Gait-combined transcranial alternating current stimulation modulates cortical control of muscle activities during gait.

Non-invasive brain stimulation has been of interest as a therapeutic tool to modulate cortical excitability. However, there is little evidence that oscillatory brain stimulation can modulate the cortical control of muscle activities during gait, which can be assessed using coherence analysis of paired surface electromyographic (EMG) recordings. This study aimed to investigate the effects of gait-combined transcranial alternating current stimulation (tACS) at the gait cycle frequency on the cortical control of muscle activities during gait using EMG-EMG coherence analysis. Fourteen healthy young adults participated in this study. All participants underwent 2 test conditions (real tACS and sham stimulation over the leg area of the primary motor cortex during 10-min treadmill walking). The average peak-to-peak amplitudes of the motor evoked potentials (MEPs) from the tibialis anterior (TA) and lateral gastrocnemius muscles in the sitting position and EMG-EMG coherences in the TA muscle, triceps surae muscles, quadriceps muscles, and hamstring muscles during gait were measured before and after stimulation. Entrainment effect was significantly higher during real tACS than during sham stimulation. After real tACS, the MEP amplitude and beta band (13-33 Hz) coherence area increased in the TA muscle. The change in MEP amplitude from the TA muscle was positively correlated with the change in beta band coherence area in the TA muscle. Gait-combined tACS can modulate the strength of descending neural drive to TA motoneurons during gait. This suggests that oscillatory brain stimulation is a useful therapeutic tool to modulate the cortical control of muscle activities during gait.

Cerebellar transcranial alternating current stimulation modulates human gait rhythm.

Although specific brain regions are important for regularly patterned limb movements, the rhythm generation system that governs bipedal locomotion in humans is not thoroughly understood. We investigated whether rhythmic transcranial brain stimulation over the cerebellum could alter walking rhythm. Fourteen healthy subjects performed over-ground walking for 10 min during which they were given, in a random order, transcranial alternating current stimulation (tACS) over the left cerebellum at the approximated frequency of their gait cycle, tACS over the skin of the scalp, and during sham stimulation. Cerebellar tACS showed a significant entrainment of gait rhythm compared with the control conditions. When the direction of the tACS currents was symmetrically inverted, some subjects showed entrainment at an approximately 180° inverted phase, suggesting that gait modulation is dependent on current orientation. These findings indicate that tACS over cerebellum can modulate gait generation system in cerebellum and become an innovative approach for the recovery of locomotion in patients with gait disturbances caused by CNS disorders.

Gait-synchronized oscillatory brain stimulation modulates common neural drives to ankle muscles in patients after stroke: A pilot study.

The present study aimed to investigate the long-term effects of gait intervention with transcranial alternating current stimulation (tACS) synchronized with gait cycle frequency on the cortical control of muscle activity during gait, using coherence analyses, in patients after stroke. Eight chronic post-stroke patients participated in a single-blinded crossover study, and 7 patients completed the long-term intervention. Each patient received tACS over the primary motor cortex foot area on the affected side, which was synchronized with individual gait cycle frequency, and sham stimulation during treadmill gait in a random order. Electrical neuromuscular stimulation was used to assist the paretic ankle movement in both conditions. After gait intervention with tACS, beta band (15-35 Hz) coherence, which is considered to have a cortical origin, significantly increased in the paretic tibialis anterior (TA) muscle during 6-min of over-ground gait. The change in beta band coherence in the paretic TA muscle was positively correlated with the change in gait distance. These results indicate that gait intervention with tACS synchronized with gait cycle frequency may induce gait-specific plasticity that modulates the common neural drive to the TA motoneurons on the paretic side during gait and leads to changes in gait function in patients after stroke.

Gait-Synchronized Rhythmic Brain Stimulation Improves Poststroke Gait Disturbance: A Pilot Study.

Background and Purpose- Gait disturbance is one of serious impairments lowering activity of daily life in poststroke patients. The patients often show reduced hip and knee joint flexion and ankle dorsiflexion of the lower limbs during the swing phase of gait, which is partly controlled by the primary motor cortex (M1). In the present study, we investigated whether gait-synchronized rhythmic brain stimulation targeting swing phase-related M1 activity can improve gait function in poststroke patients. Methods- Eleven poststroke patients in the chronic phase participated in this single-blind crossover study. Each patient received oscillatory transcranial direct current stimulation over the affected M1 foot area and sham stimulation during treadmill gait. The brain stimulation was synchronized with individual gait rhythm, and the electrical current peaks reached immediately before initiation of the swing phase of the paretic lower limb. Ankle dorsiflexion was assisted by electrical neuromuscular stimulation in both real and sham conditions. Results- Regarding the effects of a single intervention, the speed of self-paced gait was significantly increased after oscillatory transcranial direct current stimulation, but not after sham stimulation (paired t test, P=0.009). After we administered the intervention repeatedly, self- and maximally paced gait speed and timed up and go test performance were significantly improved (self-paced: F(1,21)=8.91, P=0.007, maximally paced: F(1,21)=7.09, P=0.015 and timed up and go test: F(1,21)=12.27, P=0.002), along with improved balance function and increased joint flexion of the paretic limbs during gait. Conclusions- These findings suggest that rhythmic brain stimulation synchronized with gait rhythm might be a promising approach to induce gait recovery in poststroke patients. Clinical Trial Registration- URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000013676.

Anodal transcranial patterned stimulation of the motor cortex during gait can induce activity-dependent corticospinal plasticity to alter human gait.

The corticospinal system and local spinal circuits control human bipedal locomotion. The primary motor cortex is phase-dependently activated during gait; this cortical input is critical for foot flexor activity during the swing phase. We investigated whether gait-combined rhythmic brain stimulation can induce neuroplasticity in the foot area of the motor cortex and alter gait parameters. Twenty-one healthy subjects participated in the single-blinded, cross-over study. Each subject received anodal transcranial patterned direct current stimulation over the foot area of the right motor cortex during gait, sham stimulation during gait, and anodal transcranial patterned direct current stimulation during rest in a random order. Six subjects were excluded due to a failure in the experimental recording procedure. Complete-case analysis was performed using the data from the remaining 15 subjects. Self-paced gait speed and left leg stride length were significantly increased after the stimulation during gait, but not after the sham stimulation during gait or the stimulation during rest. In addition, a significant increase was found in the excitability of the corticospinal pathway of the left tibialis anterior muscle 30 min after stimulation during gait. Anodal transcranial patterned direct current stimulation during gait entrained the gait cycle to enhance motor cortical activity in some subjects. These findings suggest that the stimulation during gait induced neuroplasticity in corticospinal pathways driving flexor muscles during gait.

Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain Stimulation.

Neurofeedback has been a powerful method for self-regulating brain activities to elicit potential ability of human mind. GABA is a major inhibitory neurotransmitter in the central nervous system. Transcranial magnetic stimulation (TMS) is a tool that can evaluate the GABAergic system within the primary motor cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI). Herein we investigated whether neurofeedback learning using SICI enabled us to control the GABAergic system within the M1 area. Forty-five healthy subjects were randomly divided into two groups: those receiving SICI neurofeedback learning or those receiving no neurofeedback (control) learning. During both learning periods, subjects made attempts to change the size of a circle, which was altered according to the degree of SICI in the SICI neurofeedback learning group, and which was altered independent of the degree of SICI in the control learning group. Results demonstrated that the SICI neurofeedback learning group showed a significant enhancement in SICI. Moreover, this group showed a significant reduction in choice reaction time compared to the control group. Our findings indicate that humans can intrinsically control the intracortical GABAergic system within M1 and can thus improve motor behaviors by SICI neurofeedback learning. SICI neurofeedback learning is a novel and promising approach to control our neural system and potentially represents a new therapy for patients with abnormal motor symptoms caused by CNS disorders.

Motion-induced disturbance of auditory-motor synchronization and its modulation by transcranial direct current stimulation.

The timing of personal movement with respect to external events has previously been investigated using a synchronized finger-tapping task with a sequence of auditory or visual stimuli. While visuomotor synchronization is more accurate with moving stimuli than with stationary stimuli, it remains unclear whether the same principle holds true in the auditory domain. Although the right inferior-superior parietal lobe (IPL/SPL), a center of auditory motion processing, is expected to be involved in auditory-motor synchronization with moving sounds, its functional relevance has not yet been investigated. The aim of the present study was thus to clarify whether horizontal auditory motion affects the accuracy of finger-tapping synchronized with sounds, as well as whether the application of transcranial direct current stimulation (tDCS) to the right IPL/SPL affects this. Nineteen healthy right-handed participants performed a task in which tapping was synchronized with both stationary sounds and sounds that created apparent horizontal motion. This task was performed before and during anodal, cathodal and sham tDCS application to the right IPL/SPL in separate sessions. The time difference between the onset of the sounds and tapping was larger with apparently moving sounds than with stationary sounds. Cathodal tDCS decreased this difference, anodal tDCS increased the variance of the difference and sham stimulation had no effect. These results supported the hypothesis that auditory motion disturbs efficient auditory-motor synchronization and that the right IPL/SPL plays an important role in tapping in synchrony with moving sounds via auditory motion processing.

Isolation and identification of new vasodilative substances in diesel exhaust particles.

BACKGROUND, AIM, AND SCOPE: We recently developed a new isolation method for diesel exhaust particles (DEP), involving successive extraction with H(2)O, sodium bicarbonate, and sodium hydroxide, in which the sodium hydroxide extract was found to consist of phenolic components. Analysis of the extract revealed that vasodilative-active nitrophenols are in DEP in significantly higher concentrations than those estimated by an earlier method involving a combination of solvent extraction and repeated chromatography. These findings indicated that our new procedure offers a simple, efficient, and reliable method for the isolation and identification of bioactive substances in DEP. This encouraged us to extend our work toward investigating new vasodilatory substances in the sodium bicarbonate extract. MATERIALS AND METHODS: DEP were collected from the exhaust of a 4JB1-type engine (ISUZU Automobile Co., Tokyo, Japan). GC-MS analysis was performed with a GCMS-QP2010 instrument (Shimadzu, Kyoto, Japan). RESULTS: DEP dissolved in 1-butanol was successively extracted with water, sodium bicarbonate, and then aqueous sodium hydroxide. The sodium bicarbonate extract was neutralized and the resulting mixture of acidic components was subjected to reverse-phase (RP) column chromatography followed by RP-HPLC with fractions assayed for vasodilative activity. This led to the identification of terephthalic acid, p-hydroxybenzoic acid, isophthalic acid, phthalic acid, 3-hydroxy-4-nitrobenzoic acid, 4-hydroxy-3-nitrophenol, and 1,4,5-naphthalene tricarboxylic acid as components of DEP. DISCUSSION: The sodium bicarbonate extract was rich in aromatic carboxylic acid components. Repeated reverse-phase chromatography resulted in the successful isolation of several acidic substances including the new vasodilative materials, 4-hydroxy-3-nitrobenzoic acid, and 3-hydroxy-4-nitrobenzoic acid. CONCLUSIONS: Our new fractionation method for DEP has made possible the isolation of new vasodilative compounds from the sodium bicarbonate extract.

Supported silver nanoparticle catalyst for selective hydration of nitriles to amides in water.

Hydroxyapatite-supported silver nanoparticles (AgHAP) acted as a highly efficient reusable heterogeneous catalyst for hydration of diverse nitriles, including heteroaromatic ones, into amides in water.

Copper nanoparticles on hydrotalcite as a heterogeneous catalyst for oxidant-free dehydrogenation of alcohols.

We have developed a highly efficient heterogeneous catalytic system using hydrotalcite-supported Cu nanoparticles (Cu/HT) that can successfully promote the oxidant-free dehydrogenation of various alcohols under liquid-phase conditions.

Improvement of an efficient separation method for chemicals in diesel exhaust particles: analysis for nitrophenols.

GOAL, SCOPE, AND BACKGROUND: Diesel exhaust is believed to consist of thousands of organic constituents and is a major cause of urban pollution. We recently reported that a systematic separation procedure involving successive solvent extractions, followed by repeated column chromatography, resulted in the isolation of vasodilatory active nitrophenols. These findings indicated that the estimation of the amount of nitrophenols in the environment is important to evaluate their effect on human health. The isolation procedure, however, involved successive solvent extractions followed by tedious, repeated chromatography, resulting in poor fractionation and in a significant loss of accuracy and reliability. Therefore, it was crucial to develop an alternative, efficient, and reliable analytical method. Here, we describe a facile and efficient acid-base extraction procedure for the analysis of nitrophenols. MATERIALS AND METHODS: Diesel exhaust particles (DEP) were collected from the exhaust of a 4JB1-type engine (ISUZU Automobile Co., Tokyo, Japan). Gas chromatography-mass spectrometry (GC-MS) analysis was performed with a GCMS-QP2010 instrument (Shimadzu, Kyoto, Japan). RESULTS: A solution of DEP in 1-butanol was extracted with aqueous NaOH to afford a nitrophenol-rich oily extract. The resulting oil was methylated with trimethylsilyldiazomethane and subsequently subjected to GC-MS analysis, revealing that 4-nitrophenol, 3-methyl-4-nitrophenol, 2-methyl-4-nitrophenol, and 4-nitro-3-phenylphenol were present in significantly higher concentrations than those reported previously. DISCUSSION: Simple acid-base extraction followed by the direct analysis of the resulting extract by GC-MS gave only broad peaks of nitrophenols with a poor detection limit, while the GC-MS analysis of the sample pretreated with (trimethylsilyl)diazomethane gave satisfactorily clear chromatograms with sharp peaks and with a significantly lowered detection limit (0.5 ng/ml, approximately 100 times). CONCLUSION: The present method involving an acid-base extraction, in situ derivatization, and GC-MS analysis has shown to be a simple, efficient, and reliable method for the isolation and identification of the chemical substances in DEP.