Avrielle Rykman

Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke.

PURPOSE Anodal transcranial direct current stimulation (tDCS) can transiently increase corticomotor excitability of intrinsic hand muscles and improve upper limb function in patients with chronic stroke. As a preliminary study, we tested whether increased corticomotor excitability would be similarly observed in muscles acting about the wrist, and remain present during robotic training involving active wrist movements, in six chronic stroke patients with residual motor deficit. METHODS Transcranial magnetic stimulation (TMS) generated motor evoked potentials (MEP) in the flexor carpi radialis (FCR) and provided a measure of corticomotor excitability and short-interval cortical inhibition (SICI) before and immediately after a period of tDCS (1 mA, 20 min, anode and TMS applied to the lesioned hemisphere), and robotic wrist training (1hr). RESULTS Following tDCS, the same TMS current strength evoked an increased MEP amplitude (mean 168 +/- 22%SEM; p < 0.05), that remained increased after robot training (166 +/- 23%; p < 0.05). Conditioned MEPs were of significantly lower amplitude relative to unconditioned MEPs prior to tDCS (62 +/- 6%, p < 0.05), but not after tDCS (89 +/- 14%, p = 0.40), or robot training (91 +/- 8%, p = 0.28), suggesting that the increased corticomotor excitability is associated with reduced intracortical inhibition. CONCLUSION The persistence of these effects after robotic motor training, indicates that a motor learning and retraining program can co-exist with tDCS-induced changes in cortical motor excitability, and supports the concept of combining brain stimulation with physical therapy to promote recovery after brain injury.

Robotic devices as therapeutic and diagnostic tools for stroke recovery.

The understanding that recovery of brain function after stroke is imperfect has prompted decades of effort to engender speedier and better recovery through environmental manipulation. Clinical evidence has shown that the performance plateau exhibited by patients with chronic stroke, usually signaling an end of standard rehabilitation, might represent a period of consolidation rather than a performance optimum. These results highlight the difficulty of translating pertinent neurological data into pragmatic changes in clinical programs. This opinion piece focuses on upper limb impairment reduction after robotic training. We propose that robotic devices be considered as novel tools that might be used alone or in combination with novel pharmacology and other bioengineered devices. Additionally, robotic devices can measure motor performance objectively and will contribute to a detailed phenotype of stroke recovery.

Robotic Measurement of Arm Movements After Stroke Establishes Biomarkers of Motor Recovery

Background and Purpose— Because robotic devices record the kinematics and kinetics of human movements with high resolution, we hypothesized that robotic measures collected longitudinally in patients after stroke would bear a significant relationship to standard clinical outcome measures and, therefore, might provide superior biomarkers. Methods— In patients with moderate-to-severe acute ischemic stroke, we used clinical scales and robotic devices to measure arm movement 7, 14, 21, 30, and 90 days after the event at 2 clinical sites. The robots are interactive devices that measure speed, position, and force so that calculated kinematic and kinetic parameters could be compared with clinical assessments. Results— Among 208 patients, robotic measures predicted well the clinical measures (cross-validated R2 of modified Rankin scale=0.60; National Institutes of Health Stroke Scale=0.63; Fugl-Meyer=0.73; Motor Power=0.75). When suitably scaled and combined by an artificial neural network, the robotic measures demonstrated greater sensitivity in measuring the recovery of patients from day 7 to day 90 (increased standardized effect=1.47). Conclusions— These results demonstrate that robotic measures of motor performance will more than adequately capture outcome, and the altered effect size will reduce the required sample size. Reducing sample size will likely improve study efficiency.

Transcranial direct current stimulation (tDCS) and robotic practice in chronic stroke: the dimension of timing.

BACKGROUND Combining tDCS with robotic therapy is a new and promising form of neurorehabilitation after stroke, however the effectiveness of this approach is likely to be influenced by the relative timing of the brain stimulation and the therapy. OBJECTIVE To measure the kinematic and neurophysiological effects of delivering tDCS before, during and after a single session of robotic motor practice (wrist extension). METHODS We used a within-subjects repeated-measurement design in 12 chronic (>6 months) stroke survivors. Twenty minutes of anodal tDCS was delivered to the affected hemisphere before, during, or after a 20-minute session of robotic practice. Sham tDCS was also applied during motor practice. Robotic motor performance and corticomotor excitability, assessed through transcranial magnetic stimulation (TMS), were evaluated pre- and post-intervention. RESULTS Movement speed was increased after motor training (sham tDCS) by ∼20%. Movement smoothness was improved when tDCS was delivered before motor practice (∼15%). TDCS delivered during practice did not offer any benefit, whereas it reduced speed when delivered after practice (∼10%). MEPs were present in ∼50% of patients at baseline; in these subjects motor practice increased corticomotor excitability to the trained muscle. CONCLUSIONS In a cohort of stroke survivors, motor performance kinematics improved when tDCS was delivered prior to robotic training, but not when delivered during or after training. The temporal relationship between non-invasive brain stimulation and neurorehabilitation is important in determining the efficacy and outcome of this combined therapy.

Preserved corticospinal conduction without voluntary movement after spinal cord injury

Study design:Case report.Objectives:To identify preserved corticomotor connection in chronic spinal cord injury (SCI) in the absence of clinically observable movement.Setting:Rehabilitation Hospital and Medical Research Institute, NY, USA.Methods:The motor-evoked potential (MEP) response to transcranial magnetic stimulation (TMS) was recorded using surface electromyography from the right biceps brachii, extersor carpi radialis (ECR), flexor carpi radialis (FCR) and abductor pollicis brevis (APB) muscles in a 31-year-old male traumatic SCI chronic patient—ASIA B, injury level C5. Motor power scores were additionally obtained from a clinician blinded to the results of TMS.Results:TMS could consistently elicit MEPs of normal latency, phase and amplitude, in the severely affected ECR muscle but not the similarly affected FCR muscle. The response in proximal and unaffected biceps muscle was larger than the healthy subject, whereas no response was obtained in the distal APB muscle as expected.Conclusion:TMS can identify residual pathways not apparent from clinical assessment alone, which may have prescriptive value for rehabilitation.

Improved motor performance in chronic spinal cord injury following upper-limb robotic training

BACKGROUND Recovering upper-limb motor function has important implications for improving independence of patients with tetraplegia after traumatic spinal cord injury (SCI). OBJECTIVE To evaluate the feasibility, safety and effectiveness of robotic-assisted training of upper limb in a chronic SCI population. METHODS A total of 10 chronic tetraplegic SCI patients (C4 to C6 level of injury, American Spinal Injury Association Impairment Scale, A to D) participated in a 6-week wrist-robot training protocol (1 hour/day 3 times/week). The following outcome measures were recorded at baseline and after the robotic training: a) motor performance, assessed by robot-measured kinematics, b) corticospinal excitability measured by transcranial magnetic stimulation (TMS), and c) changes in clinical scales: motor strength (Upper extremity motor score), pain level (Visual Analog Scale) and spasticity (Modified Ashworth scale). RESULTS No adverse effects were observed during or after the robotic training. Statistically significant improvements were found in motor performance kinematics: aim (pre 1.17 ± 0.11 raduans, post 1.03 ± 0.08 raduans, p = 0.03) and smoothness of movement (pre 0.26 ± 0.03, post 0.31 ± 0.02, p = 0.03). These changes were not accompanied by changes in upper-extremity muscle strength or corticospinal excitability. No changes in pain or spasticity were found. CONCLUSIONS Robotic-assisted training of the upper limb over six weeks is a feasible and safe intervention that can enhance movement kinematics without negatively affecting pain or spasticity in chronic SCI. In addition, robot-assisted devices are an excellent tool to quantify motor performance (kinematics) and can be used to sensitively measure changes after a given rehabilitative intervention.

Predicting efficacy of robot-aided rehabilitation in chronic stroke patients using an MRI-compatible robotic device

We are investigating the neural correlates of motor recovery promoted by robot-mediated therapy in chronic stroke. This pilot study asked whether efficacy of robot-aided motor rehabilitation in chronic stroke could be predicted by a change in functional connectivity within the sensorimotor network in response to a bout of motor rehabilitation. To address this question, two stroke patients participated in a functional connectivity MRI study pre and post a 12-week robot-aided motor rehabilitation program. Functional connectivity was evaluated during three consecutive scans before the rehabilitation program: resting-state; point-to-point reaching movements executed by the paretic upper extremity (UE) using a newly developed MRI-compatible sensorized passive manipulandum; resting-state. A single resting-state scan was conducted after the rehabilitation program. Before the program, UE movement reduced functional connectivity between the ipsilesional and contralesional primary motor cortex. Reduced interhemispheric functional connectivity persisted during the second resting-state scan relative to the first and during the resting-state scan after the rehabilitation program. Greater reduction in interhemispheric functional connectivity during the resting-state was associated with greater gains in UE motor function induced by the 12-week robotic therapy program. These findings suggest that greater reduction in interhemispheric functional connectivity in response to a bout of motor rehabilitation may predict greater efficacy of the full rehabilitation program.

Stroke subtype and motor impairment influence contralesional excitability

Objective: The nonlesioned motor cortex (M1NL) is thought to be hyperexcitable in patients with subacute or chronic stroke and offers a promising therapeutic target. However, whether M1NL excitability behaves the same for subcortical and cortical strokes is unknown. The aim of the present study was to determine whether cortical, or purely subcortical, strokes have a different effect on M1NL excitability. Methods: We looked for correlations between the Fugl-Meyer (FM) score and M1NL resting motor threshold (RMTNL) in 34 stroke survivors classified according to lesion location (cortico-subcortical or purely subcortical). In addition to the FM, the Wolf Motor Score and motor power were measured. Results: FM correlated with RMTNL for subcortical (r = 0.82; p = 0.001) but not for cortical strokes (r = 0.11; p = 0.62). Likewise, Wolf Motor Score (r = −0.62; p = 0.03) and motor power (r = 0.64; p = 0.023) were correlated with RMTNL for the subcortical group, but not for the cortical group. Conclusion: We show that the impact on M1NL depends on lesion location and conclude that protocols aimed at reducing M1NL cortical excitability may be worth exploring for subcortical but not for cortical stroke.

The Epigenetics of Stroke Recovery and Rehabilitation: From Polycomb to Histone Deacetylases

Classical de-afferentation studies, as well as experience-dependent visual plasticity paradigms, have confirmed that both the developing and adult nervous system are capable of unexpected levels of plasticity. This capacity is underscored by the significant spontaneous recovery that can occur in patients with mild-to-moderate impairment following stroke. An evolving model is that an interaction of biological and environmental factors during all epochs post-stroke influences the extent and quality of this plasticity. Here, we discuss data that have implicated specific epigenetic proteins as integrators of environmental influences in 3 aspects of stroke recovery: spontaneous impairment reduction in humans; peri-infarct rewiring in animals as a paradigm for developing therapeutically-driven impairment reduction beyond natural spontaneous recovery; and, finally, classical hippocampal learning and memory paradigms that are theoretically important in skill acquisition for both impairment reduction and compensatory strategies in the rehabilitation setting. Our discussion focuses primarily on B lymphoma Mo-MLV1 insertion region proteins of the polycomb repressive complex, alpha thalassemia/mental retardation syndrome X-linked chromatin remodeling factors, and the best known and most dynamic gene repressors, histone deacetylases. We will highlight exciting current data associated with these proteins and provide promising speculation about how they can be manipulated by drugs, biologics, or noninvasive stimulation for stroke recovery.

The corticomotor projection to liminally-contractable forearm muscles in chronic spinal cord injury: a transcranial magnetic stimulation study

Study design:A cross-sectional study in chronic spinal cord injury with cervical lesions (cSCI).Objective:To determine the corticomotor projection and motor cortex organization of paralyzed forearm muscles that presented only liminal voluntary activation.Setting:Burke Medical Research Institute, White Plains, NY, USA.Methods:We identified ten people with chronic SCI who had a wrist flexor or extensor muscle with a motor power (MP) of 1 over 5. We recorded motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) over the primary motor cortex of the hemisphere contralateral to the target muscle. We measured resting motor threshold (RMT), corticomotor latency (LTY), MEP amplitude (AMP) and performed cortical motor mapping to determine the optimal site (OPT) and map area (AREA). Results were compared with the data from 18 controls.Results:A MEP in the target muscle was observed for all cSCI cases. LTY was normal, while corticomotor excitability (as determined by RMT and AMP) was reduced in about half of the group. The OPT site of the motor maps was within control range for all cSCI cases, while AREA was reduced in three cases.Conclusions:Corticomotor conduction and cortical topography were appreciably normal despite only liminal activation of the target muscle with voluntary effort. Muscles with these characteristics may benefit from a targeted rehabilitation program even in the chronic phase after SCI.