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.

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.

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.

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.

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.

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.

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.

Neurorehabilitation Strategies Focusing on Ankle Control Improve Mobility and Posture in Persons With Multiple Sclerosis.

BACKGROUND AND PURPOSE: The neuromuscular impairments seen in the ankle plantarflexors have been identified as a primary factor that limits the mobility and standing postural balance of individuals with multiple sclerosis (MS). However, few efforts have been made to find effective treatment strategies that will improve the ankle plantarflexor control. Our objective was to determine whether an intensive 14-week neurorehabilitation protocol has the potential to improve the ankle plantarflexor control of individuals with MS. The secondary objectives were to determine whether the protocol would also improve postural control, plantarflexion strength, and mobility. METHODS: Fifteen individuals with MS participated in a 14-week neurorehabilitation protocol, and 20 healthy adults served as a comparison group. The primary measure was the amount of variability in the submaximal steady-state isometric torque, which assessed plantarflexor control. Secondary measures were the Sensory Organization Test composite score, maximum plantarflexion torque, and the spatiotemporal gait kinematics. RESULTS: There was less variability in the plantarflexion torques after the neurorehabilitation protocol (preintervention, 4.15% ± 0.5%; postintervention, 2.27% ± 0.3%). In addition, there were less postural sway (preintervention, 51.87 ± 0.2 points; postintervention, 67.8 ± 0.5 points), greater plantarflexion strength (preintervention, 0.46 ± 0.04 Nm/kg; postintervention, 0.57 ± 0.05 Nm/kg), and faster walking speeds (preferred preintervention, 0.71 ± 0.05 m/s; preferred postintervention, 0.81 ± 0.05 m/s; fast-as-possible preintervention, 0.95 ± 0.06 m/s; postintervention, 1.11 ± 0.07 m/s). All of the outcome variables matched or trended toward those seen in the controls. DISCUSSION AND CONCLUSIONS: The outcomes of this exploratory study suggest that the neurorehabilitation protocol employed in this investigation has the potential to promote clinically relevant improvements in the ankle plantarflexor control, standing postural balance, ankle plantarflexion strength, and the mobility of individuals with MS. Video abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A110).

Functional specialization within the supplementary motor area: a fNIRS study of bimanual coordination.

Bimanual movements can be performed by flexing and extending the target effectors (e.g., hand muscles) in unison, or by flexing units on one side in unison with extension of the same units on the opposite side. The former movement patterns are generally referred to as in-phase or parallel, whereas the latter patterns are often termed anti-phase movements. It is well known that anti-phase patterns are unstable and tend to spontaneously transition to in-phase movements at higher repetition rates, but the mechanisms and brain regions involved are not fully understood. In the current study, we utilized functional near-infrared spectroscopy (fNIRS) to evaluate whether anterior/posterior subdivisions of the supplementary motor complex (SMA) have distinct functional roles in maintaining in-phase and anti-phase movement patterns. Twelve healthy adult participants completed a bimanual coordination task comprised of anti-phase and in-phase trials as 24-channel fNIRS data was recorded from dorsal-medial motor areas. We examined the relative concentrations of oxygenated and deoxygenated hemoglobin in the channels that were located over the anterior SMA (e.g., pre-SMA) and the SMA proper. Our most interesting results indicated that oxygenated hemoglobin responses were greater in the anterior SMA during performance of anti-phase compared to in-phase movements. In the SMA proper, oxygenated hemoglobin responses did not differ between the two movement patterns. These data suggest that the anterior SMA is critical to programming and maintaining the less stable anti-phase movement patterns, and support the conceptual framework of an anterior-directed gradient of progressively more complex functionality in the SMA.

Aberrant synchrony in the somatosensory cortices predicts motor performance errors in children with cerebral palsy.

Cerebral palsy (CP) results from a perinatal brain injury that often results in sensory impairments and greater errors in motor performance. Although these impairments have been well catalogued, the relationship between sensory processing networks and errors in motor performance has not been well explored. Children with CP and typically developing age-matched controls participated in this investigation. We used high-density magnetoencephalography to measure event-related oscillatory changes in the somatosensory cortices following tactile stimulation to the bottom of the foot. In addition, we quantified the amount of variability or errors in the isometric ankle joint torques as these children attempted to match a target. Our results showed that neural populations in the somatosensory cortices of children with CP were desynchronized by the tactile stimulus, whereas those of typically developing children were clearly synchronized. Such desynchronization suggests that children with CP were unable to fully integrate the external stimulus into ongoing sensorimotor computations. Our results also indicated that children with CP had a greater amount of errors in their motor output when they attempted to match the target force, and this amount of error was negatively correlated with the degree of synchronization present in the somatosensory cortices. These results are the first to show that the motor performance errors of children with CP are linked with neural synchronization within the somatosensory cortices.

Improving the motor skill of children with posterior fossa syndrome: a case series.

Children who receive treatment for medulloblastoma have a high survival rate, but also a high likelihood of developing posterior fossa syndrome, a condition that includes devastating balance and motor problems. This case series used 2 novel neuromodulation devices in conjunction with an intensive physical therapy intervention for 2 children who were 5 years post tumor treatment with a diagnosis of posterior fossa syndrome. Pre- and postclinical measures, in addition to magnetoencephalography brain imaging, describe positive behavioral and neuroplastic changes resulting from the intervention. The positive outcomes in these cases suggest that further study is needed using neuromodulatory devices and long-term rehabilitation in children with balance and movement disorders resulting from cancer treatment.

Overground body-weight-supported gait training for children and youth with neuromuscular impairments.

The aim of this investigation was to determine if body-weight-supported (BWS) overground gait training has the potential to improve the walking abilities of children and youth with childhood onset motor impairments and intellectual disabilities. Eight participants (mean age of 16.3 years) completed 12 weeks of BWS overground gait training that was performed two times a week. BWS was provided during the training sessions by an overhead harness system that rolls overground. There was a significant improvement in the preferred walking speed after the training (p < .01; pre = 0.51 ± 0.2 m/s; post = 0.67 ± 0.3 m/s; Cohen's d = 0.80) and cadence (p = .04; pre = 37 ± 7 steps/min; post = 43 ± 8 steps/min; Cohen's d = 0.94). Our results indicate that overground BWS gait training may be an effective treatment strategy for improving the preferred walking speed of children and youth with motor impairments.

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.

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.

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.

Stride-time variability and sensorimotor cortical activation during walking.

The time it takes between consecutive foot contacts from the same leg is referred to as the stride-time interval. Several investigations have shown that the variations that are present in the stride time intervals are linked to walking balance. In this study, functional near infrared spectroscopy (fNIRS) was utilized to evaluate whether activation in the medial sensorimotor cortices reflects the amount of variations seen in the stride-time intervals. Thirteen healthy adults (Age=23.7 ± 1.4 yrs.) walked forwards and backwards on a programmable treadmill. Each walking condition consisted of two sessions, with each being comprised of five alternating blocks of standing still or walking at 0.45 m/s. Activation in the medial sensorimotor cortices was measured using an fNIRS system, which consisted of a 4 × 4 grid of infrared optode emitter/detector pairs. The optodes were positioned on the participant's head using the International 10/20 system with Cz located beneath the center of the front two rows of optodes. We evaluated the block-wise changes in the amount of oxygenated (oxyHb) and deoxygenated hemoglobin (deoxyHb) in the channels that were located over the supplementary motor area, pre-central gyrus, post-central gyrus and superior parietal lobule. Throughout the experiment, a footswitch system was used to concurrently measure the amount of variation present in the stride-time intervals. Our results showed that oxyHb was greater in the supplementary motor area, pre-central gyrus, and superior parietal lobule when participants walked backwards rather than forwards, which suggests that backward walking presents more of a challenge to the nervous system as it controls the stepping pattern. Additionally, there was a significant decrease in the amount of deoxyHb present in the supplementary motor area while walking backward. Consistent with previous investigations, we noted that the amount of variability present in the stride-time intervals was greater during backward walking compared to forward walking. In addition, the amount of variation in the stride-time intervals while walking forward was positively correlated with the maximum oxyHb response found in the pre-central gyrus and supplementary motor area, which has not been previously shown. This neurobehavioral relationship supports the notion that the subtle variations found in the stride-time intervals are partly associated with processing demands by the motor cortices for regulating the forward temporal kinematics.

Influence of lower body pressure support on the walking patterns of healthy children and adults.

The purpose of this investigation was to evaluate the effect of a lower body positive pressure support system on the joint kinematics and activity of the lower extremity antigravity musculature of adults and children during walking. Adults (age = 25 ± 4 years) and children (age = 13 ± 2 years) walked at a preferred speed and a speed that was based on the Froude number, while 0-80% of their body weight was supported. Electrogoniometers were used to monitor knee and ankle joint kinematics. Surface electromyography was used to quantify the magnitude of the vastus lateralis and gastrocnemius muscle activity. There were three key findings: (1) The lower extremity joint angles and activity of the lower extremity antigravity muscles of children did not differ from those of adults. (2) The magnitude of the changes in the lower extremity joint motion and antigravity muscle activity was dependent upon an interaction between body weight support and walking speed. (3) Lower body positive pressure support resulted in reduced activation of the antigravity musculature, and reduced range of motion of the knee and ankle joints.