Effects of Transcranial Direct Current Stimulation over the Supplementary Motor Area Combined with Walking on the Intramuscular Coherence of the Tibialis Anterior in a Subacute Post-Stroke Patient: A Single-Case Study.

The role of corticospinal excitability and corticospinal lesion load in recovery of manual dexterity after stroke: A longitudinal pilot study

IntroductionGait impairment is a common and disabling consequence of stroke. While walking speed is a key indicator of recovery, gait variability is closely associated with fall risk and long-term functional decline. Previous studies have suggested that functional interaction between the supplementary motor area (SMA) and primary motor cortex (M1) plays a key role in post-stroke gait control. Rather than stimulating these regions independently, simultaneous activation of the SMA—critical for rhythm modulation and motor planning—and gait-synchronized stimulation of the M1—essential for motor execution—may offer enhanced benefits for gait stability.ObjectiveTo assess the feasibility, safety, and preliminary effects of a combined brain stimulation intervention targeting the SMA and M1 on gait variability and balance in individuals with post-stroke hemiparesis.MethodsSixteen individuals with stroke within 180 days after the onset, aged 40–90 years, who were able to walk on a treadmill were recruited in this study of multi-center, randomized, controlled pilot trial with a parallel-group design. Participants were randomly allocated to either an intervention group (n = 8) receiving 20 min of simultaneous transcranial direct current stimulation (tDCS) to the SMA and gait-synchronized rhythmic stimulation to the M1 during treadmill walking, or to a control group (n = 8) receiving sham stimulation. Both groups underwent 15 sessions of walking practice over 3 weeks. Primary outcomes were feasibility indicators including recruitment, retention, adherence and adverse events and preliminary estimates of effect on gait variability such as coefficient of variation for stride, stance, and swing times on the paretic side. Balance was assessed using the Mini-Balance Evaluation Systems Test (Mini-BESTest).ResultsAll 16 participants completed the intervention without adverse events, indicating high feasibility. The intervention group showed significantly reduced stride time variability on the paretic side and improved Mini-BESTest scores compared to the control group. A significant correlation was observed between reductions in gait variability and improvements in balance.ConclusionsThis pilot trial supports the feasibility and safety of a combined SMA and M1 stimulation approach. Preliminary findings suggest potential benefits in reducing gait variability and improving balance after stroke, warranting further investigation in a definitive trial.

IntroductionHigh-intensity readmill training (FAST) and functional electrical stimulation (FES) are both evidence-supported interventions that improve gait function post-stroke, but their neural mechanisms are unclear. Here, we tested the hypothesis that FAST–FES training, which incorporates task-specific sensorimotor stimulation to paretic ankle muscles, would induce greater upregulation of lesioned corticospinal tract (CST) excitability compared to dose-matched training without FES in individuals post-stroke.MethodsIn this repeated-measures crossover study, 11 participants >6 months post-stroke (66.25 ± 8.15 years, six females) received FAST–FES or FAST gait training protocols (comprising three training sessions) in a randomized order, with an intervening >3-week washout period. FES was applied to the paretic dorsi- and plantar-flexor muscles during the paretic swing and terminal stance phases of gait, respectively. CST excitability was measured before and after each training protocol from bilateral tibialis anterior and soleus muscles in three different test positions: sit–rest, sit–active, and quiet standing.ResultsWe found a significant main effect of intervention on training-induced change in motor evoked potential (MEP) amplitude (p=0.02). Post hoc comparisons revealed that FAST–FES caused a larger training-induced increase in MEPs than FAST training (p=0.01). FAST–FES did not affect CST excitability of the nonlesioned hemisphere, with no significant changes in MEP amplitude of the nonparetic ankle muscles.ConclusionsFAST–FES training increased corticospinal excitability in paretic ankle muscles without upregulating nonparetic ankle corticospinal drive, suggesting preferential induction of neuroplasticity in the lesioned CST.

Spinal and corticospinal excitability changes with voluntary modulation of motor cortex oscillations.

This study was carried out in order to compare stride time (gait) variability of walking not only between young and older adults, but also between “fallers” and “non-fallers”. Moreover, this study aimed to clarify the relationship between stride time variability, balance ability, muscular strength and fall experience. The subjects were 12 young women aged 21.2±2.2 years (young group) and 27 older women aged 66.6±4.4 years (older group). The older group included 14 fallers and 13 non-fallers. They wore an accelerometer on their back and walked at a slow, preferred or fast pace. The time of heel contact was detected by acceleration waveform, and stride time was estimated. The stride time variability was computed by the coefficient of variance (CV) of stride time. The subjects underwent balance tests and muscular strength tests. The CV of stride time at the preferred and fast pace were significantly larger in the older group than in the young group, even though there was no difference in any of the gait speeds between the two. The CV of stride time was significantly larger in fallers than in non-fallers at the fast pace. Path analysis showed that fall experience was affected by an increase in the CV of stride time and decreased balance ability, but less affected by decreased muscular strength. Therefore, this study suggested that stride time variability when walking fast is useful as an early assessment of fall risk in middle-aged and elderly people and that fall experience was affected by stride time variability and balance ability.

Objective To explore the pattern of functional reorganization in the cortex after corticospinal tract (CST) injury and its relationship with the recovery of upper limb motor function. Methods Fifteen patients with complete paralysis on one side after acute cerebral infarction were studied. Within 1 week after the onset, functional magnetic resonance imaging (fMRI ) and diffusion tensor tractography (DTT) were performed in parallel with timed finger flexion and extension movements in all subjects. The number of nerve fibers in corticospinal tract (CST) in the affected and healthy sides was measured by using Dtv.Ⅱ.R2 software.One and three months later, fMRI was performed while the affected fingers were flexed and extended passively and any cortical activation was observed. In addition, Fugl-Meyer arm motor function scores were assessed one week, one month and three months after the stroke. Results According to the reconstructed nerve fiber number in CST on the affected side, the patients were classified into three types. Type I: the number of newly-built CST nerve fibers is more than 2/3 of that on the healthy side; type II: the ratio is between 1/3 and 2/3; and type III: the ratio is less than 1/3. For typeⅠpatients, blood oxygenation level-dependent fMRI (bold-fMRI) showed initial activation of the bilateral sensorimotor cortex (SMC) and the supplementary motor area (SMA) on the affected side. That was followed by a gradual decrease in the activity in the healthy SMC and an increase in the affected SMC at 1 and 3 months. Among the type II patients bold-fMRI indicated activation of the SMC and SMA on the affected side initially, significant activation of the bilateral SMC and SMA one month later and then stronger activation in the SMC on the healthy side and a weakening of activation in the SMC on the affected side. For type Ⅲ patients, initially the SMA and the posterior parietal cortex were found to be slightly activated. One month later SM1 on the unaffected side was slightly activated, and 3 months later neither the SMC nor the SMA on either side was activated. One week after the onset, the average upper extremity FM scores of the three types of subjects were not significantly different. After one month the three groups′ averages were all significantly different from one another. But after three months the averages for types I and II were again not significantly different, but significantly better than the average of the type III patients. Conclusion Different CST injuries induce different modes of cortical reorganization. The reorganization is a dynamic process, and different activation patterns are closely correlated with clinical prognosis. Key words: Stroke; Functional magnetic resonance imaging; Tractography; Brain reorganization

Alpha and beta oscillations have been assessed thoroughly during walking due to their potential role as proxies of the corticoreticulospinal tract (CReST) and corticospinal tract (CST), respectively. Given that damage to a descending tract after stroke can cause walking deficits, detailed knowledge of how these oscillations mechanistically contribute to walking could be utilized in strategies for post-stroke locomotor recovery. In this review, the goal was to summarize, synthesize, and discuss the existing evidence on the potential differential role of these oscillations on the motor descending drive, the effect of transcranial alternate current stimulation (tACS) on neurotypical and post-stroke walking, and to discuss remaining gaps in knowledge, future directions, and methodological considerations. Electrophysiological studies of corticomuscular, intermuscular, and intramuscular coherence during walking clearly demonstrate that beta oscillations are predominantly present in the dorsiflexors during the swing phase and may be absent post-stroke. The role of alpha oscillations, however, has not been pinpointed as clearly. We concluded that both animal and human studies should focus on the electrophysiological characterization of alpha oscillations and their potential role to the CReST. Another approach in elucidating the role of these oscillations is to modulate them and then quantify the impact on walking behavior. This is possible through tACS, whose beneficial effect on walking behavior (including boosting of beta oscillations in intramuscular coherence) has been recently demonstrated in both neurotypical adults and stroke patients. However, these studies still do not allow for specific roles of alpha and beta oscillations to be delineated because the tACS frequency used was much lower (i.e., individualized calculated gait frequency was used). Thus, we identify a main gap in the literature, which is tACS studies actually stimulating at alpha and beta frequencies during walking. Overall, we conclude that for beta oscillations there is a clear connection to descending drive in the corticospinal tract. The precise relationship between alpha oscillations and CReST remains elusive due to the gaps in the literature identified here. However, better understanding the role of alpha (and beta) oscillations in the motor control of walking can be used to progress and develop rehabilitation strategies for promoting locomotor recovery.

IntroductionActivation of the unaffected hemisphere contributes to motor function recovery post stroke in patients with severe upper limb motor paralysis. Transcranial direct current stimulation (tDCS) has been used in stroke rehabilitation to increase the excitability of motor-related areas. tDCS has been reported to improve upper limb motor function; nonetheless, its effects on corticospinal tract excitability and muscle activity patterns during upper limb exercise remain unclear. Additionally, it is unclear whether simultaneously applied bihemispheric tDCS is more effective than anodal tDCS, which stimulates only one hemisphere. This study examined the effects of bihemispheric tDCS training on corticospinal tract excitability and muscle activity patterns during upper limb movements in a patient with subacute stroke.MethodsIn this single-case retrospective study, the Fugl–Meyer Assessment, Box and Block Test, electromyography, and intermuscular coherence measurement were performed. Intermuscular coherence was calculated at 15–30 Hz, which reflects corticospinal tract excitability.ResultsThe results indicated that bihemispheric tDCS improved the Fugl–Meyer Assessment, Box and Block Test, co-contraction, and intermuscular coherence results, as compared with anodal tDCS. Discussion: These results reveal that upper limb training with bihemispheric tDCS improves corticospinal tract excitability and muscle activity patterns in patients with subacute stroke.

P 71. The effects of cathodal transcranial direct current stimulation of the supplementary motor area on the function of anticipatory postural adjustments

Lyapunov exponent is a promising parameter to ascertain the stability of the human gait. In this work, we use a time-series model based on a second-order delay-system with inertial measurement units placed on the foot and wrist. Stability is analyzed in a localized sense, with the Lyapunov exponent computed in the temporal region between two heel-strike points, which are determined using a peak-detection algorithm. We have attempted to show correlations between variations in the stride time and stability of the gait under normal and abnormal conditions. In the latter case, we attach a weight on foot to emulate weakness. On comparison between both cases, we observe a statistical significance of p=0.0039 using Wilcoxon’s rank-sum test. Moreover, on observing the correlations between Lyapunov Exponent and Stride Time Variability, we notice a left-shift in the abnormal case, indicating a lower threshold for instability, with the Stride Time Variability being 0.07 as compared to 0.11 in the normal case.The results indicate that by exploiting the correlation between stride time variability and Lyapunov exponents, one can establish a threshold for gait stability.

Understanding neural adaptations to training, and their relation to functional improvements, plays an important role in designing and evaluating training programs. Neural adaptations to strength training have yet to be completely characterized, with disagreement regarding the role of motor cortex (M1). Unlike skill training, which is consistently associated with an increase in excitability and a decrease in inhibition within M1, adaptations to strength training are equivocal. There is evidence that rate of muscleactivation (ROA) used during a training protocol may influence M1 plasticity. In the present study, the role of ROA on acute, neural adaptations to a single session of strength training was evaluated. Thirty subjects participated in a single session of maximal, isometric knee extension testing and training. Subjects were randomized into groups that were tested with high ROA and trained with high ROA (Ballistic), low ROA (Ramp), or did not train (Control). Changes in performance (maximal torque, maximal rate of torque development, muscle activation) were assessed during training and 24 hours after. Transcranial magnetic stimulation, femoral nerve stimulation, and short-interval intracortical inhibition were used to assess changes in corticospinal tract (CST) excitability, spinal reflex excitability, and M1 inhibition for rectus femoris during training and 24 hours after. All three groups improved rate of torque development, with Control apparently due to training effects of the test contractions. Neural adaptations were also similar among groups. Training/testing resulted in an immediate depression of resting M1 excitability, which recovered within ten minutes, and no change in CST excitability during voluntary muscle activation. Training/testing was also associated with increased spinal reflex excitability during voluntary muscle activation, but not rest. M1 inhibition

To find out the optimal treatment sessions of repetitive transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) for upper extremity dysfunction after stroke during the 6-week treatment and to explore its mechanism using motor-evoked potentials (MEPs) and resting-state functional magnetic resonance imaging (rs-fMRI), 72 participants with upper extremity motor dysfunction after ischemic stroke were randomly divided into the control group, 10-session, 20-session, and 30-session rTMS groups. Low-frequency (1 Hz) rTMS over the contralesional M1 was applied in all rTMS groups. The motor function of the upper extremity was assessed before and after treatment. In addition, MEPs and rs-fMRI data were analyzed to detect its effect on brain reorganization. After 6 weeks of treatment, there were significant differences in the Fugl-Meyer Assessment of the upper extremity and the Wolf Motor Function Test scores between the 10-session group and the 30-session group and between the 20- and 30-session groups and the control group, while there was no significant difference between the 20-session group and the 30-session group. Meanwhile, no significant difference was found between the 10-session group and the control group. The 20-session group of rTMS decreased the excitability of the contralesional corticospinal tract represented by the amplitudes of MEPs and enhanced the functional connectivity of the ipsilesional M1 or premotor cortex with the the precentral gyrus, postcentral gyrus, and cingulate gyrus, etc. In conclusion, the 20-session of rTMS protocol is the optimal treatment sessions of TMS for upper extremity dysfunction after stroke during the 6-week treatment. The potential mechanism is related to its influence on the excitability of the corticospinal tract and the remodeling of corticomotor functional networks.

The authors reply

Foot drop and toe walking are frequent concerns in children with cerebral palsy. The main underlying cause of these problems is early damage and lack of maturation of the corticospinal tract. In the present study we investigated whether 4 weeks of daily treadmill training with an incline may facilitate corticospinal transmission and improve the control of the ankle joint in children with cerebral palsy. Sixteen children with cerebral palsy (Gross Motor Classification System I:6, II:6, III:4) aged 5-14 years old, were recruited for the study. Evaluation of gait ability and intramuscular coherence was made twice before and twice after training with an interval of 1 month. Gait kinematics were recorded by 3D video analysis during treadmill walking with a velocity chosen by the child at the first evaluation. Foot pressure was measured by force sensitive foot soles during treadmill and over ground walking. EMG-EMG coherence was calculated from two separate electrode recordings placed over the tibialis anterior muscle. Training involved 30 min of walking daily on a treadmill with an incline for 30 days. Gait training was accompanied by significant increases in gait speed, incline on the treadmill, the maximal voluntary dorsiflexion torque, the number and amplitude of toe lifts late in the swing phase during gait and the weight exerted on the heel during the early stance phase of the gait cycle. EMG-EMG coherence in the beta and gamma frequency bands recorded from tibialis anterior muscle increased significantly when compared to coherence before training. The largest changes in coherence with training were observed for children <10 years of age. Importantly, in contrast to training-induced EMG increases, the increase in coherence was maintained at the follow-up measurement 1 month after training. Changes in the strength of coherence in the beta and gamma band were positively correlated with improvements in the subjects' ability to lift the toes in the swing phase. These data show that daily intensive gait training increases beta and gamma oscillatory drive to ankle dorsiflexor motor neurons and that it improves toe lift and heel strike in children with cerebral palsy. We propose that intensive gait training may produce plastic changes in the corticospinal tract, which are responsible for improvements in gait function.

Locomotor adaptations to a novel environment can be measured through changes in muscle activity patterns and lower limb kinematics. The location and mechanisms underlying these adaptive changes are unknown. The purposes of the current study were (1) to determine whether corticospinal tract (CST) excitability is altered by resisted walking and (2) to ascertain whether changes in cortical excitability are muscle specific. Forty healthy participants walked with a robotic gait device (Lokomat) that applied a velocity-dependent resistance against hip and knee movements during walking. CST excitability was assessed by quantifying motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation immediately before and after baseline and resisted walking. MEPs were measured in either the biceps femoris (BF) or the rectus femoris (RF). Recruitment curves were collected by stimulating in 5 % increments from 105 to 145 % of active motor threshold. Results demonstrated a significant increase in MEP amplitude in the BF following baseline walking in the Lokomat. The RF did not demonstrate these changes. There was no further change in MEP size following resisted walking in either muscle group. These results suggest that locomotion increases CST excitability in a muscle-specific fashion. As such, it may be important for determining how to enhance the central nervous system's ability to integrate adaptive strategies during walking.