Motor cortical functional connectivity changes due to short-term immobilization of upper limb: an fNIRS case report.

Introduction: A short-term immobilization of one hand affects musculoskeletal functions, and the associated brain network adapts to the alterations happening to the body due to injuries. It was hypothesized that the injury-associated temporary disuse of the upper limb would alter the functional interactions of the motor cortical processes and will produce long-term changes throughout the immobilization and post-immobilization period. Methods: The case participant (male, 12 years old, right arm immobilized for clavicle fracture) was scanned using optical imaging technology of fNIRS over immobilization and post-immobilization. Pre-task data was collected for 3 min for RSFC analysis, processed, and analyzed using the Brain AnalyzIR toolbox. Connectivity was measured using Pearson correlation coefficients (R) from NIRS Toolbox's connectivity module. Results: The non-affected hand task presented an increased ipsilateral response during the immobilization period, which then decreased over the follow-up visits. The right-hand task showed a bilateral activation pattern following immobilization, but the contralateral activation pattern was restored during the 1-year follow-up visit. Significant differences in the average connection strength over the study period were observed. The average Connection strength decreased from the third week of immobilization and continued to be lower than the baseline value. Global network efficiency decreased in weeks two and three, while the network settled into a higher efficient state during the follow-up periods after post-immobilization. Discussion: Short-term immobilization of the upper limb is shown to have cortical changes in terms of activations of brain regions as well as connectivity. The short-term dis-use of the upper limb has shifted the unilateral activation pattern to the bilateral coactivation of the motor cortex from both hemispheres. Resting-state data reveals a disruption in the motor cortical network during the immobilization phase, and the network is reorganized into an efficient network over 1 year after the injury. Understanding such cortical reorganization could be informative for studying the recovery from neurological disorders affecting motor control in the future.

Phantom limb therapy improves cortical efficiency of the sensorimotor network in a targeted muscle reinnervation amputee: a case report.

Targeted muscle reinnervation (TMR) surgery involves the coaptation of amputated nerves to nearby motor nerve branches with the purpose of reclosing the neuromuscular loop in order to reduce phantom limb pain. The purpose of this case study was to create a phantom limb therapy protocol for an amputee after undergoing TMR surgery, where the four main nerves of his right arm were reinnervated into the chest muscles. The goal of this phantom limb therapy was to further strengthen these newly formed neuromuscular closed loops. The case participant (male, 21- years of age, height = 5'8″ and weight = 134 lbs) presented 1- year after a trans-humeral amputation of the right arm along with TMR surgery and participated in phantom limb therapy for 3 months. Data collections for the subject occurred every 2 weeks for 3 months. During the data collections, the subject performed various movements of the phantom and intact limb specific to each reinnervated nerve and a gross manual dexterity task (Box and Block Test) while measuring brain activity and recording qualitative feedback from the subject. The results demonstrated that phantom limb therapy produced significant changes of cortical activity, reduced fatigue, fluctuation in phantom pain, improved limb synchronization, increased sensory sensation, and decreased correlation strength between intra-hemispheric and inter-hemispheric channels. These results suggest an overall improved cortical efficiency of the sensorimotor network. These results add to the growing knowledge of cortical reorganization after TMR surgery, which is becoming more common to aid in the recovery after amputation. More importantly, the results of this study suggest that the phantom limb therapy may have accelerated the decoupling process, which provides direct clinical benefits to the patient such as reduced fatigue and improved limb synchronization.

Chronic Stimulation Improves Motor Performance in an Ambulatory Rat Model of Spinal Cord Injury.

BACKGROUND: The purpose of this proof-of-concept feasibility study was to determine if spike-triggered intraspinal microstimulation (ISMS), a form of activity dependent stimulation (ADS), results in improved motor performance in an ambulatory rat model of spinal cord injury (SCI). METHODS: Experiments were carried out in adult male Sprague Dawley rats with moderate thoracic contusion injury. Rats were assigned to one of two groups: Control or ADS therapy. Four weeks post-SCI, all rats were implanted with a recording microelectrode in the left hindlimb motor cortex and a fine-wire stimulating electrode in the contralateral lumbar spinal cord. ADS was administered for 4 hours/day, 4 days/week, for 4 weeks. During therapy sessions, single-unit spikes were discriminated in real time in the hindlimb motor cortex and used to trigger stimulation in the spinal cord ventral horn. Control rats were similarly implanted with electrodes but did not receive stimulation therapy. RESULTS: Motor performances of each rat were evaluated before SCI contusion, once a week post-SCI for four weeks (prior to electrode implantation), and once a week post-conditioning for four weeks. Basso, Beattie, and Bresnahan (BBB) locomotor scores were significantly improved in ADS rats compared to Control rats at 1 and 2 weeks after initiation of therapy. Foot fault scores on the Horizontal Ladder were significantly improved in ADS rats compared to pre-therapy ADS and Control rats after 1 week of therapy and recovered to near pre-injury scores after 3 weeks of therapy. The Ledged Beam test showed deficits after SCI in both ADS and Control rats but there were no significant differences between groups after 4 weeks of ADS therapy. CONCLUSIONS: These results show that chronic stimulation after spinal cord injury using a methodology of spike-triggered ISMS enhances behavioral recovery of locomotor function as measured by the BBB score and the Horizontal Ladder task. However, it is still uncertain if the behavioral improvements seen were dependent on spike-triggered ISMS.

Laterality Index Calculations in a Control Study of Functional Near Infrared Spectroscopy.

Hemispheric dominance has been used to understand the influence of central and peripheral neural damage on the motor function of individuals with stroke, cerebral palsy, and limb loss. It has been well established that greater activation occurs in the contralateral hemisphere to the side of the body used to perform the task. However, there is currently a large variability in calculation procedures for brain laterality when using functional near-infrared spectroscopy (fNIRS) as a non-invasive neuroimaging tool. In this study, we used fNIRS to measure brain activity over the left and right sensorimotor cortices while participants (n = 20, healthy and uninjured) performed left and right-hand movement tasks. Then, we analyzed the fNIRS data using two different processing pipelines (block averaging or general linear model [GLM]), two different criteria of processing for negative values (include all beta values or include only positive beta values), and three different laterality index (LI) formulas. The LI values produced using the block averaging analysis indicated an expected contralateral dominance with some instances of bilateral dominance, which agreed with the expected contralateral activation. However, the inclusion criteria nor the LI formulas altered the outcome. The LI values produced using the GLM analysis displayed a robust left hemisphere dominance regardless of the hand performing the task, which disagreed with the expected contralateral activation but did provide instances of correctly identifying brain laterality. In conclusion, both analysis pipelines were able to correctly determine brain laterality, but processes to account for negative beta values were recommended especially when utilizing the GLM analysis to determine brain laterality.

Home intervention for children and adolescents with unilateral trans-radial and partial carpal reduction deficiencies.

Current training interventions assessing pediatric functional motor skills do not account for children and adolescents with upper limb reductions who utilize a prosthesis. Prosthesis rejection showed that 1 out of 5 prosthesis users will reject their prosthesis due to lack of durability, lack of function, not meeting the participant's needs, perceived lack of need, and medical restrictions indicating that prosthetic users believed they were more functional without the device. It was hypothesized that an 8-week Home Intervention program will result in significant improvements in gross manual dexterity, bimanual coordination, and the functional activities performed during the program. It was also hypothesized that the novel Prosthesis Measurement of Independent Function (PMIF) score will reflect the Home Intervention performance improvements. Five pediatric participants (ages 5-19 years) with congenital upper limb reductions were fitted with a 3D printed upper extremity prosthesis for their affected limb. Participants then completed the 8-week Home Intervention which included Training activities completed 2×/week for 8 weeks and Non-Training activities completed only at week 1 and week 8. Participant's times were recorded along with each participant receiving a PMIF score ranging from 0 = unable to complete activity, to 7 = complete independence with activity completion. Results showed a decrease in overall averaged activity times amongst all activities. For all activities performed, individual averaged time decreased with the exception of Ball Play which increased over the 8-week intervention period. There was significant interaction for Home Intervention performance with F = 2.904 (p = 0.003). All participants increased their PMIF scores to 7 (complete independence) at the end of the 8 week intervention period. Decreases in time averages and increases in PMIF scores indicate that learning and functional use of the prostheses have occurred amongst the pediatric participants.

Activity dependent stimulation increases synaptic efficacy in spared pathways in an anesthetized rat model of spinal cord contusion injury.

BACKGROUND: Closed-loop neuromodulation systems have received increased attention in recent years as potential therapeutic approaches for treating neurological injury and disease. OBJECTIVE: The purpose of this study was to assess the ability of intraspinal microstimulation (ISMS), triggered by action potentials (spikes) recorded in motor cortex, to alter synaptic efficacy in descending motor pathways in an anesthetized rat model of spinal cord injury (SCI). METHODS: Experiments were carried out in adult, male, Sprague Dawley rats with a moderate contusion injury at T8. For activity-dependent stimulation (ADS) sessions, a recording microelectrode was used to detect neuronal spikes in motor cortex that triggered ISMS in the spinal cord grey matter. SCI rats were randomly assigned to one of four experimental groups differing by: a) cortical spike-ISMS stimulus delay (10 or 25 ms) and b) number of ISMS pulses (1 or 3). Four weeks after SCI, ADS sessions were conducted in three consecutive 1-hour conditioning bouts for a total of 3 hours. At the end of each conditioning bout, changes in synaptic efficacy were assessed using intracortical microstimulation (ICMS) to examine the number of spikes evoked in spinal cord neurons during 5-minute test bouts. A multichannel microelectrode recording array was used to record cortically-evoked spike activity from multiple layers of the spinal cord. RESULTS: The results showed that ADS resulted in an increase in cortically-evoked spikes in spinal cord neurons at specific combinations of spike-ISMS delays and numbers of pulses. Efficacy in descending motor pathways was increased throughout all dorsoventral depths of the hindlimb spinal cord. CONCLUSIONS: These results show that after an SCI, ADS can increase synaptic efficacy in spared pathways between motor cortex and spinal cord. This study provides further support for the potential of ADS therapy as an effective method for enhancing descending motor control after SCI.

Use-Dependent Prosthesis Training Strengthens Contralateral Hemodynamic Brain Responses in a Young Adult With Upper Limb Reduction Deficiency: A Case Report.

The purpose of the current case study was to determine the influence of an 8-week home intervention training utilizing a partial hand prosthesis on hemodynamic responses of the brain and gross dexterity in a case participant with congenital unilateral upper-limb reduction deficiency (ULD). The case participant (female, 19 years of age) performed a gross manual dexterity task (Box and Block Test) while measuring brain activity (functional near-infrared spectroscopy; fNIRS) before and after an 8-weeks home intervention training. During baseline, there was a broad cortical activation in the ipsilateral sensorimotor cortex and a non-focalized cortical activation in the contralateral hemisphere, which was non-focalized, while performing a gross manual dexterity task using a prosthesis. After the 8-week home intervention training, however, cortical activation shifted to the contralateral motor cortex while cortical activation was diminished in the ipsilateral hemisphere. Specifically, the oxygenated hemodynamics (HbO) responses increased in the medial aspects of the contralateral primary motor and somatosensory cortices. Thus, these results suggest that an 8-week prosthetic home intervention was able to strengthen contralateral connections in this young adult with congenital partial hand reduction. This was supported by the case participant showing after training an increased flexor tone, increased range of motion of the wrist, and decreased times to complete various gross dexterity tasks. Changes in HbO responses due to the home intervention training follow the mechanisms of use-dependent plasticity and further guide the use of prostheses as a rehabilitation strategy for individuals with ULD.

Effects of a contusive spinal cord injury on cortically-evoked spinal spiking activity in rats.

Objective.The purpose of this study was to determine the effects of spinal cord injury (SCI) on spike activity evoked in the hindlimb spinal cord of the rat from cortical electrical stimulation.Approach.Adult, male, Sprague Dawley rats were randomly assigned to a Healthy or SCI group. SCI rats were given a 175 kDyn dorsal midline contusion injury at the level of the T8 vertebrae. At 4 weeks post-SCI, intracortical microstimulation (ICMS) was delivered at several sites in the hindlimb motor cortex of anesthetized rats, and evoked neural activity was recorded from corresponding sites throughout the dorsoventral depths of the spinal cord and EMG activity from hindlimb muscles.Main results.In healthy rats, post-ICMS spike histograms showed reliable, evoked spike activity during a short-latency epoch 10-12 ms after the initiation of the ICMS pulse train (short). Longer latency spikes occurred between ∼20 and 60 ms, generally following a Gaussian distribution, rising above baseline at timeLON, followed by a peak response (Lp), and then falling below baseline at timeLOFF. EMG responses occurred betweenLONandLp( 25-27 ms). In SCI rats, short-latency responses were still present, long-latency responses were disrupted or eliminated, and EMG responses were never evoked. The retention of the short-latency responses indicates that spared descending spinal fibers, most likely via the cortico-reticulospinal pathway, can still depolarize spinal cord neurons after a dorsal midline contusion injury.Significance.This study provides novel insights into the role of alternate pathways for voluntary control of hindlimb movements after SCI that disrupts the corticospinal tract in the rat.

A Brain-Spinal Interface (BSI) System-on-Chip (SoC) for Closed-Loop Cortically-Controlled Intraspinal Microstimulation.

This paper reports on a fully miniaturized brain-spinal interface (BSI) system for closed-loop cortically-controlled intraspinal microstimulation (ISMS). Fabricated in AMS 0.35µm two-poly four-metal complementary metal-oxide-semiconductor (CMOS) technology, this system-on-chip (SoC) measures ~ 3.46mm × 3.46mm and incorporates two identical 4-channel modules, each comprising a spike-recording front-end, embedded digital signal processing (DSP) unit, and programmable stimulating back-end. The DSP unit is capable of generating multichannel trigger signals for a wide array of ISMS triggering patterns based on real-time discrimination of a programmable number of intracortical neural spikes within a pre-specified time-bin duration via thresholding and user-adjustable time-amplitude windowing. The system is validated experimentally using an anesthetized rat model of a spinal cord contusion injury at the T8 level. Multichannel neural spikes are recorded from the cerebral cortex and converted in real time into electrical stimuli delivered to the lumbar spinal cord below the level of the injury, resulting in distinct patterns of hindlimb muscle activation.

A 3D map of the hindlimb motor representation in the lumbar spinal cord in Sprague Dawley rats.

OBJECTIVE: Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. APPROACH: Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a 3D (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and electromyographic (EMG) activity. Via fine wire EMG electrodes, stimulus-triggered averaging (StTA) was used on rectified EMG data to determine response latency. MAIN RESULTS: Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. SIGNIFICANCE: The derived motor map provides insight into the parameters needed for future neuromodulatory devices.