Adaptive Brain-Computer Interface with Attention Alterations in Patients with Amyotrophic Lateral Sclerosis.

The users' mental state such as attention variations can have an effect on the brain-computer interface (BCI) performance. In this project, we implemented an adaptive online BCI system with alterations in the users' attention. Twelve electroencephalography (EEG) signals were obtained from six patients with Amyotrophic Lateral Sclerosis (ALS). Participants were asked to execute 40 trials of ankle dorsiflexion concurrently with an auditory oddball task. EEG channels, classifiers and features with superior offline performance in the training phase of the classification of attention level were selected to use in the online mode for prediction the attention status. A feedback was provided to the users to reduce the amount of attention diversion created by the oddball task. The findings revealed that the users' attention can control an online BCI system and real-time neurofeedback can be applied to focus the attention of the user back onto the main task.

Modulation of soleus stretch reflexes during walking in people with chronic incomplete spinal cord injury.

In people with spasticity due to chronic incomplete spinal cord injury (SCI), it has been presumed that the abnormal stretch reflex activity impairs gait. However, locomotor stretch reflexes across all phases of walking have not been investigated in people with SCI. Thus, to understand modulation of stretch reflex excitability during spastic gait, we investigated soleus stretch reflexes across the entire gait cycle in nine neurologically normal participants and nine participants with spasticity due to chronic incomplete SCI (2.5-11 year post-injury). While the participant walked on the treadmill at his/her preferred speed, unexpected ankle dorsiflexion perturbations (6° at 250°/s) were imposed every 4-6 steps. The soleus H-reflex was also examined. In participants without SCI, spinal short-latency "M1", spinal medium latency "M2", and long-latency "M3" were clearly modulated throughout the step cycle; the responses were largest in the mid-stance and almost completely suppressed during the stance-swing transition and swing phases. In participants with SCI, M1 and M2 were abnormally large in the mid-late-swing phase, while M3 modulation was similar to that in participants without SCI. The H-reflex was also large in the mid-late-swing phase. Elicitation of H-reflex and stretch reflexes in the late swing often triggered clonus and affected the soleus activity in the following stance. In individuals without SCI, moderate positive correlation was found between H-reflex and stretch reflex sizes across the step cycle, whereas in participants with SCI, such correlation was weak to non-existing, suggesting that H-reflex investigation would not substitute for stretch reflex investigation in individuals after SCI.

Acquisition of a simple motor skill: task-dependent adaptation and long-term changes in the human soleus stretch reflex.

Changing the H reflex through operant conditioning leads to CNS multisite plasticity and can affect previously learned skills. To further understand the mechanisms of this plasticity, we operantly conditioned the initial component (M1) of the soleus stretch reflex. Unlike the H reflex, the stretch reflex is affected by fusimotor control, comprises several bursts of activity resulting from temporally dispersed afferent inputs, and may activate spinal motoneurons via several different spinal and supraspinal pathways. Neurologically normal participants completed 6 baseline sessions and 24 operant conditioning sessions in which they were encouraged to increase (M1up) or decrease (M1down) M1 size. Five of eight M1up participants significantly increased M1; the final M1 size of those five participants was 143 ± 15% (mean ± SE) of the baseline value. All eight M1down participants significantly decreased M1; their final M1 size was 62 ± 6% of baseline. Similar to the previous H-reflex conditioning studies, conditioned reflex change consisted of within-session task-dependent adaptation and across-session long-term change. Task-dependent adaptation was evident in conditioning session 1 with M1up and by session 4 with M1down. Long-term change was evident by session 10 with M1up and by session 16 with M1down. Task-dependent adaptation was greater with M1up than with the previous H-reflex upconditioning. This may reflect adaptive changes in muscle spindle sensitivity, which affects the stretch reflex but not the H reflex. Because the stretch reflex is related to motor function more directly than the H reflex, M1 conditioning may provide a valuable tool for exploring the functional impact of reflex conditioning and its potential therapeutic applications. NEW & NOTEWORTHY Since the activity of stretch reflex pathways contributes to locomotion, changing it through training may improve locomotor rehabilitation in people with CNS disorders. Here we show for the first time that people can change the size of the soleus spinal stretch reflex through operant conditioning. Conditioned stretch reflex change is the sum of task-dependent adaptation and long-term change, consistent with H-reflex conditioning yet different from it in the composition and amount of the two components.

Age at onset prediction in spinocerebellar ataxia type 3 changes according to population of origin.

BACKGROUND AND PURPOSE: In spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the length of CAG repeat expansions in ATXN3 shows an inverse correlation with age at onset (AO). Recently, a formula for predicting AO based on CAG expansion was developed for European carriers. We tested this formula in SCA3/MJD carriers from distinct origins and developed population-specific models to predict AO. METHODS: This was a parametric survival modelling study. RESULTS: The European formula (EF) was tested in 739 independent SCA3/MJD carriers from South Brazil, Taiwan and the Portuguese Azorean islands, and it largely underestimated AO in South Brazilian and Taiwanese test cohorts. This finding challenged the universal use of the EF, leading us to develop and validate population-specific models for AO prediction. Using validation cohorts, we showed that Brazilian and Taiwanese formulas largely outperformed the EF in a population-specific manner. Inversely, the EF was more accurate at predicting AO among Portuguese Azorean patients. Hence, specific prediction models were required for each SCA3/MJD ethnic group. CONCLUSIONS: Our data strongly support the existence of as yet unknown factors that modulate AO in SCA3/MJD in a population-dependent manner, independent of CAG expansion length. The generated models are made available to the scientific community as they can be useful for future studies on SCA3/MJD carriers from distinct geographical origins.

Adaptive learning in the detection of Movement Related Cortical Potentials improves usability of associative Brain-Computer Interfaces.

Brain-computer interfaces have increasingly found applications in motor function recovery in stroke patients. In this context, it has been demonstrated that associative-BCI protocols, implemented by means the movement related cortical potentials (MRCPs), induce significant cortical plasticity. To date, no methods have been proposed to deal with brain signal (i.e. MRCP feature) non-stationarity. This study introduces adaptive learning methods in MRCP detection and aims at comparing a no-adaptive approach based on the Locality Sensitive Discriminant Analysis (LSDA) with three LSDA-based adaptive approaches. As a proof of concept, EEG and force data were collected from six healthy subjects while performing isometric ankle dorsiflexion. Results revealed that adaptive algorithms increase the number of true detections and decrease the number of false positives per minute. Moreover, the markedly reduction of BCI system calibration time suggests that these methods have the potential to improve the usability of associative-BCI in post-stroke motor recovery.

Effects of wobble board training on single-leg landing neuromechanics.

Balance training programs have been shown to reduce ankle sprain injuries in sports, but little is known about the transfer from this training modality to motor coordination and ankle joint biomechanics in sport-specific movements. This study aimed to investigate the effects of wobble board training on motor coordination and ankle mechanics during early single-leg landing from a lateral jump. Twenty-two healthy men were randomly assigned to either a control or a training group, who engaged in 4 weeks of wobble board training. Full-body kinematics, ground reaction force, and surface electromyography (EMG) from 12 lower limb muscles were recorded during landing. Ankle joint work in the sagittal, frontal, and transverse plane was calculated from 0 to 100 ms after landing. Non-negative matrix factorization (NMF) was applied on the concatenated EMG Pre- and Post-intervention. Wobble board training increased the ankle joint eccentric work 1.2 times in the frontal (P < .01) and 4.4 times in the transverse plane (P < .01) for trained participants. Wobble board training modified the modular organization of muscle recruitment in the early landing phase by separating the activation of plantar flexors and mediolateral ankle stabilizers. Furthermore, the activation of secondary muscles across motor modules was reduced after training, refocusing the activation on the main muscles involved in the mechanical main subfunctions for each module. These results suggest that wobble board training may modify motor coordination when landing from a lateral jump, focusing on the recruitment of specific muscles/muscle groups that optimize ankle joint stability during early ground contact in single-leg landing.

The effect of type of afferent feedback timed with motor imagery on the induction of cortical plasticity.

A peripherally generated afferent volley that arrives at the peak negative (PN) phase during the movement related cortical potential (MRCP) induces significant plasticity at the cortical level in healthy individuals and chronic stroke patients. Transferring this type of associative brain-computer interface (BCI) intervention into the clinical setting requires that the proprioceptive input is comparable to the techniques implemented during the rehabilitation process. These consist mainly of functional electrical stimulation (FES) and passive movement induced by an actuated orthosis. In this study, we compared these two interventions (BCIFES and BCIpassive) where the afferent input was timed to arrive at the motor cortex during the PN of the MRCP. Twelve healthy participants attended two experimental sessions. They were asked to perform 30 dorsiflexion movements timed to a cue while continuous electroencephalographic (EEG) data were collected from FP1, Fz, FC1, FC2, C3, Cz, C4, CP1, CP2, and Pz, according to the standard international 10-20 system. MRCPs were extracted and the PN time calculated. Next, participants were asked to imagine the same movement 30 times while either FES (frequency: 20Hz, intensity: 8-35mAmp) or a passive ankle movement (amplitude and velocity matched to a normal gait cycle) was applied such that the first afferent inflow would coincide with the PN of the MRCP. The change in the output of the primary motor cortex (M1) was quantified by applying single transcranial magnetic stimuli to the area of M1 controlling the tibialis anterior (TA) muscle and measuring the motor evoked potential (MEP). Spinal changes were assessed pre and post by eliciting the TA stretch reflex. Both BCIFES and BCIpassive led to significant increases in the excitability of the cortical projections to TA (F(2,22)=4.44, p=0.024) without any concomitant changes at the spinal level. These effects were still present 30min after the cessation of both interventions. There was no significant main effect of intervention, F(1,11)=0.38, p=0.550, indicating that the changes in MEP occurred independently of the type of afferent inflow. An afferent volley generated from a passive movement or an electrical stimulus arrives at the somatosensory cortex at similar times. It is thus likely that the similar effects observed here are strictly due to the tight coupling in time between the afferent inflow and the PN of the MRCP. This provides further support to the associative nature of the proposed BCI system.

Spinocerebellar ataxia type 3/Machado-Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions.

Controversies about Mendelian segregation and CAG expansion (CAGexp) instabilities during meiosis in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) need clarification. Additional evidence about these issues was obtained from the cohort of all SCA3/MJD individuals living in South Brazil. A survey was carried out to update information registered since 2001. Deaths were checked with the Public Information System, and data was made anonymous. Anticipation and delta-CAGexp from parent-offspring pairs, and delta-CAGexp between siblings were obtained. One hundred and fifty-nine families (94% of the entire registry) were retrieved, comprising 3725 living individuals as of 2015, 625 of these being symptomatic. Minimal prevalence was 6:100,000. Carriers of a CAGexp represented 65.6% of sibs in the genotyped offspring (p < 0.001). Median instability was larger among paternal than maternal transmissions, and instabilities correlated with anticipation (r = 0.38; p = 0.001). Age of the parent correlated to delta-CAGexp among 115 direct parent-offspring CAGexp transmissions (ρ = 0.23, p = 0.014). In 98 additional kindreds, the delta-CAGexp between 269 siblings correlated with their delta-of-age (ρ = 0.27, p < 0.0001). SCA3/MJD was associated with a segregation distortion favoring the expanded allele in our cohort. Instability of expansion during meiosis was weakly influenced by the age of the transmitting parent at the time of conception.

Motor Cortex Reorganization and Impaired Function in the Transition to Sustained Muscle Pain.

Primary motor cortical (M1) adaptation has not been investigated in the transition to sustained muscle pain. Daily injection of nerve growth factor (NGF) induces hyperalgesia reminiscent of musculoskeletal pain and provides a novel model to study M1 in response to progressively developing muscle soreness. Twelve healthy individuals were injected with NGF into right extensor carpi radialis brevis (ECRB) on Days 0 and 2 and with hypertonic saline on Day 4. Quantitative sensory and motor testing and assessment of M1 organization and function using transcranial magnetic stimulation were performed prior to injection on Days 0, 2, and 4 and again on Day 14. Pain and disability increased at Day 2 and increased further at Day 4. Reorganization of M1 was evident at Day 4 and was characterized by increased map excitability. These changes were accompanied by reduced intracortical inhibition and increased intracortical facilitation. Interhemispheric inhibition was reduced from the "affected" to the "unaffected" hemisphere on Day 4, and this was associated with increased pressure sensitivity in left ECRB. These data provide the first evidence of M1 adaptation in the transition to sustained muscle pain and have relevance for the development of therapies that seek to target M1 in musculoskeletal pain.

Short-latency crossed spinal responses are impaired differently in sub-acute and chronic stroke patients.

OBJECTIVE: Investigate if patients with supraspinal lesions have impaired interlimb spinal reflex pathways. The short-latency crossed spinal response will be investigated during sitting from the non-paretic to paretic and paretic to non-paretic extremities at different stimulation intensities in chronic and sub-acute stroke patients. METHODS: The ipsilateral tibial nerve of the paretic and non-paretic extremities were stimulated at motor threshold, 35% M-max and 85% M-max of the ipsilateral soleus while the contralateral soleus was contracted from 5% to 15% of the maximum voluntary contraction of the paretic soleus. RESULTS: Chronic patients (from both extremities) had significantly less prominent inhibitory responses than healthy controls (post hoc tests: P<.01-P<.05). The responses were significantly modulated by stimulus intensity in healthy controls and chronic patients (P<.001-P<.05) but not sub-acute patients (P>.05). Some sub-acute patients had significantly more variable responses than chronic patients and healthy controls (P<.001-P⩽.05). CONCLUSIONS: Short-latency interlimb reflexes are impaired differently in sub-acute vs. chronic patients, are impaired from the non-paretic and paretic extremity, and abnormal when compared to healthy controls. SIGNIFICANCE: The inappropriate coordination could result in an inability to quickly avoid obstacles following a mechanical disturbance to the ipsilateral extremity. It also indicates that bilateral descending projections affect the response.

Changes in excitability of the cortical projections to the human tibialis anterior after paired associative stimulation.

Paired associative stimulation (PAS) based on Hebb's law of association can induce plastic changes in the intact human. The optimal interstimulus interval (ISI) between the peripheral nerve and transcranial magnetic stimulus is not known for muscles of the lower leg. The aims of this study were to investigate the effect of PAS for a variety of ISIs and to explore the efficacy of PAS when applied during dynamic activation of the target muscle. PAS was applied at 0.2 Hz for 30 min with the tibialis anterior (TA) at rest. The ISI was varied randomly in seven sessions (n = 5). Subsequently, PAS was applied (n = 14, ISI = 55 ms) with the TA relaxed or dorsi-flexing. Finally, an optimized ISI based on the subject somatosensory evoked potential (SEP) latency plus a central processing delay (6 ms) was used (n = 13). Motor-evoked potentials (MEPs) were elicited in the TA before and after the intervention, and the size of the TA MEP was extracted. ISIs of 45, 50, and 55 ms increased and 40 ms decreased TA MEP significantly (P = 0.01). PAS during dorsi-flexion increased TA MEP size by 92% (P = 0.001). PAS delivered at rest resulted in a nonsignificant increase; however, when the ISI was optimized from SEP latency recordings, all subjects showed significant increases (P = 0.002). No changes in MEP size occurred in the antagonist. Results confirm that the excitability of the corticospinal projections to the TA but not the antagonist can be increased after PAS. This is strongly dependent on the individualized ISI and on the activation state of the muscle.

Evidence for a supraspinal contribution to the human quadriceps long-latency stretch reflex.

In sitting humans a rapid unexpected lengthening of the knee extensors elicits a stretch reflex (SR) response as recorded by the electromyogram (EMG) which comprises multiple bursts. These are termed short latency responses (SLR), medium latency responses (MLR) and long latency responses (LLR). The aim of this study was to determine if a transcortical pathway contributes to any of these bursts. Flexion perturbations (amplitude =4 degrees, velocity=150 degrees/s) were imposed on the right knee joint of sitting subjects (n=11). The effect of the perturbation on the electromyographic (EMG) response of the pre-contracted quadriceps muscle to magnetic stimulation of the contralateral motor cortex was quantified. Transcranial magnetic stimulation (TMS) was applied to elicit a compound motor evoked potential (MEP) in the target muscle rectus femoris (RF), in the vastus lateralis (VL), vastus medialis (VM) and biceps femoris (BF). The MEP and SR were elicited either in combination or separately. When applied in combination the delay between the SR and the MEP varied from 0 to 150 ms in steps of 4, 5 and 10 ms. Somatosensory evoked potentials (SEPs) were recorded from four subjects during the imposed stretch to quantify the latency of the resulting afferent volley. Onset latencies of responses in RF were 25+/-2 ms for the SR and 20+/-4 ms for the MEP. The average SEP latency was 24+/-2 ms. A transcortical pathway thus has the potential to contribute to the RF SR no earlier than 54+/-6 ms (SEP + MEP + 10 ms central processing delay) following the stretch onset. The duration of the total reflex burst was 85+/-6 ms. Significant facilitation of the MEP commenced at 78 ms, coinciding with the LLR component of the stretch response. No such facilitation was observed in the synergists VL and VM, or in the antagonist BF. Our results indicate that the LLR of the RF likely involves supraspinal pathways. More importantly, of the investigated muscles, this involvement of higher centers in the shaping of the LLR is specific to the RF muscle during the investigated task.

Characterisation of the quadriceps stretch reflex during the transition from swing to stance phase of human walking.

The main objective of this study was to characterize the stretch reflex response of the human thigh muscles to an unexpected knee flexion at the transition from stance to swing during walking. Eleven healthy subjects walked on a treadmill at their preferred speed. Reliable and constant knee flexions (6-12 degrees amplitude, 230-350 degrees /s velocity, 220 ms duration) were applied during the late swing and early stance phase of human walking by rotating the knee joint with a specifically designed portable stretch apparatus affixed to the left knee. Responses from rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), medial hamstrings (MH) and medial gastrocnemius (GM) were recorded via bipolar surface electromyograms (EMG). The onset of the response in the RF, VL and VM, remained stable and independent of the time in the step cycle when the stretch was applied. Across all subjects the response onset (mean +/- SD) occurred at 23+/-1, 24+/-1 and 23+/-1 ms for RF, VL and VM, respectively. The duration of the initial response was 90-110 ms, at which time the EMG signal returned towards baseline levels. Three reflex response windows, labelled the short latency reflex (SLR), the medium latency reflex (MLR) and the late latency reflex response (LLR), were analysed. The medium and late reflex responses of all knee extensors increased significantly ( p=0.008) as the gait cycle progressed from swing to stance. This was not related to the background EMG activity. In contrast, during standing at extensor EMG levels similar to those attained during walking the reflex responses were dependent on background EMG. During walking, LLR amplitudes expressed as a function of the background activity were on average two to three times greater than SLR and MLR reflex amplitudes. Distinct differences in SLR and LLR amplitude were observed for RF, VL and VM but not in the MLR amplitude. This may be related to the different pathways mediating the SLR, MLR and LLR components of the stretch response. As for the knee extensor antagonists, they exhibited a response to the stretch of the quadriceps at latencies short enough to be monosynaptic. This is in agreement with the suggestion by Eccles and Lundberg (1958) that there may be functional excitatory connections between the knee extensors and flexors in mammals.

Reflex and non-reflex torque responses to stretch of the human knee extensors.

Reflex responses to unexpected stretches are well documented for selected muscles in both animal and human. Moreover, investigations of their possible functional significance have revealed that stretch reflexes can contribute substantially to the overall stiffness of a joint. In the lower extremity only the muscles spanning the human ankle joint have been investigated in the past. This study implemented a unique hydraulic actuator to study the contributions of the knee extensor stretch reflex to the overall knee joint torque. The quadriceps muscles were stretched at various background torques, produced either voluntarily or by electrical stimulation, and thus the purely reflex mediated torque could be calculated. The stretch had a velocity of 67 degrees /s and an amplitude of 20 degrees. A reflex response as measured by electromyography (EMG) was observed in all knee extensors at latencies of 26 - 36 ms. Both phasic and tonic EMG stretch responses increased with increasing background torques. Lines of best fit produced correlation coefficients of 0.59 - 0.78. This study is the first to examine the reflex contribution of the knee extensors to the total torque at background torques of 0 - 90% MVC. The contribution of the reflex mediated torque is initially low and peaked at background torques of 20 - 40% MVC. In terms of the total torque the reflex contributed 16 - 52% across all levels of background torque. It is concluded that during medium background torque levels such as those obtained during walking, the stretch reflex of the quadriceps muscle group contributes substantially to the total torque around the knee joint.