Altered Cortical Activity during a Finger Tap in People with Stroke.

This study describes electroencephalography (EEG) measurements during a simple finger movement in people with stroke to understand how temporal patterns of cortical activation and network connectivity align with prolonged muscle contraction at the end of a task. We investigated changes in the EEG temporal patterns in the beta band (13-26 Hz) of people with chronic stroke (N = 10, 7 F/3 M) and controls (N = 10, 7 F/3 M), during and after a cued movement of the index finger. We quantified the change in beta band EEG power relative to baseline as activation at each electrode and the change in task-based phase-locking value (tbPLV) and beta band task-based coherence (tbCoh) relative to baseline coherence as connectivity between EEG electrodes. Finger movements were associated with a decrease in beta power (event related desynchronization (ERD)) followed by an increase in beta power (event related resynchronization (ERS)). The ERS in the post task period was lower in the stroke group (7%), compared to controls (44%) (p < 0.001) and the transition from ERD to ERS was delayed in the stroke group (1.43 s) compared to controls (0.90 s) in the C3 electrode (p = 0.007). In the same post movement period, the stroke group maintained a heightened tbPLV (p = 0.030 for time to baseline of the C3:Fz electrode pair) and did not show the decrease in connectivity in electrode pair C3:Fz that was observed in controls (tbPLV: p = 0.006; tbCoh: p = 0.023). Our results suggest that delays in cortical deactivation patterns following movement coupled with changes in the time course of connectivity between the sensorimotor and frontal cortices in the stroke group might explain clinical observations of prolonged muscle activation in people with stroke. This prolonged activation might be attributed to the combination of cortical reorganization and changes to sensory feedback post-stroke.

Sex differences in laterality of motor unit firing behavior of the first dorsal interosseous muscle in strength-matched healthy young males and females.

PURPOSE: The purpose of this study was to compare laterality in motor unit firing behavior between females and males. METHODS: Twenty-seven subjects (14 females) were recruited for this study. The participants performed ramp up and hold isometric index finger abduction at 10, 30, and 60% of their maximum voluntary contraction (MVC). High-density surface electromyography (HD-sEMG) signals were recorded in the first dorsal interosseous (FDI) muscle and decomposed into individual motor unit (MU) firing behavior using a convolution blind source separation method. RESULTS: In total, 769 MUs were detected (females, n = 318 and males, n = 451). Females had a significantly higher discharge rate than males at each relative torque level (10%: male dominant hand, 13.4 ± 2.7 pps vs. female dominant hand, 16.3 ± 3.4 pps; 30%: male dominant hand, 16.1 ± 3.9 pps vs. female dominant hand, 20.0 ± 5.0 pps; and 60%: male dominant hand, 19.3 ± 3.8 vs. female dominant hand, 25.3 ± 4.8 pps; p < 0.0001). The recruitment threshold was also significantly higher in females than in males at 30 and 60% MVC. Furthermore, males exhibited asymmetrical discharge rates at 30 and 60% MVC and recruitment thresholds at 30 and 60% MVC, whereas no asymmetry was observed in females. CONCLUSION: In the FDI muscle, compared to males, females exhibited different neuromuscular strategies with higher discharge rates and recruitment thresholds and no asymmetrical MU firing behavior. Notably, the findings that sex differences in neuromuscular activity also occur in healthy individuals provide important information for understanding the pathogenesis of various diseases.

Association between the Degree of Pre-Synaptic Dopaminergic Pathway Degeneration and Motor Unit Firing Behavior in Parkinson's Disease Patients.

The relationship between motor unit (MU) firing behavior and the severity of neurodegeneration in Parkinson's disease (PD) is not clear. This study aimed to elucidate the association between degeneration with dopaminergic pathways and MU firing behavior in people with PD. Fourteen females with PD (age, 72.6 ± 7.2 years, disease duration, 3.5 ± 2.1 years) were enrolled in this study. All participants performed a submaximal, isometric knee extension ramp-up contraction from 0% to 80% of their maximal voluntary contraction strength. We used high-density surface electromyography with 64 electrodes to record the muscle activity of the vastus lateralis muscle and decomposed the signals with the convolution kernel compensation technique to extract the signals of individual MUs. We calculated the degree of degeneration of the central lesion-specific binding ratio by dopamine transporter single-photon emission computed tomography. The primary, novel results were as follows: (1) moderate-to-strong correlations were observed between the degree of degeneration of the central lesion and MU firing behavior; (2) a moderate correlation was observed between clinical measures of disease severity and MU firing behavior; and (3) the methods of predicting central nervous system degeneration from MU firing behavior abnormalities had a high detection accuracy with an area under the curve >0.83. These findings suggest that abnormalities in MU activity can be used to predict central nervous system degeneration following PD.

A Principal Components Analysis Approach to Quantifying Foot Clearance and Foot Clearance Variability.

Low foot clearance and high variability may be related to falls risk. Foot clearance is often defined as the local minimum in toe height during swing; however, not all strides have this local minimum. The primary purpose of this study was to identify a nondiscrete measure of foot clearance during all strides, and compare discrete and nondiscrete measures in ability to rank individuals on foot clearance and variability. Thirty-five participants (young adults [n = 10], older fallers [n = 10], older nonfallers [n = 10], and stroke survivors [n = 5]) walked overground while lower extremity 3D kinematics were recorded. Principal components analysis (PCA) of the toe height waveform yielded representation of toe height when it was closest to the ground. Spearman's rank order correlation assessed the association of foot clearance and variability between PCA and discrete variables, including the local minimum. PCA had significant (P < .05) moderate or strong associations with discrete measures of foot clearance and variability. An approximation of the discrete local minimum had a weak association with PCA and other discrete measures of foot clearance. A PCA approach to quantifying foot clearance can be used to identify the behavioral components of toe height when it is closest to the ground, even for strides without a local minimum.

Stroke-related effects on maximal dynamic hip flexor fatigability and functional implications.

INTRODUCTION: Stroke-related changes in maximal dynamic hip flexor muscle fatigability may be more relevant functionally than isometric hip flexor fatigability. METHODS: Ten chronic stroke survivors performed 5 sets of 30 hip flexion maximal dynamic voluntary contractions (MDVC). A maximal isometric voluntary contraction (MIVC) was performed before and after completion of the dynamic contractions. Both the paretic and nonparetic legs were tested. RESULTS: Reduction in hip flexion MDVC torque in the paretic leg (44.7%) was larger than the nonparetic leg (31.7%). The paretic leg had a larger reduction in rectus femoris EMG (28.9%) between the first and last set of MDVCs than the nonparetic leg (7.4%). Reduction in paretic leg MDVC torque was correlated with self-selected walking speed (r2=0.43), while reduction in MIVC torque was not (r2=0.11). CONCLUSIONS: Reductions in maximal dynamic torque of paretic hip flexors may be a better predictor of walking function than reductions in maximal isometric contractions.

Movement strategies for maintaining standing balance during arm tracking in people with multiple sclerosis.

The purpose of this study was to quantify hip and ankle movement strategies during a standing arm tracking task in people with multiple sclerosis (MS). Full-body kinematics and kinetics were assessed with motion analysis cameras and force plates in nine MS and nine age-matched control subjects. While standing, participants used their dominant hand to track a target moving around a large horizontal or vertical figure eight on a screen in front of them. The target moved at constant speed, or linearly increasing speeds, with a frequency between 0.05 Hz and 0.35 Hz. Hip and ankle moments and angles during tracking were calculated from kinematic and kinetic measurements. Ratios of peak-to-peak (PP) hip/ankle moments (kinetics) and angles (kinematics) were calculated to determine the strategies of the hips and ankles used to maintain balance during arm movements. Center of mass (CoM) root mean square (RMS) acceleration was calculated as a measure of overall balance performance. The MS group produced larger PP hip/ankle moments at all speeds compared with the control group (P < 0.05). The CoM RMS acceleration increased with tracking speed for both groups but was not significantly different between groups. Additionally, the ratios of hip to ankle moments were highly correlated with the Berg Balance Scale during horizontal steady-speed tracking in MS. These results suggest that people with MS increase the use of the hip during standing arm tracking compared with age-matched control subjects. This adapted strategy might allow people with MS to achieve balance performance similar to control subjects, possibly increasing the importance of the hip in maintaining balance during voluntary movements.

Functional implications of impaired control of submaximal hip flexion following stroke.

INTRODUCTION: We quantified submaximal torque regulation during low to moderate intensity isometric hip flexion contractions in individuals with stroke and the associations with leg function. METHODS: Ten participants with chronic stroke and 10 controls performed isometric hip flexion contractions at 5%, 10%, 15%, 20%, and 40% of maximal voluntary contraction (MVC) in paretic, nonparetic, and control legs. RESULTS: Participants with stroke had larger torque fluctuations (coefficient of variation, CV), for both the paretic and nonparetic legs, than controls (P < 0.05) with the largest CV at 5% MVC in the paretic leg (P < 0.05). The paretic CV correlated with walking speed (r2 = 0.54) and Berg Balance Score (r2 = 0.40). At 5% MVC, there were larger torque fluctuations in the contralateral leg during paretic contractions compared with the control leg. CONCLUSIONS: Impaired low-force regulation of paretic leg hip flexion can be functionally relevant and related to control versus strength deficits poststroke.

Sensory electrical stimulation improves foot placement during targeted stepping post-stroke.

Proper foot placement is vital for maintaining balance during walking, requiring the integration of multiple sensory signals with motor commands. Disruption of brain structures post-stroke likely alters the processing of sensory information by motor centers, interfering with precision control of foot placement and walking function for stroke survivors. In this study, we examined whether somatosensory stimulation, which improves functional movements of the paretic hand, could be used to improve foot placement of the paretic limb. Foot placement was evaluated before, during, and after application of somatosensory electrical stimulation to the paretic foot during a targeted stepping task. Starting from standing, twelve chronic stroke participants initiated movement with the non-paretic limb and stepped to one of five target locations projected onto the floor with distances normalized to the paretic stride length. Targeting error and lower extremity kinematics were used to assess changes in foot placement and limb control due to somatosensory stimulation. Significant reductions in placement error in the medial-lateral direction (p = 0.008) were observed during the stimulation and post-stimulation blocks. Seven participants, presenting with a hip circumduction walking pattern, had reductions (p = 0.008) in the magnitude and duration of hip abduction during swing with somatosensory stimulation. Reductions in circumduction correlated with both functional and clinical measures, with larger improvements observed in participants with greater impairment. The results of this study suggest that somatosensory stimulation of the paretic foot applied during movement can improve the precision control of foot placement.

People with degenerative cervical myelopathy have impaired reactive balance during walking.

BACKGROUND: People with degenerative cervical myelopathy are known to have impaired standing balance and walking abilities, but less is known about balance responses during walking. RESEARCH QUESTION: The aim of this project was to assess reactive balance impairments during walking in people with degenerative cervical myelopathy (PwDCM). We hypothesized that center of mass motion following perturbations would be larger in PwDCM and gluteus medius electromyographic amplitude responses would be decreased in PwDCM. METHODS: Reactive balance responses were quantified during unanticipated lateral pulls to the waist while treadmill walking. Walking biomechanics data were collected from 10 PwDCM (F=6) and 10 non-myelopathic controls (F=7) using an 8 camera Vicon System (Vicon MX T-Series). Electromyography was collected from lower limb muscles. Participants walked on an instrumented treadmill and received lateral pulls at random intervals and in randomized direction at 5% and 2.5% body mass. Participants walked at 3 prescribed foot placements to control for effects of the size of base of support. RESULTS: As compared with controls, the perturbation-related positional change of the center of mass motion (ΔCOM) was increased in PwDCM (p=0.001) with similar changes in foot placement (p>0.05). Change in gluteus medius electromyography, however, was less in PwDCM than in controls (p<0.001). SIGNIFICANCE: After experimentally controlling step width, people with mild-to-moderate degenerative cervical myelopathy at least 3 months following cervical spine surgery have impaired reactive balance during walking likely coupled with reduced gluteus medius electromyographic responses. Rehabilitation programs focusing on reactive balance and power are likely necessary for this population.

Non-Invasive Estimation of Skeletal Muscle Oxygen Consumption Rate and Microvascular Reactivity in Chronic Stroke Survivors using Near Infrared Spectroscopy.

BACKGROUND: Understanding post-stroke changes in skeletal muscle oxidative metabolism and microvascular reactivity could help create therapeutic targets that optimize rehabilitative interventions. Due to disuse atrophy, we hypothesized that basal muscle oxygen consumption rate and microvascular endothelial function would be impaired in the tibialis anterior (TA) muscle of the affected leg of chronic stroke survivors compared to the non-affected leg and vs. matched controls. METHODS: Fifteen chronic stroke survivors (10 female) and 15 matched controls (9 female) completed this study. A near infrared spectroscopy oximeter measured tissue oxygen saturation (StO2) of the TA in both legs of stroke survivors and the dominant leg of controls. A cuff was placed around the thigh and inflated to 225 mmHg for five minutes while StO2 was continuously measured. The rate of change in StO2 was calculated during cuff occlusion and immediately post-cuff release. RESULTS: The rate of oxygen desaturation was similar between the legs of the stroke survivors (paretic -0.12±0.04 %∙s-1 vs non-paretic -0.16±011 %∙s-1; p=0.49), but the paretic leg had a reduced desaturation rate vs. controls (-0.25±0.18%∙s-1; p=0.007 vs. paretic leg). After cuff release, there was a greater oxygen resaturation rate in the non-paretic leg compared to the paretic leg (3.13±2.08 %∙s-1 vs. 1.60±1.11 %∙s-1, respectively; p=0.01). The control leg had a similar resaturation rate vs. the non-paretic leg (control = 3.41±1.79%∙s-1; p=0.69) but was greater than the paretic leg (p=0.003). CONCLUSION: The TA in the paretic leg had an impaired muscle oxygen consumption rate and reduced microvascular endothelial function compared to controls.

Push-pull control of motor output.

Inhibition usually decreases input-output excitability of neurons. If, however, inhibition is coupled to excitation in a push-pull fashion, where inhibition decreases as excitation increases, neuron excitability can be increased. Although the presence of push-pull organization has been demonstrated in single cells, its functional impact on neural processing depends on its effect on the system level. We studied push-pull in the motor output stage of the feline spinal cord, a system that allows independent control of inhibitory and excitatory components. Push-pull organization was clearly present in ankle extensor motoneurons, producing increased peak-to-peak modulation of synaptic currents. The effect at the system level was equally strong. Independent control of the inhibitory component showed that the stronger the background of inhibition, the greater the peak force production. This illustrates the paradox at the heart of push-pull organization: increased force output can be achieved by increasing background inhibition to provide greater disinhibition.

Cortical effects of wrist tendon vibration during an arm tracking task in chronic stroke survivors: An EEG study.

The purpose of this study was to characterize changes in cortical activity and connectivity in stroke survivors when vibration is applied to the wrist flexor tendons during a visuomotor tracking task. Data were collected from 10 chronic stroke participants and 10 neurologically-intact controls while tracking a target through a figure-8 pattern in the horizontal plane. Electroencephalography (EEG) was used to measure cortical activity (beta band desynchronization) and connectivity (beta band task-based coherence) with movement kinematics and performance error also being recorded during the task. All participants came into our lab on two separate days and performed three blocks (16 trials each, 48 total trials) of tracking, with the middle block including vibration or sham applied at the wrist flexor tendons. The order of the sessions (Vibe vs. Sham) was counterbalanced across participants to prevent ordering effects. During the Sham session, cortical activity increased as the tracking task progressed (over blocks). This effect was reduced when vibration was applied to controls. In contrast, vibration increased cortical activity during the vibration period in participants with stroke. Cortical connectivity increased during vibration, with larger effect sizes in participants with stroke. Changes in tracking performance, standard deviation of hand speed, were observed in both control and stroke groups. Overall, EEG measures of brain activity and connectivity provided insight into effects of vibration on brain control of a visuomotor task. The increases in cortical activity and connectivity with vibration improved patterns of activity in people with stroke. These findings suggest that reactivation of normal cortical networks via tendon vibration may be useful during physical rehabilitation of stroke patients.

Reduced oxygen desaturation in the vastus lateralis of chronic stroke survivors during graded muscle contractions.

BACKGROUND: Few studies have examined changes in skeletal muscle physiology post-stroke. This study examined changes in tissue oxygen saturation (StO2) of the vastus lateralis (VL) muscle of stroke survivors and age-matched control participants during maximal and submaximal isometric contractions of the knee extensor muscles. OBJECTIVES: We hypothesized that tissue oxygen desaturation (ΔStO2) during knee extensor muscle contractions would be less in the VL in the paretic vs. the non-paretic and control legs. METHODS: Ten chronic stroke survivors (>6 months post-stroke) with lower extremity muscle weakness and 10 age-matched controls completed this prospective cohort study. Maximum voluntary contractions (MVCs) of the knee extensor muscles were assessed with a Biodex dynamometer and StO2 of the VL was measured using near-infrared spectroscopy. RESULTS: In the paretic leg of the stroke survivors little change in StO2 of the VL was observed during an MVC (ΔStO2 = -1.7 ± 1.8%) compared to the non-paretic (ΔStO2 = -5.1 ± 6.1%; p < 0.05) and control legs (ΔStO2 = -14.4 ± 8.8%; p < 0.05 vs. paretic and non-paretic leg). These differences remained when normalizing for strength differences between the legs. Compared to controls, both the paretic and non-paretic VL showed pronounced reductions in ΔStO2 during ramp and hold contractions equal to 20%, 40%, or 60% of the MVC (p < 0.05 vs. controls at all load levels). CONCLUSIONS: These results indicate that oxygen desaturation in response to isometric muscle contractions is impaired in both the paretic and non-paretic leg muscle of stroke survivors compared to age-matched controls, and these differences are independent of differences in muscle strength.

Quantification of Tissue Oxygen Saturation in the Vastus Lateralis Muscle of Chronic Stroke Survivors during a Graded Exercise Test.

Purpose: This study examined tissue oxygen saturation (StO2) of the vastus lateralis (VL) muscles of chronic stroke survivors during a graded exercise test (GXT). We hypothesized the reduction in StO2 will be blunted in the paretic vs. non-paretic VL during a maximum-effort GXT. Methods: Chronic stroke survivors performed a GXT and StO2 of the VL in each leg was measured using near infrared spectroscopy. Twenty-six stroke survivors performed a GXT. Results: At rest, there was no difference in StO2 between the paretic and non-paretic VL (65±9% vs. 68±7%, respectively, p=0.32). The maximum change in StO2 from rest during the GXT was greater in the non-paretic vs. the paretic VL (-16±14% vs. -9±10%, respectively, p<0.001). The magnitude of the oxygen resaturation response was also greater in the non-paretic vs. the paretic VL (29±23% vs. 18±15%, respectively, p<0.001). VO2 Peak was associated with the magnitude of the VL StO2 change during (r2=0.54, p<0.0001) and after (r2=0.56, p<0.001) the GXT. Conclusions: During a GXT there is a blunted oxygen desaturation response in the paretic vs. the non-paretic VL of chronic stroke survivors. In the paretic VL there was a positive correlation between the oxygen desaturation response during the GXT and VO2 Peak.

Detecting motor unit abnormalities in amyotrophic lateral sclerosis using high-density surface EMG.

OBJECTIVE: The purpose of this study was to detect specific motor unit (MU) abnormalities in people with amyotrophic lateral sclerosis (ALS) compared to controls using high-density surface electromyography (HD-SEMG). METHODS: Sixteen people with ALS and 16 control subjects. The participants performed ramp up and sustained contractions at 30% of their maximal voluntary contraction. HD-SEMG signals were recorded in the vastus lateralis muscle and decomposed into individual MU firing behavior using a convolution blind source separation method. RESULTS: In total, 339 MUs were detected (people with ALS; n = 93, control subjects; n = 246). People with ALS showed significantly higher mean firing rate, recruitment threshold, coefficient of variation of the MU firing rate, MU firing rate at recruitment, and motoneurons excitability than those of control subjects (p < 0.001). The number of MU, MU firing rate, recruitment threshold, and MU firing rate at recruitment were significantly correlated with disease severity (p < 0.001). Multivariable analysis revealed that an increased MU firing rate at recruitment was independently associated with ALS. CONCLUSIONS: These results suggest increased excitability at recruitment, which is consistent with neurodegeneration results in a compensatory increase in MU activity. SIGNIFICANCE: Abnormal MU firing behavior provides an important physiological index for understanding the pathophysiology of ALS.

Developing Peri-Operative Rehabilitation in Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 6]: An Unexplored Opportunity?

STUDY DESIGN: Narrative review. OBJECTIVE: Degenerative cervical myelopathy is one of the most frequent impairments of the spinal cord encountered internationally in adults. Currently, surgical decompression is the recommended treatment for people with DCM (PwCM) presenting with moderate to severe symptoms or neurological deficits. However, despite surgical intervention, not all patients make a complete recovery due to the irreversible tissue damage within the spinal cord. The objective of this review is to describe the state and gaps in the current literature on rehabilitation for PwCM and possible innovative rehabilitation strategies. METHODS: Literature search. RESULTS: In other neurological disorders such as stroke and acute traumatic spinal cord injury (SCI), timely and strategic rehabilitation has been shown to be indispensable for maximizing functional outcomes, and it is imperative that appropriate perioperative rehabilitative interventions accompany surgical approaches in order to enable the best outcomes. In this review, the current state of knowledge regarding rehabilitation for PwCM is described. Additionally, various therapies that have shown to improve outcomes in comparable neurological conditions such as stroke and SCI which may be translated to DCM will be reviewed. CONCLUSIONS: We conclude that locomotor training and arm/hand therapy may benefit PwCM. Further, we conclude that body weight support, robotic assistance, and virtual/augmented reality therapies may be beneficial therapeutic analogs to locomotor and hand therapies.

Intrinsic electrical properties of spinal motoneurons vary with joint angle.

The dendrites of spinal motoneurons amplify synaptic inputs to a marked degree through persistent inward currents (PICs). Dendritic amplification is subject to neuromodulatory control from the brainstem by axons releasing the monoamines serotonin and norepinephrine; however, the monoaminergic projection to the cord is diffusely organized and does not allow independent adjustment of amplification in different motor pools. Using in vivo voltage-clamp techniques, here we show that dendritic PICs in ankle extensor motoneurons in the cat are reduced about 50% by small rotations (+/-10 degrees ) of the ankle joint. This reduction is primarily due to reciprocal inhibition, a tightly focused input shared only among strict muscle antagonists. These results demonstrate how a specific change in limb position can regulate intrinsic cellular properties set by a background of diffuse descending neuromodulation.

Improving gait efficiency to increase movement and physical activity - The impact of abnormal gait patterns and strategies to correct.

Increasing daily steps is important to maintain health and prevent both initial and subsequent cardiovascular (CV) disease (CVD) events. Even 5000 steps have been associated with reduced risk of CVD, however many adults and those with CVD walk fewer than 5000 daily steps. Reduced gait speed is a precursor to decreased physical engagement and is associated with biomarker changes linked to higher risk of CVD. Gait speed is decreased in those with CVD, which may be from changes in biomechanics including reduced step length and increased gait variability. Changes in gait and daily steps are often most discernable post-stroke, which may be from limitations of the CV system in meeting the metabolic demands of walking and the nervous system in exciting motoneuron pools to generate muscle force. This leads to gait asymmetries and decreased speed. Information regarding the effects of rehabilitation interventions (e.g., physical therapy) to increase physical activity (PA) in stroke survivors is limited. Current interventions include high intensity gait training and ischemic conditioning to improve walking speed and fatigability. Given the potential benefits of increased PA and daily steps following stroke, there is a need for more research investigating optimal dosage of daily steps and interventions to improve PA.

Electroencephalography resting-state networks in people with Stroke.

INTRODUCTION: The purpose of this study was to characterize resting-state cortical networks in chronic stroke survivors using electroencephalography (EEG). METHODS: Electroencephalography data were collected from 14 chronic stroke and 11 neurologically intact participants while they were in a relaxed, resting state. EEG power was normalized to reduce bias and used as an indicator of network activity. Correlations of orthogonalized EEG activity were used as a measure of functional connectivity between cortical regions. RESULTS: We found reduced cortical activity and connectivity in the alpha (p < .05; p = .05) and beta (p < .05; p = .03) bands after stroke while connectivity in the gamma (p = .031) band increased. Asymmetries, driven by a reduction in the lesioned hemisphere, were also noted in cortical activity (p = .001) after stroke. CONCLUSION: These findings suggest that stroke lesions cause a network alteration to more local (higher frequency), asymmetric networks. Understanding changes in cortical networks after stroke could be combined with controllability models to identify (and target) alternate brain network states that reduce functional impairment.

Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity.

Background: Botulinum NeuroToxin-A (BoNT-A) relieves muscle spasticity and increases range of motion necessary for stroke rehabilitation. Determining the effects of BoNT-A therapy on brain neuroplasticity could help physicians customize its use and predict its outcome. Objective: The purpose of this study was to investigate the effects of Botulinum Toxin-A therapy for treatment of focal spasticity on brain activation and functional connectivity. Design: We used functional Magnetic Resonance Imaging (fMRI) to track changes in blood oxygen-level dependent (BOLD) activation and functional connectivity associated with BoNT-A therapy in nine chronic stroke participants, and eight age-matched controls. Scans were acquired before BoNT-A injections (W0) and 6 weeks after the injections (W6). The task fMRI scan consisted of a block design of alternating mass finger flexion and extension. The voxel-level changes in BOLD activation, and pairwise changes in functional connectivity were analyzed for BoNT-A treatment (stroke W0 vs. W6). Results: BoNT-A injection therapy resulted in significant increases in brain activation in the contralesional premotor cortex, cingulate gyrus, thalamus, superior cerebellum, and in the ipsilesional sensory integration area. Lastly, cerebellar connectivity correlated with the Fugl-Meyer assessment of motor impairment before injection, while premotor connectivity correlated with the Fugl-Meyer score after injection. Conclusion: BoNT-A therapy for treatment of focal spasticity resulted in increased brain activation in areas associated with motor control, and cerebellar connectivity correlated with motor impairment before injection. These results suggest that neuroplastic effects might take place in response to improvements in focal spasticity.