Frequency of ERD as observed in ALS patients
According to the results of our research, the mean magnitude of ERD with ALS patients was smaller than that of control and about 60% of both groups showed ERD in the beta frequency band. We presumed that there would be a relationship between the magnitude of ERD and frequency. However, there were no correlations between ERD and frequency in either the ALS patients or the control subjects.
In previous reports about BCI research, alpha band components were selected as the relevant frequency with hand imagery in healthy control
. However, in several studies of BCI in ALS patients, beta band components were selected as the relevant frequency band
[15–18]. In these reports, the frequency band was selected for the sake of better classification accuracy with the BCI performance; specificity of the frequency band was not discussed at length.
We supposed that aging would affect the selection of the relevant frequency band because there was no difference between the ALS and controls on the age and frequencies that showed ERD. A progressive loss of corticospinal motor neurons during aging has been reported previously
. In an analysis of EEG in aging, Hamada reported that alpha band frequency (mu rhythm) decreased with age
. Less consistent findings have been found concerning beta desynchronization; one report indicated an increase with aging
 while another found beta desynchronization to be unaffected
We presumed that cortical degenerative changes from ALS would affect the selection of the relevant frequency band in the patients. There were few previous reports about the EEG itself with resting state in ALS patients. Mai and colleagues evaluated quantitative EEG (QEEG) in ALS patients to see if the confined cortical degeneration found in anatomical and functional examinations of central (rolandic) regions could give rise to abnormalities of cortical electrical activity
. QEEG in ALS patients showed a significant and well-localized decrease of alpha activity only in the central regions. They suggested that this EEG change was probably due to loss of cells in the sensorimotor cortex. We could not deny the possibility that the ERD in alpha frequency band was decreased due to neuronal loss from the progression of ALS.
The magnitude of ERD might not depend on the number of surviving cortico-motoneural cells, but rather on the concentration for the task to drive the surviving cortico-motoneural cells.
Correlation between impairments and ERD in the ALS patients
In accord with clinical knowledge, the results of Experiment 1 showed that disease duration and bulbar scale were negatively correlated. Similarly, a worse bulbar scale indicated a smaller ERD (Figure
2A, B, and C). However, contrary to our hypothesis, the ERD was not correlated with strength of the upper extremities.
To evaluate these relationships in individual ALS patients longitudinally, Experiment 2 was conducted using the same task as Experiment 1, with measurements at three time-points. In this experiment, disease duration and ERD were both negatively correlated longitudinally with bulbar scale in ALS patients (Figure
3A). However, these tendencies were not found in controls, and the ranges of change in ERD magnitude were small (Figure
According to our results, grasping motor imagery yielding large ERD might be associated not with intact hand function or ADL, but rather with intact bulbar function.
Motor imagery is the ability to create a vivid mental image of movement
. A previous study reported a greater enhancement of ERD in subjects with vivid imagery than in those with non-vivid imagery
. Vivid imagery needs alertness and concentration. Subjects with motor deficits may have greater difficulty compared to normal subjects focusing attention on motor tasks including imagining movement
. ALS patients with severe bulbar dysfunction might also find it difficult to concentrate on motor imagery owing to inattention and general fatigue. Generalized tiredness is commonly a result of sleep difficulties that can arise from saliva aspiration due to severe bulbar dysfunction and positioning needs
. In fact, in this study and other previous reports, ALS patients complained of fatigue and requested breaks several times during the experiment
. We believed it was one of the reasons why the patients with worsened bulbar scale had smaller ERDs. These results suggest it is necessary to take care of drooling or tiredness of ALS patients in this state in order to use a BCI system effectively.
Several studies have shown that the act of mastication, even without calorie intake, has beneficial psychological effects, alters the state of arousal, and facilitates high scores on working memory tests
[26, 27]. Sakamoto and colleagues reported mastication influenced cognitive processing time as reflected by reaction time and the latency of event-related potentials
. We speculated there was a possibility that a prolonged state without oral food intake due to severe dysphagia, especially in subject No 7, affected cognition and thus motor imagery indirectly.
According to the previous reports, the presence of pseudobulbar palsy in ALS is associated with frontal lobe impairment
. In particular, the patients with pronounced bulbar deficits could have had more breathing difficulties leading to oxygen deficit and additional impact on cognitive function
. However in our cases, monitoring of oxyhemoglobin saturation and evaluation of arterial blood gas was within normal, they did not use intermittent positive pressure ventilation and artificial ventilation. And patients were alert and cooperative with experiments, they were clinically diagnosed as non-demented. On the other hand, we could not evaluate their cognition with psychological battery due to severe bulbar and limb dysfunction, we could not strictly deny the possibility with presence of cognitive dysfunction that affected the ERD. Future research should be performed to confirm these relationships.
In order to find an effective BCI system using ERD classification in ALS patients, it is necessary to modify the EEG analysis system individually with the progression of symptoms for each patient. The environmental setting is indispensable for minimizing fatigue and for concentrating on imagery, especially given the progressive state of ALS patients with bulbar dysfunction.
Magnitude of ERD, its frequencies, and its laterality
In a previous report, right-handed subjects showed larger lateralization of ERD with right-finger movements compared to left-finger movements
, and the right-hand movement with electrodes close to position C3 (contralateral to the imaged side) provided the highest classification accuracy for BCI control
. However, in our study there was no significant difference with averaged ERD between C3 Laplacian and C4 Laplacian during either left or right hand imagery in ALS patients and controls. We suggest two possible reasons for this result.
First, feedback training might be insufficient in our task. As mentioned previously, the lateralization of ERD during imagery is reinforced by training with feedback
. As our experiment did not involve feedback training, potential lateralization could not be reinforced.
Second, age might affect the results. In our study, mean ages of the two groups were over sixty-five years old. Using ERD analysis of the mu and beta rhythm, increased and earlier activation of the ipsilateral sensorimotor areas in older subjects has been reported
[32, 33]. Labyt and colleagues reported that increased and wider spread cortical activity may be necessary to generate the correct motor program in elderly subjects compared to young subjects. They hypothesized that to compensate for a loss of specificity of subcortical inputs from the thalamus and basal ganglia, an increase of activity occurred in these subcortical nuclei. Given the above, handedness did not affect the lateralization of ERD significantly for the elderly subjects, even ALS patients, on single EEG trials without feedback training.