Chaithanya K. Mummidisetty

Primary motor and premotor cortex in implicit sequence learning - evidence for competition between implicit and explicit human motor memory systems

Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1‐AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd‐AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1‐AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd‐AtDCS during practice attenuated offline stabilization compared with M1‐AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition.

Locomotor training improves premotoneuronal control after chronic spinal cord injury

Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans. In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level. Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day. The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training. The soleus H reflexes evoked at 1.0, 0.33, 0.20, 0.14, and 0.11 Hz were normalized to the H reflex evoked at 0.09 Hz. Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle. Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI. Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients. In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest. During stepping, presynaptic inhibition was modulated in a phase-dependent manner. Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg. The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking.

Effects of a wearable exoskeleton stride management assist system (SMA®) on spatiotemporal gait characteristics in individuals after stroke: a randomized controlled trial

BackgroundRobots offer an alternative, potentially advantageous method of providing repetitive, high-dosage, and high-intensity training to address the gait impairments caused by stroke. In this study, we compared the effects of the Stride Management Assist (SMA®) System, a new wearable robotic device developed by Honda R&D Corporation, Japan, with functional task specific training (FTST) on spatiotemporal gait parameters in stroke survivors.MethodsA single blinded randomized control trial was performed to assess the effect of FTST and task-specific walking training with the SMA® device on spatiotemporal gait parameters. Participants (n = 50) were randomly assigned to FTST or SMA. Subjects in both groups received training 3 times per week for 6–8 weeks for a maximum of 18 training sessions. The GAITRite® system was used to collect data on subjects’ spatiotemporal gait characteristics before training (baseline), at mid-training, post-training, and at a 3-month follow-up.ResultsAfter training, significant improvements in gait parameters were observed in both training groups compared to baseline, including an increase in velocity and cadence, a decrease in swing time on the impaired side, a decrease in double support time, an increase in stride length on impaired and non-impaired sides, and an increase in step length on impaired and non-impaired sides. No significant differences were observed between training groups; except for SMA group, step length on the impaired side increased significantly during self-selected walking speed trials and spatial asymmetry decreased significantly during fast-velocity walking trials.ConclusionsSMA and FTST interventions provided similar, significant improvements in spatiotemporal gait parameters; however, the SMA group showed additional improvements across more parameters at various time points. These results indicate that the SMA® device could be a useful therapeutic tool to improve spatiotemporal parameters and contribute to improved functional mobility in stroke survivors. Further research is needed to determine the feasibility of using this device in a home setting vs a clinic setting, and whether such home use provides continued benefits.Trial registrationThis study is registered under the title “Development of walk assist device to improve community ambulation” and can be located in clinicaltrials.gov with the study identifier: NCT01994395.

Reduced reciprocal inhibition during assisted stepping in human spinal cord injury

The aim of this study was to establish the modulation pattern of the reciprocal inhibition exerted from tibialis anterior (TA) group I afferents onto soleus motoneurons during body weight support (BWS) assisted stepping in people with spinal cord injury (SCI). During assisted stepping, the soleus H-reflex was conditioned by percutaneous stimulation of the ipsilateral common peroneal nerve at one fold TA M-wave motor threshold with a single pulse delivered at a short conditioning-test interval. To counteract movement of recording and stimulating electrodes, a supramaximal stimulus at 80-100 ms after the test H-reflex was delivered. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. The conditioned soleus H-reflex was significantly facilitated throughout the stance phase, while during swing no significant changes on the conditioned H-reflex were observed when compared to the unconditioned soleus H-reflex recorded during stepping. Spontaneous clonic activity in triceps surae muscle occurred in multiple phases of the step cycle at a mean frequency of 7 Hz for steps with and without stimulation. This suggests that electrical excitation of TA and soleus group Ia afferents did not contribute to manifestation of ankle clonus. Absent reciprocal inhibition is likely responsible for lack of soleus H-reflex depression in swing phase observed in these patients. The pronounced reduced reciprocal inhibition in stance phase may contribute to impaired levels of co-contraction of antagonistic ankle muscles. Based on these findings, we suggest that rehabilitation should selectively target to transform reciprocal facilitation to inhibition through computer controlled reflex conditioning protocols.

Soleus H-reflex phase-dependent modulation is preserved during stepping within a robotic exoskeleton.

OBJECTIVE To investigate to what extent the phase-dependent modulation of the soleus H-reflex is preserved when bilateral leg movements are electromechanically driven by a robotic exoskeleton at different levels of body weight support (BWS) in healthy subjects. METHODS The soleus H-reflex was elicited by posterior tibial nerve stimulation with a 1-ms single pulse at an intensity that the M-waves ranged from 4% to 9% of the maximal M-wave across subjects. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. At each bin, a maximal M-wave was elicited 100 ms after the test H-reflex and was used to normalize the associated M-wave and H-reflex. Electromyographic (EMG) activity from major hip, knee, and ankle muscles was recorded with surface bipolar electrodes. For each subject and muscle, the integrated EMG profile was established and plotted as a function of the step cycle phases. The H-reflex gain was determined as the slope of the relationship between the H-reflex and soleus EMG amplitudes at 100 ms before the H-reflex for each bin. RESULTS During robotic assisted stepping, the phase-dependent soleus H-reflex modulation pattern was preserved and was similar at 25% and 50% BWS, a linear relationship between soleus H-reflex amplitude and background activity was found, and the reflex gain did not change with alterations of the BWS level. EMG amplitudes were smaller at 50% compared to 25% BWS. CONCLUSIONS Body unloading, decreased EMG amplitude of ankle extensors, and reduced ankle movement are not key factors for the soleus H-reflex phasic excitability to be manifested. SIGNIFICANCE Robotic devices are utilized for rehabilitation of gait in neurological disorders. Based on our findings, spinal interneuronal circuits involved in the phase-dependent modulation of the soleus H-reflex will be engaged in a physiological manner during robotic assisted stepping in neurological disorders.

Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury

In humans, a chronic spinal cord injury (SCI) impairs the excitability of pathways mediating early flexor reflexes and increases the excitability of late, long-lasting flexor reflexes. We hypothesized that in individuals with SCI, locomotor training will alter the behavior of these spinally mediated reflexes. Nine individuals who had either chronic clinically motor complete or incomplete SCI received an average of 44 locomotor training sessions. Flexor reflexes, elicited via sural nerve stimulation of the right or left leg, were recorded from the ipsilateral tibialis anterior (TA) muscle before and after body weight support (BWS)-assisted treadmill training. The modulation pattern of the ipsilateral TA responses following innocuous stimulation of the right foot was also recorded in 10 healthy subjects while they stepped at 25% BWS to investigate whether body unloading during walking affects the behavior of these responses. Healthy subjects did not receive treadmill training. We observed a phase-dependent modulation of early TA flexor reflexes in healthy subjects with reduced body weight during walking. The early TA flexor reflexes were increased at heel contact, progressively decreased during the stance phase, and then increased throughout the swing phase. In individuals with SCI, locomotor training induced the reappearance of early TA flexor reflexes and changed the amplitude of late TA flexor reflexes during walking. Both early and late TA flexor reflexes were modulated in a phase-dependent pattern after training. These new findings support the adaptive capability of the injured nervous system to return to a prelesion excitability and integration state.

Corticospinal Reorganization after Locomotor Training in a Person with Motor Incomplete Paraplegia

Activity-dependent plasticity as a result of reorganization of neural circuits is a fundamental characteristic of the central nervous system that occurs simultaneously in multiple sites. In this study, we established the effects of subthreshold transcranial magnetic stimulation (TMS) over the primary motor cortex region on the tibialis anterior (TA) long-latency flexion reflex. Neurophysiological tests were conducted before and after robotic gait training in one person with a motor incomplete spinal cord injury (SCI) while at rest and during robotic-assisted stepping. The TA flexion reflex was evoked following nonnociceptive sural nerve stimulation and was conditioned by TMS at 0.9 TA motor evoked potential resting threshold at conditioning-test intervals that ranged from 70 to 130 ms. Subthreshold TMS induced a significant facilitation on the TA flexion reflex before training, which was reversed to depression after training with the subject seated at rest. During stepping, corticospinal facilitation of the flexion reflex at early and midstance phases before training was replaced with depression at early and midswing followed by facilitation at late swing after training. These results constitute the first neurophysiologic evidence that locomotor training reorganizes the cortical control of spinal interneuronal circuits that generate patterned motor activity, modifying spinal reflex function, in the chronic lesioned human spinal cord.

Modulation of reciprocal and presynaptic inhibition during robotic-assisted stepping in humans

OBJECTIVE To establish the modulation pattern of reciprocal inhibition and presynaptic inhibition of soleus Ia afferents during robot-assisted stepping in healthy subjects. METHODS During stepping, the soleus H-reflex was conditioned by percutaneous stimulation of the ipsilateral common peroneal nerve with a single pulse at stimulation intensities that ranged from 0.9 to 1.2 TA M-wave motor thresholds across subjects. To control for movement of recording and stimulating electrodes, a supramaximal stimulus 80ms after the conditioned and/or unconditioned H-reflexes was delivered to the posterior tibial nerve. The short (2, 3, 4ms) and long (60-80ms) conditioning-test intervals at which the largest amount of reflex depression was observed with the subjects seated were utilized during stepping. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. RESULTS Reciprocal inhibition exerted from flexor group I afferents onto soleus motoneurons was decreased at mid-stance and increased and late-stance and throughout the swing phase. Presynaptic inhibition of soleus Ia afferents was increased at heel strike and decreased at late-stance and early swing phases. CONCLUSION Reciprocal inhibition between ankle antagonistic muscles and presynaptic inhibition of soleus Ia afferents are modulated in a similar pattern to that reported during walking on a treadmill with full weight bearing and without robot-assisted leg movement. SIGNIFICANCE The activity of spinal interneuronal circuits engaged in patterned locomotor activity supports a reciprocal gait pattern during robot-assisted stepping in healthy humans.

Automatic analysis of EMG during clonus.

Clonus can disrupt daily activities after spinal cord injury. Here an algorithm was developed to automatically detect contractions during clonus in 24h electromyographic (EMG) records. Filters were created by non-linearly scaling a Mother (Morlet) wavelet to envelope the EMG using different frequency bands. The envelope for the intermediate band followed the EMG best (74.8-193.9 Hz). Threshold and time constraints were used to reduce the envelope peaks to one per contraction. Energy in the EMG was measured 50 ms either side of each envelope (contraction) peak. Energy values at 5% and 95% maximal defined EMG start and end time, respectively. The algorithm was as good as a person at identifying contractions during clonus (p=0.946, n=31 spasms, 7 subjects with cervical spinal cord injury), and marking start and end times to determine clonus frequency (intra class correlation coefficient, α: 0.949), contraction intensity using root mean square EMG (α: 0.997) and EMG duration (α: 0.852). On average the algorithm was 574 times faster than manual analysis performed independently by two people (p ≤ 0.001). This algorithm is an important tool for characterization of clonus in long-term EMG records.

Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs.