Michelle Harris-love | George Mason University (original) (raw)

Papers by Michelle Harris-love

Neurorehabilitation and Neural Repair, 2010

Motor disability continues to be a major cause of morbidity after stroke. The neural underpinning... more Motor disability continues to be a major cause of morbidity after stroke. The neural underpinnings of disability and of functional recovery are still unclear. Here, we review recent evidence obtained using transcranial magnetic stimulation (TMS) that provides new insight into these mechanisms. We briefly discuss the use of TMS in the diagnosis, prognosis, and therapy of post-stroke motor disability. Differently from previous reviews, particular emphasis is placed in the discussion of the use of TMS as a tool to explore in detailed mechanisms of neuroplasticity during spontaneous and treatmentinduced recovery of motor function. TMS can be used to acquire the understanding of these mechanisms required for the development of more rational and clinically useful interventions in stroke neurorehabilitation.

Archives of Physical Medicine and Rehabilitation, 2015

Brain : a journal of neurology, Jan 31, 2015

The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive... more The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive. Although older evidence suggested that right hemisphere language homologues compensate for damage in left hemisphere language areas, the current prevailing theory suggests that right hemisphere engagement is ineffective or even maladaptive. Using a novel combination of support vector regression-based lesion-symptom mapping and voxel-based morphometry, we aimed to determine whether local grey matter volume in the right hemisphere independently contributes to aphasia outcomes after chronic left hemisphere stroke. Thirty-two left hemisphere stroke survivors with aphasia underwent language assessment with the Western Aphasia Battery-Revised and tests of other cognitive domains. High-resolution T1-weighted images were obtained in aphasia patients and 30 demographically matched healthy controls. Support vector regression-based multivariate lesion-symptom mapping was used to identify critical...

Archives of Physical Medicine and Rehabilitation, 2015

Journal of applied biomechanics, 2008

The purpose of this study was to determine whether the phenomenon of bilateral deficit in muscula... more The purpose of this study was to determine whether the phenomenon of bilateral deficit in muscular force production observed in healthy subjects and mildly impaired stroke patients also exists in patients with more chronic and greater levels of stroke impairment. Ten patients with chronic hemiparesis resulting from stroke performed unilateral and bilateral maximal voluntary isometric contractions of the elbow flexors. When the total force produced by both arms was compared, 12% less force was produced in the bilateral compared with unilateral condition (p=0.01). However, studying the effect of task conditions on each arm separately revealed a significant decline in nonparetic (p=0.01) but not paretic elbow flexor force in the bilateral compared with unilateral condition. Results suggest that a significant bilateral force deficit exists in the nonparetic but not the paretic arm in individuals with chronic stroke. Bilateral task conditions do not seem to benefit or impair paretic arm ...

Brain Stimulation, 2015

ABSTRACT We report a TMS-related seizure. A 51-year-old man 8 months post superior sagittal vein ... more ABSTRACT We report a TMS-related seizure. A 51-year-old man 8 months post superior sagittal vein thrombosis reported “twitching” in his affected arm, leg, and face one day after participating in a TMS trial. The day prior to the seizure event, the patient received 70 trials of single pulse TMS over the unaffected hemisphere primary motor cortex and double-pulse stimulation applied first over dorsal premotor cortex of the affected hemisphere (80 trials) and then over primary motor cortex of the affected hemisphere (70 trials). The twitching persisted nearly continuously for two days despite administration of lorazepam and low doses of levetiracetam. It is unclear if the prolonged seizure in this case was directly related to TMS, having occurred approximately 20 hours after stimulation. Nevertheless, the timing of event is suggestive. The duration of the seizure and persistence of motor effects afterwards are noteworthy.

Journal of Neurophysiology, 2005

Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophreni... more Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia. Pharmacopsychiatry 37: 74 -80, 2004. Boroojerdi B, Hungs M, Mull M, Topper R, and Noth J. Interhemispheric inhibition in patients with multiple sclerosis. Electroencephalogr Clin Neurophysiol 109: 230 -237, 1998. Boroojerdi B, Topper R, Foltys H, and Meincke U. Transcallosal inhibition and motor conduction studies in patients with schizophrenia using transcranial magnetic stimulation. . One-hertz repetitive transcranial magnetic stimulation of the unaffected hemisphere ameliorates contralesional visuospatial neglect in humans. Neurosci Lett 336: 131-133, 2003. Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, and Cohen LG. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48: 1398 -1403, 1997. Daskalakis ZJ, Christensen BK, Chen R, Fitzgerald PB, Zipursky RB, and Kapur S. Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation. Arch Gen Psychiatry 59: 347-354, 2002a. Daskalakis ZJ, Christensen BK, Fitzgerald PB, Roshan L, and Chen R. The mechanisms of interhemispheric inhibition in the human motor cortex. J Physiol 15: 317-326, 2002b. Di Lazzaro V, Oliviero A, Profice P, Insola A, Mazzone P, Tonali P, and Rothwell JC. Direct demonstration of interhemispheric inhibition of the human motor cortex produced by transcranial magnetic stimulation. Exp Brain Res 124: 520 -524, 1999. Ferbert A, Priori A, Rothwell JC, Day BL, Colebatch JG, and Marsden CD. Interhemispheric inhibition of the human motor cortex. J Physiol 453: 525-546, 1992. Gazzaniga MS. Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain 123: 1293-1326, 2000. Geffen GM, Jones DL, and Geffen LB. Interhemispheric control of manual motor activity. Behav Brain Res 20: 131-140, 1994. Gerloff C, Cohen LG, Floeter MK, Chen R, Corwell B, and Hallett M. Inhibitory influence of the ipsilateral cortex on responses to stimulation of the human cortex and pyramidal tract. J Physiol 510: 249 -259, 1998. Hanajima R, Ugawa Y, Okabe S, Yuasa K, Shiio Y, Iwata NK, and Kanazawa I. Interhemispheric interaction between the hand motor areas in patients with cortical myclonus. magnetic stimulation as a complementary treatment for aphasia. Semin Speech Lang 25: 181-191, 2004. Murase N, Duque J, Mazzocchio R, and Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke.

Archives of physical medicine and rehabilitation, 2006

To test the necessity of videotaping, test-retest reliability, and item stability and validity of... more To test the necessity of videotaping, test-retest reliability, and item stability and validity of a modified Wolf Motor Function Test (WMFT) for people with mild and moderate chronic upper-extremity (UE) hemiparesis caused by stroke. Raters of videotape versus direct observation; test-retest reliability over 3 observations, item stability, and criterion validity with upper-extremity Fugl-Meyer Assessment (FMA) in the mildly and moderately impaired groups. Academic research center. Sixty-six subjects with chronic UE hemiparesis who participated in a large intervention study. Subjects were classified into mild and moderate groups for additional analyses. Not applicable. Mean and median times of task completion, functional ability, and strength (weight to box) measures of the WMFT. FMA scores for validity assessment. In a subgroup of 10 subjects, the intraclass correlation coefficient (ICC) for videotape versus direct observation ranged from .96 to .99. For the whole group, test-retest...

Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination le... more Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination leading to functional limitations and disability. The effects of UE hemiparesis on bilateral functional reaching have not been studied even though most activities of daily living are bilateral tasks. We examined the characteristics of bilateral simultaneous (SIM-B) and bilateral sequential paretic-lead (SEQ-P) and nonparetic-lead (SEQ-NP) functional reaching tasks at preferred and fast speeds. Sixteen patients with chronic hemiparesis completed three bilateral reaching tasks as fast as possible. A subset of eight participants attempted to complete the tasks at both preferred and fastest possible speeds. Paretic (P) and nonparetic (NP) arms were not different from each other in movement time (MT) or peak velocity in the SIM-B condition. MT and peak velocity differed between the two arms during both SEQ tasks. P MT was shorter and NP MT longer in the SIM-B task compared to SEQ-P and SEQ-NP. The P arm MT was the shortest when moving with the NP arm in a simultaneous task compared to both P and NP lead sequential movements. Despite hemiparesis, the two arms demonstrate a temporal coupling when moving simultaneously. When attempting to move at fastest speed, P arm MT time is better when reaching before or with the NP arm than when reaching after the NP arm showing coupling to the NP limb and increased speed of movement. These coupling effects support the rationale for bilateral arm training for individuals with UE hemiparesis.

Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corti... more Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

In this update on rehabilitation technology, transcranial magnetic stimulation (TMS), a technique... more In this update on rehabilitation technology, transcranial magnetic stimulation (TMS), a technique that allows non-invasive stimulation of the brain, is examined. The background and basic principles of TMS are reviewed and its usefulness as a tool to inform and possibly augment the rehabilitation process is discussed. The 3 main paradigms by which TMS is applied, 1) physiological measurement, 2) disruption/virtual lesion studies and 3) modulation of cortical excitability, are discussed relative to the types of scientific information each paradigm can provide and their potential clinical usefulness in the future. One of the more exciting prospects is that, when combined with rehabilitation training, TMS modulation of cortical excitability could potentially enhance the effects of rehabilitation and lead to greater levels of recovery than are currently attainable with rehabilitation alone. It is concluded that current studies must focus on the mechanisms of recovery based on the specific structures and processes affected by the disorder and the neural effects of specific rehabilitation interventions in order for the potential of TMSaugmented rehabilitation to be realized.

Experimental Brain Research, 2014

In the human upper extremity (UE), unintended effects of proximal muscle activation on muscles co... more In the human upper extremity (UE), unintended effects of proximal muscle activation on muscles controlling the hand could be an important aspect of motor control due to the necessary coordination of distal and proximal segments during functional activities. This study aimed to elucidate the effects of concurrent activation of elbow muscles on the coordination between hand muscles performing a grip task. Eleven healthy subjects performed precision grip tasks while a constant extension or flexion moment was applied to their elbow joints, inducing a sustained submaximal contraction of elbow muscles to counter the applied torque. Activation of four hand muscles was measured during each task condition using surface electromyography (EMG). When concurrent activation of elbow muscles was induced, significant changes in the activation levels of the hand muscles were observed, with greater effects on the extrinsic finger extensor (23.2 % increase under 30 % elbow extensor activation; p = 0.003) than extrinsic finger flexor (14.2 % increase under 30 % elbow flexor activation; p = 0.130). Elbow muscle activation also induced involuntary changes in the intrinsic thumb flexor activation (44.6 % increase under 30 % elbow extensor activation; p = 0.005). EMG-EMG coherence analyses revealed that elbow muscle activation significantly reduced intermuscular coherence between distal muscle pairs, with its greatest effects on coherence in the β-band (13-25 Hz) (average of 17 % decrease under 30 % elbow flexor activation). The results of this study provide evidence for involuntary, muscle-specific interactions between distal and proximal UE muscles, which may contribute to UE motor performance in health and disease.

Archives of Physical Medicine and Rehabilitation, 2006

Whitall J, Savin DN, Harris-Love M, McCombe Waller S. Psychometric properties of a modified Wolf ... more Whitall J, Savin DN, Harris-Love M, McCombe Waller S. Psychometric properties of a modified Wolf Motor Function Test for people with mild and moderate upper-extremity hemiparesis. Arch Phys Med Rehabil 2006;87:656-60.

Experimental Brain Research, 2006

Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination le... more Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination leading to functional limitations and disability. The effects of UE hemiparesis on bilateral functional reaching have not been studied even though most activities of daily living are bilateral tasks. We examined the characteristics of bilateral simultaneous (SIM-B) and bilateral sequential paretic-lead (SEQ-P) and nonparetic-lead (SEQ-NP) functional reaching tasks at preferred and fast speeds. Sixteen patients with chronic hemiparesis completed three bilateral reaching tasks as fast as possible. A subset of eight participants attempted to complete the tasks at both preferred and fastest possible speeds. Paretic (P) and nonparetic (NP) arms were not different from each other in movement time (MT) or peak velocity in the SIM-B condition. MT and peak velocity differed between the two arms during both SEQ tasks. P MT was shorter and NP MT longer in the SIM-B task compared to SEQ-P and SEQ-NP. The P arm MT was the shortest when moving with the NP arm in a simultaneous task compared to both P and NP lead sequential movements. Despite hemiparesis, the two arms demonstrate a temporal coupling when moving simultaneously. When attempting to move at fastest speed, P arm MT time is better when reaching before or with the NP arm than when reaching after the NP arm showing coupling to the NP limb and increased speed of movement. These coupling effects support the rationale for bilateral arm training for individuals with UE hemiparesis.

Frontiers in Neurology, 2015

Limited rehabilitation strategies are available for movement restoration when paresis is too seve... more Limited rehabilitation strategies are available for movement restoration when paresis is too severe following stroke. Previous research has shown that high-intensity resistance training of one muscle group enhances strength of the homologous, contralateral muscle group in neurologically intact adults. How this "cross education" phenomenon might be exploited to moderate severe weakness in an upper extremity muscle group after stroke is not well understood. The primary aim of this study was to examine adaptations in force-generating capacity of severely paretic wrist extensors resulting from high intensity, dynamic contractions of the non-paretic wrist extensors. A secondary, exploratory aim was to probe neural adaptations in a subset of participants from each sample using a single-pulse, transcranial magnetic stimulation (TMS) protocol. Separate samples of neurologically intact controls (n = 7) and individuals ≥4 months post stroke (n = 6) underwent 16 sessions of training. Following training, one-repetition maximum of the untrained wrist extensors in the control group and active range of motion of the untrained, paretic wrist extensors in the stroke group were significantly increased. No changes in corticospinal excitability, intracortical inhibition, or interhemispheric inhibition were observed in control participants. Both stroke participants who underwent TMS testing, however, exhibited increased voluntary muscle activation following the intervention. In addition, motor-evoked potentials that were unobtainable prior to the intervention were readily elicited afterwards in a stroke participant. Results of this study demonstrate that high-intensity resistance training of a non-paretic upper extremity muscle group can enhance voluntary muscle activation and force-generating capacity of a severely paretic muscle group after stroke. There is also preliminary evidence that corticospinal adaptations may accompany these gains.

Archives of Physical Medicine and Rehabilitation, 2005

Harris-Love ML, McCombe Waller S, Whitall J. Exploiting interlimb coupling to improve paretic arm... more Harris-Love ML, McCombe Waller S, Whitall J. Exploiting interlimb coupling to improve paretic arm reaching performance in people with chronic stroke. Arch Phys Med Rehabil 2005;86:2131-7.

Archives of Physical Medicine and Rehabilitation, 2013

Archives of Physical Medicine and Rehabilitation, 2013

ABSTRACT Objective To investigate behavioral and physiological effects of unilateral and bilatera... more ABSTRACT Objective To investigate behavioral and physiological effects of unilateral and bilateral reaching practice in individuals with chronic stroke. Design Repeated measures, crossover design, in which reaching performance and cortical physiology were measured before and after (immediately, 24 hours and 30 days) a session of unilateral or bilateral reaching practice with trunk restraint. Setting Hospital-based research lab Participants Individuals with chronic stroke (n = 10) and severe arm impairment (UE Fugl-Meyer = 29.0 ± 7.9; maximum possible score = 66). Interventions In separate sessions (at least 30 days apart), participants performed unilateral (paretic arm only) and bilateral reaching practice (order counterbalanced; 200 repetitions each). Main Outcome Measure(s) The primary outcome measure was paretic arm reaching response time (RT). In addition, transcranial magnetic stimulation was used to measure cortical excitability before and after practice. Results There was a significant main effect of Test Session (p = 0.01) but no Interaction, indicating that the amount of RT improvement did not differ between the 2 types of practice. For both types of practice, RT was faster 24 hours after practice than immediately after. Neurophysiological responses to practice varied widely among participants. Individual response patterns will be described. Conclusions A single session of both unilateral and bilateral reaching practice can result in improved paretic arm reaching performance. Further study is needed to determine the behavioral and physiological effects of longer-term practice. Key Words Reaching, stroke, transcranial magnetic stimulation, practice.

Archives of Physical Medicine and Rehabilitation, 2014

measures. Rehabilitation therapists completed FIM ratings at discharge from the IRF. Results: A p... more measures. Rehabilitation therapists completed FIM ratings at discharge from the IRF. Results: A principal components analysis (PCA) of the discharge FIM scores (nZ337) identified three distinct factors accounting for 75% of the total variance: an ADL/mobility factor (factor 1), a cognitive-linguistic factor (factor 2), and a wheelchair factor (factor 3). In stepwise regression analyses, 36% of FIM factor 1 variance was predicted by age and NIHSS only.Factor 2 was predicted by the presence of aphasia, SBT and BNT scores (34% of the variance). No significant variance in factor 3 (wheelchair use) was predicted by acute measures. The presence of neglect did not account for any factor variance. Conclusions: Beyond age, early NIHSS score predicts IRF discharge FIM scores that involve ADLs and mobility, but cognitive-linguistic performance does not. About a third of the variance in cognitive and languagerelated FIM items is explained by the presence of acute aphasia and cognitive impairment (as measured by the SBT). We conclude that early post-stroke rehabilitation assessments can predict discharge independence weeks later in an impairment-specific fashion.

Neurorehabilitation and Neural Repair, 2015

In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to inte... more In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to interhemispheric and intracortical inhibition in affected hand muscles. In less fully recovered patients unable to move their hand, the neural substrates of recovered arm movements, crucial for performance of daily living tasks, are not well understood. Here, we evaluated interhemispheric and intracortical inhibition in paretic arm muscles of patients with no recovery of hand movement (n = 16, upper extremity Fugl-Meyer Assessment = 27.0 ± 8.6). We recorded silent periods (contralateral and ipsilateral) induced by transcranial magnetic stimulation during voluntary isometric contraction of the paretic biceps and triceps brachii muscles (correlates of intracortical and interhemispheric inhibition, respectively) and investigated links between the silent periods and motor recovery, an issue that has not been previously explored. We report that interhemispheric inhibition, stronger in the paretic triceps than biceps brachii muscles, significantly correlated with the magnitude of residual impairment (lower Fugl-Meyer scores). In contrast, intracortical inhibition in the paretic biceps brachii, but not in the triceps, correlated positively with motor recovery (Fugl-Meyer scores) and negatively with spasticity (lower Modified Ashworth scores). Our results suggest that interhemispheric inhibition and intracortical inhibition of paretic upper arm muscles relate to motor recovery in different ways. While interhemispheric inhibition may contribute to poorer recovery, muscle-specific intracortical inhibition may relate to successful motor recovery and lesser spasticity.

Neurorehabilitation and Neural Repair, 2010

Motor disability continues to be a major cause of morbidity after stroke. The neural underpinning... more Motor disability continues to be a major cause of morbidity after stroke. The neural underpinnings of disability and of functional recovery are still unclear. Here, we review recent evidence obtained using transcranial magnetic stimulation (TMS) that provides new insight into these mechanisms. We briefly discuss the use of TMS in the diagnosis, prognosis, and therapy of post-stroke motor disability. Differently from previous reviews, particular emphasis is placed in the discussion of the use of TMS as a tool to explore in detailed mechanisms of neuroplasticity during spontaneous and treatmentinduced recovery of motor function. TMS can be used to acquire the understanding of these mechanisms required for the development of more rational and clinically useful interventions in stroke neurorehabilitation.

Archives of Physical Medicine and Rehabilitation, 2015

Brain : a journal of neurology, Jan 31, 2015

The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive... more The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive. Although older evidence suggested that right hemisphere language homologues compensate for damage in left hemisphere language areas, the current prevailing theory suggests that right hemisphere engagement is ineffective or even maladaptive. Using a novel combination of support vector regression-based lesion-symptom mapping and voxel-based morphometry, we aimed to determine whether local grey matter volume in the right hemisphere independently contributes to aphasia outcomes after chronic left hemisphere stroke. Thirty-two left hemisphere stroke survivors with aphasia underwent language assessment with the Western Aphasia Battery-Revised and tests of other cognitive domains. High-resolution T1-weighted images were obtained in aphasia patients and 30 demographically matched healthy controls. Support vector regression-based multivariate lesion-symptom mapping was used to identify critical...

Archives of Physical Medicine and Rehabilitation, 2015

Journal of applied biomechanics, 2008

The purpose of this study was to determine whether the phenomenon of bilateral deficit in muscula... more The purpose of this study was to determine whether the phenomenon of bilateral deficit in muscular force production observed in healthy subjects and mildly impaired stroke patients also exists in patients with more chronic and greater levels of stroke impairment. Ten patients with chronic hemiparesis resulting from stroke performed unilateral and bilateral maximal voluntary isometric contractions of the elbow flexors. When the total force produced by both arms was compared, 12% less force was produced in the bilateral compared with unilateral condition (p=0.01). However, studying the effect of task conditions on each arm separately revealed a significant decline in nonparetic (p=0.01) but not paretic elbow flexor force in the bilateral compared with unilateral condition. Results suggest that a significant bilateral force deficit exists in the nonparetic but not the paretic arm in individuals with chronic stroke. Bilateral task conditions do not seem to benefit or impair paretic arm ...

Brain Stimulation, 2015

ABSTRACT We report a TMS-related seizure. A 51-year-old man 8 months post superior sagittal vein ... more ABSTRACT We report a TMS-related seizure. A 51-year-old man 8 months post superior sagittal vein thrombosis reported “twitching” in his affected arm, leg, and face one day after participating in a TMS trial. The day prior to the seizure event, the patient received 70 trials of single pulse TMS over the unaffected hemisphere primary motor cortex and double-pulse stimulation applied first over dorsal premotor cortex of the affected hemisphere (80 trials) and then over primary motor cortex of the affected hemisphere (70 trials). The twitching persisted nearly continuously for two days despite administration of lorazepam and low doses of levetiracetam. It is unclear if the prolonged seizure in this case was directly related to TMS, having occurred approximately 20 hours after stimulation. Nevertheless, the timing of event is suggestive. The duration of the seizure and persistence of motor effects afterwards are noteworthy.

Journal of Neurophysiology, 2005

Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophreni... more Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia. Pharmacopsychiatry 37: 74 -80, 2004. Boroojerdi B, Hungs M, Mull M, Topper R, and Noth J. Interhemispheric inhibition in patients with multiple sclerosis. Electroencephalogr Clin Neurophysiol 109: 230 -237, 1998. Boroojerdi B, Topper R, Foltys H, and Meincke U. Transcallosal inhibition and motor conduction studies in patients with schizophrenia using transcranial magnetic stimulation. . One-hertz repetitive transcranial magnetic stimulation of the unaffected hemisphere ameliorates contralesional visuospatial neglect in humans. Neurosci Lett 336: 131-133, 2003. Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, and Cohen LG. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48: 1398 -1403, 1997. Daskalakis ZJ, Christensen BK, Chen R, Fitzgerald PB, Zipursky RB, and Kapur S. Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation. Arch Gen Psychiatry 59: 347-354, 2002a. Daskalakis ZJ, Christensen BK, Fitzgerald PB, Roshan L, and Chen R. The mechanisms of interhemispheric inhibition in the human motor cortex. J Physiol 15: 317-326, 2002b. Di Lazzaro V, Oliviero A, Profice P, Insola A, Mazzone P, Tonali P, and Rothwell JC. Direct demonstration of interhemispheric inhibition of the human motor cortex produced by transcranial magnetic stimulation. Exp Brain Res 124: 520 -524, 1999. Ferbert A, Priori A, Rothwell JC, Day BL, Colebatch JG, and Marsden CD. Interhemispheric inhibition of the human motor cortex. J Physiol 453: 525-546, 1992. Gazzaniga MS. Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain 123: 1293-1326, 2000. Geffen GM, Jones DL, and Geffen LB. Interhemispheric control of manual motor activity. Behav Brain Res 20: 131-140, 1994. Gerloff C, Cohen LG, Floeter MK, Chen R, Corwell B, and Hallett M. Inhibitory influence of the ipsilateral cortex on responses to stimulation of the human cortex and pyramidal tract. J Physiol 510: 249 -259, 1998. Hanajima R, Ugawa Y, Okabe S, Yuasa K, Shiio Y, Iwata NK, and Kanazawa I. Interhemispheric interaction between the hand motor areas in patients with cortical myclonus. magnetic stimulation as a complementary treatment for aphasia. Semin Speech Lang 25: 181-191, 2004. Murase N, Duque J, Mazzocchio R, and Cohen LG. Influence of interhemispheric interactions on motor function in chronic stroke.

Archives of physical medicine and rehabilitation, 2006

To test the necessity of videotaping, test-retest reliability, and item stability and validity of... more To test the necessity of videotaping, test-retest reliability, and item stability and validity of a modified Wolf Motor Function Test (WMFT) for people with mild and moderate chronic upper-extremity (UE) hemiparesis caused by stroke. Raters of videotape versus direct observation; test-retest reliability over 3 observations, item stability, and criterion validity with upper-extremity Fugl-Meyer Assessment (FMA) in the mildly and moderately impaired groups. Academic research center. Sixty-six subjects with chronic UE hemiparesis who participated in a large intervention study. Subjects were classified into mild and moderate groups for additional analyses. Not applicable. Mean and median times of task completion, functional ability, and strength (weight to box) measures of the WMFT. FMA scores for validity assessment. In a subgroup of 10 subjects, the intraclass correlation coefficient (ICC) for videotape versus direct observation ranged from .96 to .99. For the whole group, test-retest...

Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination le... more Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination leading to functional limitations and disability. The effects of UE hemiparesis on bilateral functional reaching have not been studied even though most activities of daily living are bilateral tasks. We examined the characteristics of bilateral simultaneous (SIM-B) and bilateral sequential paretic-lead (SEQ-P) and nonparetic-lead (SEQ-NP) functional reaching tasks at preferred and fast speeds. Sixteen patients with chronic hemiparesis completed three bilateral reaching tasks as fast as possible. A subset of eight participants attempted to complete the tasks at both preferred and fastest possible speeds. Paretic (P) and nonparetic (NP) arms were not different from each other in movement time (MT) or peak velocity in the SIM-B condition. MT and peak velocity differed between the two arms during both SEQ tasks. P MT was shorter and NP MT longer in the SIM-B task compared to SEQ-P and SEQ-NP. The P arm MT was the shortest when moving with the NP arm in a simultaneous task compared to both P and NP lead sequential movements. Despite hemiparesis, the two arms demonstrate a temporal coupling when moving simultaneously. When attempting to move at fastest speed, P arm MT time is better when reaching before or with the NP arm than when reaching after the NP arm showing coupling to the NP limb and increased speed of movement. These coupling effects support the rationale for bilateral arm training for individuals with UE hemiparesis.

Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corti... more Transcranial magnetic stimulation (TMS) was initially used to evaluate the integrity of the corticospinal tract in humans non-invasively. Since these early studies, the development of paired-pulse and repetitive TMS protocols allowed investigators to explore inhibitory and excitatory interactions of various motor and non-motor cortical regions within and across cerebral hemispheres. These applications have provided insight into the intracortical physiological processes underlying the functional role of different brain regions in various cognitive processes, motor control in health and disease and neuroplastic changes during recovery of function after brain lesions. Used in combination with neuroimaging tools, TMS provides valuable information on functional connectivity between different brain regions, and on the relationship between physiological processes and the anatomical configuration of specific brain areas and connected pathways. More recently, there has been increasing interest in the extent to which these physiological processes are modulated depending on the behavioural setting. The purpose of this paper is (a) to present an up-to-date review of the available electrophysiological data and the impact on our understanding of human motor behaviour and (b) to discuss some of the gaps in our present knowledge as well as future directions of research in a format accessible to new students and/or investigators. Finally, areas of uncertainty and limitations in the interpretation of TMS studies are discussed in some detail.

In this update on rehabilitation technology, transcranial magnetic stimulation (TMS), a technique... more In this update on rehabilitation technology, transcranial magnetic stimulation (TMS), a technique that allows non-invasive stimulation of the brain, is examined. The background and basic principles of TMS are reviewed and its usefulness as a tool to inform and possibly augment the rehabilitation process is discussed. The 3 main paradigms by which TMS is applied, 1) physiological measurement, 2) disruption/virtual lesion studies and 3) modulation of cortical excitability, are discussed relative to the types of scientific information each paradigm can provide and their potential clinical usefulness in the future. One of the more exciting prospects is that, when combined with rehabilitation training, TMS modulation of cortical excitability could potentially enhance the effects of rehabilitation and lead to greater levels of recovery than are currently attainable with rehabilitation alone. It is concluded that current studies must focus on the mechanisms of recovery based on the specific structures and processes affected by the disorder and the neural effects of specific rehabilitation interventions in order for the potential of TMSaugmented rehabilitation to be realized.

Experimental Brain Research, 2014

In the human upper extremity (UE), unintended effects of proximal muscle activation on muscles co... more In the human upper extremity (UE), unintended effects of proximal muscle activation on muscles controlling the hand could be an important aspect of motor control due to the necessary coordination of distal and proximal segments during functional activities. This study aimed to elucidate the effects of concurrent activation of elbow muscles on the coordination between hand muscles performing a grip task. Eleven healthy subjects performed precision grip tasks while a constant extension or flexion moment was applied to their elbow joints, inducing a sustained submaximal contraction of elbow muscles to counter the applied torque. Activation of four hand muscles was measured during each task condition using surface electromyography (EMG). When concurrent activation of elbow muscles was induced, significant changes in the activation levels of the hand muscles were observed, with greater effects on the extrinsic finger extensor (23.2 % increase under 30 % elbow extensor activation; p = 0.003) than extrinsic finger flexor (14.2 % increase under 30 % elbow flexor activation; p = 0.130). Elbow muscle activation also induced involuntary changes in the intrinsic thumb flexor activation (44.6 % increase under 30 % elbow extensor activation; p = 0.005). EMG-EMG coherence analyses revealed that elbow muscle activation significantly reduced intermuscular coherence between distal muscle pairs, with its greatest effects on coherence in the β-band (13-25 Hz) (average of 17 % decrease under 30 % elbow flexor activation). The results of this study provide evidence for involuntary, muscle-specific interactions between distal and proximal UE muscles, which may contribute to UE motor performance in health and disease.

Archives of Physical Medicine and Rehabilitation, 2006

Whitall J, Savin DN, Harris-Love M, McCombe Waller S. Psychometric properties of a modified Wolf ... more Whitall J, Savin DN, Harris-Love M, McCombe Waller S. Psychometric properties of a modified Wolf Motor Function Test for people with mild and moderate upper-extremity hemiparesis. Arch Phys Med Rehabil 2006;87:656-60.

Experimental Brain Research, 2006

Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination le... more Upper extremity (UE) hemiparesis results in decreased movement speed and impaired coordination leading to functional limitations and disability. The effects of UE hemiparesis on bilateral functional reaching have not been studied even though most activities of daily living are bilateral tasks. We examined the characteristics of bilateral simultaneous (SIM-B) and bilateral sequential paretic-lead (SEQ-P) and nonparetic-lead (SEQ-NP) functional reaching tasks at preferred and fast speeds. Sixteen patients with chronic hemiparesis completed three bilateral reaching tasks as fast as possible. A subset of eight participants attempted to complete the tasks at both preferred and fastest possible speeds. Paretic (P) and nonparetic (NP) arms were not different from each other in movement time (MT) or peak velocity in the SIM-B condition. MT and peak velocity differed between the two arms during both SEQ tasks. P MT was shorter and NP MT longer in the SIM-B task compared to SEQ-P and SEQ-NP. The P arm MT was the shortest when moving with the NP arm in a simultaneous task compared to both P and NP lead sequential movements. Despite hemiparesis, the two arms demonstrate a temporal coupling when moving simultaneously. When attempting to move at fastest speed, P arm MT time is better when reaching before or with the NP arm than when reaching after the NP arm showing coupling to the NP limb and increased speed of movement. These coupling effects support the rationale for bilateral arm training for individuals with UE hemiparesis.

Frontiers in Neurology, 2015

Limited rehabilitation strategies are available for movement restoration when paresis is too seve... more Limited rehabilitation strategies are available for movement restoration when paresis is too severe following stroke. Previous research has shown that high-intensity resistance training of one muscle group enhances strength of the homologous, contralateral muscle group in neurologically intact adults. How this "cross education" phenomenon might be exploited to moderate severe weakness in an upper extremity muscle group after stroke is not well understood. The primary aim of this study was to examine adaptations in force-generating capacity of severely paretic wrist extensors resulting from high intensity, dynamic contractions of the non-paretic wrist extensors. A secondary, exploratory aim was to probe neural adaptations in a subset of participants from each sample using a single-pulse, transcranial magnetic stimulation (TMS) protocol. Separate samples of neurologically intact controls (n = 7) and individuals ≥4 months post stroke (n = 6) underwent 16 sessions of training. Following training, one-repetition maximum of the untrained wrist extensors in the control group and active range of motion of the untrained, paretic wrist extensors in the stroke group were significantly increased. No changes in corticospinal excitability, intracortical inhibition, or interhemispheric inhibition were observed in control participants. Both stroke participants who underwent TMS testing, however, exhibited increased voluntary muscle activation following the intervention. In addition, motor-evoked potentials that were unobtainable prior to the intervention were readily elicited afterwards in a stroke participant. Results of this study demonstrate that high-intensity resistance training of a non-paretic upper extremity muscle group can enhance voluntary muscle activation and force-generating capacity of a severely paretic muscle group after stroke. There is also preliminary evidence that corticospinal adaptations may accompany these gains.

Archives of Physical Medicine and Rehabilitation, 2005

Harris-Love ML, McCombe Waller S, Whitall J. Exploiting interlimb coupling to improve paretic arm... more Harris-Love ML, McCombe Waller S, Whitall J. Exploiting interlimb coupling to improve paretic arm reaching performance in people with chronic stroke. Arch Phys Med Rehabil 2005;86:2131-7.

Archives of Physical Medicine and Rehabilitation, 2013

Archives of Physical Medicine and Rehabilitation, 2013

ABSTRACT Objective To investigate behavioral and physiological effects of unilateral and bilatera... more ABSTRACT Objective To investigate behavioral and physiological effects of unilateral and bilateral reaching practice in individuals with chronic stroke. Design Repeated measures, crossover design, in which reaching performance and cortical physiology were measured before and after (immediately, 24 hours and 30 days) a session of unilateral or bilateral reaching practice with trunk restraint. Setting Hospital-based research lab Participants Individuals with chronic stroke (n = 10) and severe arm impairment (UE Fugl-Meyer = 29.0 ± 7.9; maximum possible score = 66). Interventions In separate sessions (at least 30 days apart), participants performed unilateral (paretic arm only) and bilateral reaching practice (order counterbalanced; 200 repetitions each). Main Outcome Measure(s) The primary outcome measure was paretic arm reaching response time (RT). In addition, transcranial magnetic stimulation was used to measure cortical excitability before and after practice. Results There was a significant main effect of Test Session (p = 0.01) but no Interaction, indicating that the amount of RT improvement did not differ between the 2 types of practice. For both types of practice, RT was faster 24 hours after practice than immediately after. Neurophysiological responses to practice varied widely among participants. Individual response patterns will be described. Conclusions A single session of both unilateral and bilateral reaching practice can result in improved paretic arm reaching performance. Further study is needed to determine the behavioral and physiological effects of longer-term practice. Key Words Reaching, stroke, transcranial magnetic stimulation, practice.

Archives of Physical Medicine and Rehabilitation, 2014

measures. Rehabilitation therapists completed FIM ratings at discharge from the IRF. Results: A p... more measures. Rehabilitation therapists completed FIM ratings at discharge from the IRF. Results: A principal components analysis (PCA) of the discharge FIM scores (nZ337) identified three distinct factors accounting for 75% of the total variance: an ADL/mobility factor (factor 1), a cognitive-linguistic factor (factor 2), and a wheelchair factor (factor 3). In stepwise regression analyses, 36% of FIM factor 1 variance was predicted by age and NIHSS only.Factor 2 was predicted by the presence of aphasia, SBT and BNT scores (34% of the variance). No significant variance in factor 3 (wheelchair use) was predicted by acute measures. The presence of neglect did not account for any factor variance. Conclusions: Beyond age, early NIHSS score predicts IRF discharge FIM scores that involve ADLs and mobility, but cognitive-linguistic performance does not. About a third of the variance in cognitive and languagerelated FIM items is explained by the presence of acute aphasia and cognitive impairment (as measured by the SBT). We conclude that early post-stroke rehabilitation assessments can predict discharge independence weeks later in an impairment-specific fashion.

Neurorehabilitation and Neural Repair, 2015

In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to inte... more In well-recovered stroke patients with preserved hand movement, motor dysfunction relates to interhemispheric and intracortical inhibition in affected hand muscles. In less fully recovered patients unable to move their hand, the neural substrates of recovered arm movements, crucial for performance of daily living tasks, are not well understood. Here, we evaluated interhemispheric and intracortical inhibition in paretic arm muscles of patients with no recovery of hand movement (n = 16, upper extremity Fugl-Meyer Assessment = 27.0 ± 8.6). We recorded silent periods (contralateral and ipsilateral) induced by transcranial magnetic stimulation during voluntary isometric contraction of the paretic biceps and triceps brachii muscles (correlates of intracortical and interhemispheric inhibition, respectively) and investigated links between the silent periods and motor recovery, an issue that has not been previously explored. We report that interhemispheric inhibition, stronger in the paretic triceps than biceps brachii muscles, significantly correlated with the magnitude of residual impairment (lower Fugl-Meyer scores). In contrast, intracortical inhibition in the paretic biceps brachii, but not in the triceps, correlated positively with motor recovery (Fugl-Meyer scores) and negatively with spasticity (lower Modified Ashworth scores). Our results suggest that interhemispheric inhibition and intracortical inhibition of paretic upper arm muscles relate to motor recovery in different ways. While interhemispheric inhibition may contribute to poorer recovery, muscle-specific intracortical inhibition may relate to successful motor recovery and lesser spasticity.