Introduction: Non-invasive brain-computer interface (BCI) therapy with contingent (i.e., closed-loop) functional electrical stimulation (FES) shows efficacy improving motor function. However, it is not well understood why some stroke survivors respond better to closed-looped BCI-FES intervention than others. Contingent BCI-FES intervention drives neuroplastic change toward adaptive functional connectivity in stroke-impaired sensorimotor brain areas by enriching the afferent feedback environment. The interruption of afferent-efferent feedback circuits is a neural correlate of long-term acquired disability and intactness of functional connections predicts recovery capacity. Studies suggest that proprioception is essential for motor learning and performance. Therefore, we hypothesize that proprioceptive intactness is essential for recovery of motor performance when using a BCI-FES. Methods: Participants with upper extremity motor loss resulting from stroke (n=35) completed up to 30 hours of closed-loop BCI-FES. Results: Change in ARAT scores over the course of the control period were compared to ARAT change scores over the intervention period at a one-month follow up assessment. On average, participants in the intervention realized greater change in ARAT (M = 2.11, SD = 4.68) than during the control phase (M = 0.294, SD = 3.53). An independent-samples t-test indicated this difference, 1.82, 95%CI [-4.17, 0.534], was not statistically significant, t (40.901) = -1.56, p = 0.126. Preliminary results indicate that Proprioceptive sensory loss has a greater limiting effect on recovery than cutaneous somatosensory loss. Discussion: Rehabilitating motor capacity after stroke depends on the intactness of sensorimotor neural circuits. If afference signals are missing or degraded due to stroke, motor recovery is poor. When the stroke spares afferent connectivity to the peripheral muscles, the sensorimotor cortex can leverage plasticity-based motor rehab strategies such as BCI-FES. Conclusion: Intactness of sensorimotor circuits is related to baseline severity of motor impairment as well as recovery of motor function. Efficacious prescription of BCI-FES intervention is best suited for patients with stroke-spared proprioception.

An increasing number of research teams are investigating the efficacy of brain-computer interface (BCI)-mediated interventions for promoting motor recovery following stroke. A growing body of evidence suggests that of the various BCI designs, most effective are those that deliver functional electrical stimulation (FES) of upper extremity (UE) muscles contingent on movement intent. More specifically, BCI-FES interventions utilize algorithms that isolate motor signals-user-generated intent-to-move neural activity recorded from cerebral cortical motor areas-to drive electrical stimulation of individual muscles or muscle synergies. BCI-FES interventions aim to recover sensorimotor function of an impaired extremity by facilitating and/or inducing long-term motor learning-related neuroplastic changes in appropriate control circuitry. We developed a non-invasive, electroencephalogram (EEG)-based BCI-FES system that delivers closed-loop neural activity-triggered electrical stimulation of targeted distal muscles while providing the user with multimodal sensory feedback. This BCI-FES system consists of three components: (1) EEG acquisition and signal processing to extract real-time volitional and task-dependent neural command signals from cerebral cortical motor areas, (2) FES of muscles of the impaired hand contingent on the motor cortical neural command signals, and (3) multimodal sensory feedback associated with performance of the behavioral task, including visual information, linked activation of somatosensory afferents through intact sensorimotor circuits, and electro-tactile stimulation of the tongue. In this report, we describe device parameters and intervention protocols of our BCI-FES system which, combined with standard physical rehabilitation approaches, has proven efficacious in treating UE motor impairment in stroke survivors, regardless of level of impairment and chronicity.

Stroke is a leading cause of acquired long-term upper extremity motor disability. Current standard of care trajectories fail to deliver sufficient motor rehabilitation to stroke survivors. Recent research suggests that use of brain-computer interface (BCI) devices improves motor function in stroke survivors, regardless of stroke severity and chronicity, and may induce and/or facilitate neuroplastic changes associated with motor rehabilitation. The present sub analyses of ongoing crossover-controlled trial NCT02098265 examine first whether, during movements of the affected hand compared to rest, ipsilesional Mu rhythm desynchronization of cerebral cortical sensorimotor areas [Brodmann's areas (BA) 1-7] is localized and tracks with changes in grip force strength. Secondly, we test the hypothesis that BCI intervention results in changes in frequency-specific directional flow of information transmission (direct path functional connectivity) in BA 1-7 by measuring changes in isolated effective coherence (iCoh) between cerebral cortical sensorimotor areas thought to relate to electrophysiological signatures of motor actions and motor learning. A sample of 16 stroke survivors with right hemisphere lesions (left hand motor impairment), received a maximum of 18-30 h of BCI intervention. Electroencephalograms were recorded during intervention sessions while outcome measures of motor function and capacity were assessed at baseline and completion of intervention. Greater desynchronization of Mu rhythm, during movements of the impaired hand compared to rest, were primarily localized to ipsilesional sensorimotor cortices (BA 1-7). In addition, increased Mu desynchronization in the ipsilesional primary motor cortex, Post vs. Pre BCI intervention, correlated significantly with improvements in hand function as assessed by grip force measurements. Moreover, the results show a significant change in the direction of causal information flow, as measured by iCoh, toward the ipsilesional motor (BA 4) and ipsilesional premotor cortices (BA 6) during BCI intervention. Significant iCoh increases from ipsilesional BA 4 to ipsilesional BA 6 were observed in both Mu [8-12 Hz] and Beta [18-26 Hz] frequency ranges. In summary, the present results are indicative of improvements in motor capacity and behavior, and they are consistent with the view that BCI-FES intervention improves functional motor capacity of the ipsilesional hemisphere and the impaired hand.

Objective: This study is part of a clinical trial designed to test the efficacy of an EEG-based BCI intervention for upper extremity motor rehabilitation in stroke survivors. The analyses presented here focus on the effectiveness of BCI intervention as a function of somatosensory integrity. Introduction: Human motor control requires integration of sensory and motor signals in the generation of motor commands. Stroke lesions often result in sensorimotor impairments and survivors may require rehabilitation to regain motor function and capacity. Stroke affects individuals differentially, based on a range of factors, including, but not limited to, lesion location and volume. Such factors may restrain recovery potential. Hypothesis: We tested the hypothesis that stroke survivors with measurable somatosensory impairments realize the same amount of motor recovery as those participants without somatosensory impairments. Methods: N= 23 stroke survivors participated in up to 30 hours of BCI intervention (13.8 ±1.3, mean + SD) for upper extremity rehabilitation, as measured by the ARAT. Participants were grouped post-hoc on presence or absence of somatosensory impairments, as measured by the NIHSS subdomains of Sensory (i.e. cutaneous), and Motor Arm (i.e. proprioceptive) and their group means compared. Results: The hypothesis was not confirmed. Mean ARAT scores at completion and follow up differed between groups (Cutaneous loss: ARAT mean change at completion: 0.9 ± 2.23, p= 0.234; ARAT mean change at follow-up: 1.20 ± 2.860, p = 0.217), (No Cutaneous loss: ARAT mean change at completion: 2.15 ± 6.34, p= 0.244; ARAT mean change at follow-up: 4.39 ± 6.41, p= 0.0297) (Proprioceptive loss: ARAT mean change at completion: 0.867 ± 3.66, p= 0.375, ARAT mean change at follow-up: 2.47 ± 5.38, p= 0.097), (No Proprioceptive loss: ARAT mean change at completion: 3 ± 6.80, p= 0.252, ARAT mean change at follow-up: 4 ± 5.42, p= 0.075). Conclusions: These results suggest that BCI intervention is more effective at delivering motor improvements in participants with less somatosensory impairments. These results are consistent with the view that somatosensory system integrity may be key to BCI motor rehabilitation of brain injuries following stroke.

This research seeks to identify source localization of neuromechanical changes associated with gains in hand grip function following BCI intervention sessions for upper extremity motor recovery. Mu rhythm desynchronization (ERD) of contralateral brain motor areas is thought to occur during movement and changes in brain motor area ERD relate to changes in behavioral measures, hand grip function, with BCI intervention. N=16 right hemisphere survivors participated in 9-15 sessions with BCI. Participants executed hand movements in response to visual cues on a computer screen with the corresponding audio instructions (e.g., Left, Right, Rest). The sessions (i.e. pre and post BCI intervention) contained two runs, each consisting of 15 trials for rest, left hand, and right hand movements (i.e., 5 trials for each of the three conditions) presented in random order. Data from the pre and post conditions were then grand averaged. sLORETA estimates were calculated as follows: 1) Clean EEG data segmented (LEFT hand attempted movements and REST) separately for PRE and POST conditions. 2) Cross-spectra (MU[8-12 Hz]) were computed then averaged (i.e. 1 average per each subject separately for left, right and rest trials. 3) sLORETA of MU power estimates at 6239 cortical locations/voxels were obtained, normalized across subjects. In the sLORETA implementation, computations made in realistic head model using the MNI152 template, with 3D solution space restricted to cortical gray matter, as determined by the probabilistic Talairach atlas. The specific frequency band cross-spectra (frequency-domain) obtained from the average-reference potential data, were the inputs for source localization. 4) sLORETA estimates between the 2 conditions [Movement - Rest] were then calculated in cortical space. Pearson correlation of voxel-wise Mu ERD with the change in Hand Grip were calculated. A stronger Mu ERD in the ipsilesional primary motor cortical area (BA 4) at ‘post’ intervention (i.e., more negative values compared to ‘pre’) was associated with a greater change in hand grip (r=-0.435, p=0.046 [1-tailed]). Increases in functional recovery of the impaired upper extremity (Hand Grip) have a direct correlation with greater changes in Mu ERD of ipsilesional motor brain areas.

Loss of motor function is a common deficit following stroke insult and often manifests as persistent upper extremity (UE) disability which can affect a survivor's ability to participate in activities of daily living. Recent research suggests the use of brain-computer interface (BCI) devices might improve UE function in stroke survivors at various times since stroke. This randomized crossover-controlled trial examines whether intervention with this BCI device design attenuates the effects of hemiparesis, encourages reorganization of motor related brain signals (EEG measured sensorimotor rhythm desynchronization), and improves movement, as measured by the Action Research Arm Test (ARAT). A sample of 21 stroke survivors, presenting with varied times since stroke and levels of UE impairment, received a maximum of 18-30 h of intervention with a novel electroencephalogram-based BCI-driven functional electrical stimulator (EEG-BCI-FES) device. Driven by spectral power recordings from contralateral EEG electrodes during cued attempted grasping of the hand, the user's input to the EEG-BCI-FES device modulates horizontal movement of a virtual cursor and also facilitates concurrent stimulation of the impaired UE. Outcome measures of function and capacity were assessed at baseline, mid-therapy, and at completion of therapy while EEG was recorded only during intervention sessions. A significant increase in r-squared values [reflecting Mu rhythm (8-12 Hz) desynchronization as the result of attempted movements of the impaired hand] presented post-therapy compared to baseline. These findings suggest that intervention corresponds with greater desynchronization of Mu rhythm in the ipsilesional hemisphere during attempted movements of the impaired hand and this change is related to changes in behavior as a result of the intervention. BCI intervention may be an effective way of addressing the recovery of a stroke impaired UE and studying neuromechanical coupling with motor outputs. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT02098265.

Loss of motor function is a common deficit following stroke insult and often manifests as persistent upper extremity (UE) disability which can affect a survivor's ability to participate in activities of daily living. Recent research suggests the use of brain-computer interface (BCI) devices might improve UE function in stroke survivors at various times since stroke. This randomized crossover-controlled trial examines whether intervention with this BCI device design attenuates the effects of hemiparesis, encourages reorganization of functional connectivity, and improves movement, as measured by the Action Research Arm Test (ARAT). 21 stroke survivors, presenting with varied times since stroke and levels of UE impairment, received a maximum of 18 - 30 hours of intervention with a novel electroencephalogram based BCI driven functional electrical stimulator (EEG-BCI-FES) device. Driven by spectral power recordings from contralateral EEG electrodes during cued attempted grasping of the hand, the EEG-BCI-FES device modulates horizontal movement of a virtual cursor as well as facilitating concurrent FES stimulation of only the impaired upper extremity. Primary outcome measure of function, ARAT was assessed at baseline, mid-therapy, and at completion of therapy. The signed r-squared value (at the ipsilesional C4 or C3 sites) for the Mu (8-12Hz) rhythm significantly decreased in the post-therapy stage compared to the pre-therapy stage (one-tailed paired t-test: t(20)= 1.85; p = 0.039; meanPRE = -0.142; meanPOST = -0.161), while the subject attempted movements of the impaired hand. These findings suggests that as the result of the intervention sessions, the “desynchronization” of the Mu rhythm signals significantly increases post-therapy at the ipsilesional motor site and this change is related to changes in behavior as a result of intervention. BCI intervention may be an effective way of addressing the stroke recovery of a stroke impaired upper extremity.

Stroke is a leading cause of persistent upper extremity (UE) motor disability in adults. Brain–computer interface (BCI) intervention has demonstrated potential as a motor rehabilitation strategy for stroke survivors. This sub-analysis of ongoing clinical trial (NCT02098265) examines rehabilitative efficacy of this BCI design and seeks to identify stroke participant characteristics associated with behavioral improvement. Stroke participants (n = 21) with UE impairment were assessed using Action Research Arm Test (ARAT) and measures of function. Nine participants completed three assessments during the experimental BCI intervention period and at 1-month follow-up. Twelve other participants first completed three assessments over a parallel time-matched control period and then crossed over into the BCI intervention condition 1-month later. Participants who realized positive change (≥1 point) in total ARAT performance of the stroke affected UE between the first and third assessments of the intervention period were dichotomized as “responders” (<1 = “non-responders”) and similarly analyzed. Of the 14 participants with room for ARAT improvement, 64% (9/14) showed some positive change at completion and approximately 43% (6/14) of the participants had changes of minimal detectable change (MDC = 3 pts) or minimally clinical important difference (MCID = 5.7 points). Participants with room for improvement in the primary outcome measure made significant mean gains in ARATtotal score at completion (ΔARATtotal = 2, p = 0.028) and 1-month follow-up (ΔARATtotal = 3.4, p = 0.0010), controlling for severity, gender, chronicity, and concordance. Secondary outcome measures, SISmobility, SISadl, SISstrength, and 9HPTaffected, also showed significant improvement over time during intervention. Participants in intervention through follow-up showed a significantly increased improvement rate in SISstrength compared to controls (p = 0.0117), controlling for severity, chronicity, gender, as well as the individual effects of time and intervention type. Participants who best responded to BCI intervention, as evaluated by ARAT score improvement, showed significantly increased outcome values through completion and follow-up for SISmobility (p = 0.0002, p = 0.002) and SISstrength (p = 0.04995, p = 0.0483). These findings may suggest possible secondary outcome measure patterns indicative of increased improvement resulting from this BCI intervention regimen as well as demonstrating primary efficacy of this BCI design for treatment of UE impairment in stroke survivors. Clinical Trial Registration: ClinicalTrials.gov, NCT02098265.

Coordinated reach-to-grasp movements require precise spatiotemporal synchrony between proximal forelimb muscles (shoulder, elbow) that transport the hand toward a target during reach, and distal muscles (wrist, digit) that simultaneously preshape and orient the hand for grasp. The precise mechanisms through which the redundant neuromuscular circuitry coordinates reach with grasp, however, remain unclear. Recently, Geed and Van Kan (2016) demonstrated, using exploratory factor analysis (EFA), that limited numbers of global, template-like transport/preshape- and grasp-related muscle components underlie the complexity and variability of intramuscular electromyograms (EMGs) of up to 21 distal and proximal muscles recorded while monkeys performed reach-to-grasp tasks. Importantly, transport/preshape- and grasp-related muscle components showed invariant spatiotemporal coupling, which provides a potential mechanism for coordinating forelimb muscles during reach-to-grasp movements. In the present study, we tested whether ensemble discharges of forelimb neurons in the cerebellar nucleus interpositus (NI) and its target, the magnocellular red nucleus (RNm), a source of rubrospinal fibers, function as neuronal correlates of the transport/preshape- and grasp-related muscle components we identified. EFA applied to single-unit discharges of populations of NI and RNm neurons recorded while the same monkeys that were used previously performed the same reach-to-grasp tasks, revealed neuronal components in the ensemble discharges of both NI and RNm neuronal populations with characteristics broadly similar to muscle components. Subsets of NI and RNm neuronal components were strongly and significantly cross-correlated with subsets of muscle components, suggesting that similar functional units of reach-to-grasp behavior are expressed by NI and RNm neuronal populations and forelimb muscles. Importantly, like transport/preshape- and grasp-related muscle components, their NI and RNm neuronal correlates showed invariant spatiotemporal coupling. Clinical and lesion studies have reported disruption of coupling between reach and grasp following cerebellar damage; the present results expand on those studies by identifying a neuronal mechanism that may underlie cerebellar contributions to spatiotemporal coordination of distal and proximal limb muscles during reaching to grasp. We conclude that finding similar functional units of behavior expressed at multiple levels of information processing along interposito-rubrospinal pathways and forelimb muscles supports the hypothesis that functionally related populations of NI and RNm neurons act synergistically in the control of complex coordinated motor behaviors.

Purpose/Hypothesis: We examined the kinematics of reaching to grasp in humans to determine the role of the cerebellum in the timing of finger opening with proximal joint movement. The cerebellum is important for the control of multijoint, coordinated movements, such as reaching to grasp. An unresolved question is whether the cerebellum specifically controls temporal relations between reach, hand preshaping, and grasp components or whether the cerebellum integrates reach, hand preshaping, and grasp components into a single central program. Number of Subjects: 5 subjects with cerebellar damage and 6 healthy, age-matched controls were studied. Materials/Methods: We measured kinematics of reach, hand pre-shaping, and grasp while subjects with cerebellar damage (n=5) and matched controls (n=6) performed reaches with a precision grip that required opposition of the index finger and thumb. The task was performed under two conditions: as fast and accurately as possible, and slowly and accurately. Transport of the hand was characterized by angular velocity of elbow and shoulder joints, wrist trajectory, and amplitude and timing of tangential wrist velocity. Hand preshaping was characterized by amplitude and variability of peak grip aperture and its timing relative to the reach. Grasp was characterized by relative timing of contact of the index finger and thumb with the target. Results: Results showed that PGA is tightly coupled to both peak shoulder velocity (PSV) and peak elbow velocity (PEV) in healthy controls. Cerebellar subjects showed disruptions in timing of PGA with PSV and PEV, with both joints contributing to an overall disruption in timing of PGA with peak wrist deceleration (PWD). These disruptions were more profound in the fast and accurate condition. In addition, cerebellar subjects were much more variable in the timing of multiple aspects of reaching to grasp including time of PGA relative to total movement time, timing of peak wrist velocity (PWV), time of PSV, time of PEV, as well as relative timing of PGA with PWD, PSV, and PEV. Conclusions: Kinematics of reaching to grasp in subjects with cerebellar damage are characterized by increased variability. The increased variability uncouples reach, hand preshaping, and grasp components in both spatial and temporal domains. Clinical Relevance: Current recommendations to patients with cerebellar lesions include learning to slow their movement down and to decompose movement into a series of single joint movements (Bastian 1997). This study supports the usefulness of slowing movements, as timing of proximal joints with finger opening is less disrupted in slower movements. If patients can be trained to move more slowly, disruptions to the proximal joint coordination are minimized and the overall movement of reaching to grasp is more normalized. However, at slower speeds, increased variability in magnitude and timing of PGA should still be expected based on the current results.

Background and Purpose. This case report documents a rare opportunity to observe the motor function of an individual for nearly 6 months following a primary pontine hemorrhage in the medial pontine tegmentum of the brain stem. The purpose of this report is to illustrate how knowledge of the location of the hemorrhage, in conjunction with knowledge of brain-stem structure-function relationships, informs physical therapist examination and intervention. Case Description. RM, a right-handed 81-year-old man with hypertension, had a hemorrhagic brain-stem stroke that severely compromised control of posture and whole-limb movements. Some residual ability to use the right hand and fingers remained, provided the trunk and right upper arm were stabilized. RM had undiminished intellectual abilities and unaltered memory because of sparing of cerebral cortices. RM's cognitive abilities, however, were obscured by severe impairments in interpersonal communication because of extensive damage to cranial nerve structures. Computed tomographic scans verified that the hematoma crossed the midline and was confined to the medial pontine tegmentum. Discussion. We interpret motor deficits resulting from stoke in the medial pontine tegmentum in terms of damage to brain-stem descending motor systems and ascending somatosensory systems. Recognition of cognitive and residual motor abilities following brain-stem stroke can aid in the development of rehabilitation strategies.

Reaching to grasp is of fundamental importance to primate motor behavior. One descending motor pathway that contributes to the control of this behavior is the rubrospinal tract. An important source of origin of the rubrospinal tract is the magnocellular red nucleus (RNm). Forelimb RNm neurons discharge vigorously during reach-to-grasp movements. RNm discharge is important for hand use, as coordinated whole-limb movements without hand use are not associated with strong discharge. Because RNm is functionally linked to muscles of the entire forelimb, RNm discharge may also contribute to use of the proximal limb that accompanies hand use. If RNm contributes to proximal limb use, we predict discharge to differ for reaches that differ in proximal limb involvement but require the same grasp. We tested this prediction by measuring discharge of individual RNm neurons while monkeys reached to grasp objects in four spatial locations in front of them. The animals reached from the waist to locations to the left, right, above, and below the shoulder of the "reaching" limb. RNm neurons of our sample were activated strongly during reach-to-grasp, and discharge of a third of the neurons tested depended on the spatial location of the object grasped. Discharge of RNm neurons and EMG activity of many of the distal and proximal forelimb muscles we tested were larger for reaching to grasp in the upper and/or right than lower and left target locations. Based on comparisons of each individual neuron's discharge patterns during reaches with and without preshaping the hand, we conclude that target location-dependent modulations in discharge rate of the majority of RNm neurons whose discharge differed for reaching to grasp in the four target locations contributed to aspects of hand preshaping that covaried with reach direction.

In this chapter we examine the role of intermediate cerebellum in the control of a reach to grasp. Our arguments rest on data from two nuclei: nucleus interpositus, the output nucleus of intermediate cerebellum, and the magnocellular red nucleus (RNm), which receives signals from interpositus and projects to the spinal cord. Interpositus and RNm contain neurons that increase discharge rate during movement of large body parts, such as the forelimb or hind limb. However, when forelimb neurons are tested with movement about specific joints, most cells show little or no change in discharge rate. During a reach to grasp the same cells show large increases in discharge rate. In monkey interpositus, the grasp component is necessary to elicit discharge modulation. Variation in the reach component of a reach to grasp changes neither the pattern nor amplitude of discharge modulation. Temporary inactivation of the cat RNm results in a severe deficit in the ability to grasp a lever, but only a mild deficit in the ability to reach. We conclude that intermediate cerebellum is specialized for the control of specific hand movements. The grasp in the reach to grasp relies on this control circuitry. Jeannerod's [I] hypothesis that the reach to grasp is composed of transport and grasp components controlled by separate channels is strengthened by our findings: intermediate cerebellum may provide a neural substrate for the grasp channel. Presumably additional neural circuitry, possibly involving other divisions of the cerebellum, is specialized for the control of the transport phase of the reach to grasp.

Pages 74–94: Peter L. E. van Kan, Alan R. Gibson, and James C. Houk, “Movement-related inputs to intermediate cerebellum of the monkey.” Page 86, left column, Fig. 12 legend, the last 3 lines are printed incorrectly; they should read: The modulation in discharge during active finger extension ( E) was considerably larger than the perturbation response ( F). Every 4th spike is plotted in the rasters.

The activity of pairs of neurons in the visual cortex (area 17) of anaesthetized, paralysed cats was recorded using two independently manipulated micropipettes. The number of spikes in the evoked responses of pairs of single neurons were analyzed for response covariance. Responses of the majority of cell pairs (83%) did not covary. Covariance was restricted to closeby neurons with distances of less than 150 μm and with identical orientation and ocular dominance preference.