Magnetic Resonance Imaging and Nuclear Imaging of Parkinsonian Disorders: Where do we go from here?

Parkinsonian disorders are a heterogeneous group of incurable neurodegenerative diseases that significantly reduce quality of life and constitute a substantial economic burden. Nuclear imaging (NI) and magnetic resonance imaging (MRI) have played and continue to play a key role in research aimed at understanding and monitoring these disorders. MRI is cheaper, more accessible, nonirradiating, and better at measuring biological structures and hemodynamics than NI. NI, on the other hand, can track molecular processes, which may be crucial for the development of efficient diseasemodifying therapies. Given the strengths and weaknesses of NI and MRI, how can they best be applied to Parkinsonism research going forward? This review aims to examine the effectiveness of NI and MRI in three areas of Parkinsonism research (differential diagnosis, prodromal disease identification, and disease monitoring) to highlight where they can be most impactful. Based on the available literature, MRI can assist with differential diagnosis, prodromal disease identification, and disease monitoring as well as NI. However, more work is needed, to confirm the value of MRI for monitoring prodromal disease and predicting phenoconversion. Although NI can complement or be a substitute for MRI in all the areas covered in this review, we believe that its most meaningful impact will emerge once reliable Parkinsonian proteinopathy tracers become available. Future work in tracer development and high-field imaging will continue to influence the landscape for NI and MRI.

Distinct cortical and subcortical predictors of Purdue Pegboard decline in Parkinson's disease and atypical parkinsonism.

Objective measures of disease progression are critically needed in research on Parkinson's disease (PD) and atypical Parkinsonism but may be hindered by both practicality and cost. The Purdue Pegboard Test (PPT) is objective, has high test-retest reliability, and has a low cost. The goals of this study were to determine: (1) longitudinal changes in PPT in a multisite cohort of patients with PD, atypical Parkinsonism, and healthy controls; (2) whether PPT performance reflects brain pathology revealed by neuroimaging; (3) quantify kinematic deficits shown by PD patients during PPT. Parkinsonian patients showed a decline in PPT performance that correlated with motor symptom progression, which was not seen in controls. Neuroimaging measures from basal ganglia were significant predictors of PPT performance in PD, whereas cortical, basal ganglia, and cerebellar regions were predictors for atypical Parkinsonism. Accelerometry in a subset of PD patients showed a diminished range of acceleration and irregular patterns of acceleration, which correlated with PPT scores.

Behavioral Classification of Sequential Neural Activity Using Time Varying Recurrent Neural Networks.

Shifts in data distribution across time can strongly affect early classification of time-series data. When decoding behavior from neural activity, early detection of behavior may help in devising corrective neural stimulation before the onset of behavior. Recurrent Neural Networks (RNNs) are common models for sequence data. However, standard RNNs are not able to handle data with temporal distributional shifts to guarantee robust classification across time. To enable the network to utilize all temporal features of the neural input data, and to enhance the memory of an RNN, we propose a novel approach: RNNs with time-varying weights, here termed Time-Varying RNNs (TV-RNNs). These models are able to not only predict the class of the time-sequence correctly but also lead to accurate classification earlier in the sequence than standard RNNs. In this work, we focus on early sequential classification of brain-wide neural activity across time using TV-RNNs applied to a variety of neural data from mice and humans, as subjects perform motor tasks. Finally, we explore the contribution of different brain regions on behavior classification using SHapley Additive exPlanation (SHAP) value, and find that the somatosensory and premotor regions play a large role in behavioral classification.

Exploration of a novel physical therapy protocol that uses a sensory substitution device to improve the standing postural balance of children with balance disorders.

OBJECTIVE: To explore if an intensive balance training protocol that incorporated the BrainPort sensory substitution device improves the standing postural balance of children with balance disorders. METHODS: Eight children with balance disorders received 8-weeks of balance training while using the BrainPort device. Pre- and post-intervention changes in the Bruininks-Oseretsky Test of Motor Proficiency balance subtest (BOT-2) scores, standing duration on an unstable surface, and center of pressure (COP) sway were assessed. RESULTS: Post-intervention, the BOT-2 balance subtest scores increased by 29.6% and demonstrated clinically meaningful improvements. Overall, the standing duration with vision increased. The standing duration on the unstable surface without vision increased significantly from pre- to post-intervention. However, anterior-posterior (AP) and medial-lateral (ML) sway did not change post-intervention. The children also reported new functional activities (i.e. riding a bike, standing on unsteady or narrow surfaces). CONCLUSION: Balance training with the BrainPort sensory substitution device has the potential to result in clinically relevant improvements in the standing postural balance of children with balance disorders.

Diffusion Magnetic Resonance Imaging Detects Progression in Parkinson's Disease: A Placebo-Controlled Trial of Rasagiline.

BACKGROUND: Rasagiline has received attention as a potential disease-modifying therapy for Parkinson's disease (PD). Whether rasagiline is disease modifying remains in question. OBJECTIVE: The main objective of this study was to determine whether rasagiline has disease-modifying effects in PD over 1 year. Secondarily we evaluated two diffusion magnetic resonance imaging pulse sequences to determine the best sequence to measure disease progression. METHODS: This prospective, randomized, double-blind, placebo-controlled trial assessed the effects of rasagiline administered at 1 mg/day over 12 months in early-stage PD. The primary outcome was 1-year change in free-water accumulation in posterior substantia nigra (pSN) measured using two diffusion magnetic resonance imaging pulse sequences, one with a repetition time (TR) of 2500 ms (short TR; n = 90) and one with a TR of 6400 ms (long TR; n = 75). Secondary clinical outcomes also were assessed. RESULTS: Absolute change in pSN free-water accumulation was not significantly different between groups (short TR: P = 0.346; long TR: P = 0.228). No significant differences were found in any secondary clinical outcomes between groups. Long TR, but not short TR, data show pSN free-water increased significantly over 1 year (P = 0.025). Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III increased significantly over 1 year (P = 0.009), and baseline free-water in the pSN correlated with the 1-year change in Movement Disorder Society Unified Parkinson's Disease Rating Scale testing of motor function, Part III (P = 0.004) and 1-year change in bradykinesia score (P = 0.044). CONCLUSIONS: We found no evidence that 1 mg/day rasagiline has a disease-modifying effect in PD over 1 year. We found pSN free-water increased over 1 year, and baseline free-water relates to clinical motor progression, demonstrating the importance of diffusion imaging parameters for detecting and predicting PD progression. © 2021 International Parkinson and Movement Disorder Society.

Unraveling somatotopic organization in the human brain using machine learning and adaptive supervoxel-based parcellations.

In addition to the well-established somatotopy in the pre- and post-central gyrus, there is now strong evidence that somatotopic organization is evident across other regions in the sensorimotor network. This raises several experimental questions: To what extent is activity in the sensorimotor network effector-dependent and effector-independent? How important is the sensorimotor cortex when predicting the motor effector? Is there redundancy in the distributed somatotopically organized network such that removing one region has little impact on classification accuracy? To answer these questions, we developed a novel experimental approach. fMRI data were collected while human subjects performed a precisely controlled force generation task separately with their hand, foot, and mouth. We used a simple linear iterative clustering (SLIC) algorithm to segment whole-brain beta coefficient maps to build an adaptive brain parcellation and then classified effectors using extreme gradient boosting (XGBoost) based on parcellations at various spatial resolutions. This allowed us to understand how data-driven adaptive brain parcellation granularity altered classification accuracy. Results revealed effector-dependent activity in regions of the post-central gyrus, precentral gyrus, and paracentral lobule. SMA, regions of the inferior and superior parietal lobule, and cerebellum each contained effector-dependent and effector-independent representations. Machine learning analyses showed that increasing the spatial resolution of the data-driven model increased classification accuracy, which reached 94% with 1755 supervoxels. Our SLIC-based supervoxel parcellation outperformed classification analyses using established brain templates and random simulations. Occlusion experiments further demonstrated redundancy across the sensorimotor network when classifying effectors. Our observations extend our understanding of effector-dependent and effector-independent organization within the human brain and provide new insight into the functional neuroanatomy required to predict the motor effector used in a motor control task.

Gamma somatosensory cortical oscillations are attenuated during the stance phase of human walking.

It is well appreciated that processing of peripheral feedback by the somatosensory cortices plays a prominent role in the control of human motor actions like walking. However, very few studies have actually quantified the somatosensory cortical activity during walking. In this investigation, we used electroencephalography (EEG) and beamforming source reconstruction methods to quantify the frequency specific neural oscillations that are induced by an electrical stimulation that is applied to the right tibial nerve under the following experimental conditions: 1) sitting, 2) standing in place, and 3) treadmill walking. Our experimental results revealed that the peripheral stimulation induced a transient increase in theta-alpha (4-12 Hz; 50-350 ms) and gamma (40-80 Hz; 40-100 ms) activity in the leg region of the contralateral somatosensory cortices. The strength of the gamma oscillations were similar while sitting and standing, but were markedly attenuated while walking. Conversely, the strength of the theta-alpha oscillations were not different across the respective experimental conditions. Prior research suggests the afferent feedback from the Ia sensory fibers are likely attenuated during walking, while afferent feedback from the ß polysynaptic sensory fibers are not. We suggest that the attenuated gamma oscillations seen during walking reflect the gating of the Ia afferents, while the similarity of theta-alpha oscillations across the experimental conditions is associated with the afferent information from the type II (Aα and ß) polysynaptic sensory fibers.

The Strength of the Movement-related Somatosensory Cortical Oscillations Differ between Adolescents and Adults.

Adolescents demonstrate increasing mastery of motor actions with age. One prevailing hypothesis is that maturation of the somatosensory system during adolescence contributes to the improved motor control. However, limited efforts have been made to determine if somatosensory cortical processing is different in adolescents during movement. In this study, we used magnetoencephalographic brain imaging to begin addressing this knowledge gap by applying an electrical stimulation to the tibial nerve as adolescents (Age = 14.8 ± 2.5 yrs.) and adults (Age = 36.8 ± 5.0 yrs.) produced an isometric ankle plantarflexion force, or sat with no motor activity. Our results showed strong somatosensory cortical oscillations for both conditions in the alpha-beta (8-30 Hz) and gamma (38-80 Hz) ranges that occurred immediately after the stimulation (0-125 ms), and a beta (18-26 Hz) oscillatory response shortly thereafter (300-400 ms). Compared with the passive condition, all of these frequency specific cortical oscillations were attenuated while producing the ankle force. The attenuation of the alpha-beta response was greater in adolescents, while the adults had a greater attenuation of the beta response. These results imply that altered attenuation of the somatosensory cortical oscillations might be central to the under-developed somatosensory processing and motor performance characteristics in adolescents.

Optimizing Neuromuscular Electrical Stimulation Pulse Width and Amplitude to Promote Central Activation in Individuals With Severe Spinal Cord Injury.

Neuromuscular electrical stimulation (NMES) is one of the most effective treatments for counteracting the deleterious skeletal muscle adaptations that occur after spinal cord injury (SCI). Additionally, previous findings suggest that NMES can activate motor units via both peripheral and central mechanisms; however, this NMES-promoted central activation is not well understood. In this study, we aimed at investigating the effects of NMES on central activation in 10 individuals with motor complete SCI, focusing on understanding how to optimize NMES pulse width and amplitude for promoting central activation in this population. To this end, we used NMES to generate isometric contractions of the knee extensors and ankle plantarflexors while electromyographic (EMG) activity was recorded from the vastus lateralis and gastrocnemius medialis, respectively. We used EMG activity that persisted after the termination of NMES delivery (post-NMES) as a neurophysiological marker to assess central activation and explored differences in post-NMES EMG activity promoted by 500 and 1,000 µs pulse width NMES. Additionally, we explored the relationships between post-NMES EMG amplitude, torque output, and stimulation amplitude. Our results show that the higher pulse width (1,000 µs) demonstrated a greater effect on central activation as quantified by more frequent occurrences of post-NMES EMG activity (p = 0.002) and a 3.551 µV higher EMG amplitude (p = 0.003) when controlling for the torque output generated by 500 and 1,000 µs pulse width NMES. Importantly, we also found that the interplay among central activation, stimulation amplitude, and muscle torque output differs across SCI individuals, conceivably because of the individual-specific characteristics of the cord lesion and following plasticity of the spinal circuitry. These results suggest that NMES can be optimized to promote central activation, which may lead to novel opportunities for motor function recovery after SCI.

Practice modulates motor-related beta oscillations differently in adolescents and adults.

KEY POINTS: Magnetoencephalography data were acquired during a leg force task in pre-/post-practice sessions in adolescents and adults. Strong peri-movement alpha and beta oscillations were mapped to the cortex. Following practice, performance improved and beta oscillations were altered. Beta oscillations decreased in the sensorimotor cortex in adolescents after practice, but increased in adults. No pre-/post-practice differences were detected for alpha oscillations. ABSTRACT: There is considerable evidence that there are motor performance and practice differences between adolescents and adults. Behavioural studies have suggested that these motor performance differences are simply due to experience. However, the neurophysiological nexus for these motor performance differences remains unknown. The present study investigates the short-term changes (e.g. fast motor learning) in the alpha and beta event-related desynchronizations (ERDs) associated with practising an ankle plantarflexion motor action. To this end, we utilized magnetoencephalography to identify changes in the alpha and beta ERDs in healthy adolescents (n = 21; age = 14 ± 2.1 years) and middle-aged adults (n = 22; age = 36.6 ± 5 years) after practising an isometric ankle plantarflexion target-matching task. After practice, all of the participants matched more targets and matched the targets faster, and had improved accuracy, faster reaction times and faster force production. However, the motor performance of the adults exceeded what was seen in the adolescents regardless of practice. In conjunction with the behavioural results, the strength of the beta ERDs across the motor planning and execution stages was reduced after practice in the sensorimotor cortices of the adolescents, but was stronger in the adults. No pre-/post-practice changes were found in the alpha ERDs. These outcomes suggest that there are age-dependent changes in the sensorimotor cortical oscillations after practising a motor task. We suspect that these noted differences might be related to familiarity with the motor task, GABA levels and/or maturational differences in the integrity of the white matter fibre tracts that comprise the respective cortical areas.

Submaximal Marker for Investigating Peak Muscle Torque Using Neuromuscular Electrical Stimulation after Paralysis.

Spinal cord injury (SCI) results in deleterious skeletal muscle adaptations, such as relevant atrophy and loss of force. In particular, the relevant loss of lower-limb force-generating capacity may limit functional mobility even if neuronal control was sufficient. Currently, methods of assessing maximal force-generating capacity using neuromuscular electrical stimulation (NMES) are limited in individuals who cannot tolerate higher stimulation amplitudes, such as those with residual sensation and those at risk of fracture. In this study, we examined the relationship between NMES amplitude and muscle torque exerted (recruitment curve) in order to determine whether maximal torque output can be characterized by a submaximal marker. Recruitment curves for knee extensors, knee flexors, and ankle plantarflexors were recorded from 30 individuals with motor complete SCI. NMES was delivered starting with an amplitude of 5 mA, and increasing by 5 mA for every subsequent stimulation until either the participant requested to stop the stimulation or the maximum stimulation amplitude (140 mA) was reached. Significant correlations between peak slope of the recruitment curve and peak torque for all muscle groups were found (knee extensors, r = 0.75; p < 0.0001; knee flexors, r = 0.68; p < 0.0001; ankle plantarflexors, r = 0.91; p < 0.0001), indicating that muscles that show greater peak slope of the recruitment curve tend to generate a greater peak torque. This suggests that peak slope, which was achieved at an average stimulation intensity (55.0 mA) that was 43% smaller than that corresponding to peak torque (97.4 mA), may be used as a submaximal marker for characterizing maximal torque output in individuals with SCI.

Neurophysiological changes in the visuomotor network after practicing a motor task.

Although it is well appreciated that practicing a motor task updates the associated internal model, it is still unknown how the cortical oscillations linked with the motor action change with practice. The present study investigates the short-term changes (e.g., fast motor learning) in the α- and ß-event-related desynchronizations (ERD) associated with the production of a motor action. To this end, we used magnetoencephalography to identify changes in the α- and ß-ERD in healthy adults after participants practiced a novel isometric ankle plantarflexion target-matching task. After practicing, the participants matched the targets faster and had improved accuracy, faster force production, and a reduced amount of variability in the force output when trying to match the target. Parallel with the behavioral results, the strength of the ß-ERD across the motor-planning and execution stages was reduced after practice in the sensorimotor and occipital cortexes. No pre/postpractice changes were found in the α-ERD during motor planning or execution. Together, these outcomes suggest that fast motor learning is associated with a decrease in ß-ERD power. The decreased strength likely reflects a more refined motor plan, a reduction in neural resources needed to perform the task, and/or an enhancement of the processes that are involved in the visuomotor transformations that occur before the onset of the motor action. These results may augment the development of neurologically based practice strategies and/or lead to new practice strategies that increase motor learning. NEW & NOTEWORTHY We aimed to determine the effects of practice on the movement-related cortical oscillatory activity. Following practice, we found that the performance of the ankle plantarflexion target-matching task improved and the power of the ß-oscillations decreased in the sensorimotor and occipital cortexes. These novel findings capture the ß-oscillatory activity changes in the sensorimotor and occipital cortexes that are coupled with behavioral changes to demonstrate the effects of motor learning.

Movement-Related Somatosensory Activity Is Altered in Patients with Multiple Sclerosis.

During active movement the somatosensory cortical responses are often attenuated. This attenuation is referred to as movement-related sensory gating. It is well known that patients with multiple sclerosis (MS) have sensory processing deficits, and recent work has also suggested that these patients display impaired motor control of the ankle musculature. The primary goal of the current study was to: (1) examine the movement-related somatosensory gating in patients with MS and demographically-matched controls, and (2) identify the relationship between the sensory gating and motor control of the ankle musculature. To this end, we used magnetoencephalography brain imaging to assess the neural responses to a tibial nerve electrical stimulation that was applied at rest (passive) and during an ankle plantarflexion motor task (active condition). All participants also completed an ankle isometric motor control task that was performed outside the scanner. Our results indicated that the controls, but not patients with MS, exhibited significantly reduced somatosensory responses during the active relative to passive conditions, and that patients with MS had stronger responses compared with controls during the active condition. Additionally, control of the ankle musculature was related to the extent of movement-related sensory attenuation, with poor motor control being associated with reduced gating. Overall, these results show that patients with MS do not attenuate the somatosensory cortical activity during motor actions, and that the inability to modulate somatosensory cortical activity is partially related to the poor ankle motor control seen in these patients.

Changes in lower extremity strength may be related to the walking speed improvements in children with cerebral palsy after gait training.

BACKGROUND: Cerebral palsy (CP) has a high probability of resulting in lower extremity strength and walking deficits. Numerous studies have shown that gait training has the potential to improve the walking abilities of these children; however, the factors governing these improvements are unknown. AIMS: This study aimed to evaluate the relationship between change in lower extremity strength, walking speed and endurance of children with CP following gait training. METHODS AND PROCEDURES: Eleven children with CP (GMFCS levels=II-III) completed a gait training protocol three days a week for six weeks. Outcome measures included a 10m fast-as-possible walk test, 6min walking endurance test and lower extremity strength. OUTCOMES AND RESULTS: The group results indicated there were improvements in walking speed, walking endurance and lower extremity strength. In addition, there was a positive correlation between percent change in lower extremity strength and walking speed and a negative correlation between the percent change in lower extremity strength and the child's age. CONCLUSIONS: Our results imply that changes in lower extremity strength might be related to the degree of the walking speed changes seen after gait training. Younger children may be more likely to show improvements in lower extremity strength after gait training.

A reduced somatosensory gating response in individuals with multiple sclerosis is related to walking impairment.

When identical stimuli are presented in rapid temporal succession, neural responses to the second stimulation are often weaker than those observed for the first. This phenomenon is termed sensory gating and is believed to be an adaptive feature that helps prevent higher-order cortical centers from being flooded with unnecessary information. Recently, sensory gating in the somatosensory system has been linked to deficits in tactile discrimination. Additionally, studies have linked poor tactile discrimination with impaired walking and balance in individuals with multiple sclerosis (MS). In this study, we examine the neural basis of somatosensory gating in patients with MS and healthy controls and assess the relationship between somatosensory gating and walking performance. We used magnetoencephalography to record neural responses to paired-pulse electrical stimulation applied to the right posterior tibial nerve. All participants also walked across a digital mat, which recorded their spatiotemporal gait kinematics. Our results showed the amplitude of the response to the second stimulation was sharply reduced only in controls, resulting in a significantly reduced somatosensory gating in the patients with MS. No group differences were observed in the amplitude of the response to the first stimulation nor the latency of the neural response to either the first or second stimulation. Interestingly, the altered somatosensory gating responses were correlated with aberrant spatiotemporal gait kinematics in the patients with MS. These results suggest that inhibitory GABA circuits may be altered in patients with MS, which impacts somatosensory gating and contributes to the motor performance deficits seen in these patients.NEW & NOTEWORTHY We aimed to determine whether somatosensory gating in patients with multiple sclerosis (MS) differed compared with healthy controls and whether a relationship exists between somatosensory gating and walking performance. We found reduced somatosensory gating responses in patients with MS, and these altered somatosensory gating responses were correlated with the mobility impairments. These novel findings show that somatosensory gating is impaired in patients with MS and is related to the mobility impairments seen in these patients.

Altered sensorimotor cortical oscillations in individuals with multiple sclerosis suggests a faulty internal model.

Multiple sclerosis (MS) is a demyelinating disease that results in a broad array of symptoms, including impaired motor performance. How such demyelination of fibers affects the inherent neurophysiological activity in motor circuits, however, remains largely unknown. Potentially, the movement errors associated with MS may be due to imperfections in the internal model used to make predictions of the motor output that will meet the task demands. Prior magnetoencephalographic (MEG) and electroencephalographic brain imaging experiments have established that the beta (15-30 Hz) oscillatory activity in the sensorimotor cortices is related to the control of movement. Specifically, it has been suggested that the strength of the post-movement beta rebound may indicate the certainty of the internal model. In this study, we used MEG to evaluate the neural oscillatory activity in the sensorimotor cortices of individuals with MS and healthy individuals during a goal-directed isometric knee force task. Our results showed no difference between the individuals with MS and healthy individuals in the beta activity during the planning and execution stages of movement. However, we did find that individuals with MS exhibited a weaker post-movement beta rebound in the pre/postcentral gyri relative to healthy controls. Additionally, we found that the behavioral performance of individuals with MS was aberrant, and related to the strength of the post-movement beta rebound. These results suggest that the internal model may be faulty in individuals with MS. Hum Brain Mapp 38:4009-4018, 2017. © 2017 Wiley Periodicals, Inc.

Two Different Types of High-Frequency Physical Therapy Promote Improvements in the Balance and Mobility of Persons With Multiple Sclerosis.

OBJECTIVE: To evaluate the mobility and postural balance improvements that could be achieved in a cohort of persons with multiple sclerosis (MS) who participated in a motor adaptation protocol and a cohort of persons with MS who participated in a therapeutic exercise protocol. DESIGN: A cohort design, where subjects were evaluated before and after a 6-week intervention period. SETTING: Clinical laboratory setting. PARTICIPANTS: Individuals (N=42) with relapsing-remitting or secondary progressive MS (Expanded Disability Status Scale [EDSS] scores, 3.0-6.5) were initially screened for eligibility for participation in the study, from which those who fit the inclusion criteria (n=32) were enrolled in the study. Subjects were pseudorandomly assigned to a treatment group and matched based on EDSS scores. Fourteen individuals in the motor adaptation cohort (MAC) (mean age ± SD, 52.6±9y; mean EDSS score ± SD, 5.5±0.9) and 13 individuals in the therapeutic exercise cohort (TEC) (mean age ± SD, 54.0±9y; mean EDSS score ± SD, 5.3±0.9) completed the entire duration of their respective programs. INTERVENTIONS: Both cohorts completed their therapy twice a day, 5 days each week, for 6 weeks. Each session of the MAC program consisted of balance and gait training that encouraged new ways to adapt to challenging task demands. The TEC program was similar to a traditional exercise program. MAIN OUTCOME MEASURES: The Sensory Organization Test, 6-minute walk test, and gait spatiotemporal kinematics. RESULTS: Collectively, both treatment groups had improvements in postural balance (P=.001), walking endurance (P=.002), walking speed (P=.004), and step length (P<.001) after therapy. However, there were no statistical differences between the 2 treatment groups for any of the outcome variables (P values >.01). CONCLUSIONS: Our exploratory results suggest that a high frequency of physical therapy rather than a specific activity focus might be an important parameter for persons with MS.

Developmental Trajectory of Beta Cortical Oscillatory Activity During a Knee Motor Task.

There is currently a void in the scientific literature on the cortical beta oscillatory activity that is associated with the production of leg motor actions. In addition, we have limited data on how these cortical oscillations may progressively change as a function of development. This study began to fill this vast knowledge gap by using high-density magnetoencephalography to quantify the beta cortical oscillatory activity over a cross-section of typically developing children as they performed an isometric knee target matching task. Advanced beamforming methods were used to identify the spatiotemporal changes in beta oscillatory activity during the motor planning and motor action time frames. Our results showed that a widespread beta event-related desynchronization (ERD) was present across the pre/postcentral gyri, supplementary motor area, and the parietal cortices during the motor planning stage. The strength of this beta ERD sharply diminished across this fronto-parietal network as the children initiated the isometric force needed to match the target. Rank order correlations indicated that the older children were more likely to initiate their force production sooner, took less time to match the targets, and tended to have a weaker beta ERD during the motor planning stage. Lastly, we determined that there was a relationship between the child's age and the strength of the beta ERD within the parietal cortices during isometric force production. Altogether our results suggest that there are notable maturational changes during childhood and adolescence in beta cortical oscillatory activity that are associated with the planning and execution of leg motor actions.

Cue-related Temporal Factors Modulate Movement-related Beta Oscillatory Activity in the Human Motor Circuit.

In humans, there is a strong beta (15-30 Hz) event-related desynchronization (ERD) that begins before movement, which has been tentatively linked to motor planning operations. The dynamics of this response are strongly modulated by whether a pending movement is cued and the inherent parameters of the cue. However, previous studies have focused on the information content of cues and not on parameters such as the timing of the cue relative to other events. Variations in such timing are critical, as they directly impact the amount of time that participants have to plan pending movements. In this study, participants performed finger-tapping sequences during magnetoencephalography, and we manipulated the amount of time (i.e., "long" vs. "short") between the presentation of the to-be-executed sequence and the cue to initiate the sequence. We found that the beta ERD was stronger immediately after the cue to move in the contralateral postcentral gyrus and bilateral parietal cortices during the short compared with long planning time condition. During movement execution, the beta ERD was stronger in the premotor cortex and the SMA in the short relative to long condition. Finally, peak latency in the SMA significantly correlated with RT, such that the closer the peak beta ERD was to the cue to move, the quicker the participant responded. The results of this study establish that peri-movement beta ERD activity across the cortical motor circuit is highly sensitive to cue-related temporal factors, with a direct link to motor performance.

Multiple sclerosis influences the precision of the ankle plantarflexon muscular force production.

OBJECTIVE: To quantify the precision of the steady-state isometric control of the ankle plantarflexors musculature of individuals with multiple sclerosis (MS), and to evaluate if the precision is related to the mobility impairments. METHODS: Individuals with MS and healthy adults performed a submaximal steady-state isometric contraction with the ankle plantarflexors. The coefficient of variation was used to assess the amount of variability or error in the precision of the torques generated by the ankle plantarflexor musculature. The participants also walked across a digital mat at their preferred and fast-as-possible walking speeds, which recorded their spatiotemporal gait kinematics. RESULTS: The individuals with MS: (1) had reduced maximal voluntary torques at the ankle, (2) a greater amount of variability in the precision of the isometric ankle torques, (3) altered and more variable spatiotemporal gait kinematics, and (4) a greater amount of variability in the isometric ankle torques were related to a slower walking speed and cadence, shorter step length and a greater amount of gait variability. CONCLUSIONS: These results further fuels the impression that a reduction in control of the ankle joint musculature may be a key factor in the mobility and balance impairments seen in individuals with MS.