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Biomedical subjects

Bruce H Dobkin

Publications and source records attributed to Bruce H Dobkin.

At least 19 recordsLinked to original sources

Brain-computer interface technology as a tool to augment plasticity and outcomes for neurological rehabilitation.

Brain-computer interfaces (BCIs) are a rehabilitation tool for tetraplegic patients that aim to improve quality of life by augmenting communication, control of the environment, and self-care. The neurobiology of both rehabilitation and BCI control depends upon learning to modify the efficacy of spared neural ensembles that represent movement, sensation and cognition through progressive practice with feedback and reward. To serve patients, BCI systems must become safe, reliable, cosmetically acceptable, quickly mastered with minimal ongoing technical support, and highly accurate even in the face of mental distractions and the uncontrolled environment beyond a laboratory. BCI technologies may raise ethical concerns if their availability affects the decisions of patients who become locked-in with brain stem stroke or amyotrophic lateral sclerosis to be sustained with ventilator support. If BCI technology becomes flexible and affordable, volitional control of cortical signals could be employed for the rehabilitation of motor and cognitive impairments in hemiplegic or paraplegic patients by offering on-line feedback about cortical activity associated with mental practice, motor intention, and other neural recruitment strategies during progressive task-oriented practice. Clinical trials with measures of quality of life will be necessary to demonstrate the value of near-term and future BCI applications.

Brain↗

Motor cortex activation during treatment may predict therapeutic gains in paretic hand function after stroke.

BACKGROUND AND PURPOSE: Functional brain imaging after stroke offers insight into motor network adaptations. This exploratory study examined whether motor cortical activation captured during arm-focused therapy can predict paretic hand functional gains. METHODS: Eight hemiparetic patients had serial functional MRI (fMRI) while performing a pinch task before, midway, and after 2 weeks of constraint-induced therapy. The Wolf Motor Function Test (WMFT) was performed before and after intervention. RESULTS: There was a linear reduction in ipsilateral (contralesional) primary motor (M1) activation (voxel counts) across time. The midpoint M1 Laterality Index anticipated post-therapeutic change in time to perform the WMFT. The change in ipsilateral M1 voxel count (pre- to mid-) correlated with the change in mean WMFT time (pre- to post-). CONCLUSIONS: The relationship between brain activation during treatment and functional gains suggests a use for serial fMRI in predicting the success and optimal duration for a focused therapeutic intervention.

Aged↗

Short-distance walking speed and timed walking distance: redundant measures for clinical trials?

The velocity of a 15-meter walk and walking endurance (distance covered in 6 minutes) are considered distinct outcomes in clinical trials of stroke rehabilitation. Comfortable velocities used for each task in 24 subjects with chronic hemiparesis were not significantly different, however. Although speed and endurance did not reflect different domains of efficacy in outpatients whose usual speed was >0.5 m/s, the fastest feasible 15-meter velocity augmented these measures.

Clinical Trials as Topic↗

Cellular transplants in China: observational study from the largest human experiment in chronic spinal cord injury.

BACKGROUND: In China, fetal brain tissue has been transplanted into the lesions of more than 400 patients with spinal cord injury (SCI). Anecdotal reports have been the only basis for assuming that the procedure is safe and effective. OBJECTIVE: To compare available reports to the experiences and objective findings of patients who received pre-operative and postoperative assessments before and up to 1 year after receiving cellular implants. METHODS: Independent observational study of 7 chronic SCI subjects undergoing surgery by Dr Hongyun Huang in Beijing. Assessments included lesion location by magnetic resonance imaging, protocol of the American Spinal Injury Association (ASIA), change in disability, and detailed history of the perioperative course. RESULTS: Inclusion and exclusion criteria were not clearly defined, as subjects with myelopathies graded ASIA A through D and of diverse causes were eligible. Cell injection sites did not always correlate with the level of injury and included the frontal lobes of a subject with a high cervical lesion. Complications, including meningitis, occurred in 5 subjects. Transient postoperative hypotonicity may have accounted for some physical changes. No clinically useful sensorimotor, disability, or autonomic improvements were found. CONCLUSIONS: The phenotype and the fate of the transplanted cells, described as olfactory ensheathing cells, are unknown. Perioperative morbidity and lack of functional benefit were identified as the most serious clinical shortcomings. The procedures observed did not attempt to meet international standards for either a safety or efficacy trial. In the absence of a valid clinical trials protocol, physicians should not recommend this procedure to patients.

Aborted Fetus↗

Reliability and validity of bilateral thigh and foot accelerometry measures of walking in healthy and hemiparetic subjects.

OBJECTIVE: Measures of walking ability in large clinical trials are usually limited to a timed short-distance walk and the distance walked in a fixed time. A new integrated system of 5 accelerometers was tested for reliability and compared to a footswitch system to determine if the accelerometers offered a practical option for the acquisition of spatiotemporal gait parameters. METHODS: Leg accelerations and decelerations were defined in relation to simultaneous kinematic and electromyographic data acquired from a healthy subject. Eight healthy adults and 6 independent ambulators with hemiparetic stroke walked 15 m at 2 different speeds wearing both the accelerometers and footswitches. Twelve healthy subjects walked at 5 different speeds repeated 3 times on each of 2 days wearing the accelerometers. Walking speed, cadence, stride length, and single- and double-limb support, swing, and stance times were calculated. RESULTS: No differences (t test, P > 0.2) were found between footswitch and accelerometer variables when comparing all left or right legs in healthy subjects and all paretic or unaffected legs in stroke subjects. A 2-way nested ANOVA model (speed, left and right legs, trial, and session) with the accelerometers at walking speeds from 0.5 to 1.8 m/s revealed high reproducibility of all measures. CONCLUSIONS: The accelerometry system provided reliable and valid spatiotemporal measures of gait for the upper range of speeds likely to be targeted for rehabilitation interventions in ambulatory subjects.

Acceleration↗

Underappreciated statin-induced myopathic weakness causes disability.

INTRODUCTION: Myopathic syndromes induced by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) include muscle complaints, myalgia, myositis, and rhabdomyolysis. No prospective study of statins, however, included tests of strength, so the incidence of weakness, with or without muscle symptoms and elevated enzymes, is unknown, and perhaps overlooked. METHODS: From a convenience sample of patients referred to an outpatient neurorehabilitation clinic over the course of 1 year, 8 patients with hemiparetic stroke and 10 patients with other presumed neurologic diseases presented with new difficulty walking by 3 to 12 months after starting one of 3 statins. They reported no myalgias, exercise-induced aches, or weakness. Examination revealed proximal paresis graded 4/5 on the unaffected side in the hemiparetic patients and symmetrical bilateral proximal limb and neck flexor weakness graded 4/5 in the others. They stood up with difficulty and walked with bilateral hip drop and imbalance on turns. RESULTS: Laboratory tests did not reveal myositis or other causes for paresis. No improvement in strength or mobility was found 6 weeks after initiating resistance exercises. The statin agent was stopped. By 3 months off statin, all recovered 5/5 proximal strength. Walking improved, and they arose from a chair without pushing off with their arms. DISCUSSION: Serial manual muscle testing after initiating a statin may detect a reversible cause of disability. A genetic predisposition to statin-induced myopathic proximal weakness with normal creatine kinase is consistent with a continuum of previously reported symptoms and signs but may be underappreciated.

Aged↗

Rehabilitation and functional neuroimaging dose-response trajectories for clinical trials.

BACKGROUND: In clinical trials, behavioral outcomes and physiological measures of activity-dependent plasticity that evolve with task-oriented therapies may fail to reach statistical significance. When significant, clinical effectiveness may not be robust enough to alter professional practices. OBJECTIVE: Provide the conceptual basis for a research design to optimize the effect of an experimental treatment. METHODS: Literature review. RESULTS: Research designs usually do not take into consideration the dynamic state of each subject's potential responsiveness to an intervention. Providing a rational, rather than convenient, intensity and duration of therapy may remedy this potential confounder for clinical trials. To determine whether a most effective dose of a therapy exists, investigators could assess subjects before the intervention, administer interim measures at planned intervals, and continue the intervention until the primary behavioral outcomes or functional imaging parameters or both reach a plateau for at least 15 h of additional treatment. CONCLUSION: Promising interventions ought to be continued in phase II/III trials until subjects reach an asymptote in the primary outcome for behavioral gains. For neuroimaging studies that aim to correlate brain-behavior measures during rehabilitation, the specific intervention should also continue until behavioral gains and cerebral adaptations have attained a persistent plateau. Future trials can investigate whether functional neuroimaging performed in parallel with repeated behavioral assessments can better inform researchers about the optimal duration of an experimental therapy and a subject's maximal capacity for intervention-induced cerebral reorganization.

Brain↗

Ankle dorsiflexion as an fMRI paradigm to assay motor control for walking during rehabilitation.

The ability to walk independently with the velocity and endurance that permit home and community activities is a highly regarded goal for neurological rehabilitation after stroke. This pilot study explored a functional magnetic resonance imaging (fMRI) activation paradigm for its ability to reflect phases of motor learning over the course of locomotor rehabilitation-mediated functional gains. Ankle dorsiflexion is an important kinematic aspect of the swing and initial stance phase of the gait cycle. The motor control of dorsiflexion depends in part on descending input from primary motor cortex. Thus, an fMRI activation paradigm using voluntary ankle dorsiflexion has face validity for the serial study of walking-related interventions. Healthy control subjects consistently engaged contralateral primary sensorimotor cortex (S1M1), supplementary motor area (SMA), premotor (PM) and cingulate motor (CMA) cortices, and ipsilateral cerebellum. Four adults with chronic hemiparetic stroke evolved practice-induced representational plasticity associated with gains in speed, endurance, motor control, and kinematics for walking. For example, an initial increase in activation within the thoracolumbar muscle representation of S1M1 in these subjects was followed by more focused activity toward the foot representation with additional pulses of training. Contralateral CMA and the secondary sensory area also reflected change with practice and gains. We demonstrate that the supraspinal sensorimotor network for the neural control of walking can be assessed indirectly by ankle dorsiflexion. The ankle paradigm may serve as an ongoing physiological assay of the optimal type, duration, and intensity of rehabilitative gait training.

Adult↗

Strategies for stroke rehabilitation.

Rehabilitation after hemiplegic stroke has typically relied on the training of patients in compensatory strategies. The translation of neuroscientific research into care has led to new approaches and renewed promise for better outcomes. Improved motor control can progress with task-specific training incorporating increased use of proximal and distal movements during intensive practice of real-world activities. Functional gains are incorrectly said to plateau by 3-6 months. Many patients retain latent sensorimotor function that can be realised any time after stroke with a pulse of goal-directed therapy. The amount of practice probably best determines gains for a given level of residual movement ability. Clinicians should encourage patients to build greater strength, speed, endurance, and precision of multijoint movements on tasks that increase independence and enrich daily activity. Imaging tools may help clinicians determine the capacity of residual networks to respond to a therapeutic approach and help establish optimal dose-response curves for training. Promising adjunct approaches include practice with robotic devices or in a virtual environment, electrical stimulation to increase cortical excitability during training, and drugs to optimise molecular mechanisms for learning. Biological strategies for neural repair may augment rehabilitation in the next decade.

Arm↗

Basic advances and new avenues in therapy of spinal cord injury.

The prospects for successful clinical trials of neuroprotective and neurorestorative interventions for patients with acute and chronic myelopathies depend on preclinical animal models of injury and repair that reflect the human condition. Remarkable progress continues in the attempt to promote connections between the brain and the sensory and motor neurons below a spinal cord lesion. Recent experiments demonstrate the potential for biological therapies to regenerate or remyelinate axons and to incorporate new neural cells into the milieu of a traumatic spinal cord injury. The computational flexibility and plasticity of the sensorimotor systems of the brain, spinal cord, and motor unit make functional use of new circuitry feasible in patients. To incorporate residual and new pathways, neural repair strategies must be coupled to rehabilitation therapies that drive activity-dependent plasticity for walking, for reaching and grasping, and for bowel and bladder control. Prevention of pain and dysautonomia are also clinical targets. Research aims to define the temporal windows of opportunity for interventions, test the safety and efficacy of delivery systems of agents and cells, and provide a better understanding of the cascades of gene expression and cell interactions both acutely and chronically after injury. These bench-to-bedside studies are defining the neurobiology of spinal cord injury rehabilitation.

Animals↗

Immediate and long-term changes in corticomotor output in response to rehabilitation: correlation with functional improvements in chronic stroke.

The goal of this study was to determine whether transcranial magnetic stimulation (TMS) measures of the corticomotor pathways might reflect and predict functional improvements during rehabilitation of a hemiparetic upper extremity. Ten patients with variable levels of functional impairment in upper extremity use were enrolled at least 3 months after a stroke. TMS was used to obtain serial measures of motor thresholds and motor-evoked potential (MEP) size for a muscle from both hands before and after each session of an intervention aimed at improving functional motor control. Functional ability and cortical map area and volume were measured before each therapy session. At intake, all TMS measures from the affected side were impaired compared with the unaffected side but they did not reliably predict the level of functional improvement. Motor thresholds decreased, whereas MEP amplitude and map size increased with treatment. The amount of change in affected side measures was correlated with the amount of improvement in hand/arm function. Normalization of MEP amplitude asymmetry in response to the 1st 2 therapy sessions predicted long-term improvement in Fugl-Meyer motor score. Within limits, TMS appears to be useful in both moderate and more impaired patients as a physiological assay of treatment-induced plasticity and behavioral gains. Methodological differences in the literature, however, currently obscure a full understanding of the potential contributions of TMS to rehabilitation research.

Adult↗

Neurobiology of rehabilitation.

Rehabilitation aims to lessen the physical and cognitive impairments and disabilities of patients with stroke, multiple sclerosis, spinal cord or brain injury, and other neurologic diseases. Conventional approaches beyond compensatory adjustments to disability may be augmented by applying some of the myriad experimental results about mechanisms of intrinsic biological changes after injury and the effects of extrinsic manipulations on spared neuronal assemblies. The organization and inherent adaptability of the anatomical nodes within distributed pathways of the central nervous system offer a flexible substrate for treatment strategies that drive activity-dependent plasticity. Opportunities for a new generation of approaches are manifested by rodent and non-human primate studies that reveal morphologic and physiologic adaptations induced by injury, by learning-associated practice, by the effects of pharmacologic neuromodulators, by the behavioral and molecular bases for enhancing activity-dependent synaptic plasticity, and by cell replacement, gene therapy, and regenerative biologic strategies. Techniques such as functional magnetic resonance imaging and transcranial magnetic stimulation will help determine the most optimal physiologic effects of interventions in patients as the cortical representations for skilled movements and cognitive processes are modified by the combination of conventional and biologic therapies. As clinicians digest the finer details of the neurobiology of rehabilitation, they will translate laboratory data into controlled clinical trials. By determining how much they can influence neural reorganization, clinicians will extend the opportunities for neurorestoration.

Animals↗