Dinesh G. Nair

Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients

Objective: Motor recovery after stroke depends on the integrity of ipsilesional motor circuits and interactions between the ipsilesional and contralesional hemispheres. In this sham-controlled randomized trial, we investigated whether noninvasive modulation of regional excitability of bilateral motor cortices in combination with physical and occupational therapy improves motor outcome after stroke. Methods: Twenty chronic stroke patients were randomly assigned to receive 5 consecutive sessions of either 1) bihemispheric transcranial direct current stimulation (tDCS) (anodal tDCS to upregulate excitability of ipsilesional motor cortex and cathodal tDCS to downregulate excitability of contralesional motor cortex) with simultaneous physical/occupational therapy or 2) sham stimulation with simultaneous physical/occupational therapy. Changes in motor impairment (Upper Extremity Fugl-Meyer) and motor activity (Wolf Motor Function Test) assessments were outcome measures while functional imaging parameters were used to identify neural correlates of motor improvement. Results: The improvement of motor function was significantly greater in the real stimulation group (20.7% in Fugl-Meyer and 19.1% in Wolf Motor Function Test scores) when compared to the sham group (3.2% in Fugl-Meyer and 6.0% in Wolf Motor Function Test scores). The effects outlasted the stimulation by at least 1 week. In the real-stimulation group, stronger activation of intact ipsilesional motor regions during paced movements of the affected limb were found postintervention whereas no significant activation changes were seen in the control group. Conclusions: The combination of bihemispheric tDCS and peripheral sensorimotor activities improved motor functions in chronic stroke patients that outlasted the intervention period. This novel approach may potentiate cerebral adaptive processes that facilitate motor recovery after stroke. Classification of evidence: This study provides Class I evidence that for adult patients with ischemic stroke treated at least 5 months after their first and only stroke, bihemispheric tDCS and simultaneous physical/occupational therapy given over 5 consecutive sessions significantly improves motor function as measured by the Upper Extremity Fugl-Meyer assessment (raw change treated 6.1 ± 3.4, sham 1.2 ± 1.0).

Transcranial Direct Current Stimulation in Stroke Recovery

Transcranial direct current stimulation (TDCS) is an emerging technique of noninvasive brain stimulation that has been found useful in examining cortical function in healthy subjects and in facilitating treatments of various neurologic disorders. A better understanding of adaptive and maladaptive poststroke neuroplasticity and its modulation through noninvasive brain stimulation has opened up experimental treatment options using TDCS for patients recovering from stroke. We review the role of TDCS as a facilitator of stroke recovery, the different modes of TDCS, and the potential mechanisms underlying the neural effects of TDCS.

Cortical and cerebellar activity of the human brain during imagined and executed unimanual and bimanual action sequences: a functional MRI study.

The neural (blood oxygenation level dependent) correlates of executed and imagined finger sequences, both unimanual and bimanual, were studied in adult right-handed volunteers using functional magnetic resonance imaging (fMRI) of the entire brain. The finger to thumb opposition tasks each consisted of three conditions, two unimanual and one bimanual. Each experimental condition consisted of overt movement of the fingers in a prescribed sequence and imagery of the same task. An intricate network consisting of sensorimotor cortex, supplementary motor area (SMA), superior parietal lobule and cerebellum was identified when the tasks involved both planning and execution. During imagery alone, however, cerebellar activity was largely absent. This apparent decoupling of sensorimotor cortical and cerebellar areas during imagined movement sequences, suggests that cortico-cerebellar loops are engaged only when action sequences are both intended and realized. In line with recent models of motor control, the cerebellum may monitor cortical output and feed back corrective information to the motor cortex primarily during actual, not imagined, movements. Although parietal cortex activation occurred during both execution and imagery tasks, it was most consistently present during bimanual action sequences. The engagement of the superior parietal lobule appears to be related to the increased attention and memory resources associated, in the present instance, with coordinating difficult bimanual sequences.

Contralateral and ipsilateral motor effects after transcranial direct current stimulation.

Transcranial direct current stimulation over the left motor area influenced both contralateral and ipsilateral finger sequence movements in seven healthy adults. Effects for the two hands were reversed: anodal stimulation improved right-hand performance significantly more than cathodal stimulation, whereas cathodal stimulation improved left-hand performance significantly more than anodal stimulation. The results show that stimulating a motor region directly, or indirectly by modulating activity in the homologous region on the opposite hemisphere, can affect motor skill acquisition, presumably by facilitating effective synaptic connectivity. This outcome provides evidence for the role of interhemispheric inhibition in corticomotor functioning, and also has implications for treatment methods aimed at facilitating motor recovery after stroke.

Optimizing recovery potential through simultaneous occupational therapy and non-invasive brain-stimulation using tDCS

PURPOSE It is thought that following a stroke the contralesional motor region exerts an undue inhibitory influence on the lesional motor region which might limit recovery. Pilot studies have shown that suppressing the contralesional motor region with cathodal transcranial Direct Current Stimulation (tDCS) can induce a short lasting functional benefit; greater and longer lasting effects might be achieved with combining tDCS with simultaneous occupational therapy (OT) and applying this intervention for multiple sessions. METHODS We carried out a randomized, double blind, sham controlled study of chronic stroke patients receiving either 5 consecutive days of cathodal tDCS (for 30 minutes) applied to the contralesional motor region and simultaneous OT, or sham tDCS+OT. RESULTS we showed that cathodal tDCS+OT resulted in significantly more improvement in Range-Of-Motion in multiple joints of the paretic upper extremity and in the Upper-Extremity Fugl-Meyer scores than sham tDCS+OT, and that the effects lasted at least one week post-stimulation. Improvement in motor outcome scores was correlated with decrease in fMRI activation in the contralesional motor region exposed to cathodal stimulation. CONCLUSIONS This suggests that cathodal tDCS combined with OT leads to significant motor improvement after stroke due to a decrease in the inhibitory effect that the contralesional hemisphere exerts onto the lesional hemisphere.

Imaging correlates of motor recovery from cerebral infarction and their physiological significance in well-recovered patients

We studied motor representation in well-recovered stroke patients. Eighteen right-handed stroke patients and eleven age-matched control subjects underwent functional Magnetic Resonance Imaging (fMRI) while performing unimanual index finger (abduction-adduction) and wrist movements (flexion-extension) using their recovered and non-affected hand. A subset of these patients underwent Transcranial Magnetic Stimulation (TMS) to elicit motor evoked potentials (MEP) in the first dorsal interosseous muscle of both hands. Imaging results suggest that good recovery utilizes both ipsi- and contralesional resources, although results differ for wrist and index finger movements. Wrist movements of the recovered arm resulted in significantly greater activation of the contralateral (lesional) and ipsilateral (contralesional) primary sensorimotor cortex (SM1), while comparing patients to control subjects performing the same task. In contrast, recovered index finger movements recruited a larger motor network, including the contralateral SM1, Supplementary Motor Area (SMA) and cerebellum when patients were compared to control subjects. TMS of the lesional hemisphere but not of the contralesional hemisphere induced MEPs in the recovered hand. TMS parameters also revealed greater transcallosal inhibition, from the contralesional to the lesional hemisphere than in the reverse direction. Disinhibition of the contralesional hemisphere observed in a subgroup of our patients suggests persistent alterations in intracortical and transcallosal (interhemispheric) interactions, despite complete functional recovery.

Modulating activity in the motor cortex affects performance for the two hands differently depending upon which hemisphere is stimulated

We modulated neural excitability in the human motor cortex to investigate behavioral effects for both hands. In a previous study, we showed that decreasing excitability in the dominant motor cortex led to a decline in performance for the contralateral hand and an improvement for the ipsilateral hand; increasing excitability produced the opposite effects. Research suggests that the ipsilateral effects were mediated by interhemispheric inhibition. Physiological evidence points to an asymmetry in interhemispheric inhibition between the primary motor cortices, with stronger inhibitory projections coming from the dominant motor cortex. In the present study, we examined whether there is a hemispheric asymmetry in the effects on performance when modulating excitability in the motor cortex. Anodal and cathodal transcranial direct current stimulation were applied to the motor cortex of 17 participants, targeting the non‐dominant hemisphere on one day and the dominant hemisphere on another day, along with one sham session. Participants performed a finger‐sequence coordination task with each hand before and after stimulation. The dependent variable was calculated as the percentage of change in the number of correct keystrokes. We found that the effects of transcranial direct current stimulation depended upon which hemisphere was stimulated; modulating excitability in the dominant motor cortex significantly affected performance for the contralateral and ipsilateral hands, whereas modulating excitability in the non‐dominant motor cortex only had a significant impact for the contralateral hand. These results provide evidence for a hemispheric asymmetry in the ipsilateral effects of modulating excitability in the motor cortex and may be important for clinical research on motor recovery.

Assessing recovery in middle cerebral artery stroke using functional MRI

Primary objective: To understand the temporal evolution of brain reorganization during recovery from stroke. Research design: A patient who suffered left middle cerebral artery stroke 9 months earlier was studied on three occasions, ∼1 month apart. Methods and procedures: Brain activation was studied using functional Magnetic Resonance Imaging (fMRI). During each session, the patient performed a finger-to-thumb opposition task, which involved one bimanual and two unimanual conditions. Each condition consisted of overt movement of fingers and imagery of the same task. Results: With recovery, greater recruitment was observed of the affected primary motor cortex (M1) and a decrease in activation of the unaffected M1 and supplementary motor area. In addition, the widespread activation of brain areas seen during the initial session changed to a more focused pattern of activation as the patient recovered. Imagery tasks resulted in similar brain activity as overt execution pointing to imagery as a potential tool for rehabilitation.

Dorsal column mapping via phase reversal method: the refined technique and clinical applications.

BACKGROUND Safe resection of intramedullary spinal cord tumors can be challenging, because they often alter the cord anatomy. Identification of neurophysiologically viable dorsal columns (DCs) and of neurophysiologically inert tissue, eg, median raphe (MR), as a safe incision site is crucial for avoiding postoperative neurological deficits. We present our experience with and improvements made to our previously described technique of DC mapping, successfully applied in a series of 12 cases. OBJECTIVE To describe a new, safe, and reliable technique for intraoperative DC mapping. METHODS The right and left DCs were stimulated by using a bipolar electric stimulator and the triggered somatosensory evoked potentials recorded from the scalp. Phase reversal and amplitude changes of somatosensory evoked potentials were used to neurophysiologically identify the laterality of DCs, the inert MR, as well as other safe incision sites. RESULTS The MR location was neurophysiologically confirmed in all patients in whom this structure was first visually identified as well as in those in whom it was not, with 1 exception. DCs were identified in all patients, regardless of whether they could be visually identified. In 3 cases, negative mapping with the use of this method enabled the surgeon to reliably identify additional inert tissue for incision. None of the patients had postoperative worsening of the DC function. CONCLUSION Our revised technique is safe and reliable, and it can be easily incorporated into routine intramedullary spinal cord tumor resection. It provides crucial information to the neurosurgeon to prevent postoperative neurological deficits.

Intraoperative somatosensory evoked potential monitoring decreases EEG burst suppression ratio during deep general anesthesia.

Purpose: The burst suppression (BS) EEG patterns induced by general anesthesia can react to somatosensory stimuli. We investigated this reactivity by studying the effect of peripheral nerve stimulation used for routine intraoperative spinal cord monitoring by somatosensory evoked potentials on BS patterns. Methods: The relative time spent in suppression expressed as BS ratio (BSR) and mean burst duration were measured before (BSRPre), during (BSRStim), and after (BSRPost) a 60-second repetitive electrical ulnar nerve stimulation in nine patients under total intravenous general anesthesia with propofol. The BS reactivity was measured as BSRPre-BSRStim. Results: Overall, 27 trials were included with BSRPre up to 77%, indistinguishable from BSRPost. During stimulation, the mean BSR transiently decreased from 42% to 35%. For each 1% increase in BSRPre, the BS reactivity increased with 0.6%, whereas the burst duration remained approximately 3 seconds. For BSRPre below 30%, the BS reactivity was negligible. Conclusions: Data from this study show that somatosensory input can evoke bursts, altering the “spontaneous” deep BS patterns (BSRPre >30%). Further studies are necessary to objectively assess the clinical relevance of stimulus-induced BS reactivity during deep general anesthesia.