intervals between target areas and deep brain stimulation frequencies.In 19 patients with Parkinson's disease with subthalamic nucleus deep brain stimulation, the premotor-motor interaction was investigated in four different deep brain stimulation conditions (off, clinically used settings, 3 Hz, 20 Hz). Transcranial magnetic pulses were applied to the premotor and motor cortex and paired at certain intervals with deep brain stimulation pulses. The volume of tissue activated by deep brain stimulation was correlated with neurophysiological findings.There was distinct motor cortex inhibition by premotor cortex conditioning at an interstimulus interval of 1 ms before the motor cortex stimulation. Subthalamic nucleus conditioning with deep brain stimulation frequencies of 3 and 20 Hz at an interstimulus interval of 10 ms between subthalamic nucleus and primary motor cortex reduced premotor-motor inhibition. The volume of tissue activated by deep brain stimulation correlated positively with this effect. Corticospinal excitability was not affected by subthalamic nucleus conditioning as used here.Premotor-motor inhibition is modulated by subthalamic nucleus conditioning, presumably through the monosynaptic hyperdirect pathway.

BackgroundAn increase in body weight is observed in the majority of patients with Parkinson’s disease (PD) who undergo deep brain stimulation (DBS) of the subthalamic nucleus (STN) although the mechanisms are unclear.ObjectivesTo identify the stimulation-dependent effects on reward-associated and attention-associated neural networks and to determine whether these alterations in functional connectivity are associated with the local impact of DBS on different STN parcellations.MethodsWe acquired functional task-related MRI data from 21 patients with PD during active and inactive STN DBS and 19 controls while performing a food viewing paradigm. Electrode placement in the STN was localised using a state-of-the-art approach. Based on the 3D model, the local impact of STN DBS was estimated.ResultsSTN DBS resulted in a mean improvement of motor function of 22.6%±15.5% (on medication) and an increase of body weight of ~4 kg within 2 years of stimulation. DBS of the limbic proportion of the STN was associated with body weight gain and an increased functional connectivity within the salience network and at the same time with a decreased activity within the reward-related network in the context of sweet food images.ConclusionsOur findings indicate increased selective attention for high-caloric foods and a sweet food seeking-like behaviour after DBS particularly when the limbic proportion of the STN was stimulated.

Background: Maintaining and manipulating sequences online is essential for language and memory. In Parkinson’s disease (PD), poor performance in sequencing tasks has been associated with basal ganglia dysfunction, especially subthalamic hyperactivity. Objective: This study is aimed to investigate the impact of high-frequency subthalamic nucleus (STN) deep brain stimulation (DBS) on sequence processing in PD. Methods: Twenty-nine patients with PD (17 women) completed a ‘before/after’ sentence task and a digit ordering task with STN DBS ON and OFF. In the sentence task, patients read a sequence of events expressed in the actual order of occurrence (‘after’ sentences) or reversed order (‘before’ sentences) for comprehension. In the digit task, patients recalled a sequence of ordered digits (ordered trials) or reordered and recalled random digits in ascending order (random trials). Volumes of tissue activated (VTAs) were estimated for the motor and associative STN. Results: Patients were slower with STN DBS ON versus OFF in both tasks, although their motor symptoms were significantly improved under DBS. In the sentence task, patients showed higher ordering-related reaction time costs (‘before’ > ‘after’) with DBS ON versus OFF. Moreover, patients with larger left associative VTAs, smaller total motor VTAs, and more daily exposure to dopaminergic drugs tended to show larger reaction time cost increases under DBS. In the digit ordering task, patients with too large or too small right associative VTAs tended to show larger reaction time cost increases under DBS. Conclusion: Stimulating the STN, especially its associative part, might impair sequence processing in language and memory.

Early diagnosis in patients with neurodegenerative disorders is crucial to initiate disease-modifying therapies at a time point where progressive neurodegeneration can still be modified.The objective of this study was to determine whether motor or non-motor signs of the disease occur as indicators of a prodromal phase of X-linked dystonia-parkinsonism (XDP), a highly-penetrant monogenic movement disorder with striking basal ganglia pathology.In addition to a comprehensive clinical assessment, sensor-based balance and gait analyses were performed in non-manifesting mutation carriers (NMCs), healthy controls (HCs), and patients with XDP. Gradient-boosted trees (GBT) methodology was utilized to classify groups of interest.There were no clinically overt disease manifestations in the NMCs. Balance analysis, however, revealed a classification accuracy of 90% for the comparison of NMC versus HC. For the gait analysis, the best-performing GBT-based model showed a balanced accuracy of 95% (NMC vs. HC; walking at maximum speed). Using a separate analysis of genetic modifiers, several gait parameters correlated strongly with the estimated age at disease onset in the NMC group.Our study unraveled balance and gait abnormalities in NMCs that preceded the onset of XDP. These findings demonstrate prodromal motor changes among NMCs who will develop XDP with a very high likelihood in the future. Gait abnormalities had a predictive value for the estimated age at onset highlighting the impact of genetic modifiers in personalized treatment in monogenic neurodegenerative disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Highlights • Mutations in the thyroid hormone receptor beta (THRB) lead to relative hyperthyroidism in the brain. • Electrophysiological biomarkers of performance monitoring (ERN and Pe components) show a pattern similar to ADHD in carriers of THRB mutations. • The phenotype of THRB mutation carriers is indistinguishable from ADHD with regard to performance monitoring., Resistance to thyroid hormone beta (RTHβ) is a syndrome of reduced responsiveness of peripheral tissue to thyroid hormone, caused by mutations in the thyroid hormone receptor beta (THRB). Its cognitive phenotype has been reported to be similar to attention deficit hyperactivity disorder (ADHD). This study used electrophysiological biomarkers of performance monitoring in RTHβ to contribute further evidence on its phenotypical similarity to ADHD. Twenty-one participants with RTHβ aged 18–67 years and 21 matched healthy controls performed a modified flanker task during EEG recording. The RTHβ and control groups were compared on behavioural measures and components of event related potentials (ERPs), i.e. the error related negativity (ERN), the error positivity (Pe) and P3 component. There were no significant group differences with regard to behaviour. RTHβ subjects displayed significantly reduced ERN and Pe amplitudes compared to the controls in the response-locked ERPs. In addition, we observed reduced P3 amplitudes in both congruent and incongruent trials, as well as prolonged P3 latencies in RTHβ subjects in the stimulus-locked ERPs. Our findings reveal alterations in error detection and performance monitoring of RTHβ patients, likely indicating reduced error awareness. The electrophysiological phenotype of RTHß subjects with regard to action monitoring is indistinguishable from ADHD.

This systematic review investigated the effects of deep brain stimulation of the subthalamic nucleus on extent and time course of body mass changes in patients with Parkinson's disease. A computerized search identified relevant articles using a priori defined inclusion and exclusion criteria. A descriptive analysis was calculated for the main outcome parameters body mass and BMI. Thirty-eight out of 206 studies fulfilled the inclusion criteria (979 patients aged 59.0±7.5 years). Considering the longest follow-up time for each study, body mass and BMI showed a mean increase across studies of +5.71kg (p < .0001; d = 0.64) and +1.8kg/m2 (p < .0001; d = 1.61). The time course of body mass gain revealed a continuous increase ranging from +3.25kg (d = 0.69) at 3 months, +3.88kg (d = 0.21) at 6 months, +6.35kg (d = 0.72) at 12 months, and +6.11kg (d = 1.02) greater than 12 months. Changes in BMI were associated with changes in disease severity (r = 0.502, p = .010) and pharmacological treatment (r = 0.440, p = .0231). Data suggest that body mass gain is one of the most common side effects of deep brain stimulation going beyond normalization of preoperative weight loss. Considering the negative health implications of overweight, we recommend the development of tailored therapies to prevent overweight and associated metabolic disorders following this treatment.

Background In Parkinson's disease (PD), dopamine replacement therapy (DRT) enhances the effective connectivity of the prefrontal cortex (PFC) and supplementary motor area (SMA). The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) go beyond DRT effects including highly beneficial tremor suppression. Objectives Here, we aimed to determine DBS-related changes of a motor network using resting state fMRI in PD patients with chronic STN DBS. Methods In a repeated-measurement design, 26 medicated PD patients (60.9 years (SD 8.9)) were investigated using resting state fMRI while bipolar STN stimulation was (i) active or (ii) switched off, and dynamic causal modelling was subsequently performed. Results DBS improved the MDS-UPDRS-III score by 26.4% (DBS ON/Med ON vs. DBS OFF/Med ON). Active stimulation resulted in an increased effective connectivity from cerebellum to putamen (p = 0.00118). In addition, there was a stronger coupling from PFC to cerebellum (p = 0.021), as well as from cerebellum to SMA (p = 0.043) on an uncorrected level. Coupling strength from PFC to cerebellum correlated with the DBS-related change of the resting tremor subscore (r = 0.54, p = 0.031). Self-connections increased as a function of DBS in the right PFC, PMC, SMA, M1, thalamus and left cerebellum. Conclusions DBS-related improvement of Parkinsonian signs appears to be driven by an interaction between the cerebellum and the putamen. Resting tremor suppression may be related to an enhanced prefronto-cerebellar network. Activation of the mesial premotor loop (PFC-SMA) as seen in DRT may thus be secondary due to the primary modulation of cerebellar networks.