Parietal theta burst TMS does not modulate bistable perception.

The role of the parietal cortex in perceptual awareness and in resolving perceptual ambiguity is unsettled. Early influential transcranial magnetic stimulation studies have revealed differences in conscious perception following parietal stimulation, fuelling the notion that parietal cortex causally contributes to resolving perceptual ambiguity. However, central to this conclusion is the reliability of the method employed. Several prior studies have revealed opposing effects, such as shortening, lengthening, or no effect on multistable perceptual transitions following parietal stimulation. Here we addressed the reliability of continuous theta-burst stimulation (cTBS) on parietal cortex on the perception of bistable stimuli. We conducted three cTBS experiments that were matched to prior experiments in terms of stimuli, stimulation protocol, and target site, and used a higher number of participants. None of our cTBS experiments replicated prior cTBS results. The only experiment using individual functional localizers led to weak effects, while the two others led to null results. Individual variability of motor cortex cTBS did not predict parietal cTBS effects. In view of recent reports of highly variable cTBS effects over motor cortex, our results suggest that cTBS is particularly unreliable in modulating bistable perception when applied over parietal cortex.

Long-Term Follow-Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare. OBJECTIVES: We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. METHODS: The STIM-CP trial was a prospective, single-arm, multicenter study in which patients from the parental trial agreed to be followed-up for up to 36 months. Assessments included motor and non-motor domains. RESULTS: Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented. CONCLUSION: DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Paradoxical pharmacological dissociations result from drugs that enhance delta oscillations but preserve consciousness.

Low-frequency (<4 Hz) neural activity, particularly in the delta band, is generally indicative of loss of consciousness and cortical down states, particularly when it is diffuse and high amplitude. Remarkably, however, drug challenge studies of several diverse classes of pharmacological agents-including drugs which treat epilepsy, activate GABAB receptors, block acetylcholine receptors, or produce psychedelic effects-demonstrate neural activity resembling cortical down states even as the participants remain conscious. Of those substances that are safe to use in healthy volunteers, some may be highly valuable research tools for investigating which neural activity patterns are sufficient for consciousness or its absence.

Hemispheric Differences of 1 Hz rTMS over Motor and Premotor Cortex in Modulation of Neural Processing and Hand Function.

INTRODUCTION: Non-invasive brain stimulation can modulate both neural processing and behavioral performance. Its effects may be influenced by the stimulated area and hemisphere. In this study (EC no. 09083), repetitive transcranial magnetic stimulation (rTMS) was applied to the primary motor cortex (M1) or dorsal premotor cortex (dPMC) of either the right or left hemisphere, while evaluating cortical neurophysiology and hand function. METHODS: Fifteen healthy subjects participated in this placebo-controlled crossover study. Four sessions of real 1 Hz rTMS (110% of rMT, 900 pulses) over (i) left M1, (ii) right M1, (iii) left dPMC, (iv) right dPMC, and one session of (v) placebo 1 Hz rTMS (0% of rMT, 900 pulses) over the left M1 were applied in randomized order. Motor function of both hands (Jebsen-Taylor Hand Function Test (JTHFT)) and neural processing within both hemispheres (motor evoked potentials (MEPs), cortical silent period (CSP), and ipsilateral silent period (ISP)) were evaluated prior and after each intervention session. RESULTS: A lengthening of CSP and ISP durations within the right hemisphere was induced by 1 Hz rTMS over both areas and hemispheres. No such intervention-induced neurophysiological changes were detected within the left hemisphere. Regarding JTHFT and MEP, no intervention-induced changes ensued. Changes of hand function correlated with neurophysiological changes within both hemispheres, more often for the left than the right hand. CONCLUSIONS: Effects of 1 Hz rTMS can be better captured by neurophysiological than behavioral measures. Hemispheric differences need to be considered for this intervention.

Structural-Functional Correlates of Response to Pedunculopontine Stimulation in a Randomized Clinical Trial for Axial Symptoms of Parkinson's Disease.

BACKGROUND: Axial symptoms of Parkinson's disease (PD) can be debilitating and are often refractory to conventional therapies such as dopamine replacement therapy and deep brain stimulation (DBS) of the subthalamic nuclei (STN). OBJECTIVE: Evaluate the efficacy of bilateral DBS of the pedunculopontine nucleus area (PPNa) and investigate structural and physiological correlates of clinical response. METHODS: A randomized, double-blind, cross-over clinical trial was employed to evaluate the efficacy of bilateral PPNa-DBS on axial symptoms. Lead positions and neuronal activity were evaluated with respect to clinical response. Connectomic cortical activation profiles were generated based on the volumes of tissue activated. RESULTS: PPNa-DBS modestly improved (p = 0.057) axial symptoms in the medication-off condition, with greatest positive effects on gait symptoms (p = 0.027). Electrode placements towards the anterior commissure (ρ= 0.912; p = 0.011) or foramen caecum (ρ= 0.853; p = 0.031), near the 50% mark of the ponto-mesencephalic junction, yielded better therapeutic responses. Recording trajectories of patients with better therapeutic responses (i.e., more anterior electrode placements) had neurons with lower firing-rates (p = 0.003) and higher burst indexes (p = 0.007). Structural connectomic profiles implicated activation of fibers of the posterior parietal lobule which is involved in orienting behavior and locomotion. CONCLUSION: Bilateral PPNa-DBS influenced gait symptoms in patients with PD. Anatomical and physiological information may aid in localization of a favorable stimulation target.

Not with a "zap" but with a "beep": Measuring the origins of perinatal experience.

When does the mind begin? Infant psychology is mysterious in part because we cannot remember our first months of life, nor can we directly communicate with infants. Even more speculative is the possibility of mental life prior to birth. The question of when consciousness, or subjective experience, begins in human development thus remains incompletely answered, though boundaries can be set using current knowledge from developmental neurobiology and recent investigations of the perinatal brain. Here, we offer our perspective on how the development of a sensory perturbational complexity index (sPCI) based on auditory ("beep-and-zip"), visual ("flash-and-zip"), or even olfactory ("sniff-and-zip") cortical perturbations in place of electromagnetic perturbations ("zap-and-zip") might be used to address this question. First, we discuss recent studies of perinatal cognition and consciousness using techniques such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and, in particular, magnetoencephalography (MEG). While newborn infants are the archetypal subjects for studying early human development, researchers may also benefit from fetal studies, as the womb is, in many respects, a more controlled environment than the cradle. The earliest possible timepoint when subjective experience might begin is likely the establishment of thalamocortical connectivity at 26 weeks gestation, as the thalamocortical system is necessary for consciousness according to most theoretical frameworks. To infer at what age and in which behavioral states consciousness might emerge following the initiation of thalamocortical pathways, we advocate for the development of the sPCI and similar techniques, based on EEG, MEG, and fMRI, to estimate the perinatal brain's state of consciousness.

Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Drug-Resistant Epilepsy in the MORE Multicenter Patient Registry.

BACKGROUND AND OBJECTIVES: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. METHODS: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. RESULTS: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years (p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. DISCUSSION: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy. TRIAL REGISTRATION INFORMATION: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012.

Ultrasound of the Biceps Muscle in Idiopathic Parkinson's Disease with Deep Brain Stimulation: Rigidity Can Be Quantified by Shear Wave Elastography.

Rigidity in Parkinson's disease (PD) is assessed by clinical scales, mostly the Unified Parkinson's Disease Rating Scale of the Movement Disorders Society (MDS-UPDRS). While the MDS-UPDRS-III ranges on an integer from 0 to 4, we investigated whether muscle ultrasound shear wave elastography (SWE) offers a refined assessment. Ten PD patients (five treated with deep brain stimulation (DBS) and levodopa, five with levodopa only) and ten healthy controls were included. Over a period of 80 min, both the SWE value and the item 22b-c of the MDS-UPDRS-III were measured at 5 min intervals. The measurements were performed bilaterally at the biceps brachii muscle (BB) and flexor digitorum profundus muscle in flexion and passive extension. Rigidity was modified and tracked under various therapeutic conditions (with and without medication/DBS). The feasibility of SWE for objective quantification was evaluated by correlation with the UPDRS-III: considering all positions and muscles, there was already a weak correlation (r = 0.01, p < 0.001)­in a targeted analysis, the BB in passive extension showed a markedly higher correlation (r = 0.494, p < 0.001). The application of dopaminergic medication and DBS resulted in statistically significant short-term changes in both clinical rigidity and SWE measurements in the BB (p < 0.001). We conclude that rigidity is reflected in the SWE measurements, indicating that SWE is a potential non-invasive quantitative assessment tool for PD.

Resolving equivocal gain modulation of corticospinal excitability.

The ratio between the input and output of neuronal populations, usually referred to as gain modulation, is rhythmically modulated along the oscillatory cycle. Previous research on spinal neurons, however, revealed contradictory findings: both uni- and bimodal patterns of increased responsiveness for synaptic input have been proposed for the oscillatory beta rhythm. In this study, we compared previous approaches of phase estimation directly on simulated data and empirically tested the corresponding predictions in healthy males and females. We applied single-pulse transcranial magnetic stimulation over the primary motor cortex at rest, and assessed the spinal output generated by this input. Specifically, the peak-to-peak amplitude of the motor evoked potential in the contralateral forearm was estimated as a function of the EMG phase at which the stimulus was applied. The findings indicated that human spinal neurons adhere to a unimodal pattern of increased responsiveness, and suggest that the rising phase of the upper beta band maximizes gain modulation. Importantly, a bimodal pattern of increased responsiveness was shown to result in an artifact during data analysis and filtering. This observation of invalid preprocessing could be generalized to other frequency bands (i.e., delta, theta, alpha, and gamma), different task conditions (i.e., voluntary muscle contraction), and EEG-based phase estimations. Appropriate analysis algorithms, such as broad-band filtering, enable us to accurately determine gain modulation of neuronal populations and to avoid erroneous phase estimations. This may facilitate novel phase-specific interventions for targeted neuromodulation.

Oscillatory neurofeedback networks and poststroke rehabilitative potential in severely impaired stroke patients.

Motor restoration after severe stroke is often limited. However, some of the severely impaired stroke patients may still have a rehabilitative potential. Biomarkers that identify these patients are sparse. Eighteen severely impaired chronic stroke patients with a lack of volitional finger extension participated in an EEG study. During sixty-six trials of kinesthetic motor imagery, a brain-machine interface turned event-related beta-band desynchronization of the ipsilesional sensorimotor cortex into opening of the paralyzed hand by a robotic orthosis. A subgroup of eight patients participated in a subsequent four-week rehabilitation training. Changes of the movement extent were captured with sensors which objectively quantified even discrete improvements of wrist movement. Albeit with the same motor impairment level, patients could be differentiated into two groups, i.e., with and without task-related increase of bilateral cortico-cortical phase synchronization between frontal/premotor and parietal areas. This fronto-parietal integration (FPI) was associated with a significantly higher volitional beta modulation range in the ipsilesional sensorimotor cortex. Following the four-week training, patients with FPI showed significantly higher improvement in wrist movement than those without FPI. Moreover, only the former group improved significantly in the upper extremity Fugl-Meyer-Assessment score. Neurofeedback-related long-range oscillatory coherence may differentiate severely impaired stroke patients with regard to their rehabilitative potential, a finding that needs to be confirmed in larger patient cohorts.

Direct modulation index: A measure of phase amplitude coupling for neurophysiology data.

Neural communication across different spatial and temporal scales is a topic of great interest in clinical and basic science. Phase-amplitude coupling (PAC) has attracted particular interest due to its functional role in a wide range of cognitive and motor functions. Here, we introduce a novel measure termed the direct modulation index (dMI). Based on the classical modulation index, dMI provides an estimate of PAC that is (1) bound to an absolute interval between 0 and +1, (2) resistant against noise, and (3) reliable even for small amounts of data. To highlight the properties of this newly-proposed measure, we evaluated dMI by comparing it to the classical modulation index, mean vector length, and phase-locking value using simulated data. We ascertained that dMI provides a more accurate estimate of PAC than the existing methods and that is resilient to varying noise levels and signal lengths. As such, dMI permits a reliable investigation of PAC, which may reveal insights crucial to our understanding of functional brain architecture in key contexts such as behaviour and cognition. A Python toolbox that implements dMI and other measures of PAC is freely available at https://github.com/neurophysiological-analysis/FiNN.

Additive Effect of Dopaminergic Medication on Gait Under Single and Dual-Tasking Is Greater Than of Deep Brain Stimulation in Advanced Parkinson Disease With Long-Duration Deep Brain Stimulation.

INTRODUCTION: Patients with advanced Parkinson disease (PD) often experience problems with mobility, including walking under single- (ST) and dual-tasking (DT) conditions. The effects of deep brain stimulation in the subthalamic nucleus (DBS) versus dopaminergic medication (Med) on these conditions are not well investigated. MATERIALS AND METHODS: We used two ST and two DT-gait paradigms to evaluate the effect of DBS and dopaminergic medication on gait parameters in 14 PD patients (mean age 66 ± 8 years) under DBSOFF/MedON, DBSON/MedOFF, and DBSON/MedON conditions. They performed standardized 20-meter walks with convenient and fast speed. To test DT capabilities, they performed a checking-boxes and a subtraction task during fast-paced walking. Quantitative gait analysis was performed using a tri-axial accelerometer (Dynaport, McRoberts, The Netherlands). Dual-task costs (DTC) of gait parameters and secondary task performance were compared intraindividually between DBSOFF/MedON vs DBSON/MedON, and DBSON/MedOFF vs DBSON/MedON to estimate responsiveness. RESULTS: Dopaminergic medication increased gait speed and cadence at convenient speed. It increased cadence and decreased number of steps at fast speed, and improved DTC of cadence during the checking boxes and DTC of cadence and number of steps during the subtraction tasks. DBS only improved DTC of cadence during the checking boxes and DTC of gait speed during the subtraction task. CONCLUSION: Dopaminergic medication showed larger additional effects on temporal gait parameters under ST and DT conditions in advanced PD than DBS. These results, after confirmation in independent studies, should be considered in the medical management of advanced PD patients with gait and DT deficits.

Genetic stratification of motor and QoL outcomes in Parkinson's disease in the EARLYSTIM study.

PURPOSE: The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. OBJECTIVE: First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores. METHODS: We comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters. RESULTS: The SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits predicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter. CONCLUSIONS: Our findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts.

Rewiring cortico-muscular control in the healthy and post-stroke human brain with proprioceptive beta-band neurofeedback.

In severely affected stroke survivors, cortico-muscular control is disturbed and volitional upper limb movements often absent. Mental rehearsal of the impaired movement in conjunction with sensory feedback provision are suggested as promising rehabilitation exercises. Knowledge about the underlying neural processes, however, remains vague. In male and female chronic stroke patients with hand paralysis, a brain-computer interface controlled a robotic orthosis and turned sensorimotor beta-band desynchronization during motor imagery (MI) of finger extension into contingent hand opening. Healthy control subjects performed the same task and received the same proprioceptive feedback with a robotic orthosis or visual feedback only. Only when proprioceptive feedback was provided, cortico-muscular coherence (CMC) increased with a predominant information flow from the sensorimotor cortex to the finger extensors. This effect (i) was specific to the beta frequency-band, (ii) transferred to a motor task, (iii) was proportional to subsequent corticospinal excitability and correlated with behavioral changes in the (iv) healthy and (v) post-stroke condition; notably, MI-related enhancement of beta-band CMC in the ipsilesional premotor cortex correlated with motor improvements after the intervention.In the healthy and injured human nervous system, synchronized activation of motor-related cortical and spinal neural pools facilitates, in accordance with the communication-through-coherence hypothesis, cortico-spinal communication and may, thereby, be therapeutically relevant for functional restoration after stroke, when voluntary movements are no longer possible.Significance statement:This study provides insights into the neural processes that transfer effects of brain-computer interface neurofeedback to subsequent motor behavior. Specifically, volitional control of cortical oscillations and proprioceptive feedback enhances both cortical activity and behaviorally relevant connectivity to the periphery in a topographically circumscribed and frequency-specific way. This enhanced cortico-muscular control can be induced in the healthy and post-stroke brain. Thereby, activating the motor cortex with mental rehearsal of the impaired movement and closing the loop by robot-assisted feedback synchronizes ipsilesional premotor cortex and spinal neural pools in the beta-frequency band. This facilitates, in accordance with the communication-through-coherence hypothesis, cortico-spinal communication and may, thereby, be therapeutically relevant for functional restoration after stroke, when voluntary movements are no longer possible.

Non-invasive brain stimulation for improving gait, balance, and lower limbs motor function in stroke.

OBJECTIVES: This systematic review and meta-analysis aim to summarize and analyze the available evidence of non-invasive brain stimulation/spinal cord stimulation on gait, balance and/or lower limb motor recovery in stroke patients. METHODS: The PubMed database was searched from its inception through to 31/03/2021 for randomized controlled trials investigating repetitive transcranial magnetic stimulation or transcranial/trans-spinal direct current/alternating current stimulation for improving gait, balance and/or lower limb motor function in stroke patients. RESULTS: Overall, 25 appropriate studies (including 657 stroke subjects) were found. The data indicates that non-invasive brain stimulation/spinal cord stimulation is effective in supporting recovery. However, the effects are inhomogeneous across studies: (1) transcranial/trans-spinal direct current/alternating current stimulation induce greater effects than repetitive transcranial magnetic stimulation, and (2) bilateral application of non-invasive brain stimulation is superior to unilateral stimulation. CONCLUSIONS: The current evidence encourages further research and suggests that more individualized approaches are necessary for increasing effect sizes in stroke patients.

Evaluation of signal analysis algorithms for ipsilateral motor-evoked potentials induced by transcranial magnetic stimulation.

Objective. Evaluating ipsilateral motor-evoked potentials (iMEP) induced by transcranial magnetic stimulation is challenging. In healthy adults, isometric contraction is necessary to facilitate iMEP induction; therefore, the signal may be masked by the concurrent muscle activity. Signal analysis algorithms for iMEP evaluation need to be benchmarked and evaluated.Approach. An open analysis toolbox for iMEP evaluation was implemented on the basis of 11 previously reported algorithms, which were all threshold based, and a new template-based method based on data-driven signal decomposition. The reliability and validity of these algorithms were evaluated with a dataset of 4244 iMEP from 55 healthy adults.Main results.iMEP estimation varies drastically between algorithms. Several algorithms exhibit high reliability, but some appear to be influenced by background activity of muscle preactivation. Especially in healthy subjects, template-based approaches might be more valid than threshold-based ones. Measurement of iMEP persistence requires algorithms that reject some trials as MEP negative. The stricter the algorithms reject trials, the less reliable they generally are. Our evaluation identifies an optimally strict and reliable algorithm.Significance.We show different benchmarks and propose application for different use cases.

Design and Evaluation of a Custom-Made Electromyographic Biofeedback System for Facial Rehabilitation.

Background: In the rehabilitation of postoperative facial palsy, physical therapy is of paramount importance. However, in the early rehabilitation phase, voluntary movements are often limited, and thus, the motivation of patients is impacted. In these situations, biofeedback of facial electromyographic (EMG) signals enables the visual representation of the rehabilitation progress, even without apparent facial movements. In the present study, we designed and evaluated a custom-made EMG biofeedback system enabling cost-effective facial rehabilitation. Methods: This prospective study describes a custom-made EMG system, consisting of a microcontroller board and muscle sensors, which was used to record the EMG of frontal and zygomatic facial muscles during frowning and smiling. First, the mean EMG amplitudes and movement onset detection rates (ACC) achieved with the custom-made EMG system were compared with a commercial EMG device in 12 healthy subjects. Subsequently, the custom-made device was applied to 12 patients with and without postoperative facial paresis after neurosurgical intervention. Here, the ratio [laterality index (LI)] between the mean EMG amplitude of the healthy and affected side was calculated and related to the facial function as measured by the House and Brackmann scale (H&B) ranging from 1 (normal) to 6 (total paralysis). Results: In healthy subjects, a good correlation was measured between the mean EMG amplitudes of the custom-made and commercial EMG device for both frontal (r = 0.84, p = 0.001) and zygomatic muscles (r = 0.8, p = 0.002). In patients, the LI of the frontal and zygomatic muscles correlated significantly with the H&B (r = -0.83, p = 0.001 and r = -0.65, p = 0.023). The ACC of the custom-made EMG system varied between 65 and 79% depending on the recorded muscle and cohort. Conclusion: The present study demonstrates a good application potential of our custom-made EMG biofeedback device to detect facial EMG activity in healthy subjects as well as patients with facial palsies. There is a correlation between the electrophysiological measurements and the clinical outcome. Such a device might enable cost-efficient home-based facial EMG biofeedback. However, movement detection accuracy should be improved in future studies to reach ranges of commercial devices.

Impaired phase synchronization of motor-evoked potentials reflects the degree of motor dysfunction in the lesioned human brain.

The functional corticospinal integrity (CSI) can be indexed by motor-evoked potentials (MEP) following transcranial magnetic stimulation of the motor cortex. Glial brain tumors in motor-eloquent areas are frequently disturbing CSI resulting in different degrees of motor dysfunction. However, this is unreliably mirrored by MEP characteristics. In 59 consecutive patients with diffuse glial tumors and 21 healthy controls (CTRL), we investigated the conventional MEP features, that is, resting motor threshold (RMT), amplitudes and latencies. In addition, frequency-domain MEP features were analyzed to estimate the event-related spectral perturbation (ERSP), and the induced phase synchronization by intertrial coherence (ITC). The clinical motor status was captured including the Medical Research Council Scale (MRCS), the Grooved Pegboard Test (GPT), and the intake of antiepileptic drugs (AED). Motor function was classified according to MRCS and GPT as no motor deficit (NMD), fine motor deficits (FMD) and gross motor deficits (GMD). CSI was assessed by diffusion-tensor imaging (DTI). Motor competent subjects (CTRL and NMD) had similar ERSP and ITC values. The presence of a motor deficit (FMD and GMD) was associated with an impairment of high-frequency ITC (150-300 Hz). GMD and damage to the CSI demonstrated an additional reduction of high-frequency ERSP (150-300 Hz). GABAergic AED increased ERSP but not ITC. Notably, groups were indistinguishable based on conventional MEP features. Estimating MEP phase synchronization provides information about the corticospinal transmission after transcranial magnetic stimulation and reflects the degree of motor impairment that is not captured by conventional measures.

The Contribution of Subthalamic Nucleus Deep Brain Stimulation to the Improvement in Motor Functions and Quality of Life.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. OBJECTIVES: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality-of-life questionnaire, was assessed in a subcohort of the EARLYSTIM study. METHODS: Sixty-nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters. RESULTS: Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ-39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = -13.1, z = -6.3) and the PDQ-39 differed (x = 14.8, y = -12.4, z = -4.3) ~3.8 mm. CONCLUSIONS: The main influence of DBS on QoL is likely mediated through the sensory-motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to individual symptoms of each patient. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.