Association between aphasia severity and brain network alterations after stroke assessed using the electroencephalographic phase synchrony index.

Electroencephalographic synchrony can help assess brain network status; however, its usefulness has not yet been fully proven. We developed a clinically feasible method that combines the phase synchrony index (PSI) with resting-state 19-channel electroencephalography (EEG) to evaluate post-stroke motor impairment. In this study, we investigated whether our method could be applied to aphasia, a common post-stroke cognitive impairment. This study included 31 patients with subacute aphasia and 24 healthy controls. We assessed the expressive function of patients and calculated the PSIs of three motor language-related regions: frontofrontal, left frontotemporal, and right frontotemporal. Then, we evaluated post-stroke network alterations by comparing PSIs of the patients and controls and by analyzing the correlations between PSIs and aphasia scores. The frontofrontal PSI (beta band) was lower in patients than in controls and positively correlated with aphasia scores, whereas the right frontotemporal PSI (delta band) was higher in patients than in controls and negatively correlated with aphasia scores. Evaluation of artifacts suggests that this association is attributed to true synchrony rather than spurious synchrony. These findings suggest that post-stroke aphasia is associated with alternations of two different networks and point to the usefulness of EEG PSI in understanding the pathophysiology of aphasia.

Electroencephalographic Phase Synchrony Index as a Biomarker of Poststroke Motor Impairment and Recovery.

Background. Motor recovery after stroke is of great clinical interest. Besides magnetic resonance imaging functional connectivity, electroencephalographic synchrony is also an available biomarker. However, the clinical relevance of electroencephalographic synchrony in hemiparesis has not been fully understood. Objective. We aimed to demonstrate the usefulness of the phase synchrony index (PSI) by showing associations between the PSI and poststroke outcome in patients with hemiparesis. Methods. This observational study included 40 participants with cortical ischemic stroke (aged 69.8 ± 13.8 years) and 22 healthy controls (aged 66.9 ± 6.5 years). Nineteen-channel electroencephalography was recorded at 36.9 ± 11.8 days poststroke. Upper extremity Fugl-Meyer scores were assessed at the time of admission/before discharge (FM-UE1/FM-UE2; 32.6 ± 12.3/121.0 ± 44.7 days poststroke). Then, correlations between the PSIs and FM-UE1 as well as impairment reduction after rehabilitation (FM-UEgain) were analyzed. Results. The interhemispheric PSI (alpha band) between the primary motor areas (M1s) was lower in patients than in controls and was selectively correlated with FM-UE1 (P = .001). In contrast, the PSI (theta band) centered on the contralesional M1 was higher in patients than in controls and was selectively correlated with FM-UEgain (P = .003). These correlations remained significant after adjusting for confounding factors (age, time poststroke, National Institute of Health Stroke Scale, and lesion volume). Furthermore, the latter correlation was significant in severely impaired patients (FM-UE1 ≤ 10). Conclusions. This study showed that the PSIs were selectively correlated with motor impairment and recovery. Therefore, the PSIs may be potential biomarkers in persons with a hemispheric infarction.

Neurofeedback-induced facilitation of the supplementary motor area affects postural stability.

Near-infrared spectroscopy-mediated neurofeedback (NIRS-NFB) is a promising therapeutic intervention for patients with neurological diseases. Studies have shown that NIRS-NFB can facilitate task-related cortical activation and induce task-specific behavioral changes. These findings indicate that the effect of neuromodulation depends on local cortical function. However, when the target cortical region has multiple functions, our understanding of the effects is less clear. This is true in the supplementary motor area (SMA), which is involved both in postural control and upper-limb movement. To address this issue, we investigated the facilitatory effect of NIRS SMA neurofeedback on cortical activity and behavior, without any specific task. Twenty healthy individuals participated in real and sham neurofeedback. Balance and hand dexterity were assessed before and after each NIRS-NFB session. We found a significant interaction between assessment periods (pre/post) and condition (real/sham) with respect to balance as assessed by the center of the pressure path length but not for hand dexterity as assessed by the 9-hole peg test. SMA activity only increased during real neurofeedback. Our findings indicate that NIRS-NFB itself has the potential to modulate focal cortical activation, and we suggest that it be considered a therapy to facilitate the SMA for patients with postural impairment.

Large-Scale Phase Synchrony Reflects Clinical Status After Stroke: An EEG Study.

BACKGROUND AND PURPOSE: Stroke-induced focal brain lesions often exert remote effects via residual neural network activity. Electroencephalographic (EEG) techniques can assess neural network modifications after brain damage. Recently, EEG phase synchrony analyses have shown associations between the level of large-scale phase synchrony of brain activity and clinical symptoms; however, few reports have assessed such associations in stroke patients. OBJECTIVE: The aim of this study was to investigate the clinical relevance of hemispheric phase synchrony in stroke patients by calculating its correlation with clinical status. METHODS: This cross-sectional study included 19 patients with post-acute ischemic stroke admitted for inpatient rehabilitation. Interhemispheric phase synchrony indices (IH-PSIs) were computed in 2 frequency bands (alpha [α], and beta [ß]), and associations between indices and scores of the Functional Independence Measure (FIM), the National Institutes of Health Stroke Scale (NIHSS), and the Fugl-Meyer Motor Assessment (FMA) were analyzed. For further assessments of IH-PSIs, ipsilesional intrahemispheric PSIs (IntraH-PSIs) as well as IH- and IntraH-phase lag indices (PLIs) were also evaluated. RESULTS: IH-PSIs correlated significantly with FIM scores and NIHSS scores. In contrast, IH-PSIs did not correlate with FMA scores. IntraH-PSIs correlate with FIM scores after removal of the outlier. The results of analysis with PLIs were consistent with IH-PSIs. CONCLUSIONS: The PSIs correlated with performance on the activities of daily living scale but not with scores on a pure motor impairment scale. These results suggest that large-scale phase synchrony represented by IH-PSIs provides a novel surrogate marker for clinical status after stroke.

Cortical changes underlying balance recovery in patients with hemiplegic stroke.

Balance problems are a major sequelae of stroke and are implicated in poor recovery of activities of daily living. In a cross-sectional study, using 50-channel event-related functional near-infrared spectroscopy we previously reported a significant correlation between individual balance ability after stroke and postural perturbation-related cortical activation in the supplementary motor area (SMA) and the prefrontal cortex. However, the neural mechanisms underlying balance recovery after stroke remain unclear. Herein, we examined the cortical involvement in balance recovery after stroke by determining longitudinal regional cortical activation changes in patients with hemiplegic stroke. Twenty patients with subcortical stroke admitted to our hospital for post-acute inpatient rehabilitation participated in this study. Before and after intensive inpatient physical and occupational therapy rehabilitation, we evaluated cortical activation associated with external postural perturbations induced by combined brisk forward and backward movement on a platform. Postural perturbation-related cortical activation in the SMA of the affected and unaffected hemispheres was significantly increased after intensive rehabilitation. The increment of the postural-perturbation-related oxygenated hemoglobin signals in the SMA of the unaffected hemisphere was significantly correlated with the gain in balance function measured by the Berg Balance Scale. These findings support the conclusion that the SMA plays an important role in postural balance control, and suggest that the SMA is a crucial area for balance recovery after hemiplegic stroke.

Near-infrared spectroscopy-mediated neurofeedback enhances efficacy of motor imagery-based training in poststroke victims: a pilot study.

BACKGROUND AND PURPOSE: Despite the findings that motor imagery and execution are supposed to share common neural networks, previous studies using imagery-based rehabilitation have revealed inconsistent results. In the present study, we investigated whether feedback of cortical activities (neurofeedback) using near-infrared spectroscopy could enhance the efficacy of imagery-based rehabilitation in stroke patients. METHODS: Twenty hemiplegic patients with subcortical stroke received 6 sessions of mental practice with motor imagery of the distal upper limb in addition to standard rehabilitation. Subjects were randomly allocated to REAL and SHAM groups. In the REAL group, cortical hemoglobin signals detected by near-infrared spectroscopy were fed back during imagery. In the SHAM group, irrelevant randomized signals were fed back. Upper limb function was assessed using the finger and arm subscales of the Fugl-Meyer assessment and the Action Research Arm Test. RESULTS: The hand/finger subscale of the Fugl-Meyer assessment showed greater functional gain in the REAL group, with a significant interaction between time and group (F(2,36)=15.5; P<0.001). A significant effect of neurofeedback was revealed even in severely impaired subjects. Imagery-related cortical activation in the premotor area was significantly greater in the REAL group than in the SHAM group (T(58)=2.4; P<0.05). CONCLUSIONS: Our results suggest that near-infrared spectroscopy-mediated neurofeedback may enhance the efficacy of mental practice with motor imagery and augment motor recovery in poststroke patients with severe hemiparesis.

[Contribution of brain function analysis to the evolution of neurorehabilitation].

Recent studies of functional neuroimaging and clinical neurophysiology have implied that functional recovery after stroke is associated with use-dependent plasticity of the damaged brain. However the property of the reorganized neural network depends on site and size of the lesion, which makes it difficult to assess what the adaptive plasticity is. From clinical point of view there is accumulating randomized controlled trials for the benefit of task-oriented rehabilitative intervention including constraint-induced movement therapy, robotics, and body-weight supported treadmill training. However dose-matched control intervention is usually as effective as a specific intervention. This raises a question regarding the specificity of a task-oriented intervention. Second question is whether such intervention goes beyond the biological destiny of human. Specifically there is no known strategy enhancing recovery of severely impaired hand. To augment functional gain, several methods of neuro-modulation may bring break-through on the assumption that they induce greater adaptive plasticity. Such neuro-modulative methods include neuropharmacological modulation, brain stimulation using transcranial magnetic stimulation and direct current stimulation, peripheral nerve stimulation, neurofeedback using real-time fMRI and real-time fNIRS, and brain-machine interface. A preliminary randomized controlled trial regarding real-time feedback of premotor activities revealed promising results for recovery of paretic hand in patients with stroke.

Neurofeedback using real-time near-infrared spectroscopy enhances motor imagery related cortical activation.

Accumulating evidence indicates that motor imagery and motor execution share common neural networks. Accordingly, mental practices in the form of motor imagery have been implemented in rehabilitation regimes of stroke patients with favorable results. Because direct monitoring of motor imagery is difficult, feedback of cortical activities related to motor imagery (neurofeedback) could help to enhance efficacy of mental practice with motor imagery. To determine the feasibility and efficacy of a real-time neurofeedback system mediated by near-infrared spectroscopy (NIRS), two separate experiments were performed. Experiment 1 was used in five subjects to evaluate whether real-time cortical oxygenated hemoglobin signal feedback during a motor execution task correlated with reference hemoglobin signals computed off-line. Results demonstrated that the NIRS-mediated neurofeedback system reliably detected oxygenated hemoglobin signal changes in real-time. In Experiment 2, 21 subjects performed motor imagery of finger movements with feedback from relevant cortical signals and irrelevant sham signals. Real neurofeedback induced significantly greater activation of the contralateral premotor cortex and greater self-assessment scores for kinesthetic motor imagery compared with sham feedback. These findings suggested the feasibility and potential effectiveness of a NIRS-mediated real-time neurofeedback system on performance of kinesthetic motor imagery. However, these results warrant further clinical trials to determine whether this system could enhance the effects of mental practice in stroke patients.

Cortical control of postural balance in patients with hemiplegic stroke.

Despite its remarkable effect on the activities of daily living, the precise mechanism underlying balance control after stroke remains to be elucidated. In this study, we investigated the cortical activation induced by postural perturbation in 20 patients with stroke using a 50-channel event-related functional near-infrared spectroscopy. A combination of brisk forward and backward movements of a platform without any prior cue was used as an external postural perturbation. Multi-participant analysis of oxygenated hemoglobin signals showed postural perturbation-related cortical activation in the prefrontal cortical areas in both hemispheres as well as the premotor and parietal association cortical areas in the unaffected hemisphere. Regression analysis using the individual Berg Balance Scale as the regressor showed a significant positive correlation between balance ability and the postural perturbation-related changes in oxygenated hemoglobin signals in the supplementary motor areas and prefrontal cortical areas in both hemispheres. Consistent with the previous findings in healthy participants, these findings suggest that the broad cortical network, including the prefrontal, premotor, supplementary motor, and parietal cortical areas in both hemispheres, was essential for balance control even in poststroke patients.

Impaired motor learning by a pursuit rotor test reduces functional outcomes during rehabilitation of poststroke ataxia.

BACKGROUND: Motor learning is essential to gain skills with neurorehabilitation. OBJECTIVE: To investigate whether capacity for motor learning affects rehabilitation outcome and its relevant brain activation in ataxic patients with stroke. METHODS: Twelve patients presenting with ataxia admitted for inpatient rehabilitation 2 to 3 months after infratentorial stroke and 6 control subjects performed 8 repetitions of 30-second pursuit rotor (PR) task. Cortical oxygenated hemoglobin (oxyHb) signals were measured using functional near-infrared spectroscopy. RESULTS: Both patients and controls learned the PR skill, although the gains in PR performance were significantly lower in patients. In patients, the less learning significantly correlated with smaller rehabilitation gains assessed by the Functional Independence Measure. The Fugl-Meyer score for coordination and balance did not change. Center of task-related increase of cortical oxyHb signals shifted from the presupplementary motor area (preSMA) to the supplementary motor area (SMA) with task repetitions in controls but not in patients. Accordingly, serial changes of ratio of oxyHb increase in the preSMA to SMA (preSMA/SMA ratio) were significantly different between the groups. In patients and controls, gains in PR performance and changes of the preSMA/SMA ratio correlated. CONCLUSIONS: Impaired motor sequence learning by the PR task was correlated with reduced rehabilitation gains for ataxic patients with stroke.

Cerebellar ataxia rehabilitation trial in degenerative cerebellar diseases.

OBJECTIVE: To investigate short- and long-term effects of intensive rehabilitation on ataxia, gait, and activities of daily living (ADLs) in patients with degenerative cerebellar disease. METHODS: A total of 42 patients with pure cerebellar degeneration were randomly assigned to the immediate group or the delayed-entry control group. The immediate group received 2 hours of inpatient physical and occupational therapy, focusing on coordination, balance, and ADLs, on weekdays and 1 hour on weekends for 4 weeks. The control group received the same intervention after a 4-week delay. Short-term outcome was compared between the immediate and control groups. Long-term evaluation was done in both groups at 4, 12, and 24 weeks after the intervention. Outcome measures included the assessment and rating of ataxia, Functional Independence Measure, gait speed, cadence, functional ambulation category, and number of falls. RESULTS: The immediate group showed significantly greater functional gains in ataxia, gait speed, and ADLs than the control group. Improvement of truncal ataxia was more prominent than limb ataxia. The gains in ataxia and gait were sustained at 12 weeks and 24 weeks, respectively. At least 1 measure was better than at baseline at 24 weeks in 22 patients. CONCLUSIONS: Short-term benefit of intensive rehabilitation was evident in patients with degenerative cerebellar diseases. Although functional status tended to decline to the baseline level within 24 weeks, gains were maintained in more than half of the participants.

[Clinical application of functional near-infrared spectroscopy in rehabilitation medicine].

Functional near-infrared spectroscopy (fNIRS) is an effective tool to non-invasively investigate cerebral oxygenation and hemodynamics. fNIRS as well as other functional neuroimaging techniques including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have been used for investigating the neural mechanisms of functional recovery after a stroke or a traumatic brain injury. fNIRS has several advantages over other neuroimaging techniques in terms of clinical application in the field of rehabilitation medicine. In addition to its portability and low equipment cost, fNIRS does not require strict motion restriction during measurement, unlike other functional imaging techniques. Therefore, this technique enables the examination of cortical activation during physically dynamic activities, like gait or balance perturbation. Studies using fNIRS have revealed several implications for gait recovery after stroke. These studies have shown that the medial sensorimotor cortex (SMC) and the supplementary motor area (SMA) are mainly involved in steadying gait and that the prefrontal cortex (PFC) is involved in the adjustment of walking speed. In hemiparetic patients, lateralization of SMC activation during gait is reduced, and additional cortical activations in the premotor cortex and PFC during gait became evident after focused rehabilitation for several months. The cortical activation pattern may be modified after different types of rehabilitative interventions. These results imply that fNIRS data is a potential biomarker for functional recovery and the response to rehabilitative interventions. Although further studies are required, fNIRS might provide useful information for customizing rehabilitation programs in order to enhance functional recovery.

Inferior olivary hypertrophy is associated with a lower functional state after pontine hemorrhage.

BACKGROUND: Inferior olivary hypertrophy (IOH) may develop after pontine hemorrhage and may become a pacemaker for symptomatic palatal tremor (SPT). However, there is no information available that elucidates how IOH may affect the functional outcome. The purpose of this study was to investigate how frequently IOH was associated with clinical manifestations of involuntary movements, including ocular myoclonus (OM) and SPT, and whether IOH influenced the functional outcome after pontine hemorrhage. METHODS: In 20 consecutive patients undergoing inpatient multidisciplinary rehabilitation after pontine hemorrhage, the location of lesions (tegmental vs. ventral) and the presence of IOH were examined by magnetic resonance imaging, and the functional outcome was assessed by means of Fugl-Meyer scale for neurological impairment and Functional Independence Measure for disability on admission and discharge. RESULTS: In 10 patients, IOH was detected, and the tegmentum was involved in 7 of the 10 patients. OM or SPT was present in 7 of these 10 patients. In the remaining 10 patients, IOH was not detected, and the tegmentum was involved only in 2 of these 10 patients. None of them had OM or SPT. The presence of IOH was associated with a lower functional status on admission and discharge. CONCLUSION: After pontine hemorrhage, IOH may be associated with tegmental lesions with OM or SPT and may impose a detrimental effect on the functional outcome.

Does therapeutic facilitation add to locomotor outcome of body weight--supported treadmill training in nonambulatory patients with stroke? A randomized controlled trial.

OBJECTIVE: To assess benefit of the facilitation technique (FT) coupled with body weight-supported treadmill training (BWSTT) in nonambulatory patients with stroke. DESIGN: Randomized controlled trial. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: Forty-nine patients with nonambulatory patients with stroke were randomly allocated to BWSTT coupled with the FT or mechanical assistance (control). INTERVENTIONS: Swinging and stance of the paretic leg were assisted using the FT or mechanically (control) during BWSTT. MAIN OUTCOME MEASURES: The FIM instrument, Fugl-Meyer Assessment, gait speed, and cadence. RESULTS: Demographic and clinical features of the FT (n=22) and control (n=25) groups on admission were comparable after excluding 2 dropouts. There were no differences in the gains of the main outcome measures between the FT and control groups. Patients with severe impairment in the FT group had greater gains in arm function than those in the control group. CONCLUSIONS: The FT did not add significantly to locomotor outcome of BWSTT in nonambulatory patients with stroke but it did require more therapists' assistance.

Patients with severe stroke benefit most by interdisciplinary rehabilitation team approach.

BACKGROUND: We evaluated the efficacy of a regular interdisciplinary stroke team approach on rehabilitation outcome. METHODS: We compared a stroke rehabilitation unit (SRU) with regular interdisciplinary stroke team conferences with general rehabilitation ward (GRW) without such conferences in the same rehabilitation hospital. One hundred and seventy-eight patients within 3 months after stroke were allocated to SRU or GRW, based on bed availability. Main outcome measures were the Functional Independence Measure, Stroke Impairment Assessment Set, length of hospital stay, discharge disposition and cost of hospitalization. RESULTS: The interval between stroke onset and admission to our hospital was significantly longer in the SRU (n = 91) group compared with the GRW group (n = 87, p < 0.05). Although comparable numbers of patients were discharged home (74.7% in the SRU vs. 71.3% in the GRW), significantly more patients (p < 0.0001) with severe disability were discharged home in the SRU group (47.4%) compared with the GRW group (0%). There were no significant differences in the increase in Functional Independence Measure score, Stroke Impairment Assessment Set score,length of hospital stay, or cost. CONCLUSION: Patients with severe stroke appeared to benefit most from regular interdisciplinary stroke team conferences in the SRU and had an improved discharge disposition.

Longitudinal optical imaging study for locomotor recovery after stroke.

BACKGROUND AND PURPOSE: We sought to investigate cerebral mechanisms underlying locomotor recovery after stroke. METHODS: We measured cortical activities during hemiparetic gait on the treadmill before and after 2 months of inpatient rehabilitation in 8 patients with initial stroke (5 men, 3 women; 4 with right and 4 with left hemiparesis; aged 57 years; 3 months after stroke on average), using an optical imaging system. RESULTS: On the initial evaluation, hemiparetic gait was associated with increased oxygenated hemoglobin levels in the medial primary sensorimotor cortex (SMC) that were greater in the unaffected hemisphere than in the affected hemisphere as well as in the premotor cortex (PMC) and supplementary motor area. On the second examination, the asymmetry in SMC activation significantly improved, and there was enhanced PMC activation in the affected hemisphere. Improvement of the asymmetrical SMC activation significantly correlated with improvement of gait parameters. CONCLUSIONS: Locomotor recovery after stroke may be associated with improvement of asymmetry in SMC activation and enhanced PMC activation in the affected hemisphere.

Benefit of inpatient multidisciplinary rehabilitation up to 1 year after stroke.

OBJECTIVE: To analyze the benefit of inpatient multidisciplinary rehabilitation up to 1 year after stroke. DESIGN: Retrospective cohort study. SETTING: Inpatient rehabilitation hospital in Japan. PARTICIPANTS: A total of 1056 patients with stroke were divided into 3 groups based on the interval between stroke onset and admission to the rehabilitation hospital: group I, within 90 days (n=507, 48%); group II, 91 to 180 days (n=377, 36%); and group III, more than 180 days (n=172, 16%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional outcome (A to D; independent to totally dependent) in walking, affected upper extremity, and activities of daily living (ADLs) and discharge disposition. RESULTS: Walking status improved in 70.9% of nonambulatory patients in group I, in 54.8% in group II, and in 43.9% in group III. Similarly, ADLs improved in 66.7% of the totally dependent patients in group I and in approximately 50% in groups II and III. Functional gain in those with a totally nonfunctional upper extremity at admission was poor (29.7%). Initial functional categories affected each outcome (P<.0001). On discharge, 73.8% in group I and approximately 60% in groups II and III went home. CONCLUSION: Approximately half of all patients regained their abilities in walking and ADLs after inpatient multidisciplinary rehabilitation up to 1 year after stroke. However, there was considerable limitation in functional recovery of the affected upper extremity.

Premotor cortex is involved in restoration of gait in stroke.

Cortical activation during hemiplegic gait was assessed in six nonambulatory patients with severe stroke (four men, two women; four with right and two with left hemiplegia; 57 years old and 3 months after stroke on average), using a near-infrared spectroscopic imaging system. Each patient performed tasks of treadmill walking (0.2km/hr), alternated with rest every 30 seconds for four repetitions, under partial body weight support, either with mechanical assistance in swinging the paretic leg control (CON) or with a facilitation technique that enhanced swinging of the paretic leg (FT), provided by physical therapists. Gait performance was associated with increased oxygenated hemoglobin levels in the medial primary sensorimotor cortex in the unaffected hemisphere greater than in the affected hemisphere. Both cortical mappings and quantitative data showed that the premotor activation in the affected hemisphere was enhanced during hemiplegic gait. There was also a prominent activation in the presupplementary motor area. Overall cortical activations and gait performance were greater in walking with FT than with CON. These indicate that multiple motor areas including the premotor cortex and presupplementary motor area might play important roles in restoration of gait in patients with severe stroke.