Mitsuaki Takemi

Event-related desynchronization reflects downregulation of intracortical inhibition in human primary motor cortex

There is increasing interest in electroencephalogram (EEG)-based brain-computer interface (BCI) as a tool for rehabilitation of upper limb motor functions in hemiplegic stroke patients. This type of BCI often exploits mu and beta oscillations in EEG recorded over the sensorimotor areas, and their event-related desynchronization (ERD) following motor imagery is believed to represent increased sensorimotor cortex excitability. However, it remains unclear whether the sensorimotor cortex excitability is actually correlated with ERD. Thus we assessed the association of ERD with primary motor cortex (M1) excitability during motor imagery of right wrist movement. M1 excitability was tested by motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) with transcranial magnetic stimulation (TMS). Twenty healthy participants were recruited. The participants performed 7 s of rest followed by 5 s of motor imagery and received online visual feedback of the ERD magnitude of the contralateral hand M1 while performing the motor imagery task. TMS was applied to the right hand M1 when ERD exceeded predetermined thresholds during motor imagery. MEP amplitudes, SICI, and ICF were recorded from the agonist muscle of the imagined hand movement. Results showed that the large ERD during wrist motor imagery was associated with significantly increased MEP amplitudes and reduced SICI but no significant changes in ICF. Thus ERD magnitude during wrist motor imagery represents M1 excitability. This study provides electrophysiological evidence that a motor imagery task involving ERD may induce changes in corticospinal excitability similar to changes accompanying actual movements.

Sensorimotor event-related desynchronization represents the excitability of human spinal motoneurons.

Amplitudes of mu and beta (7-26Hz) oscillations measured by electroencephalography over the sensorimotor areas are suppressed during motor imagery as well as during voluntary movements. This phenomenon is referred to as event-related desynchronization (ERD) and is known to reflect motor cortical excitability. The increased motor cortical excitability associated with ERD during hand motor imagery would induce a descending cortical volley to spinal motoneurons, resulting in facilitation of spinal motoneuronal excitability. Therefore, in the present study, we tested the association of ERD during motor imagery with the excitability of spinal motoneurons in 15 healthy participants. Spinal excitability was tested using the F-wave recorded from the right abductor pollicis brevis muscle. The F-wave results from antidromic activation of spinal motoneurons and is induced by peripheral nerve stimulation. Participants performed 5s of motor imagery of right thumb abduction following 7s of rest. The right median nerve was stimulated at wrist level when the ERD magnitude of the contralateral hand sensorimotor area exceeded predetermined thresholds during motor imagery. The results showed ERD magnitude during hand motor imagery was associated with an increase in F-wave persistence, but not with the response average of F-wave amplitude or F-wave latency. These findings suggest that the ERD magnitude may be a biomarker representing increases in the excitability of both cortical and spinal levels.

Is event-related desynchronization a biomarker representing corticospinal excitability?

Brain computer interfaces (BCIs) using event-related desynchronization (ERD) of the electroencephalogram (EEG), which is believed to represent increased activation of the sensorimotor cortex, have attracted attention as tools for rehabilitation of upper limb motor functions in hemiplegic stroke patients. However, it remains unclear whether the corticospinal excitability is actually correlated with ERD. The purpose of this study was to assess the association between the ERD magnitude and the excitability of primary motor cortex (M1) and spinal motoneurons. M1 excitability was tested by motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) using transcranial magnetic stimulation, and spinal motoneuronal excitability was tested by F-waves using peripheral nerve stimulation. Results showed that large ERD during motor imagery was associated with significantly increased F-wave persistence and reduced SICI, but no significant changes in ICF and the response average of F-wave amplitudes. Our findings suggest that ERD magnitude during motor imagery represents the instantaneous excitability of both M1 and spinal motoneurons. This study provides electrophysiological evidence that ERD-based BCI with motor imagery task increases corticospinal excitability as changes accompanying actual movements.

Three-dimensional motion analysis of arm-reaching movements in healthy and hemispinalized common marmosets.

Spinal cord injury (SCI) is a devastating neurological injury. At present, pharmacological, regenerative, and rehabilitative approaches are widely studied as therapeutic interventions for motor recovery after SCI. Preclinical research has been performed on model animals with experimental SCI, and those studies often evaluate hand and arm motor function using various indices, such as the success rate of the single pellet reaching test and the grip force. However, compensatory movement strategies, involuntary muscle contraction, and the subjects motivation could affect the scores, resulting in failure to assess direct recovery from impairment. Identifying appropriate assessments of motor impairment is thus important for understanding the mechanisms of motor recovery. In this study, we developed a motion capture system capable of reconstructing three-dimensional hand positions with millimeter and millisecond accuracy and evaluated hand kinematics during food retrieval movement in both healthy and hemispinalized common marmosets. As a result, the endpoint jerk, representing the accuracy of hand motor control, was asserted to be an appropriate index of upper limb motor impairment by eliminating the influence of the subjects motivation, involuntary muscle contraction, and compensatory strategies. The result also suggested that the kinematics of the limb more consistently reflects motor restoration from deficit due to spinal cord injury than the performance in the single pellet reaching test. Because of recent attention devoted to the common marmoset as a nonhuman primate model for human diseases, the present study, which clarified arm-reaching movements in spinalized marmosets, provides fundamental knowledge for future therapeutic studies.

Cortical control of object-specific grasp relies on adjustments of both activity and effective connectivity: A common marmoset study

The cortical mechanisms of grasping have been extensively studied in macaques and humans; here, we investigated whether common marmosets could rely on similar mechanisms despite strong differences in hand morphology and grip diversity. We recorded electrocorticographic activity over the sensorimotor cortex of two common marmosets during the execution of different grip types, which allowed us to study cortical activity (power spectrum) and physiologically inferred connectivity (phase‐slope index). Analyses were performed in beta (16–35 Hz) and gamma (75–100 Hz) frequency bands and our results showed that beta power varied depending on grip type, whereas gamma power displayed clear epoch‐related modulation. Strength and direction of inter‐area connectivity varied depending on grip type and epoch. These findings suggest that fundamental control mechanisms are conserved across primates and, in future research, marmosets could represent an adequate model to investigate primate brain mechanisms.

Synchronizing the transcranial magnetic pulse with electroencephalographic recordings effectively reduces inter-trial variability of the pulse artefact

Background Electroencephalography (EEG) can capture the cortical response evoked by transcranial magnetic stimulation (TMS). The TMS pulse provokes a large artefact, which obscures the cortical response in the first milliseconds after TMS. Removing this artefact remains a challenge. Methods We delivered monophasic and biphasic TMS to a melon as head phantom and to four healthy participants and recorded the pulse artefact at 5 kHz with a TMS-compatible EEG system. Pulse delivery was either synchronized or non-synchronized to the clock of the EEG recording system. The effects of synchronization were tested at 10 and 20 kHz using the head phantom. We also tested the effect of a soft sheet placed between the stimulation coil and recording electrodes in both human and melon. Results & conclusion Synchronizing TMS and data acquisition markedly reduced trial-to-trial variability of the pulse artefact in recordings from the phantom or from the scalp. Reduced trial-to-trial variability was also observed at high sampling frequencies. The use of a soft sheet reduced the variability in recordings on the head phantom, but not in human participants. Effective reduction of the trial-to-trial variability renders it possible to create an artefact template for off-line filtering. Template-based subtraction of the artefact from the EEG signals is a prerequisite to effectively recover the immediate physiological response in the stimulated cortex and inter-connected areas.

Muscle-selective disinhibition of corticomotor representations using a motor imagery-based brain-computer interface

&NA; Bridging between brain activity and machine control, brain‐computer interface (BCI) can be employed to activate distributed neural circuits implicated in a specific aspect of motor control. Using a motor imagery‐based BCI paradigm, we previously found a disinhibition within the primary motor cortex contralateral to the imagined movement, as evidenced by event‐related desynchronization (ERD) of oscillatory cortical activity. Yet it is unclear whether this BCI approach does selectively facilitate corticomotor representations targeted by the imagery. To address this question, we used brain state‐dependent transcranial magnetic stimulation while participants performed kinesthetic motor imagery of wrist movements with their right hand and received online visual feedback of the ERD. Single and paired‐pulse magnetic stimulation were given to the left primary motor cortex at a low or high level of ERD to assess intracortical excitability. While intracortical facilitation showed no modulation by ERD, short‐latency intracortical inhibition was reduced the higher the ERD. Intracortical disinhibition was only found in the agonist muscle targeted by motor imagery at high ERD level, but not in the antagonist muscle. Single pulse motor‐evoked potential was also increased the higher the ERD. However, at high ERD level, this facilitatory effect on overall corticospinal excitability was not selective to the agonist muscle. Analogous results were found in two independent experiments, in which participants either performed kinesthetic motor imagery of wrist extension or flexion. Our results showed that motor imagery‐based BCI can selectively disinhibit the corticomotor output to the agonist muscle, enabling effector‐specific training in patients with motor paralysis.

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation

OBJECTIVE Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. APPROACH ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. MAIN RESULTS Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. SIGNIFICANCE Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

Rapid identification of cortical motor areas in rodents by high-frequency automatic cortical stimulation and novel motor threshold algorithm

Cortical stimulation mapping is a valuable tool to test the functional organization of the motor cortex in both basic neurophysiology (e.g., elucidating the process of motor plasticity) and clinical practice (e.g., before resecting brain tumors involving the motor cortex). However, compilation of motor maps based on the motor threshold (MT) requires a large number of cortical stimulations and is therefore time consuming. Shortening the time for mapping may reduce stress on the subjects and unveil short-term plasticity mechanisms. In this study, we aimed to establish a cortical stimulation mapping procedure in which the time needed to identify a motor area is reduced to the order of minutes without compromising reliability. We developed an automatic motor mapping system that applies epidural cortical surface stimulations (CSSs) through one-by-one of 32 micro-electrocorticographic electrodes while examining the muscles represented in a cortical region. The next stimulus intensity was selected according to previously evoked electromyographic responses in a closed-loop fashion. CSS was repeated at 4 Hz and electromyographic responses were submitted to a newly proposed algorithm estimating the MT with smaller number of stimuli with respect to traditional approaches. The results showed that in all tested rats (n = 12) the motor area maps identified by our novel mapping procedure (novel MT algorithm and 4-Hz CSS) significantly correlated with the maps achieved by the conventional MT algorithm with 1-Hz CSS. The reliability of the both mapping methods was very high (intraclass correlation coefficients ≧0.8), while the time needed for the mapping was one-twelfth shorter with the novel method. Furthermore, the motor maps assessed by intracortical microstimulation and the novel CSS mapping procedure in two rats were compared and were also significantly correlated. Our novel mapping procedure that determined a cortical motor area within a few minutes could help to study the functional significance of short-term plasticity in motor learning and recovery from brain injuries. Besides this advantage, particularly in the case of human patients or experimental animals that are less trained to remain at rest, shorter mapping time is physically and mentally less demanding and might allow the evaluation of motor maps in awake individuals as well.

Event-related desynchronization by hand motor imagery is associated with corticospinal excitability: Physiological evidence for BCI based neurorehabilitation

The purpose of this study was to assess the association between the magnitude of event-related desynchronization (ERD) of electroencephalogram, which is believed to represent increased activation of the sensorimotor cortex, and the excitability of primary motor cortex (M1) and spinal motoneurons. M1 excitability was tested by motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) using transcranial magnetic stimulation, and spinal motoneuronal excitability was tested by F-waves using peripheral nerve stimulation. Results showed that MEP amplitude was significantly increased during motor imagery and large ERD during motor imagery was associated with significantly reduced SICI and increased F-wave persistence, but no significant changes in ICF and the response average of F-wave amplitudes. Our findings suggest that ERD magnitude during motor imagery reflects the instantaneous excitability of both M1 and spinal motoneurons.