George Wittenberg
University of Maryland, Neurology, Faculty Member
Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor... more
Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is involved in sensorimotor behavior but has not been widely studied within the context of post-stroke upper limb sensorimotor impairment. The hippocampus is vulnerable to secondary degeneration after stroke, and damage to this region could further weaken sensorimotor circuits, leading to greater chronic sensorimotor impairment. The purpose of this study was to investigate the cross-sectional association between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke. We hypothesized that smaller ipsilesional hippocampal volumes would be associated with worse upper-limb sensorimotor impairment.Cross-sectional T1-weighted brain MRIs were pooled from 357 participants at the chronic stage after stroke (>180 days post-stroke) compiled from 18 research cohorts worldwide in the ENIGMA Stroke Recovery Working Group (age: median = 61 years, ...
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To investigate motor cortical map patterns in children with diplegic and hemiplegic cerebral palsy (CP), and the relationships between motor cortical geometry and motor function in CP. Transcranial magnetic stimulation (TMS) was used to... more
To investigate motor cortical map patterns in children with diplegic and hemiplegic cerebral palsy (CP), and the relationships between motor cortical geometry and motor function in CP. Transcranial magnetic stimulation (TMS) was used to map motor cortical representations of the first dorsal interosseus (FDI) and tibialis anterior (TA) muscles in 13 children with CP (age 9-16 years, 6 males.) The Gross Motor Function Measure (GMFM) and Melbourne upper extremity function were used to quantify motor ability. In the hemiplegic participants (N = 7), the affected (right) FDI cortical representation was mapped on the ipsilateral (N = 4), contralateral (N = 2), or bilateral (N = 1) cortex. Participants with diplegia (N = 6) showed either bilateral (N = 2) or contralateral (N = 4) cortical hand maps. The FDI and TA motor map center-of-gravity mediolateral location ranged from 2-8 cm and 3-6 cm from the midline, respectively. Among diplegics, more lateral FDI representation locations were associated with lower Melbourne scores, i.e. worse hand motor function (Spearman's rho = -0.841, p = 0.036). Abnormalities in TMS-derived motor maps cut across the clinical classifications of hemiplegic and diplegic CP. The lateralization of the upper and lower extremity motor representation demonstrates reorganization after insults to the affected hemispheres of both diplegic and hemiplegic children. The current study is a step towards defining the relationship between changes in motor maps and functional impairments in CP. These results suggest the need for further work to develop improved classification schemes that integrate clinical, radiologic, and neurophysiologic measures in CP.
Research Interests: Engineering, Transcranial Magnetic Stimulation, Cerebral Palsy, Adolescent, Brain Mapping, and 15 moreHumans, Child, Female, Clinical, Male, Hemiplegia, Motor Cortex, Clinical Neurophysiology, Motor Evoked Potentials, Hand, Ankle, Functional Laterality, Disability Evaluation, Psychology and Cognitive Sciences, and Medical and Health Sciences
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The objective of this study was to examine age-related differences in arm and trunk responses during first and repeated step induced balance perturbations. Young and older adults received 10 trials of unpredictable lateral platform... more
The objective of this study was to examine age-related differences in arm and trunk responses during first and repeated step induced balance perturbations. Young and older adults received 10 trials of unpredictable lateral platform translations. Outcomes included maximum arm and trunk displacement within 1 s of perturbation and at first foot lift off (FFLO), arm and neck muscle activity as recorded using electromyography (EMG), initial step type, balance confidence, and percentage of harness-assisted trials. Compared to young adults, older adults demonstrated greater arm and trunk angular displacements during the first trial, which were present at FFLO and negatively associated with balance confidence. Unlike young adults, recovery steps in older adults were directed towards the fall with a narrowed base of support. Over repeated trials, rapid habituation of first-trial responses of bilateral arm and trunk displacement and EMG amplitude was demonstrated in young adults, but was abse...
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Inhibitory deficits in motor cortex in schizophrenia have been well demonstrated using short-interval intracortical inhibition (SICI) by transcranial magnetic stimulation. However, it remains unknown whether these deficits originate from... more
Inhibitory deficits in motor cortex in schizophrenia have been well demonstrated using short-interval intracortical inhibition (SICI) by transcranial magnetic stimulation. However, it remains unknown whether these deficits originate from dysfunction of motor cortex itself or reflect abnormal modulations of motor cortex by other schizophrenia-related brain areas. The study was completed by 24 patients with schizophrenia spectrum disorders and 30 healthy control subjects. SICI was obtained by delivering transcranial magnetic stimulation over the left motor cortex. Resting-state functional magnetic resonance imaging and diffusion tensor imaging fractional anisotropy were used to measure functional connectivity (FC) and white matter microstructures, respectively. Stimulation sites for SICI at motor cortex were used as the seeds to obtain whole-brain FC maps. Clinical symptoms were assessed with the Brief Psychiatric Rating Scale. In schizophrenia, left prefrontal cortex-motor cortex FC was inversely associated with SICI but positively associated with the underlying white matter microstructure at the left corona radiata and also associated with overall symptoms (all corrected p < .05). Mediation analysis showed that the prefrontal-motor cortex FC significantly mediated the corona radiata white matter effects on SICI (p = .007). Higher resting-state left prefrontal-motor cortex FC, accompanied by a higher fractional anisotropy of left corona radiata, predicted fewer inhibitory deficits, suggesting that the inhibitory deficits in motor cortex in schizophrenia may in part be mediated by a top-down prefrontal influence. SICI may serve as a robust biomarker indexing inhibitory dysfunction at anatomic as well as circuitry levels in schizophrenia.
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Cerebellar-prefrontal connectivity has been recognized as important for behaviors ranging from motor coordination to cognition. Many of these behaviors are known to involve excitatory or inhibitory modulations from the prefrontal cortex.... more
Cerebellar-prefrontal connectivity has been recognized as important for behaviors ranging from motor coordination to cognition. Many of these behaviors are known to involve excitatory or inhibitory modulations from the prefrontal cortex. We used cerebellar transcranial magnetic stimulation (TMS) with simultaneous electroencephalography (EEG) to probe cerebellar-evoked electrical activity in prefrontal cortical areas and used magnetic resonance spectroscopy (MRS) measures of prefrontal GABA and glutamate levels to determine if they are correlated with those potentials. Cerebellar-evoked bilateral prefrontal synchrony in the theta to gamma frequency range showed patterns that reflect strong GABAergic inhibitory function (r = - 0.66, p = 0.002). Stimulation of prefrontal areas evoked bilateral prefrontal synchrony in the theta to low beta frequency range that reflected, conversely, glutamatergic excitatory function (r = 0.66, p = 0.002) and GABAergic inhibitory function (r = - 0.65, p ...
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Robots designed for rehabilitation of the upper extremity after stroke facilitate high rates of repetition during practice of movements and record precise kinematic data, providing a method to investigate motor recovery profiles over... more
Robots designed for rehabilitation of the upper extremity after stroke facilitate high rates of repetition during practice of movements and record precise kinematic data, providing a method to investigate motor recovery profiles over time. To determine how motor recovery profiles during robotic interventions provide insight into improving clinical gains. A convenience sample (n = 22), from a larger randomized control trial, was taken of chronic stroke participants completing 12 sessions of arm therapy. One group received 60 minutes of robotic therapy (Robot only) and the other group received 45 minutes on the robot plus 15 minutes of translation-to-task practice (Robot + TTT). Movement time was assessed using the robot without powered assistance. Analyses (ANOVA, random coefficient modeling [RCM] with 2-term exponential function) were completed to investigate changes across the intervention, between sessions, and within a session. Significant improvement (P < .05) in movement tim...
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In recovered stroke patients, performance of motor tasks with the affected limb has been reported to activate cortical areas ipsilateral to the affected side. The better to determine the causal role these areas play in recovery of motor... more
In recovered stroke patients, performance of motor tasks with the affected limb has been reported to activate cortical areas ipsilateral to the affected side. The better to determine the causal role these areas play in recovery of motor function, we assessed cerebral activation during motor activity longitudinally after hemiparesis due to cerebral infarction. A secondary goal was to ascertain the relation between mirror movements and activation ipsilateral to motor activity. Positron emission tomography with oxygen-15 water measured regional cerebral blood flow during wrist movement early and late in the course of recovery from hemiparesis. Surface electromyography recorded muscular activity, and computer-assisted video analysis quantified movement during the scans. Mirror movements, movements contralateral to the instructed movement of the hemiparetic arm, were often seen. Activation of motor areas in the hemisphere ipsilateral to the affected limb roughly correlated with presence ...
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The human gamma-globulin (HGG)-specific helper T cell clone AB.7.D7 can reconstitute the plaque-forming cell response of HGG-primed B cells. Tolerance induction at the level of T cell help results from exposure of the AB.7.D7 cells to 10... more
The human gamma-globulin (HGG)-specific helper T cell clone AB.7.D7 can reconstitute the plaque-forming cell response of HGG-primed B cells. Tolerance induction at the level of T cell help results from exposure of the AB.7.D7 cells to 10 micrograms monomeric HGG. The monokine IL 1 was found to interfere with tolerance induction in AB.7.D7 cells in a dose-dependent manner. Furthermore, interference with tolerance induction was dependent upon the T cells being presented with IL 1 at the same time as monomeric HGG, the tolerogen. IL 1 and monomeric HGG could not be demonstrated to interact to make nontolerogenic soluble aggregates, however. It was found that monomeric HGG was unable to stimulate the production of either membrane or secreted IL 1 by splenic macrophages and in addition was not degraded by peritoneal exudate cells. Heat-aggregated HGG, which is highly antigenic and nontolerogenic, is a good stimulus for IL 1 production and is processed by macrophages into peptides of vary...
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The objective was to determine how stimulation timing applied during reaching influenced neuroplasticity related to practice. Older adult participants were studied to increase relevance for stroke rehabilitation and aging. Sixteen... more
The objective was to determine how stimulation timing applied during reaching influenced neuroplasticity related to practice. Older adult participants were studied to increase relevance for stroke rehabilitation and aging. Sixteen participants completed 3 sessions of a reaching intervention with 480 planar robotic movement trials. Sub-threshold, single-pulse transcranial magnetic stimulations (TMS) were delivered during the late reaction time (LRT) period, when muscle activity exceeded a threshold (EMG-triggered), or randomly. Assessments included motor evoked potentials (MEP), amplitude, and direction of supra-threshold TMS-evoked movements and were calculated as change scores from baseline. The direction of TMS-evoked movements significantly changed after reaching practice (p<0.05), but was not significantly different between conditions. Movement amplitude changes were significantly different between conditions (p<0.05), with significant increases following the LRT and rando...
Research Interests: Engineering, Robotics, Transcranial Magnetic Stimulation, Humans, Movement, and 14 moreFemale, Male, Reaction Time, Neuronal Plasticity, Motor Cortex, Clinical Neurophysiology, Motor Evoked Potentials, Aged, Skeletal Muscle, Adult, Age Factors, Motor Skills, Psychology and Cognitive Sciences, and Medical and Health Sciences
Skeletal muscles that are under the influence of tetanus toxin show an exaggerated reflex response to stretch. We examined which changes in the stretch reflex may underlie the exaggerated response. H-reflexes were obtained from the... more
Skeletal muscles that are under the influence of tetanus toxin show an exaggerated reflex response to stretch. We examined which changes in the stretch reflex may underlie the exaggerated response. H-reflexes were obtained from the tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles in rats 7 days after intramuscular injection of tetanus toxin into the TA. We found effects of the toxin on the threshold, amplitude, and duration of H-waves from the TA. The toxin inhibited rate-dependent depression in the FDB between the stimulation frequencies of 0.5–50 HZ and when a conditioning magnetic stimulus applied to the brain preceded a test electrical stimulus delivered to the plantar nerve. Tetanus toxin increased the amplitude of the Hwave and reduced the normal depression of H-wave amplitude that is associated with closely timed stimuli, two phenomena that could contribute to hyperactivity of the stretch reflex.
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This is a presentation of a biomechanics project from almost 30 years ago, that, despite the long delay, is both relevant today and may be interesting from a historical perspective. Premature rupture of the amniotic sac membranes... more
This is a presentation of a biomechanics project from almost 30 years ago, that, despite the long delay, is both relevant today and may be interesting from a historical perspective. Premature rupture of the amniotic sac membranes enclosing the fetus is, as yet, a not fully understood process, but may related to the mechanical properties of those membranes. The late biomechanics pioneer Tom McMahon and I developed a method for testing the yield stress of fetal membranes and found it to be homogeneous throughout individual samples. The method was: 1. insensitive to initial stretch, 2. avoided damaging contact with the membrane during stress-testing, and 3. modeled the mechanical properties using a power-law relationship. Because the clinical samples were from normal deliveries, clinical correlation remains as an unfinished aim of this project.
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In recovered stroke patients, performance of motor tasks with the affected limb has been reported to activate cortical areas ipsilateral to the affected side. The better to determine the causal role these areas play in recovery of motor... more
In recovered stroke patients, performance of motor tasks with the affected limb has been reported to activate cortical areas ipsilateral to the affected side. The better to determine the causal role these areas play in recovery of motor function, we assessed cerebral activation during motor activity longitudinally after hemiparesis due to cerebral infarction. A secondary goal was to ascertain the relation between mirror movements and activation ipsilateral to motor activity. Positron emission tomography with oxygen-15 water measured regional cerebral blood flow during wrist movement early and late in the course of recovery from hemiparesis. Surface electromyography recorded muscular activity, and computer-assisted video analysis quantified movement during the scans. Mirror movements, movements contralateral to the instructed movement of the hemiparetic arm, were often seen. Activation of motor areas in the hemisphere ipsilateral to the affected limb roughly correlated with presence ...
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We have investigated possible mechanisms underlying immune complex suppression of resistance to Listeria monocytogenes. Inhibition of resistance was found when immune complexes were formed in vivo in immune mice or in nonimmune mice... more
We have investigated possible mechanisms underlying immune complex suppression of resistance to Listeria monocytogenes. Inhibition of resistance was found when immune complexes were formed in vivo in immune mice or in nonimmune mice adoptively transferred with specific antibody. Suppression was also found when nonimmune mice were injected with immune complexes preformed in vitro. We investigated the role of complement by decomplementing mice with cobra venom factor purified by high-pressure liquid chromatography. Complete depletion of serum C3 did not eliminate immune complex suppression of resistance to L. monocytogenes, suggesting that complement activation is not required for immune complex suppression. Infection-induced changes in the surface phenotype and functional properties of macrophages from normal and immune complex-suppressed mice were also investigated. Macrophage expression of both H-2K and Ia molecules increased during the response of normal mice to L. monocytogenes. ...
Research Interests: Immunology, Cell Adhesion, Membrane Proteins, Macrophages, Innate immunity, and 15 moreBiological Sciences, Infection and immunity, Antibodies, Mice, Animals, Listeria monocytogenes, Immunosuppression, T lymphocytes, Time Factors, Listeriosis, Immune Tolerance, Epitopes, Interleukin, Ovalbumin , and Medical and Health Sciences
We investigated the effects of immune complexes on macrophage functions in vitro. Immune complexes inhibit lymphokine induction of both I-Ak expression and cytotoxic activity by fetal calf serum elicited macrophages during long-term (7... more
We investigated the effects of immune complexes on macrophage functions in vitro. Immune complexes inhibit lymphokine induction of both I-Ak expression and cytotoxic activity by fetal calf serum elicited macrophages during long-term (7 days) culture. In addition, induction of antigen presentation was significantly inhibited by immune complexes. Expression of membrane interleukin 1 (IL-1) (a membrane-bound bound form of the T cell mitogen required for antigen presentation by fixed cells) was minimally inhibited by immune complexes. Therefore, inhibition of antigen presentation was primarily due to effects on Ia expression rather than membrane IL 1 expression. The inhibitory effect of immune complexes was not found during short-term culture (4 to 48 hr) when activated macrophages (bearing high levels of Ia) from mice infected with Listeria monocytogenes were examined. Immune complexes maintained or even increased levels of both I-Ak and cytotoxicity in activated macrophages. The impli...
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1. To understand how a multisegmental animal coordinates motor activity over more than one segment, we studied shortening behavior in the medicinal leech, in which several segments contract longitudinally in response to a moderately... more
1. To understand how a multisegmental animal coordinates motor activity over more than one segment, we studied shortening behavior in the medicinal leech, in which several segments contract longitudinally in response to a moderately strong mechanical stimulus. 2. We first demonstrated that the neuronal activity responsible for shortening behavior occurred in semi-intact and isolated nerve cord preparations, and then characterized the responses of motor neurons in isolated preparations. The motor output during shortening was simultaneous excitation of motor neurons innervating dorsal longitudinal muscle and of motor neurons innervating ventral longitudinal muscle. 3. The stronger the stimulus, the more segments produced the shortening motor output, with the segments nearest the stimulus recruited first. 4. Although the shortening response was produced in several segments near the site of stimulation, it was never produced in the stimulated segment, where the local bending motor outpu...
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Constraint-induced movement therapy (CIMT) has been shown to improve upper extremity voluntary movement and change cortical movement representation after stroke. Direct comparison of the differential degree of cortical reorganization... more
Constraint-induced movement therapy (CIMT) has been shown to improve upper extremity voluntary movement and change cortical movement representation after stroke. Direct comparison of the differential degree of cortical reorganization according to chronicity in stroke subjects receiving CIMT has not been performed and was the purpose of this study. We hypothesized that a higher degree of cortical reorganization would occur in the early (less than 9 months post-stroke) compared to the late group (more than 12 months post-stroke). 17 early and 9 late subjects were enrolled. Each subject was evaluated using transcranial magnetic stimulation (TMS) and the Wolf Motor Function Test (WMFT) and received CIMT for 2 weeks. The early group showed greater improvement in WMFT compared with the late group. TMS motor maps showed persistent enlargement in both groups but the late group trended toward more enlargement. The map shifted posteriorly in the late stroke group. The main limitation was the ...
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The aim of this study was to determine the relationship between motor skill and attentional reserve. Participants practiced a reaching task with the dominant upper extremity, to which a distortion of the visual feedback was applied, while... more
The aim of this study was to determine the relationship between motor skill and attentional reserve. Participants practiced a reaching task with the dominant upper extremity, to which a distortion of the visual feedback was applied, while a control group performed the same task without distortion. Event-related brain potentials (ERPs), elicited by auditory stimuli were recorded throughout practice. Performance, as measured by initial directional error, was initially worse relative to controls and improved over trials. Analyses of the ERPs revealed that exogenous components, N1 and P2, were undifferentiated between the groups and did not change with practice. Notably, amplitude of the novelty P3 component, an index of the involuntary orienting of attention, was initially attenuated relative to controls, but progressively increased in amplitude over trials in the learning group only. The results provide psychophysiological evidence that attentional reserve increases as a function of motor skill acquisition.
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The effect of the neurosteroid dehydroepiandrosterone sulfate on inhibitory synaptic transmission was studied in area CA1 of the rat hippocampus using an in vitro hippocampal slice preparation. Synaptic responses elicited by stimulation... more
The effect of the neurosteroid dehydroepiandrosterone sulfate on inhibitory synaptic transmission was studied in area CA1 of the rat hippocampus using an in vitro hippocampal slice preparation. Synaptic responses elicited by stimulation of Schaffer collateral fibers were recorded extracellularly as population spikes in the somatic region and as synaptic field potentials in the dendritic region. Bath application of dehydroepiandrosterone sulfate (10 microM) enhanced the synaptically evoked somatic population spike with no effect on the dendritic synaptic potential. Isolation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor-mediated component of the synaptic response by addition of antagonists of N-methyl-D-aspartate and GABA receptors to the perfusion saline demonstrated that dehydroepiandrosterone sulfate had no effect on this component of the dendritic synaptic potential. In contrast, dehydroepiandrosterone sulfate antagonized GABA receptor-mediated inhibitory effects in the somatic region, resulting in an augmentation of the somatic population spike amplitude. Paired-pulse facilitation was unaltered by dehydroepiandrosterone sulfate, thus arguing against possible presynaptic sites of dehydroepiandrosterone sulfate&#39;s actions. These results indicate that dehydroepiandrosterone sulfate can alter synaptic transmission in the hippocampus through selective postsynaptic actions on inhibitory synaptic transmission. A synaptic effect of dehydroepiandrosterone sulfate is consistent with a neuromodulatory role for this neurosteroid in the central nervous system, and may contribute to the reported effects of dehydroepiandrosterone sulfate on cognitive processes such as learning and memory.
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Research Interests: Neuroscience, Psychology, Clinical Trial, Humans, Movement, and 15 moreRegression Analysis, Arm, Neuronal Plasticity, Motor Cortex, Electromyography, Cortical Plasticity, Real Time, Dimensional, Adult, Analysis of Variance, Primary Motor Cortex, Individual Difference, Neurosciences, Biomechanical Phenomena, and Functional Laterality
Background. Constraint-induced movement therapy (CIMT) has received considerable attention as an intervention to enhance motor recovery and cortical reorganization after stroke. Objective. The present study represents the first... more
Background. Constraint-induced movement therapy (CIMT) has received considerable attention as an intervention to enhance motor recovery and cortical reorganization after stroke. Objective. The present study represents the first multi-center effort to measure cortical reorganization induced by CIMT in subjects who are in the subacute stage of recovery. Methods. A total of 30 stroke subjects in the subacute phase (>3 and <9 months poststroke) were recruited and randomized into experimental (receiving CIMT immediately after baseline evaluation) and control (receiving CIMT after 4 months) groups. Each subject was evaluated using transcranial magnetic stimulation (TMS) at baseline, 2 weeks after baseline, and at 4-month follow-up (ie, after CIMT in the experimental groups and before CIMT in the control groups). The primary clinical outcome measure was the Wolf Motor Function Test. Results. Both experimental and control groups demonstrated improved hand motor function 2 weeks after ...
Research Interests: Cognitive Science, Treatment Outcome, Exercise therapy, Brain Mapping, Stroke, and 13 moreHumans, Female, Male, Follow-up studies, Motor Cortex, Clinical Sciences, Middle Aged, Time Factors, Constraint-Induced Movement Therapy, Physical Restraint, Neurosciences, Motor activity, and Recovery of Function
Background. Recovery of motor function after stroke may be associated with changes in inhibitory and facilitatory circuits within the motor cortex. Objective. We explored such changes longitudinally after stroke, using transcranial... more
Background. Recovery of motor function after stroke may be associated with changes in inhibitory and facilitatory circuits within the motor cortex. Objective. We explored such changes longitudinally after stroke, using transcranial magnetic stimulation (TMS). Methods. Subjects ( N = 27) with a single cerebral infarction affecting movement of either hand were studied at <10 days poststroke, 1 month, and 6 months. Age-matched control subjects ( N = 9) were studied at 2 times. Results. In contrast to previous studies, paired-pulse inhibition was increased in patients with a subcortical stroke compared to control subjects. After a cortical stroke, paired-pulse facilitation was also increased. Stroke location affected the time course of inhibition. Subcortical stroke resulted in increased inhibition initially that decreased over time, whereas cortical stroke had no significant effect on inhibition and a more immediate and lasting effect on facilitation. Conclusions. The time course of...
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Background. Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period.... more
Background. Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. Objective. To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. Methods. The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment ≥6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. Results. A total of 127 participa...
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Animal models suggest that a month of heightened plasticity occurs in the brain after stroke, accompanied by most of the recovery from impairment. This period of peri-infarct and remote plasticity is associated with changes in... more
Animal models suggest that a month of heightened plasticity occurs in the brain after stroke, accompanied by most of the recovery from impairment. This period of peri-infarct and remote plasticity is associated with changes in excitatory/inhibitory balance and the spatial extent and activation of cortical maps and structural remodeling. The best time for experience and training to improve outcome is unclear. In animal models, very early (<5 days from onset) and intense training may lead to increased histological damage. Conversely, late rehabilitation (>30 days) is much less effective both in terms of outcome and morphological changes associated with plasticity. In clinical practice, rehabilitation after disabling stroke involves a relatively brief period of inpatient therapy that does not come close to matching intensity levels investigated in animal models and includes the training of compensatory strategies that have minimal impact on impairment. Current rehabilitation trea...
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Much work indicates that parietal cortex mediates the transformation of visual information into the motor commands necessary for successful performance of many unimanual tasks. Accumulating evidence suggests that parietal cortex also... more
Much work indicates that parietal cortex mediates the transformation of visual information into the motor commands necessary for successful performance of many unimanual tasks. Accumulating evidence suggests that parietal cortex also mediates the coordination of bimanual movements, during which the natural tendency is to couple the limbs temporally. However, the extent to which parietal oculomotor and/or visual processes contribute to temporal coupling of the limbs during bimanual task performance is unknown. In the current study, we monitored the eye movements of a patient with a left parietal infarction as she performed a series of bimanual visuomotor tasks. We demonstrate the impact of an ipsilesional (leftward) orientation bias on her ability to synchronize the onset of bimanual limb movements; the movements were performed in serial fashion, i.e., left limb before right, when the patient was permitted to freely shift saccades and the visual target cuing the left (ipsilesional) limb movement was presented at greater (leftward) eccentricities. Disruption of interlimb synchrony as such was not, however, evident when the patient was required to fixate or when visual targets were presented at lesser ipsilesional eccentricities. Additionally, despite the disruptive influence of oculomotor and visual factors on interlimb synchrony, the patient appeared capable of using visual feedback to straighten the right (contralesional) limb trajectory, thus improving the spatial component of task performance. Results suggest that parietal cortex plays an important role in the coordination of limb movements during performance of bimanual visuomotor tasks. This role appears to involve orienting gaze or attention to the goals of each limb so that the nervous system can synchronize the activity of both limbs and thereby ensure successful task completion.
Research Interests: Psychology, Cognitive Science, Magnetic Resonance Imaging, Humans, Case Study, and 15 moreFemale, Male, Parietal Cortex, Eye Movements, Task Performance, Clinical Sciences, Aged, Middle Aged, Parietal Lobe, Eye Movement, Hand, Nervous System, Motor Skills, Biomechanical Phenomena, and Functional Laterality
Research Interests: Plasticity, Neurorehabilitation, Learning, Brain Mapping, Humans, and 15 moreCerebral Cortex, Spinal Cord, Neuronal Plasticity, Animal Model, Human Brain, Nerve Regeneration, Clinical Sciences, Motor System, Neuronal Death, Critical Period, Motor Function, Neural pathways, Neurosciences, Brain Diseases, and Recovery of Function
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1. Every segmental ganglion of the leech Hirudo medicinalis contains two serotonergic Retzius cells. However, Retzius cells in the two segmental ganglia associated with reproductive function are morphologically distinct from Retzius cells... more
1. Every segmental ganglion of the leech Hirudo medicinalis contains two serotonergic Retzius cells. However, Retzius cells in the two segmental ganglia associated with reproductive function are morphologically distinct from Retzius cells elsewhere. This suggested that these Retzius cells might be physiologically distinct as well. 2. The degree of electrical coupling between Retzius cells distinguishes the reproductive Retzius cells; all Retzius cells are coupled in a non-rectifying manner, but reproductive Retzius cells are less strongly coupled. 3. Retzius cells in standard ganglia depolarize following swim motor pattern initiation or mechanosensory stimulation while Retzius cells in reproductive ganglia either do not respond or hyperpolarize. 4. In standard Retzius cells the depolarizing response caused by pressure mechanosensory neurons has fixed latency and one-to-one correspondence between the mechanosensory neuron action potentials and Retzius cell EPSPs. However, the latency is longer than for most known monosynaptic connections in the leech. 5. Raising the concentration of divalent cations in the bathing solution to increase thresholds abolishes the mechanosensory neuron-evoked EPSP in standard Retzius cells. This suggests that generation of action potentials in an interneuron is required for production of the EPSP, and therefore that the pathway from mechanosensory neuron to Retzius cell is polysynaptic. 6. P cells in reproductive segments have opposite effects on reproductive Retzius cells and standard Retzius cells in adjacent ganglia. Thus the difference in the pathway from P to Retzius is not localized specifically in the P cell, but elsewhere in the pathway, possibly in the type of receptor expressed by the Retzius cells.
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This review describes our current understanding of the changes in brain function and structure that occur in response to an intensive form of motor rehabilitation, constraint-induced movement therapy (CIMT), that has been shown to be... more
This review describes our current understanding of the changes in brain function and structure that occur in response to an intensive form of motor rehabilitation, constraint-induced movement therapy (CIMT), that has been shown to be efficacious in promoting motor function of the paretic upper limb of stroke patients. Studies using transcranial magnetic stimulation have demonstrated consistently an increase in the size of the representation of paretic hand muscles in the ipsilesional motor cortex after CIMT. This motor map expansion occurs in response to CIMT delivered at all time periods after stroke, from within days to after several years. Functional neuroimaging studies have shown varying patterns of change in activation within the sensorimotor network after CIMT. This variability may depend on the extent of stroke-induced damage to the corticospinal tract, the major descending motor pathway in the brain. This variability may also stem from interacting plastic changes in brain structure occurring in response to CIMT. CIMT is the first well defined poststroke motor rehabilitation to have identified changes in brain function and structure that accompany gains in motor function of the paretic upper limb. However, a causal link between observed changes in brain function/structure and motor gains due to CIMT has not yet been established. There is still much work to be done to understand the relationship between changes in brain function/structure and gains in motor function. Such studies should employ rigorous experimental controls to enable strong conclusions to be drawn regarding the neural effects of CIMT and how those effects confer behavioral efficacy of the therapy.