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.

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.

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.

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.

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.

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.

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.

Quality of Life After Deep Brain Stimulation of Pediatric Patients with Dyskinetic Cerebral Palsy: A Prospective, Single-Arm, Multicenter Study with a Subsequent Randomized Double-Blind Crossover (STIM-CP).

BACKGROUND: Patients with dyskinetic cerebral palsy are often severely impaired with limited treatment options. The effects of deep brain stimulation (DBS) are less pronounced than those in inherited dystonia but can be associated with favorable quality of life outcomes even in patients without changes in dystonia severity. OBJECTIVE: The aim is to assess DBS effects in pediatric patients with pharmacorefractory dyskinetic cerebral palsy with focus on quality of life. METHODS: The method used is a prospective, single-arm, multicenter study. The primary endpoint is improvement in quality of life (CPCHILD [Caregiver Priorities & Child Health Index of Life with Disabilities]) from baseline to 12 months under therapeutic stimulation. The main key secondary outcomes are changes in Burke-Fahn-Marsden Dystonia Rating Scale, Dyskinesia Impairment Scale, Gross Motor Function Measure-66, Canadian Occupational Performance Measure (COPM), and Short-Form (SF)-36. After 12 months, patients were randomly assigned to a blinded crossover to receive active or sham stimulation for 24 hours each. Severity of dystonia and chorea were blindly rated. Safety was assessed throughout. The trial was registered at ClinicalTrials.gov, number NCT02097693. RESULTS: Sixteen patients (age: 13.4 ± 2.9 years) were recruited by seven clinical sites. Primary outcome at 12-month follow-up is as follows: mean CPCHILD increased by 4.2 ± 10.4 points (95% CI [confidence interval] -1.3 to 9.7; P = 0.125); among secondary outcomes: improvement in COPM performance measure of 1.1 ± 1.5 points (95% CI 0.2 to 1.9; P = 0.02) and in the SF-36 physical health component by 5.1 ± 6.2 points (95% CI 0.7 to 9.6; P = 0.028). Otherwise, there are no significant changes. CONCLUSION: Evidence to recommend DBS as routine treatment to improve quality of life in pediatric patients with dyskinetic cerebral palsy is not yet sufficient. Extended follow-up in larger cohorts will determine the impact of DBS further to guide treatment decisions in these often severely disabled patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Rediscovery of the transcerebellar approach: improving the risk-benefit ratio in robot-assisted brainstem biopsies.

OBJECTIVE: Conventional frame-based stereotaxy through a transfrontal approach (TFA) is the gold standard in brainstem biopsies. Because of the high surgical morbidity and limited impact on therapy, brainstem biopsies are controversial. The introduction of robot-assisted stereotaxy potentially improves the risk-benefit ratio by simplifying a transcerebellar approach (TCA). The aim of this single-center cohort study was to evaluate the risk-benefit ratio of transcerebellar brainstem biopsies performed by 2 different robotic systems. In addition to standard quality indicators, a special focus was set on trajectory selection for reducing surgical morbidity. METHODS: This study included 25 pediatric (n = 7) and adult (n = 18) patients who underwent 26 robot-assisted biopsies via a TCA. The diagnostic yield, complication rate, trajectory characteristics (i.e., length, anatomical entry, and target-point location), and skin-to-skin (STS) time were evaluated. Transcerebellar and hypothetical transfrontal trajectories were reconstructed and transferred into a common MR space for further comparison with anatomical atlases. RESULTS: Robot-assisted, transcerebellar biopsies demonstrated a high diagnostic yield (96.2%) while exerting no surgical mortality and no permanent morbidity in both pediatric and adult patients. Only 3.8% of cases involved a transient neurological deterioration. Transcerebellar trajectories had a length of 48.4 ± 7.3 mm using a wide stereotactic corridor via crus I or II of the cerebellum and the middle cerebellar peduncle. The mean STS time was 49.5 ± 23.7 minutes and differed significantly between the robotic systems (p = 0.017). The TFA was characterized by longer trajectories (107.4 ± 11.8 mm, p < 0.001) and affected multiple eloquent structures. Transfrontal target points were located significantly more medial (-3.4 ± 7.2 mm, p = 0.042) and anterior (-3.9 ± 8.4 mm, p = 0.048) in comparison with the transcerebellar trajectories. CONCLUSIONS: Robot-assisted, transcerebellar stereotaxy can improve the risk-benefit ratio of brainstem biopsies by avoiding the restrictions of a TFA and conventional frame-based stereotaxy. Profound registration and anatomical-functional trajectory selection were essential to reduce mortality and morbidity.

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.

Non-invasive brain stimulation in modulation of mental rotation ability: A systematic review and meta-analysis.

Mental rotation, the ability to manipulate mental images, is an important function in human cognition. This systematic review and meta-analysis investigates the potential of non-invasive brain stimulation in modulation of this component of visuo-spatial perception. The PubMed database was reviewed prior to 31 September 2020 on randomized controlled trials investigating the effects of repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) on the mental rotation ability in healthy persons. A total of 17 studies (including 485 subjects) matched our inclusion criteria. Within their scope, overall, 46 sham-controlled experiments were performed. Methodology and results of each experiment are presented in a meta-analysis. The data show a large variety of methods and effects. The influence of (1) stimulation-technique (tDCS, tACS, and rTMS), (2) stimulation protocol (anodal, cathodal, bilateral tDCS, tACS, high-frequency rTMS, low-frequency rTMS, paired pulse rTMS, and theta burst stimulation), (3) stimulation timing (preconditioning and simultaneous), (4) stimulation location (left, right hemisphere, frontal, and parietal area), and (5) stimulus type (bodily and non-bodily) is discussed. The data indicate a beneficial effect of anodal tDCS and of tACS and no effect of cathodal tDCS on the mental rotation ability. Bilateral tDCS protocols both improved and worsened the parameters assessed. The small effect sizes obtained in mostly rTMS experiments require cautious interpretation.

Long-term effects of pallidal and thalamic deep brain stimulation in myoclonus dystonia.

OBJECTIVE: Observational study to evaluate long-term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the ventral intermediate thalamic nucleus (VIM) on patients with medically refractory myoclonus dystonia (MD). BACKGROUND: More recently, pallidal as well as thalamic DBS have been applied successfully in MD but long-term data are sparse. METHODS: We retrospectively analyzed a cohort of seven MD patients with either separate (n = 1, VIM) or combined GPi- DBS and VIM-DBS (n = 6). Myoclonus, dystonia and disability were rated at baseline (BL), short-term (ST-FU) and long-term follow-up (LT-FU) using the United Myoclonus Rating Scale, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Tsui rating scale, respectively. Quality of life (QoL) and mood were evaluated using the SF-36 and Beck Depression Inventory questionnaires, respectively. RESULTS: Patients reached a significant reduction of myoclonus at ST-FU (62% ± 7.3%; mean ± SE) and LT-FU (68% ± 3.4%). While overall motor BFMDRS changes were not significant at LT-FU, patients with GPi-DBS alone responded better and predominant cervical dystonia ameliorated significantly up to 54% ± 9.7% at long-term. Mean disability scores significantly improved by 44% ± 11.4% at ST-FU and 58% ± 14.8% at LT-FU. Mood and QoL remained unchanged between 5 and up to 20 years postoperatively. No serious long-lasting stimulation-related adverse events were observed. CONCLUSIONS: We present a cohort of MD patients with very long follow-up of pallidal and/or thalamic DBS that supports the GPi as the favourable stimulation target in MD with safe and sustaining effects on motor symptoms (myoclonus>dystonia) and disability.

Brain State-dependent Gain Modulation of Corticospinal Output in the Active Motor System.

The communication through coherence hypothesis suggests that only coherently oscillating neuronal groups can interact effectively and predicts an intrinsic response modulation along the oscillatory rhythm. For the motor cortex (MC) at rest, the oscillatory cycle has been shown to determine the brain's responsiveness to external stimuli. For the active MC, however, the demonstration of such a phase-specific modulation of corticospinal excitability (CSE) along the rhythm cycle is still missing. Motor evoked potentials in response to transcranial magnetic stimulation (TMS) over the MC were used to probe the effect of cortical oscillations on CSE during several motor conditions. A brain-machine interface (BMI) with a robotic hand orthosis allowed investigating effects of cortical activity on CSE without the confounding effects of voluntary muscle activation. Only this BMI approach (and not active or passive hand opening alone) revealed a frequency- and phase-specific cortical modulation of CSE by sensorimotor beta-band activity that peaked once per oscillatory cycle and was independent of muscle activity. The active MC follows an intrinsic response modulation in accordance with the communication through coherence hypothesis. Furthermore, the BMI approach may facilitate and strengthen effective corticospinal communication in a therapeutic context, for example, when voluntary hand opening is no longer possible after stroke.

Time Efficiency in Stereotactic Robot-Assisted Surgery: An Appraisal of the Surgical Procedure and Surgeon's Learning Curve.

BACKGROUND: Frame-based stereotactic procedures are still the gold standard in neurosurgery. However, there is an increasing interest in robot-assisted technologies. Introducing these increasingly complex tools in the clinical setting raises the question about the time efficiency of the system and the essential learning curve of the surgeon. METHODS: This retrospective study enrolled a consecutive series of patients undergoing a robot-assisted procedure after first system installation at one institution. All procedures were performed by the same neurosurgeon to capture the learning curve. The objective read-out were the surgical procedure time (SPT), the skin-to-skin time, and the intraoperative registration time (IRT) after laser surface registration (LSR), bone fiducial registration (BFR), and skin fiducial registration (SFR), as well as the quality of the registration (as measured by the fiducial registration error [FRE]). The time measures were compared to those for a patient group undergoing classic frame-based stereotaxy. RESULTS: In the first 7 months, we performed 31 robot-assisted surgeries (26 biopsies, 3 stereotactic electroencephalography [SEEG] implantations, and 2 endoscopic procedures). The SPT was depending on the actual type of surgery (biopsies: 85.0 ± 36.1 min; SEEG: 154.9 ± 75.9 min; endoscopy: 105.5 ± 1.1 min; p = 0.036). For the robot-assisted biopsies, there was a significant reduction in SPT within the evaluation period, reaching the level of frame-based surgeries (58.1 ± 17.9 min; p < 0.001). The IRT was depending on the applied registration method (LSR: 16.7 ± 2.3 min; BFR: 3.5 ± 1.1 min; SFR: 3.5 ± 1.6 min; p < 0.001). In contrast to BFR and SFR, there was a significant reduction in LSR time during that period (p = 0.038). The FRE differed between the applied registration methods (LSR: 0.60 ± 0.17 mm; BFR: 0.42 ± 0.15 mm; SFR: 2.17 ± 0.78 mm; p < 0.001). There was a significant improvement in LSR quality during the evaluation period (p = 0.035). CONCLUSION: Introducing stereotactic, robot-assisted surgery in an established clinical setting initially necessitates a prolonged intraoperative preparation time. However, there is a steep learning curve during the first cases, reaching the time level of classic frame-based stereotaxy. Thus, a stereotactic robot can be integrated into daily routine within a decent period of time, thereby expanding the neurosurgeons' armamentarium, especially for procedures with multiple trajectories.

Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial.

A 2016 published randomized multicenter phase III trial of prophylactic nimodipine treatment in vestibular schwannoma surgery showed only a tendency for higher hearing preservation rates in the treatment group. Gender was not included in statistical analysis at that time. A retrospective analysis of the trial considering gender, preoperative hearing, and nimodipine treatment was performed. The treatment group received parenteral nimodipine from the day before surgery until the seventh postoperative day. The control group was not treated prophylactically. Cochlear nerve function was determined by pure-tone audiometry with speech discrimination preoperatively, during in-patient care, and 1 year after surgery and classified according to the Gardner-Robertson grading scale (GR). Logistic regression analysis showed a statistically significant effect for higher hearing preservation rates (pre- and postoperative GR 1-4) in 40 men comparing the treatment (n = 21) and the control (n = 19) groups (p = 0.028), but not in 54 women comparing 27 women in both groups (p = 0.077). The results were also statistically significant for preservation of postoperative hearing with pre- and postoperative GR 1-3 (p = 0.024). There were no differences in tumor sizes between the treatment and the control groups in men, whereas statistically significant larger tumors were observed in the female treatment group compared with the female control group. Prophylactic nimodipine is safe, and an effect for hearing preservation in 40 men with preoperative hearing ability of GR 1-4 was shown in this retrospective investigation. The imbalance in tumor size with larger tumors in females of the treatment group may falsely suggest a gender-related effect. Further investigations are recommended to clarify whether gender has impact on nimodipine's efficacy.

Resting motor threshold in the course of hand motor recovery after stroke: a systematic review.

BACKGROUND: Resting motor threshold is an objective measure of cortical excitability. Numerous studies indicate that the success of motor recovery after stroke is significantly determined by the direction and extent of cortical excitability changes. A better understanding of this topic (particularly with regard to the level of motor impairment and the contribution of either cortical hemisphere) may contribute to the development of effective therapeutical strategies in this cohort. OBJECTIVES: This systematic review collects and analyses the available evidence on resting motor threshold and hand motor recovery in stroke patients. METHODS: PubMed was searched from its inception through to 31/10/2020 on studies investigating resting motor threshold of the affected and/or the non-affected hemisphere and motor function of the affected hand in stroke cohorts. RESULTS: Overall, 92 appropriate studies (including 1978 stroke patients and 377 healthy controls) were identified. The analysis of the data indicates that severe hand impairment is associated with suppressed cortical excitability within both hemispheres and with great between-hemispheric imbalance of cortical excitability. Favorable motor recovery is associated with an increase of ipsilesional motor cortex excitability and reduction of between-hemispheric imbalance. The direction of change of contralesional motor cortex excitability depends on the amount of hand motor impairment. Severely disabled patients show an increase of contralesional motor cortex excitability during motor recovery. In contrast, recovery of moderate to mild hand motor impairment is associated with a decrease of contralesional motor cortex excitability. CONCLUSIONS: This data encourages a differential use of rehabilitation strategies to modulate cortical excitability. Facilitation of the ipsilesional hemisphere may support recovery in general, whereas facilitation and inhibition of the contralesional hemisphere may enhance recovery in severe and less severely impaired patients, respectively.

Clinical validation of kinematic assessments of post-stroke upper limb movements with a multi-joint arm exoskeleton.

BACKGROUND: The clinical evaluation of the upper limb of severely impaired stroke patient is challenging. Sensor-based assessments may allow for an objective evaluation of this patient population. This study investigated the validity of a device-assisted approach in comparison to the clinical outcome that it is supposed to reflect. METHODS: In nineteen severely impaired chronic stroke patients, we applied a gravity-compensating, multi-joint arm exoskeleton (Armeo Spring) and compared this sensor-based assessment with the clinical outcome measure Upper Extremity Fugl-Meyer Assessment (UE-FMA) scale. Specifically, we assessed separately and subsequently the range of motion in joint space for four single joints (i.e., wrist, elbow and shoulder flexion/extension (FE), and shoulder internal/external rotation (IER)), and the closing and opening of the hand with a pressure sensor placed in the handle. RESULTS: Within the kinematic parameters, a strong correlation was observed between wrist and elbow FE (r > 0.7, p < 0.003; Bonferroni corrected). The UE-FMA was significantly predicted by a multiple regression model (F (5, 13) = 12.22, p < 0.0005, adj. R2 = 0.83). Both shoulder IER and grip pressure added significantly (p < 0.05) to the prediction with the standardized coefficients ß of 0.55 and 0.38, respectively. CONCLUSIONS: By applying an exoskeleton-based self-contained evaluation of single-joint movements, a clinically valid assessment of the upper limb range of motion in severely impaired stroke patients is feasible. Shoulder IER contributed most relevantly to the prediction of the clinical status. These findings need to be confirmed in a large, independent patient cohort.

Desynchronization of temporal lobe theta-band activity during effective anterior thalamus deep brain stimulation in epilepsy.

BACKGROUND: Bilateral cyclic high frequency deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) reduces the seizure count in a subset of patients with epilepsy. Detecting stimulation-induced alterations of pathological brain networks may help to unravel the underlying physiological mechanisms related to effective stimulation delivery and optimize target engagement. METHODS: We acquired 64-channel electroencephalography during ten ANT-DBS cycles (145 â€‹Hz, 90 â€‹µs, 3-5 â€‹V) of 1-min ON followed by 5-min OFF stimulation to detect changes in cortical activity related to seizure reduction. The study included 14 subjects (three responders, four non-responders, and seven healthy controls). Mixed-model ANOVA tests were used to compare differences in cortical activity between subgroups both ON and OFF stimulation, while investigating frequency-specific effects for the seizure onset zones. RESULTS: ANT-DBS had a widespread desynchronization effect on cortical theta and alpha band activity in responders, but not in non-responders. Time domain analysis showed that the stimulation induced reduction in theta-band activity was temporally linked to the stimulation period. Moreover, stimulation induced theta-band desynchronization in the temporal lobe channels correlated significantly with the therapeutic response. Responders to ANT-DBS and healthy-controls had an overall lower level of theta-band activity compared to non-responders. CONCLUSION: This study demonstrated that temporal lobe channel theta-band desynchronization may be a predictive physiological hallmark of therapeutic response to ANT-DBS and may be used to improve the functional precision of this intervention by verifying implantation sites, calibrating stimulation contacts, and possibly identifying treatment responders prior to implantation.

Online Mapping With the Deep Brain Stimulation Lead: A Novel Targeting Tool in Parkinson's Disease.

BACKGROUND: Beta-frequency oscillations (13-30 Hz) are a subthalamic hallmark in patients with Parkinson's disease, and there is increased interest in their utility as an intraoperative marker. OBJECTIVES: The objectives of this study were to assess whether beta activity measured directly from macrocontacts of deep brain stimulation leads could be used (a) as an intraoperative electrophysiological approach for guiding lead placements and (b) for physiologically informed stimulation delivery. METHODS: Every millimeter along the surgical trajectory, local field-potential data were collected from each macrocontact, and power spectral densities were calculated and visualized (n = 39 patients). This was done for online intraoperative functional mapping and post hoc statistical analyses using 2 methods: generating distributions of spectral activity along surgical trajectories and direct delineation (presence versus lack) of beta peaks. In a subset of patients, this approach was corroborated by microelectrode recordings. Furthermore, the match rate between beta peaks at the final target position and the clinically determined best stimulation site were assessed. RESULTS: Subthalamic recording sites were delineated by both methods of reconstructing functional topographies of spectral activity along surgical trajectories at the group level (P < 0.0001). Beta peaks were detected when any portion of the 1.5 mm macrocontact was within the microelectrode-defined subthalamic border. The highest beta peak at the final implantation site corresponded to the site of active stimulation in 73.3% of hemispheres (P < 0.0001). In 93.3% of hemispheres, active stimulation corresponded to the first-highest or second-highest beta peak. CONCLUSIONS: Online measures of beta activity with the deep brain stimulation macroelectrode can be used to inform surgical lead placement and contribute to optimization of stimulation programming procedures. © 2020 International Parkinson and Movement Disorder Society.