Ryoki Sasaki

Comparison of Three Non-Invasive Transcranial Electrical Stimulation Methods for Increasing Cortical Excitability

Transcranial direct current stimulation (tDCS) is a representative non-invasive brain stimulation method (NIBS). tDCS increases cortical excitability not only in healthy individuals, but also in stroke patients where it contributes to motor function improvement. Recently, two additional types of transcranial electrical stimulation (tES) methods have been introduced that may also prove beneficial for stimulating cortical excitability; these are transcranial random noise stimulation (tRNS) and transcranial alternating current stimulation (tACS). However, comparison of tDCS with tRNS and tACS, in terms of efficacy in cortical excitability alteration, has not been reported thus far. We compared the efficacy of the three different tES methods for increasing cortical excitability using the same subject population and same current intensity. Fifteen healthy subjects participated in this study. Similar stimulation patterns (1.0 mA and 10 min) were used for the three conditions of stimulation (tDCS, tRNS, and tACS). Cortical excitability was explored via single-pulse TMS elicited motor evoked potentials (MEPs). Compared with pre-measurements, MEPs significantly increased with tDCS, tACS, and tRNS (p < 0.05). Compared with sham measurements, significant increases in MEPs were also observed with tRNS and tACS (p < 0.05), but not with tDCS. In addition, a significant correlation of the mean stimulation effect was observed between tRNS and tACS (p = 0.019, r = 0.598). tRNS induced a significant increase in MEP compared with the Pre or Sham at all time points. tRNS resulted in the largest significant increase in MEPs. These findings suggest that tRNS is the most effective tES method and should be considered as part of a treatment plan for improving motor function in stroke patients.

Modulation of Cortical Inhibitory Circuits after Cathodal Transcranial Direct Current Stimulation over the Primary Motor Cortex

Here, we aimed to evaluate whether cathodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and primary somatosensory cortex (S1) can modulate cortical inhibitory circuits. Sixteen healthy subjects participated in this study. Cathodal tDCS was positioned over the left M1 (M1 cathodal) or left S1 (S1 cathodal) with an intensity of 1 mA for 10 min. Sham tDCS was applied for 10 min over the left M1 (sham). Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were recorded from the right abductor pollicis brevis (APB) muscle before the intervention (pre) and 10 and 30 min after the intervention (post 1 and post 2, respectively). Cortical inhibitory circuits were evaluated using short-interval intracortical inhibition (SICI) and short-latency afferent inhibition (SAI). M1 cathodal decreased single-pulse MEP amplitudes at post 1 and decreased SAI at post 1 and post 2; however, SICI did not exhibit any change. S1 cathodal and sham did not show any changes in MEP amplitudes at any of the three time points. These results demonstrated that cathodal tDCS over the M1 not only decreases the M1 excitability but also affects the cortical inhibitory circuits related to SAI.

Influence of Transcranial Direct Current Stimulation to the Cerebellum on Standing Posture Control.

Damage to the vestibular cerebellum results in dysfunctional standing posture control. Patients with cerebellum dysfunction have a larger sway in the center of gravity while standing compared with healthy subjects. Transcranial direct current stimulation (tDCS) is a noninvasive technique for selectively exciting or inhibiting specific neural structures with potential applications in functional assessment and treatment of neural disorders. However, the specific stimulation parameters for influencing postural control have not been assessed. In this study, we investigated the influence of tDCS when applied over the cerebellum on standing posture control. Sixteen healthy subjects received tDCS (20 min, 2 mA) over the scalp 2 cm below the inion. In Experiment 1, all 16 subjects received tDCS under three stimulus conditions, Sham, Cathodal, and Anodal, in a random order with the second electrode placed on the forehead. In Experiment 2, five subjects received cathodal stimulation only with the second electrode placed over the right buccinator muscle. Center of gravity sway was measured twice for 60 s before and after tDCS in a standing posture with eyes open and legs closed, and average total locus length, locus length per second, rectangular area, and enveloped area were calculated. In Experiment 1, total locus length and locus length per second decreased significantly after cathodal stimulation but not after anodal or sham stimulation, while no tDCS condition influenced rectangular or enveloped areas. In Experiment 2, cathodal tDCS again significantly reduced total locus length and locus length per second but not rectangular and enveloped areas. The effects of tDCS on postural control are polarity-dependent, likely reflecting the selective excitation or inhibition of cerebellar Purkinje cells. Cathodal tDCS to the cerebellum of healthy subjects can alter body sway (velocity).

Regulation of primary motor cortex excitability by repetitive passive finger movement frequency

Somatosensory input induced by passive movement activates primary motor cortex (M1). We applied repetitive passive movement (RPM) of different frequencies to test if modulation of M1 excitability depends on RPM frequency. Twenty-seven healthy subjects participated in this study. Motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) to left M1 were recorded from the right first dorsal interosseous muscle (FDI) to assess corticospinal excitability (experiment 1: n=15), and F-waves were measured from the right FDI as an index of spinal motoneuron excitability (experiment 2: n=15). Passive abduction/adduction of the right index finger was applied for 10min at 0.5, 1.0, 3.0, and 5.0Hz. Both 0.5Hz-RPM and 1.0Hz-RPM decreased MEPs for 2min (p<0.05), and 5.0Hz-RPM decreased MEPs for 15min compared with baseline (p<0.05); however, there was no difference in MEPs after 3.0Hz-RPM. No F-wave changes were observed following any RPM intervention. Based on the results of experiments 1 and 2, we investigated whether RPM modulates cortical inhibitory circuit using the paired-pulse TMS technique (experiment 3: n=12). Short-interval intracortical inhibition (SICI) was measured using paired-pulse TMS (inter-stimulus interval of 3ms) before and after 1.0, 3.0, and 5.0Hz-RPM. Both 1.0 and 5.0Hz-RPM increased SICI compared with baseline (p<0.05). These experiments suggest that M1 excitability decreases after RPM depending on movement frequency, possibly through frequency-dependent enhancement of cortical inhibitory circuit in M1.

Effects of Passive Finger Movement on Cortical Excitability

This study examined the effects of joint angle and passive movement direction on corticospinal excitability. The subjects were 14 healthy adults from whom consent could be obtained. We performed two experiments. In Experiment 1, we measured motor evoked potential (MEP) amplitude, F-wave and M-wave at 0° and 20° adduction during adduction or abduction movement, in the range of movement from 10° abduction to 30° adduction. In Experiment 2, MEPs were measured at static 0° and 20° adduction during passive adduction from 10° adduction to 30° adduction and static 20° adduction. MEP, F-waves and M-waves were recorded from the right first dorsal interosseous (FDI) muscle. Experiment 1 revealed significantly increased MEP amplitude at 0° during passive adduction compared to static 0° (p < 0.01). No other significant differences in MEP, M-wave and F-wave parameters were observed. In Experiment 2, MEP amplitude was significantly higher at 20° adduction during passive adduction compared with static 0° (p < 0.01). Based on these findings, it appears that fluctuations in MEP amplitude values during passive movement are not influenced by joint angle, but rather it is possible that it is due to intracortical afferent facilitation (AF) dependent on afferent input due to the start of movement and interstimulus interval (ISI) of transcranial magnetic stimulation (TMS).

Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability

Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability.

Post-exercise cortical depression following repetitive passive finger movement

This study aimed to clarify the influence of range of repetitive passive finger movement on corticospinal excitability. Thirteen healthy subjects participated in this study. Passive index finger adduction-abduction movements were performed from 15° abduction to 15° adduction, 15° abduction to 0°, 0° to 15° adduction, and 15° adduction to 30° adduction, each at 15°/s for 10min on separate days. Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation and M- and F-waves were measured before and after each repetitive passive index finger movement protocol to evaluate changes in corticospinal excitability. MEP amplitude significantly decreased after all passive movements, while F-wave amplitude, F-wave persistence, and M-wave amplitude remained stable. These results suggest that cortical excitability decreases after repetitive passive movement. However, the range of repetitive passive movement does not markedly influence the magnitude of cortical depression.

Somatosensory Inputs Induced by Passive Movement Facilitate Primary Motor Cortex Excitability Depending on the Interstimulus Interval, Movement Velocity, and Joint Angle

Somatosensory inputs affect primary motor cortex (M1) excitability; however, the effect of movement-induced somatosensory inputs on M1 excitability is unknown. This study examined whether M1 excitability is modulated by somatosensory inputs with passive movement in 29 healthy subjects. Motor-evoked potentials (MEPs), elicited by transcranial magnetic stimulation (TMS) were recorded from the first dorsal interosseous (FDI) muscle (Experiment 1). M- and F-waves were measured from the FDI muscle (Experiment 2). Passive movements of the index finger were performed in the adduction direction. TMS pulses were preceded by starting passive movements with interstimulus intervals (ISIs) of 30, 60, 90, 120, 150, 180, and 210 ms. TMS or electrical stimulation was performed in the midrange of the metacarpophalangeal joint during passive movements. MEPs were significantly facilitated at 90, 120, and 150 ms (p < 0.05). No M- or F-wave changes were observed for any ISI. In addition, we investigated whether MEP changes were dependent on passive movement velocity and joint angle. Passive movement was performed at two movement velocities (Experiment 3) or joint angles (Experiment 4). MEP facilitation was observed depending on the movement velocities or joint angles. These experiments demonstrated that somatosensory inputs induced by passive movements facilitated M1 excitability depending on the ISIs, passive movement velocity, and joint angle.

Inhibitory Mechanisms in Primary Somatosensory Cortex Mediate the Effects of Peripheral Electrical Stimulation on Tactile Spatial Discrimination

Selective afferent activation can be used to improve somatosensory function, possibly by altering cortical inhibitory circuit activity. Peripheral electrical stimulation (PES) is widely used to induce selective afferent activation, and its effect may depend on PES intensity. Therefore, we investigated the effects of high- and low-intensity PES applied to the right index finger on tactile discrimination performance and cortical somatosensory-evoked potential paired-pulse depression (SEP-PPD) in 25 neurologically healthy subjects. In Experiment 1, a grating orientation task (GOT) was performed before and immediately after local high- and low-intensity PES (both delivered as 1-s, 20-Hz trains of 0.2-ms electrical pulses at 5-s intervals). In Experiment 2, PPD of SEP components N20/P25_SEP-PPD, N20_SEP-PPD and P25_SEP-PPD, respectively, were assessed before and immediately after high- and low-intensity PES. Improved GOT discrimination performance after high-intensity PES (reduced discrimination threshold) was associated with lower baseline performance (higher baseline discrimination threshold). Subjects were classified into low and high (baseline) GOT performance groups. Improved GOT discrimination performance in the low GOT performance group was significantly associated with a greater N20_SEP-PPD decrease (weaker PPD). Subjects were also classified into GOT improvement and GOT decrement groups. High-intensity PES decreased N20_SEP-PPD in the GOT improvement group but increased N20_SEP-PPD in the GOT decrement group. Furthermore, a greater decrease in GOT discrimination threshold was significantly associated with a greater N20_SEP-PPD decrease in the GOT improvement group. These results suggest that high-intensity PES can improve somatosensory perception in subjects with low baseline function by modulating cortical inhibitory circuits in primary somatosensory cortex.

Corticospinal excitability following repetitive voluntary movement

Post-exercise cortical depression (PED) is induced by non-fatiguing finger movement. Because the type of exercise that causes PED remains unclear, we conducted two experiments to clarify which exercise factors induce PED. Fifteen healthy participants performed repetitive abduction movements of the right index finger at 2.0 Hz (simple rhythmic task) and 0.2 Hz (adjustment task) for 6 min each in experiment 1. Twelve healthy participants performed repetitive and isometric abduction contractions of the right index finger at 1.0 Hz with visuomotor tracking (visuomotor task) and without visuomotor tracking (simple isometric task) for 5 min each in experiment 2. Muscle contraction levels were 10% of the maximum voluntary contraction in all tasks. Motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation were recorded from the right first dorsal interosseous muscle before and after the movement tasks. The simple rhythmic task transiently reduced MEP amplitudes when compared with baseline in experiment 1. In contrast, the visuomotor task increased MEP amplitudes in experiment 2. No MEP changes were observed following the adjustment task in experiment 1 and the simple isometric task in experiment 2. This study suggests that PED is induced by simple rhythmic movement.