Individuals with Chronic Mild-to-Moderate Traumatic Brain Injury Exhibit Decreased Neuromuscular Complexity During Gait.

BACKGROUND: Synergy analysis provides a means of quantifying the complexity of neuromuscular control during gait. Prior studies have shown evidence of reduced neuromuscular complexity during gait in individuals with neurological disorders associated with stroke, cerebral palsy, and Parkinson's disease. OBJECTIVE: The purpose of this study was to investigate neuromuscular complexity during gait in individuals who experienced a prior traumatic brain injury (TBI) that resulted in chronic balance deficits. METHODS: We measured and analyzed lower extremity electromyographic data during treadmill and overground walking for 44 individuals with residual balance deficits from a mild-to-moderate TBI at least 1 year prior. We also tested 20 unimpaired controls as a comparison. Muscle synergies were calculated for each limb using non-negative matrix factorization of the activation patterns for 6 leg muscles. We quantified neuromuscular complexity using Walk-DMC, a normalized metric of the total variance accounted for by a single synergy, in which a Walk-DMC score of 100 represents normal variance accounted for. We compared group average synergy structures and inter-limb similarity using cosine similarity. We also quantified each individual's gait and balance using the Sensory Organization Test, the Dynamic Gait Index, and the Six-Minute Walk Test. RESULTS: Neuromuscular complexity was diminished for individuals with a prior TBI. Walk-DMC averaged 92.8 ± 12.3 for the TBI group during overground walking, which was significantly less than seen in controls (100.0 ± 10.0). Individuals with a prior TBI exhibited 13% slower overground walking speeds than controls and reduced performance on the Dynamic Gait Index (18.5 ± 4.7 out of 24). However, Walk-DMC measures were insufficient to stratify variations in assessments of gait and balance performance. Group average synergy structures were similar between groups, although there were considerable between-group differences in the inter-limb similarity of the synergy activation vectors. CONCLUSIONS: Individuals with gait and balance deficits due to a prior TBI exhibit evidence of decreased neuromuscular complexity during gait. Our results suggest that individuals with TBI exhibit similar muscle synergy weightings as controls, but altered control of the temporal activation of these muscle weightings.

Abnormal muscle activation patterns are associated with chronic gait deficits following traumatic brain injury.

BACKGROUND: Gait and balance disorders are common among individuals who have experienced a mild to moderate traumatic brain injury (TBI). However, little is known about how the neuromuscular control of gait is altered following a TBI. RESEARCH QUESTION: Investigate the relationship between lower limb muscle activation patterns and chronic gait deficits in individuals who previously experienced a mild to moderate TBI. METHODS: Lower extremity electromyographic (EMG) signals were collected bilaterally during treadmill and overground walking in 44 ambulatory individuals with a TBI >1 year prior and 20 unimpaired controls. Activation patterns of TBI muscles were cross-correlated with normative data from control subjects to assess temporal phasing of muscle recruitment. Clinical assessments of gait and balance were performed using dynamic posturography, the dynamic gait index, six-minute walk test, and preferred walking speed. RESULTS: TBI subjects exhibited abnormal activation patterns in the tibialis anterior, medial gastrocnemius, and rectus femoris muscles during both overground and treadmill walking. Activation patterns of the vastus lateralis and soleus muscles did not differ from normal. There was considerable heterogeneity in performance on clinical balance and gait assessments. Abnormal muscle activation patterns were significantly correlated with variations in the dynamic gait index among the TBI subjects. SIGNIFICANCE: Individuals who have experienced a prior TBI do exhibit characteristic changes in the temporal coordination of select lower extremity muscles, which may contribute to impairments during challenging walking tasks.

Interaction of Perceived Frequency and Intensity in Fingertip Electrotactile Stimulation: Dissimilarity Ratings and Multidimensional Scaling.

Sensations elicited by electrical stimulation of touch are multidimensional, varying in perceived intensity and quality in response to changes in stimulus current or waveform timing. This paper manipulated both current and frequency, while volunteer participants estimated the dissimilarity of all non-identical pairs of 16 stimulus conditions. Multidimensional scaling analysis revealed that a model having two perceptual dimensions was adequate in representing the electrotactile (electrocutaneous) sensations. The two dimensions were identified as perceptual frequency and intensity, and were strongly correlated with the two stimulus variables, frequency and current, although not in a 1:1 correspondence. Perception of frequency differences increased monotonically with stimulus intensity, which is consistent with other human sensory systems, such as hearing and vision. Our results are consistent with previously-reported research using a different methodology and cutaneous locus. Congruence across different methods and laboratories suggests similar underlying perceptual mechanisms.

Brain-Computer Interface Training after Stroke Affects Patterns of Brain-Behavior Relationships in Corticospinal Motor Fibers.

Background: Brain-computer interface (BCI) devices are being investigated for their application in stroke rehabilitation, but little is known about how structural changes in the motor system relate to behavioral measures with the use of these systems. Objective: This study examined relationships among diffusion tensor imaging (DTI)-derived metrics and with behavioral changes in stroke patients with and without BCI training. Methods: Stroke patients (n = 19) with upper extremity motor impairment were assessed using Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), Nine-Hole Peg Test (9-HPT), and DTI scans. Ten subjects completed four assessments over a control period during which no training was administered. Seventeen subjects, including eight who completed the control period, completed four assessments over an experimental period during which subjects received interventional BCI training. Fractional anisotropy (FA) values were extracted from each corticospinal tract (CST) and transcallosal motor fibers for each scan. Results: No significant group by time interactions were identified at the group level in DTI or behavioral measures. During the control period, increases in contralesional CST FA and in asymmetric FA (aFA) correlated with poorer scores on SIS and 9-HPT. During the experimental period (with BCI training), increases in contralesional CST FA were correlated with improvements in 9-HPT while increases in aFA correlated with improvements in ARAT but with worsening 9-HPT performance; changes in transcallosal motor fibers positively correlated with those in the contralesional CST. All correlations p < 0.05 corrected. Conclusion: These findings suggest that the integrity of the contralesional CST may be used to track individual behavioral changes observed with BCI training after stroke.

Dose-response relationships using brain-computer interface technology impact stroke rehabilitation.

Brain-computer interfaces (BCIs) are an emerging novel technology for stroke rehabilitation. Little is known about how dose-response relationships for BCI therapies affect brain and behavior changes. We report preliminary results on stroke patients (n = 16, 11 M) with persistent upper extremity motor impairment who received therapy using a BCI system with functional electrical stimulation of the hand and tongue stimulation. We collected MRI scans and behavioral data using the Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) before, during, and after the therapy period. Using anatomical and functional MRI, we computed Laterality Index (LI) for brain activity in the motor network during impaired hand finger tapping. Changes from baseline LI and behavioral scores were assessed for relationships with dose, intensity, and frequency of BCI therapy. We found that gains in SIS Strength were directly responsive to BCI therapy: therapy dose and intensity correlated positively with increased SIS Strength (p ≤ 0.05), although no direct relationships were identified with ARAT or 9-HPT scores. We found behavioral measures that were not directly sensitive to differences in BCI therapy administration but were associated with concurrent brain changes correlated with BCI therapy administration parameters: therapy dose and intensity showed significant (p ≤ 0.05) or trending (0.05 < p < 0.1) negative correlations with LI changes, while therapy frequency did not affect LI. Reductions in LI were then correlated (p ≤ 0.05) with increased SIS Activities of Daily Living scores and improved 9-HPT performance. Therefore, some behavioral changes may be reflected by brain changes sensitive to differences in BCI therapy administration, while others such as SIS Strength may be directly responsive to BCI therapy administration. Data preliminarily suggest that when using BCI in stroke rehabilitation, therapy frequency may be less important than dose and intensity.

DTI measures track and predict motor function outcomes in stroke rehabilitation utilizing BCI technology.

Tracking and predicting motor outcomes is important in determining effective stroke rehabilitation strategies. Diffusion tensor imaging (DTI) allows for evaluation of the underlying structural integrity of brain white matter tracts and may serve as a potential biomarker for tracking and predicting motor recovery. In this study, we examined the longitudinal relationship between DTI measures of the posterior limb of the internal capsule (PLIC) and upper-limb motor outcomes in 13 stroke patients (median 20-month post-stroke) who completed up to 15 sessions of intervention using brain-computer interface (BCI) technology. Patients' upper-limb motor outcomes and PLIC DTI measures including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were assessed longitudinally at four time points: pre-, mid-, immediately post- and 1-month-post intervention. DTI measures and ratios of each DTI measure comparing the ipsilesional and contralesional PLIC were correlated with patients' motor outcomes to examine the relationship between structural integrity of the PLIC and patients' motor recovery. We found that lower diffusivity and higher FA values of the ipsilesional PLIC were significantly correlated with better upper-limb motor function. Baseline DTI ratios were significantly correlated with motor outcomes measured immediately post and 1-month-post BCI interventions. A few patients achieved improvements in motor recovery meeting the minimum clinically important difference (MCID). These findings suggest that upper-limb motor recovery in stroke patients receiving BCI interventions relates to the microstructural status of the PLIC. Lower diffusivity and higher FA measures of the ipsilesional PLIC contribute toward better motor recovery in the stroke-affected upper-limb. DTI-derived measures may be a clinically useful biomarker in tracking and predicting motor recovery in stroke patients receiving BCI interventions.

Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface.

This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions.

Characterizing relationships of DTI, fMRI, and motor recovery in stroke rehabilitation utilizing brain-computer interface technology.

The relationship of the structural integrity of white matter tracts and cortical activity to motor functional outcomes in stroke patients is of particular interest in understanding mechanisms of brain structural and functional changes while recovering from stroke. This study aims to probe these underlying mechanisms using diffusion tensor imaging (DTI) and fMRI measures. We examined the structural integrity of the posterior limb of the internal capsule (PLIC) using DTI and corticomotor activity using motor-task fMRI in stroke patients who completed up to 15 sessions of rehabilitation therapy using Brain-Computer Interface (BCI) technology. We hypothesized that (1) the structural integrity of PLIC and corticomotor activity are affected by stroke; (2) changes in structural integrity and corticomotor activity following BCI intervention are related to motor recovery; (3) there is a potential relationship between structural integrity and corticomotor activity. We found that (1) the ipsilesional PLIC showed significantly decreased fractional anisotropy (FA) values when compared to the contralesional PLIC; (2) lower ipsilesional PLIC-FA values were significantly associated with worse motor outcomes (i.e., ipsilesional PLIC-FA and motor outcomes were positively correlated.); (3) lower ipsilesional PLIC-FA values were significantly associated with greater ipsilesional corticomotor activity during impaired-finger-tapping-task fMRI (i.e., ipsilesional PLIC-FA and ipsilesional corticomotor activity were negatively correlated), with an overall bilateral pattern of corticomotor activity observed; and (4) baseline FA values predicted motor recovery assessed after BCI intervention. These findings suggest that (1) greater vs. lesser microstructural integrity of the ipsilesional PLIC may contribute toward better vs. poor motor recovery respectively in the stroke-affected limb and demand lesser vs. greater cortical activity respectively from the ipsilesional motor cortex; and that (2) PLIC-FA is a promising biomarker in tracking and predicting motor functional recovery in stroke patients receiving BCI intervention.

Case report: post-stroke interventional BCI rehabilitation in an individual with preexisting sensorineural disability.

Therapies involving new technologies such as brain-computer interfaces (BCI) are being studied to determine their potential for interventional rehabilitation after acute events such as stroke produce lasting impairments. While studies have examined the use of BCI devices by individuals with disabilities, many such devices are intended to address a specific limitation and have been studied when this limitation or disability is present in isolation. Little is known about the therapeutic potential of these devices for individuals with multiple disabilities with an acquired impairment overlaid on a secondary long-standing disability. We describe a case in which a male patient with congenital deafness suffered a right pontine ischemic stroke, resulting in persistent weakness of his left hand and arm. This patient volunteer completed four baseline assessments beginning at 4 months after stroke onset and subsequently underwent 6 weeks of interventional rehabilitation therapy using a closed-loop neurofeedback BCI device with visual, functional electrical stimulation, and tongue stimulation feedback modalities. Additional assessments were conducted at the midpoint of therapy, upon completion of therapy, and 1 month after completing all BCI therapy. Anatomical and functional MRI scans were obtained at each assessment, along with behavioral measures including the Stroke Impact Scale (SIS) and the Action Research Arm Test (ARAT). Clinically significant improvements in behavioral measures were noted over the course of BCI therapy, with more than 10 point gains in both the ARAT scores and scores for the SIS hand function domain. Neuroimaging during finger tapping of the impaired hand also showed changes in brain activation patterns associated with BCI therapy. This case study demonstrates the potential for individuals who have preexisting disability or possible atypical brain organization to learn to use a BCI system that may confer some rehabilitative benefit.

Changes in functional connectivity correlate with behavioral gains in stroke patients after therapy using a brain-computer interface device.

Brain-computer interface (BCI) technology is being incorporated into new stroke rehabilitation devices, but little is known about brain changes associated with its use. We collected anatomical and functional MRI of nine stroke patients with persistent upper extremity motor impairment before, during, and after therapy using a BCI system. Subjects were asked to perform finger tapping of the impaired hand during fMRI. Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) domains of Hand Function (HF) and Activities of Daily Living (ADL) were also assessed. Group-level analyses examined changes in whole-brain task-based functional connectivity (FC) to seed regions in the motor network observed during and after BCI therapy. Whole-brain FC analyses seeded in each thalamus showed FC increases from baseline at mid-therapy and post-therapy (p < 0.05). Changes in FC between seeds at both the network and the connection levels were examined for correlations with changes in behavioral measures. Average motor network FC was increased post-therapy, and changes in average network FC correlated (p < 0.05) with changes in performance on ARAT (R (2) = 0.21), 9-HPT (R (2) = 0.41), SIS HF (R (2) = 0.27), and SIS ADL (R (2) = 0.40). Multiple individual connections within the motor network were found to correlate in change from baseline with changes in behavioral measures. Many of these connections involved the thalamus, with change in each of four behavioral measures significantly correlating with change from baseline FC of at least one thalamic connection. These preliminary results show changes in FC that occur with the administration of rehabilitative therapy using a BCI system. The correlations noted between changes in FC measures and changes in behavioral outcomes indicate that both adaptive and maladaptive changes in FC may develop with this therapy and also suggest a brain-behavior relationship that may be stimulated by the neuromodulatory component of BCI therapy.

Non-invasive neuromodulation to improve gait in chronic multiple sclerosis: a randomized double blind controlled pilot trial.

BACKGROUND: This study sought to examine the effect of targeted physical therapy with and without cranial nerve non-invasive neuromodulation (CN-NINM), on the walking ability of people with MS who exhibited a dysfunctional gait. We hypothesized that subjects who received electrical stimulation would have greater improvement than those who had a control device after a 14-week intervention. Gait disturbance is a common problem for people with multiple sclerosis (MS). Current management may include exercise, pharmacology, functional electrical stimulation, compensatory strategies, use of assistive devices, and implanted electrical devices. We have developed an effective rehabilitative strategy using neuromodulation of the cranial nerves via electrical stimulation of the tongue to enhance the plasticity of the brain. METHODS: The study is a within-subject blinded randomized control design. Twenty chronic MS subjects with an identified gait disturbance were assigned to either an active or control group. Both groups completed a 14-week intervention program using a standardized combination of exercise and a device that provided electrical stimulation to the tongue. Those in the active group received electrical stimulation on the tongue that they could perceive. Those in the control group used a device that did not provide a physiologically significant stimulus and was not perceivable. Subjects were assessed with the Dynamic Gait Index (DGI). RESULTS: The DGI scores improved for both groups. There were significant between-group differences, with the active group showing statistically greater improvement than the control group mean. CONCLUSION: People with MS demonstrated improved gait with CN-NINM training in a pilot randomized controlled trial. This study suggests that tongue-based neurostimulation may amplify the benefits of exercise for improving gait in people with chronic MS.

Altered connectivity of the balance processing network after tongue stimulation in balance-impaired individuals.

Some individuals with balance impairment have hypersensitivity of the motion-sensitive visual cortices (hMT+) compared to healthy controls. Previous work showed that electrical tongue stimulation can reduce the exaggerated postural sway induced by optic flow in this subject population and decrease the hypersensitive response of hMT+. Additionally, a region within the brainstem (BS), likely containing the vestibular and trigeminal nuclei, showed increased optic flow-induced activity after tongue stimulation. The aim of this study was to understand how the modulation induced by tongue stimulation affects the balance-processing network as a whole and how modulation of BS structures can influence cortical activity. Four volumes of interest, discovered in a general linear model analysis, constitute major contributors to the balance-processing network. These regions were entered into a dynamic causal modeling analysis to map the network and measure any connection or topology changes due to the stimulation. Balance-impaired individuals had downregulated response of the primary visual cortex (V1) to visual stimuli but upregulated modulation of the connection between V1 and hMT+ by visual motion compared to healthy controls (p ≤ 1E-5). This upregulation was decreased to near-normal levels after stimulation. Additionally, the region within the BS showed increased response to visual motion after stimulation compared to both prestimulation and controls. Stimulation to the tongue enters the central nervous system at the BS but likely propagates to the cortex through supramodal information transfer. We present a model to explain these brain responses that utilizes an anatomically present, but functionally dormant pathway of information flow within the processing network.

High-resolution fMRI detects neuromodulation of individual brainstem nuclei by electrical tongue stimulation in balance-impaired individuals.

High-resolution functional magnetic resonance imaging (fMRI) can be used to precisely identify blood oxygen level dependent (BOLD) activation of small structures within the brainstem not accessible with standard fMRI. A previous study identified a region within the pons exhibiting sustained neuromodulation due to electrical tongue stimulation, but was unable to precisely identify the neuronal structure involved. For this study, high-resolution images of neural activity induced by optic flow were acquired in nine healthy controls and nine individuals with balance dysfunction before and after information-free tongue stimulation. Subjects viewed optic flow videos to activate the structures of interest. Sub-millimeter in-plane voxels of structures within the posterior fossa were acquired using a restricted field of view. Whole-brain functional imaging verified that global activation patterns due to optic flow were consistent with previous studies. Optic flow activated the visual association cortices, the vestibular nuclei, and the superior colliculus, as well as multiple regions within the cerebellum. The anterior cingulate cortex showed decreased activity after stimulation, while a region within the pons had increased post-stimulation activity. These observations suggest the pontine region is the trigeminal nucleus and that tongue stimulation interfaces with the balance-processing network within the pons. This high-resolution imaging allows detection of activity within individual brainstem nuclei not possible using standard resolution imaging.

Electrical tongue stimulation normalizes activity within the motion-sensitive brain network in balance-impaired subjects as revealed by group independent component analysis.

Multivariate analysis of functional magnetic resonance imaging (fMRI) data allows investigations into network behavior beyond simple activations of individual regions. We apply group independent component analysis to fMRI data collected in a previous study looking at the sustained neuromodulatory effects of electrical tongue stimulation in balance-impaired individuals. Twelve subjects with balance disorders viewed optic flow in an fMRI scanner before and after 5 days of electrical tongue stimulation. Nine healthy controls also viewed the visual stimuli but did not receive any stimulation. Multiple regression of the 47 estimated components found two that were modulated by the visual stimuli. Component 7, comprised primarily of the primary visual cortex (V1), responded to all visual stimuli and showed no difference in task-related activity between the healthy controls and the balance-impaired subjects before or after stimulation. Component 11 responded only to motion in the visual field and contained multiple cortical and subcortical regions involved in processing information pertinent to balance. Two-sample t-tests of the calculated signal change revealed that the task-related activity of this network is greater in balance-impaired subjects compared with controls before stimulation (p=0.02), but that this network hypersensitivity decreases after electrical tongue stimulation (p=0.001).

Sustained cortical and subcortical neuromodulation induced by electrical tongue stimulation.

This pilot study aimed to show that information-free stimulation of the tongue can improve behavioral measures and induce sustained neuromodulation of the balance-processing network in individuals with balance dysfunction. Twelve balance-impaired subjects received one week of cranial nerve non-invasive neuromodulation (CN-NINM). Before and after the week of stimulation, postural sway and fMRI activation were measured to monitor susceptibility to optic flow. Nine normal controls also underwent the postural sway and fMRI tests but did not receive CN-NINM. Results showed that before CN-NINM balance-impaired subjects swayed more than normal controls as expected (p ≤ 0.05), and that overall sway and susceptibility to optic flow decreased after CN-NINM (p ≤ 0.005 & p ≤ 0.05). fMRI showed upregulation of visual sensitivity to optic flow in balance-impaired subjects that decreased after CN-NINM. A region of interest analysis indicated that CN-NINM may induce neuromodulation by increasing activity within the dorsal pons (p ≤ 0.01).

Spatial mapping of electrotactile sensation threshold and intensity range on the human tongue: initial results.

We have developed a novel, tongue-based electrotactile brain-machine interface. Variability of the tactile sensation intensity across the stimulated area, however, limits the amount of reliable information transmission. We have conducted an experiment to characterize local sensitivity across the region stimulated by the array. From this data we have constructed an isointensity algorithm to compensate for the variability in electrotactile sensation levels across the stimulated area of the tongue.

Polarity effect in electrovibration for tactile display.

Electrovibration is the tactile sensation of an alternating potential between the human body and a smooth conducing surface when the skin slides over the surface and where the current is too small to stimulate sensory nerves directly. It has been proposed as a high-density tactile display method, for example to display pictographic information to persons who are blind. Previous models for the electrovibration transduction mechanism are based on a parallel-plate capacitor in which the electrostatic force is insensitive to polarity. We present experimental data showing that electrovibratory perceptual sensitivity to positive pulses is less than that for negative or biphasic pulses and propose that this disparity may be due to the asymmetric electrical properties of human skin. We furthermore propose using negative pulses for insulated tactile displays based on electrovibration because their sensory thresholds were found to be more stable than for waveforms incorporating positive pulses.