Effects of active and sham tDCS on the soleus H-reflex during standing.

Weak transcranial direct current stimulation (tDCS) is known to affect corticospinal excitability and enhance motor skill acquisition, whereas its effects on spinal reflexes in actively contracting muscles are yet to be established. Thus, in this study, we examined the acute effects of Active and Sham tDCS on the soleus H-reflex during standing. In fourteen adults without known neurological conditions, the soleus H-reflex was repeatedly elicited at just above M-wave threshold throughout 30 min of Active (N = 7) or Sham (N = 7) 2-mA tDCS over the primary motor cortex in standing. The maximum H-reflex (Hmax) and M-wave (Mmax) were also measured before and immediately after 30 min of tDCS. The soleus H-reflex amplitudes became significantly larger (by 6%) ≈1 min into Active or Sham tDCS and gradually returned toward the pre-tDCS values, on average, within 15 min. With Active tDCS, the amplitude reduction from the initial increase appeared to occur more swiftly than with Sham tDCS. An acute temporary increase in the soleus H-reflex amplitude within the first minute of Active and Sham tDCS found in this study indicates a previously unreported effect of tDCS on the H-reflex excitability. The present study suggests that neurophysiological characterization of Sham tDCS effects is just as important as investigating Active tDCS effects in understanding and defining acute effects of tDCS on the excitability of spinal reflex pathways.

Inhibitory interneurons show early dysfunction in a SOD1 mouse model of amyotrophic lateral sclerosis.

Few studies in amyotrophic lateral sclerosis (ALS) measure effects of the disease on inhibitory interneurons synapsing onto motoneurons (MNs). However, inhibitory interneurons could contribute to dysfunction, particularly if altered before MN neuropathology, and establish a long-term imbalance of inhibition/excitation. We directly assessed excitability and morphology of glycinergic (GlyT2 expressing) ventral lumbar interneurons from SOD1G93AGlyT2eGFP (SOD1) and wild-type GlyT2eGFP (WT) mice on postnatal days 6-10. Patch clamp revealed dampened excitability in SOD1 interneurons, including depolarized persistent inward currents (PICs), increased voltage and current threshold for firing action potentials, along with a marginal decrease in afterhyperpolarization duration. Primary neurites of ventral SOD1 inhibitory interneurons were larger in volume and surface area than WT. GlyT2 interneurons were then divided into three subgroups based on location: (1) interneurons within 100 µm of the ventral white matter, where Renshaw cells (RCs) are located, (2) interneurons interspersed with MNs in lamina IX, and (3) interneurons in the intermediate ventral area including laminae VII and VIII. Ventral interneurons in the RC area were the most profoundly affected, exhibiting more depolarized PICs and larger primary neurites. Interneurons in lamina IX had depolarized PIC onset. In lamina VII-VIII, interneurons were least affected. In summary, inhibitory interneurons show very early region-specific perturbations poised to impact excitatory/inhibitory balance of MNs, modify motor output and provide early biomarkers of ALS. Therapeutics like riluzole that universally reduce CNS excitability could exacerbate the inhibitory dysfunction described here. KEY POINTS: Spinal inhibitory interneurons could contribute to amyotrophic lateral sclerosis (ALS) pathology, but their excitability has never been directly measured. We studied the excitability and morphology of glycinergic interneurons in early postnatal transgenic mice (SOD1G93A GlyT2eGFP). Interneurons were less excitable and had marginally smaller somas but larger primary neurites in SOD1 mice. GlyT2 interneurons were analysed according to their localization within the ventral spinal cord. Interestingly, the greatest differences were observed in the most ventrally located interneurons. We conclude that inhibitory interneurons show presymptomatic changes that may contribute to excitatory/inhibitory imbalance in ALS.

Effects of Sensorimotor Rhythm Modulation on the Human Flexor Carpi Radialis H-Reflex.

People can learn over training sessions to increase or decrease sensorimotor rhythms (SMRs) in the electroencephalogram (EEG). Activity-dependent brain plasticity is thought to guide spinal plasticity during motor skill learning; thus, SMR training may affect spinal reflexes and thereby influence motor control. To test this hypothesis, we investigated the effects of learned mu (8-13 Hz) SMR modulation on the flexor carpi radialis (FCR) H-reflex in 6 subjects with no known neurological conditions and 2 subjects with chronic incomplete spinal cord injury (SCI). All subjects had learned and practiced over more than 10 < 30-min training sessions to increase (SMR-up trials) and decrease (SMR-down trials) mu-rhythm amplitude over the hand/arm area of left sensorimotor cortex with ≥80% accuracy. Right FCR H-reflexes were elicited at random times during SMR-up and SMR-down trials, and in between trials. SMR modulation affected H-reflex size. In all the neurologically normal subjects, the H-reflex was significantly larger [116% ± 6 (mean ± SE)] during SMR-up trials than between trials, and significantly smaller (92% ± 1) during SMR-down trials than between trials (p < 0.05 for both, paired t-test). One subject with SCI showed similar H-reflex size dependence (high for SMR-up trials, low for SMR-down trials): the other subject with SCI showed no dependence. These results support the hypothesis that SMR modulation has predictable effects on spinal reflex excitability in people who are neurologically normal; they also suggest that it might be used to enhance therapies that seek to improve functional recovery in some individuals with SCI or other CNS disorders.

Independent home use of a brain-computer interface by people with amyotrophic lateral sclerosis.

OBJECTIVE: To assess the reliability and usefulness of an EEG-based brain-computer interface (BCI) for patients with advanced amyotrophic lateral sclerosis (ALS) who used it independently at home for up to 18 months. METHODS: Of 42 patients consented, 39 (93%) met the study criteria, and 37 (88%) were assessed for use of the Wadsworth BCI. Nine (21%) could not use the BCI. Of the other 28, 27 (men, age 28-79 years) (64%) had the BCI placed in their homes, and they and their caregivers were trained to use it. Use data were collected by Internet. Periodic visits evaluated BCI benefit and burden and quality of life. RESULTS: Over subsequent months, 12 (29% of the original 42) left the study because of death or rapid disease progression and 6 (14%) left because of decreased interest. Fourteen (33%) completed training and used the BCI independently, mainly for communication. Technical problems were rare. Patient and caregiver ratings indicated that BCI benefit exceeded burden. Quality of life remained stable. Of those not lost to the disease, half completed the study; all but 1 patient kept the BCI for further use. CONCLUSION: The Wadsworth BCI home system can function reliably and usefully when operated by patients in their homes. BCIs that support communication are at present most suitable for people who are severely disabled but are otherwise in stable health. Improvements in BCI convenience and performance, including some now underway, should increase the number of people who find them useful and the extent to which they are used.

P300-based brain-computer interface (BCI) event-related potentials (ERPs): People with amyotrophic lateral sclerosis (ALS) vs. age-matched controls.

OBJECTIVE: Brain-computer interfaces (BCIs) aimed at restoring communication to people with severe neuromuscular disabilities often use event-related potentials (ERPs) in scalp-recorded EEG activity. Up to the present, most research and development in this area has been done in the laboratory with young healthy control subjects. In order to facilitate the development of BCI most useful to people with disabilities, the present study set out to: (1) determine whether people with amyotrophic lateral sclerosis (ALS) and healthy, age-matched volunteers (HVs) differ in the speed and accuracy of their ERP-based BCI use; (2) compare the ERP characteristics of these two groups; and (3) identify ERP-related factors that might enable improvement in BCI performance for people with disabilities. METHODS: Sixteen EEG channels were recorded while people with ALS or healthy age-matched volunteers (HVs) used a P300-based BCI. The subjects with ALS had little or no remaining useful motor control (mean ALS Functional Rating Scale-Revised 9.4 (±9.5SD) (range 0-25)). Each subject attended to a target item as the items in a 6×6 visual matrix flashed. The BCI used a stepwise linear discriminant function (SWLDA) to determine the item the user wished to select (i.e., the target item). Offline analyses assessed the latencies, amplitudes, and locations of ERPs to the target and non-target items for people with ALS and age-matched control subjects. RESULTS: BCI accuracy and communication rate did not differ significantly between ALS users and HVs. Although ERP morphology was similar for the two groups, their target ERPs differed significantly in the location and amplitude of the late positivity (P300), the amplitude of the early negativity (N200), and the latency of the late negativity (LN). CONCLUSIONS: The differences in target ERP components between people with ALS and age-matched HVs are consistent with the growing recognition that ALS may affect cortical function. The development of BCIs for use by this population may begin with studies in HVs but also needs to include studies in people with ALS. Their differences in ERP components may affect the selection of electrode montages, and might also affect the selection of presentation parameters (e.g., matrix design, stimulation rate). SIGNIFICANCE: P300-based BCI performance in people severely disabled by ALS is similar to that of age-matched control subjects. At the same time, their ERP components differ to some degree from those of controls. Attention to these differences could contribute to the development of BCIs useful to those with ALS and possibly to others with severe neuromuscular disabilities.

A practical, intuitive brain-computer interface for communicating 'yes' or 'no' by listening.

OBJECTIVE: Previous work has shown that it is possible to build an EEG-based binary brain-computer interface system (BCI) driven purely by shifts of attention to auditory stimuli. However, previous studies used abrupt, abstract stimuli that are often perceived as harsh and unpleasant, and whose lack of inherent meaning may make the interface unintuitive and difficult for beginners. We aimed to establish whether we could transition to a system based on more natural, intuitive stimuli (spoken words 'yes' and 'no') without loss of performance, and whether the system could be used by people in the locked-in state. APPROACH: We performed a counterbalanced, interleaved within-subject comparison between an auditory streaming BCI that used beep stimuli, and one that used word stimuli. Fourteen healthy volunteers performed two sessions each, on separate days. We also collected preliminary data from two subjects with advanced amyotrophic lateral sclerosis (ALS), who used the word-based system to answer a set of simple yes-no questions. MAIN RESULTS: The N1, N2 and P3 event-related potentials elicited by words varied more between subjects than those elicited by beeps. However, the difference between responses to attended and unattended stimuli was more consistent with words than beeps. Healthy subjects' performance with word stimuli (mean 77% ± 3.3 s.e.) was slightly but not significantly better than their performance with beep stimuli (mean 73% ± 2.8 s.e.). The two subjects with ALS used the word-based BCI to answer questions with a level of accuracy similar to that of the healthy subjects. SIGNIFICANCE: Since performance using word stimuli was at least as good as performance using beeps, we recommend that auditory streaming BCI systems be built with word stimuli to make the system more pleasant and intuitive. Our preliminary data show that word-based streaming BCI is a promising tool for communication by people who are locked in.

Brain-computer interface (BCI) evaluation in people with amyotrophic lateral sclerosis.

Brain-computer interfaces (BCIs) might restore communication to people severely disabled by amyotrophic lateral sclerosis (ALS) or other disorders. We sought to: 1) define a protocol for determining whether a person with ALS can use a visual P300-based BCI; 2) determine what proportion of this population can use the BCI; and 3) identify factors affecting BCI performance. Twenty-five individuals with ALS completed an evaluation protocol using a standard 6 × 6 matrix and parameters selected by stepwise linear discrimination. With an 8-channel EEG montage, the subjects fell into two groups in BCI accuracy (chance accuracy 3%). Seventeen averaged 92 (± 3)% (range 71-100%), which is adequate for communication (G70 group). Eight averaged 12 (± 6)% (range 0-36%), inadequate for communication (L40 subject group). Performance did not correlate with disability: 11/17 (65%) of G70 subjects were severely disabled (i.e. ALSFRS-R < 5). All L40 subjects had visual impairments (e.g. nystagmus, diplopia, ptosis). P300 was larger and more anterior in G70 subjects. A 16-channel montage did not significantly improve accuracy. In conclusion, most people severely disabled by ALS could use a visual P300-based BCI for communication. In those who could not, visual impairment was the principal obstacle. For these individuals, auditory P300-based BCIs might be effective.

EEG correlates of P300-based brain-computer interface (BCI) performance in people with amyotrophic lateral sclerosis.

The purpose of this study was to identify electroencephalography (EEG) features that correlate with P300-based brain-computer interface (P300 BCI) performance in people with amyotrophic lateral sclerosis (ALS). Twenty people with ALS used a P300 BCI spelling application in copy-spelling mode. Three types of EEG features were found to be good predictors of P300 BCI performance: (1) the root-mean-square amplitude and (2) the negative peak amplitude of the event-related potential to target stimuli (target ERP) at Fz, Cz, P3, Pz, and P4; and (3) EEG theta frequency (4.5-8 Hz) power at Fz, Cz, P3, Pz, P4, PO7, PO8 and Oz. A statistical prediction model that used a subset of these features accounted for >60% of the variance in copy-spelling performance (p < 0.001, mean R(2) = 0.6175). The correlations reflected between-subject, rather than within-subject, effects. The results enhance understanding of performance differences among P300 BCI users. The predictors found in this study might help in: (1) identifying suitable candidates for long-term P300 BCI operation; (2) assessing performance online. Further work on within-subject effects needs to be done to establish whether P300 BCI user performance could be improved by optimizing one or more of these EEG features.