Kevin obtained a PhD in Neuroscience from Northwestern University while working in the Physical Therapy and Human Movement Sciences Department and a BS/BA in Psychology and English from Boston College. His dissertation research focused on understanding the neural mechanisms underlying upper extremity impairments in individuals with chronic stroke and subsequent motor improvements following novel interventions. His postdoctoral work at Stanford with Dr. Helen Bronte-Stewart focuses on the neural features associated with gait impairment in individuals with Parkinson's disease using a combination of structural imaging, neurophysiology, and kinematic analysis. He was awarded a Postdoctoral Fellowship for Basic Scientists from the Parkinson's Foundation to investigate the cognitive correlates of gait impairment in Parkinson's disease.
Bachelor of Arts, Boston College, English (2014)
Doctor of Philosophy, Northwestern University, Neuroscience (2019)
Bachelor of Science, Boston College, Psychology (2014)
Helen Bronte-Stewart, Postdoctoral Faculty Sponsor
Modulation of beta bursts in subthalamic sensorimotor circuits predicts improvement in bradykinesia.
Brain : a journal of neurology
No biomarker of Parkinson's disease exists that allows clinicians to adjust chronic therapy, either medication or deep brain stimulation, with real-time feedback. Consequently, clinicians rely on time-intensive, empirical, and subjective clinical assessments of motor behaviour and adverse events to adjust therapies. Accumulating evidence suggests that hypokinetic aspects of Parkinson's disease and their improvement with therapy are related to pathological neural activity in the beta band (beta oscillopathy) in the subthalamic nucleus. Additionally, effectiveness of deep brain stimulation may depend on modulation of the dorsolateral sensorimotor region of the subthalamic nucleus, which is the primary site of this beta oscillopathy. Despite the feasibility of utilizing this information to provide integrated, biomarker-driven precise deep brain stimulation, these measures have not been brought together in awake freely moving individuals. We sought to directly test whether stimulation-related improvements in bradykinesia were contingent on reduction of beta power and burst durations, and/or the volume of the sensorimotor subthalamic nucleus that was modulated. We recorded synchronized local field potentials and kinematic data in 16 subthalamic nuclei of individuals with Parkinson's disease chronically implanted with neurostimulators during a repetitive wrist-flexion extension task, while administering randomized different intensities of high frequency stimulation. Increased intensities of deep brain stimulation improved movement velocity and were associated with an intensity-dependent reduction in beta power and mean burst duration, measured during movement. The degree of reduction in this beta oscillopathy was associated with the improvement in movement velocity. Moreover, the reduction in beta power and beta burst durations was dependent on the theoretical degree of tissue modulated in the sensorimotor region of the subthalamic nucleus. Finally, the degree of attenuation of both beta power and beta burst durations, together with the degree of overlap of stimulation with the sensorimotor subthalamic nucleus significantly explained the stimulation-related improvement in movement velocity. The above results provide direct evidence that subthalamic nucleus deep brain stimulation-related improvements in bradykinesia are related to the reduction in beta oscillopathy within the sensorimotor region. With the advent of sensing neurostimulators, this beta oscillopathy combined with lead location could be used as a marker for real-time feedback to adjust clinical settings or to drive closed-loop deep brain stimulation in freely moving individuals with Parkinson's disease.
View details for DOI 10.1093/brain/awaa394
View details for PubMedID 33301569
Gait variability is linked to the atrophy of the Nucleus Basalis of Meynert and is resistant to STN DBS in Parkinson's disease.
Neurobiology of disease
Parkinson's disease (PD) is a systemic brain disorder where the cortical cholinergic network begins to degenerate early in the disease process. Readily accessible, quantitative, and specific behavioral markers of the cortical cholinergic network are lacking. Although degeneration of the dopaminergic network may be responsible for deficits in cardinal motor signs, the control of gait is a complex process and control of higher-order aspects of gait, such as gait variability, may be influenced by cognitive processes attributed to cholinergic networks. We investigated whether swing time variability, a metric of gait variability that is independent from gait speed, was a quantitative behavioral marker of cortical cholinergic network integrity in PD. Twenty-two individuals with PD and subthalamic nucleus (STN) deep brain stimulation (PD-DBS cohort) and twenty-nine age-matched controls performed a validated stepping-in-place (SIP) task to assess swing time variability off all therapy. The PD-DBS cohort underwent structural MRI scans to measure gray matter volume of the Nucleus Basalis of Meynert (NBM), the key node in the cortical cholinergic network. In order to determine the role of the dopaminergic system on swing time variability, it was measured ON and OFF STN DBS in the PD-DBS cohort, and on and off dopaminergic medication in a second PD cohort of thirty-two individuals (PD-med). A subset of eleven individuals in the PD-DBS cohort completed the SIP task again off all therapy after three years of continuous DBS to assess progression of gait impairment. Swing time variability was significantly greater (i.e., worse) in PD compared to controls and greater swing time variability was related to greater atrophy of the NBM, as was gait speed. STN DBS significantly improved cardinal motor signs and gait speed but did not improve swing time variability, which was replicated in the second cohort using dopaminergic medication. Swing time variability continued to worsen in PD, off therapy, after three years of continuous STN DBS, and NBM atrophy showed a trend for predicting the degree of increase. In contrast, cardinal motor signs did not progress. These results demonstrate that swing time variability is a reliable marker of cortical cholinergic health, and support a framework in which higher-order aspects of gait control in PD are reliant on the cortical cholinergic system, in contrast to other motor aspects of PD that rely on the dopaminergic network.
View details for DOI 10.1016/j.nbd.2020.105134
View details for PubMedID 33045357
Lack of progression of beta dynamics after long-term subthalamic neurostimulation.
Annals of clinical and translational neurology
OBJECTIVE: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS).METHODS: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa PC+S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale - motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6months, 1year, and yearly out to 5years of treatment. The primary endpoint was measured at 3years. At each visit, medication had been held for over 12/24h and DBS was turned off for at least 60min, by which time LFP spectra reached a steady state.RESULTS: After 3years of chronic DBS, there were no increases in STN beta band dynamics (p=0.98) but there were increases in alpha band dynamics (p=0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5years. There was no increase in the MDS-UPDRS III score.INTERPRETATION: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.
View details for DOI 10.1002/acn3.51463
View details for PubMedID 34636182
- Ramp Rate Evaluation and Configuration for Safe and Tolerable Closed-Loop Deep Brain Stimulation IEEE. 2021: 959-962
A validated measure of rigidity in Parkinson's disease using alternating finger tapping on an engineered keyboard.
Parkinsonism & related disorders
2020; 81: 161–64
INTRODUCTION: Reliable and accurate measures of rigidity have remained elusive in remote assessments of Parkinson's disease (PD). This has severely limited the utility of telemedicine in the care and treatment of people with PD. It has also had a large negative impact on the scope of available outcomes, and on the costs, of multicenter clinical trials in PD. The goal of this study was to determine if quantitative measures from an engineered keyboard were sensitive and related to clinical measures of rigidity.METHODS: Sixteen participants with idiopathic PD, off antiparkinsonian medications, and eleven age-matched control participants performed a 30second repetitive alternating finger tapping task on an engineered keyboard and were assessed with the Unified Parkinson's Disease Rating Scale - motor (UPDRS-III).RESULTS: The speed of the key release was significantly slower in the PD compared to control cohorts (p<0.0001). In the PD cohort key release speed correlated with the lateralized upper extremity UPDRS III rigidity score (r=- 0.58, p<0.0001), but not with the lateralized upper extremity tremor score (r=- 0.14, p=0.43).CONCLUSIONS: This validated measure of rigidity complements our previous validation of temporal metrics of the repetitive alternating finger tapping task with the UPDRS III, bradykinesia and with the ability to quantify tremor, arrhythmicity and freezing episodes, and suggests that 30seconds of alternating finger tapping on a portable engineered keyboard could transform the treatment of PD with telemedicine and the precision of multicenter clinical trials.
View details for DOI 10.1016/j.parkreldis.2020.10.047
View details for PubMedID 33157435
- Perspective: Evolution of Control Variables and Policies for Closed-Loop Deep Brain Stimulation for Parkinson's Disease Using Bidirectional Deep-Brain-Computer Interfaces FRONTIERS IN HUMAN NEUROSCIENCE 2020; 14
A Novel Method for Calculating Beta Band Burst Durations in Parkinson's Disease Using a Physiological Baseline.
Journal of neuroscience methods
BACKGROUND: Pathologically prolonged bursts of neural activity in the 8-30Hz frequency range in Parkinson's disease have been measured using high power event detector thresholds.NEW METHOD: This study introduces a novel method for determining beta bursts using a power baseline based on spectral activity that overlapped a simulated 1/f spectrum. We used resting state local field potentials from people with Parkinson's disease and a simulated 1/f signal to measure beta burst durations, to demonstrate how tuning parameters (i.e., bandwidth and center frequency) affect burst durations, to compare burst duration distributions with high power threshold methods, and to study the effect of increasing neurostimulation intensities on burst duration.RESULTS: The baseline method captured a broad distribution of resting state beta band burst durations. Mean beta band burst durations were significantly shorter on compared to off neurostimulation (p=0.0046), and their distribution shifted towards that of the 1/f spectrum during increasing intensities of stimulation.COMPARISON WITH EXISTING METHODS: High power event detection methods, measure duration of higher power bursts and omit portions of the neural signal. The baseline method captured the broadest distribution of burst durations and was more sensitive than high power detection methods in demonstrating the effect of neurostimulation on beta burst duration.CONCLUSIONS: The baseline method captured a broad range of fluctuations in beta band neural activity and demonstrated that subthalamic neurostimulation shortened burst durations in a dose (intensity) dependent manner, suggesting that beta burst duration is a useful control variable for closed loop algorithms.
View details for DOI 10.1016/j.jneumeth.2020.108811
View details for PubMedID 32565222
Limited capacity for ipsilateral secondary motor areas to support hand function post-stroke
JOURNAL OF PHYSIOLOGY-LONDON
2020; 598 (11): 2153–67
Ipsilateral-projecting corticobulbar pathways, originating primarily from secondary motor areas, innervate the proximal and even distal portions, although they branch more extensively at the spinal cord. It is currently unclear to what extent these ipsilateral secondary motor areas and subsequent cortical projections may contribute to hand function following stroke-induced damage to one hemisphere. In the present study, we provide both structural and functional evidence indicating that individuals increasingly rely on ipsilateral secondary motor areas, although at the detriment of hand function. Increased activity in ipsilateral secondary motor areas was associated with increased involuntary coupling between shoulder abduction and finger flexion, most probably as a result of the low resolution of these pathways, making it increasingly difficult to open the hand. These findings suggest that, although ipsilateral secondary motor areas may support proximal movements, they do not have the capacity to support distal hand function, particularly for hand opening.Recent findings have shown connections of ipsilateral cortico-reticulospinal tract (CRST), predominantly originating from secondary motor areas to not only proximal, but also distal muscles of the arm. Following a unilateral stroke, CRST from the ipsilateral side remains intact and thus has been proposed as a possible backup system for post-stroke rehabilitation even for the hand. We argue that, although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements as a result of its extensive spinal branching compared to contralateral corticospinal tract. To address this issue, we combined magnetic resonance imaging, high-density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age-matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher grey matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity when participants were attempting to generate hand opening either supported on a table or when lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, the increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability when lifting the arm as a result of involuntary coupling between the shoulder and wrist/finger flexors. Taken together, this evidence implicates a compensatory role for ipsilateral (i.e. contralesional) secondary motor areas post-stroke, although with no apparent capacity to support hand function.
View details for DOI 10.1113/JP279377
View details for Web of Science ID 000528549500001
View details for PubMedID 32144937
View details for PubMedCentralID PMC7266727
Coordination of multiple joints increases bilateral connectivity with ipsilateral sensorimotor cortices
2020; 207: 116344
Although most activities of daily life require simultaneous coordination of both proximal and distal joints, motor preparation during such movements has not been well studied. Previous results for motor preparation have focused on hand/finger movements. For simple hand/finger movements, results have found that such movements typically evoke activity primarily in the contralateral motor cortices. However, increasing the complexity of the finger movements, such as during a distal sequential finger-pressing task, leads to additional recruitment of ipsilateral resources. It has been suggested that this involvement of the ipsilateral hemisphere is critical for temporal coordination of distal joints. The goal of the current study was to examine whether increasing simultaneous coordination of multiple joints (both proximal and distal) leads to a similar increase in coupling with ipsilateral sensorimotor cortices during motor preparation compared to a simple distal movement such as hand opening. To test this possibility, 12 healthy individuals participated in a high-density EEG experiment in which they performed either hand opening or simultaneous hand opening while lifting at the shoulder on a robotic device. We quantified within- and cross-frequency cortical coupling across the sensorimotor cortex for the two tasks using dynamic causal modeling. Both hand opening and simultaneous hand opening while lifting at the shoulder elicited coupling from secondary motor areas to primary motor cortex within the contralateral hemisphere exclusively in the beta band, as well as from ipsilateral primary motor cortex. However, increasing the task complexity by combining hand opening while lifting at the shoulder also led to an increase in cross-frequency coupling within the ipsilateral hemisphere including theta, beta, and gamma frequencies, as well as a change in the coupling frequency of the interhemispheric coupling between the primary motor and premotor cortices. These findings demonstrate that increasing the demand of joint coordination between proximal and distal joints leads to increases in communication with the ipsilateral hemisphere as previously observed in distal sequential finger tasks.
View details for DOI 10.1016/j.neuroimage.2019.116344
View details for Web of Science ID 000509662600011
View details for PubMedID 31730924
View details for PubMedCentralID PMC7192312
- Neural Closed loop deep brain stimulation for freezing of Gait. Brain stimulation 2020
Intervention-induced changes in neural connectivity during motor preparation may affect cortical activity at motor execution.
2020; 10 (1): 7326
Effective interventions have demonstrated the ability to improve motor function by reengaging ipsilesional resources, which appears to be critical and feasible for hand function recovery even in individuals with severe chronic stroke. However, previous studies focus on changes in brain activity related to motor execution. How changes in motor preparation may facilitate these changes at motor execution is still unclear. To address this question, 8 individuals with severe chronic hemiparetic stroke participated in a device-assisted intervention for seven weeks. We then quantified changes in both coupling between regions during motor preparation and changes in topographical cortical activity at motor execution for both hand opening in isolation and together with the shoulder using high-density EEG. We hypothesized that intervention-induced changes in cortico-cortico interactions during motor preparation would lead to changes in activity at motor execution specifically towards an increased reliance on the ipsilesional hemisphere. In agreement with this hypothesis, we found that, following the intervention, individuals displayed a reduction in coupling from ipsilesional M1 to contralesional M1 within gamma frequencies during motor preparation for hand opening. This was followed by a reduction in activity in the contralesional primary sensorimotor cortex during motor execution. Similarly, during lifting and opening, a shift to negative coupling within ipsilesional M1 from gamma to beta frequencies was accompanied by an increase in ipsilesional primary sensorimotor cortex activity following the intervention. Together, these results show that intervention-induced changes in coupling within or between motor regions during motor preparation may affect cortical activity at execution.
View details for DOI 10.1038/s41598-020-64179-x
View details for PubMedID 32355238
View details for PubMedCentralID PMC7193567
Improving Hand Function of Severely Impaired Chronic Hemiparetic Stroke Individuals Using Task-Specific Training With the Reln-Hand System: A Case Series
FRONTIERS IN NEUROLOGY
2018; 9: 923
Purpose: In this study, we explored whether improved hand function is possible in poststroke chronic hemiparetic individuals with severe upper limb motor impairments when they participate in device-aided task-specific practice. Subjects: Eight participants suffering from chronic stroke (>1-year poststroke, mean: 11.2 years) with severely impaired upper extremity movement (Upper Extremity Subscale of the Fugl-Meyer Motor Assessment (UEFMA) score between 10 and 24) participated in this study. Methods: Subjects were recruited to participate in a 20-session intervention (3 sessions/7 weeks). During each session, participants performed 20-30 trials of reaching, grasping, retrieving, and releasing a jar with the assistance of a novel electromyography-driven functional electrical stimulation (EMG-FES) system. This EMG-FES system allows for Reliable and Intuitive use of the Hand (called ReIn-Hand device) during multi-joint arm movements. Pre-, post-, and 3-month follow-up outcome assessments included the UEFMA, Cherokee McMaster Stroke Assessment, grip dynamometry, Box and Blocks Test (BBT), goniometric assessment of active and passive ranges of motion (ROMs) of the wrist and the metacarpophalangeal flexion and extension (II, V fingers), Nottingham Sensory Assessment-Stereognosis portion (NSA), and Cutaneous Sensory Touch Threshold Assessment. Results: A nonparametric Friedman test of differences found significant changes in the BBT scores (χ2 = 10.38, p < 0.05), the passive and active ROMs (χ2 = 11.31, p < 0.05 and χ2 = 12.45, p < 0.01, respectively), and the NSA scores (χ2 = 6.42, p < 0.05) following a multi-session intervention using the ReIn-Hand device. Conclusions: These results suggest that using the ReIn-Hand device during reaching and grasping activities may contribute to improvements in gross motor function and sensation (stereognosis) in individuals with chronic severe UE motor impairment following stroke.
View details for DOI 10.3389/fneur.2018.00923
View details for Web of Science ID 000449422000001
View details for PubMedID 30464754
View details for PubMedCentralID PMC6234834
Neural Plasticity in Moderate to Severe Chronic Stroke Following a Device-Assisted Task-Specific Arm/Hand Intervention
FRONTIERS IN NEUROLOGY
2017; 8: 284
Currently, hand rehabilitation following stroke tends to focus on mildly impaired individuals, partially due to the inability for severely impaired subjects to sufficiently use the paretic hand. Device-assisted interventions offer a means to include this more severe population and show promising behavioral results. However, the ability for this population to demonstrate neural plasticity, a crucial factor in functional recovery following effective post-stroke interventions, remains unclear. This study aimed to investigate neural changes related to hand function induced by a device-assisted task-specific intervention in individuals with moderate to severe chronic stroke (upper extremity Fugl-Meyer < 30). We examined functional cortical reorganization related to paretic hand opening and gray matter (GM) structural changes using a multimodal imaging approach. Individuals demonstrated a shift in cortical activity related to hand opening from the contralesional to the ipsilesional hemisphere following the intervention. This was driven by decreased activity in contralesional primary sensorimotor cortex and increased activity in ipsilesional secondary motor cortex. Additionally, subjects displayed increased GM density in ipsilesional primary sensorimotor cortex and decreased GM density in contralesional primary sensorimotor cortex. These findings suggest that despite moderate to severe chronic impairments, post-stroke participants maintain ability to show cortical reorganization and GM structural changes following a device-assisted task-specific arm/hand intervention. These changes are similar as those reported in post-stroke individuals with mild impairment, suggesting that residual neural plasticity in more severely impaired individuals may have the potential to support improved hand function.
View details for DOI 10.3389/fneur.2017.00284
View details for Web of Science ID 000403390400001
View details for PubMedID 28659863
View details for PubMedCentralID PMC5469871