Static Magnetic Field Stimulation Enhances Shunting Inhibition via a SLC26 Family Cl- Channel, Inducing Intrinsic Plasticity.

Magnetic fields are being used for detailed anatomical and functional examination of the human brain. In addition, evidence for their efficacy in treatment of brain dysfunctions is accumulating. Transcranial static magnetic field stimulation (tSMS) is a recently developed technique for noninvasively modifying brain functions. In tSMS, a strong and small magnet when placed over the skull can temporarily suppress brain functions. Its modulatory effects persist beyond the time of stimulation. However, the neurophysiological mechanisms underlying tSMS-induced plasticity remain unclear. Here, using acute motor cortical slice preparation obtained from male C57BL/6N mice, we show that tSMS alters the intrinsic electrical properties of neurons by altering the activity of chloride (Cl-) channels in neurons. Exposure of mouse pyramidal neurons to a static magnetic field (SMF) at a strength similar to human tSMS temporarily decreased their excitability and induced transient neuronal swelling. The effects of SMF were blocked by DIDS and GlyH-101, but not by NPPB, consistent with the pharmacological profile of SLC26A11, a transporter protein with Cl- channel activity. Whole-cell voltage-clamp recordings of the GlyH-101-sensitive Cl- current component showed significant enhancement of the component at both subthreshold and depolarized membrane potentials after SMF application, resulting in shunting inhibition and reduced repetitive action potential (AP) firing at the respective potentials. Thus, this study provides the first neurophysiological evidence for the inhibitory effect of tSMS on neuronal activity and advances our mechanistic understanding of noninvasive human neuromodulation.

Influence of postural control difficulty on changes in spatial orienting of attention after leftward prism adaptation.

Prism adaptation (PA) affects visuospatial attention such as spatial orienting in both the right and left hemifields; however, the systematic after-effects of PA on visuospatial attention remain unclear. Visuospatial attention can be affected by non-spatial attentional factors, and postural control difficulty, which delays the reaction time (RT) to external stimulation, may be one such factor. Therefore, we aimed to investigate the influence of postural control difficulty on changes in spatial orienting of attention after leftward PA. Seventeen healthy young adults underwent 15-min and 5-min PA procedures for a leftward visual shift (30 diopters). Participants underwent the Posner cueing test immediately before (pre-evaluation) and in between and after the PA procedures (post-evaluations) while standing barefoot on the floor (normal standing condition) and on a balance-disc (balance standing condition). In the pre-evaluation, RTs in the balance standing condition were significantly longer compared to those in the normal standing condition for targets appearing in both the right and left hemifields. Leftward PA improved the RT for targets appearing in the right, but no left, hemifield in the balance standing condition, such that RTs for targets in the right hemifield in the post-evaluation were not significantly different between the two standing conditions. However, leftward PA did not significantly change RTs for targets in both hemifields in the normal standing condition. Therefore, postural control difficulty may enhance sensitivity to the features of the visuospatial cognitive after-effects of leftward PA.

Triple tSMS system ("SHIN jiba") for non-invasive deep brain stimulation: a validation study in healthy subjects.

BACKGROUND: Transcranial static magnetic field stimulation (tSMS) using a small and strong neodymium (NdFeB) magnet can temporarily suppress brain functions below the magnet. It is a promising non-invasive brain stimulation modality because of its competitive advantages such as safety, simplicity, and low-cost. However, current tSMS is insufficient to effectively stimulate deep brain areas due to attenuation of the magnetic field with the distance from the magnet. The aim of this study was to develop a brand-new tSMS system for non-invasive deep brain stimulation. METHODS: We designed and fabricated a triple tSMS system with three cylindrical NdFeB magnets placed close to each other. We compared the strength of magnetic field produced by the triple tSMS system with that by the current tSMS. Furthermore, to confirm its function, we stimulated the primary motor area in 17 healthy subjects with the triple tSMS for 20 min and assessed the cortical excitability using the motor evoked potential (MEP) obtained by transcranial magnetic stimulation. RESULTS: Our triple tSMS system produced the magnetic field sufficient for neuromodulation up to 80 mm depth from the magnet surface, which was 30 mm deeper than the current tSMS system. In the stimulation experiment, the triple tSMS significantly reduced the MEP amplitude, demonstrating a successful inhibition of the M1 excitability in healthy subjects. CONCLUSION: Our triple tSMS system has an ability to produce an effective magnetic field in deep areas and to modulate the brain functions. It can be used for non-invasive deep brain stimulation.

Midfrontal theta as moderator between beta oscillations and precision control.

Control of movements using visual information is crucial for many daily activities, and such visuomotor control has been revealed to be supported by alpha and beta cortical oscillations. However, it has been remained to be unclear how midfrontal theta and occipital gamma oscillations, which are associated with high-level cognitive functions, would be involved in this process to facilitate performance. Here we addressed this fundamental open question in healthy young adults by measuring high-density cortical activity during a precision force-matching task. We manipulated the amount of error by changing visual feedback gain (low, medium, and high visual gains) and analyzed event-related spectral perturbations. Increasing the visual feedback gain resulted in a decrease in force error and variability. There was an increase in theta synchronization in the midfrontal area and also in beta desynchronization in the sensorimotor and posterior parietal areas with higher visual feedback gains. Gamma de/synchronization was not evident during the task. In addition, we found a moderation effect of midfrontal theta on the positive relationship between the beta oscillations and force error. Subsequent simple slope analysis indicated that the effect of beta oscillations on force error was weaker when midfrontal theta was high. Our findings suggest that the midfrontal area signals the increased need of cognitive control to refine behavior by modulating the visuomotor processing at theta frequencies.

Clinical impact of intraoperative CCEP monitoring in evaluating the dorsal language white matter pathway.

In order to preserve postoperative language function, we recently proposed a new intraoperative method to monitor the integrity of the dorsal language pathway (arcuate fasciculus; AF) using cortico-cortical evoked potentials (CCEPs). Based on further investigations (20 patients, 21 CCEP investigations), including patients who were not suitable for awake surgery (five CCEP investigations) or those without preoperative neuroimaging data (eight CCEP investigations including four with untraceable tractography due to brain edema), we attempted to clarify the clinical impact of this new intraoperative method. We monitored the integrity of AF by stimulating the anterior perisylvian language area (AL) by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. After tumor resection, single-pulse electrical stimuli were also applied to the floor of the removal cavity to record subcortico-cortical evoked potentials (SCEPs) at AL and PL in 12 patients (12 SCEP investigations). We demonstrated that (1) intraoperative dorsal language network monitoring was feasible even when patients were not suitable for awake surgery or without preoperative neuroimaging studies, (2) CCEP is a dynamic marker of functional connectivity or integrity of AF, and CCEP N1 amplitude could even become larger after reduction of brain edema, (3) a 50% CCEP N1 amplitude decline might be a cut-off value to prevent permanent language dysfunction due to impairment of AF, (4) a correspondence (<2.0 ms difference) of N1 onset latencies between CCEP and the sum of SCEPs indicates close proximity of the subcortical stimulus site to AF (<3.0 mm). Hum Brain Mapp 38:1977-1991, 2017. © 2017 Wiley Periodicals, Inc.

Intraoperative dorsal language network mapping by using single-pulse electrical stimulation.

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico-cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language-dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High-frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single-pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high-frequency ES of the white matter produced naming impairment, this "eloquent" subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico- and subcortico-cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network.

Tackling social anxiety with targeted brain stimulation: investigating the effects of transcranial static magnetic field stimulation on self-focused attention.

Previous studies suggested that self-focused attention (SFA), implicated in social anxiety disorder (SAD), correlates with heightened activity in the right frontopolar area (rFPA), which is the right prefrontal cortex just behind the forehead. Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation method capable of temporarily suppressing brain function beneath the magnet. We explored whether tSMS on individuals with tendencies toward SAD elicited (1) suppressing rFPA activation during the resting-state and (2) reducing SFA during a subsequent speech task. Twenty-three university students with social anxiety performed two speech tasks. Between tasks, the tSMS group received neodymium magnet stimulation while the sham group received fake magnet stimulation on the rFPA for 20 min. Resting-state rFPA activities was measured using functional near-infrared spectroscopy (fNIRS), while SFA (body sensations and observer perspective), field perspective, and detached mindfulness (DM) perspective were assessed via questionnaires during both speech tasks. The observer perspective means SFA to self-imagery from others' viewpoint, while the field and DM perspectives mean appropriately focusing on the external environment. The results indicated that tSMS intervention decreased rFPA activity from pre- to post-intervention rest. Then, tSMS reduced SFA to bodily sensations and increased DM perspective from pre- to post-intervention speech, especially in those with high levels of social anxiety. Furthermore, tSMS enhanced the field perspective regardless of social anxiety tendency. The results suggest that tSMS may suppress overactivity in rFPA, reduce SFA to body sensation, and increase adaptive attention in highly socially anxious individuals. Our study suggests the possibility of the clinical application of tSMS for treating SAD.

Non-invasive Brain Stimulation in Post-stroke Dysphagia Rehabilitation: A Narrative Review of Meta-analyses in 2022.

Objectives: This study aimed to update the current knowledge on non-invasive brain stimulation (NIBS) effects, such as repetitive transcranial brain stimulation and transcranial direct current stimulation, in patients with post-stroke dysphagia (PSD). Methods: We summarized the basic principles and therapeutic strategies of NIBS. We then reviewed nine meta-analyses from 2022 that investigated the efficacy of NIBS in PSD rehabilitation. Results: Although dysphagia is a common and devastating sequela of stroke, the efficacy of conventional swallowing therapies remains controversial. NIBS techniques have been proposed as promising approaches for managing PSD via neuromodulation. Recent meta-analyses have shown that NIBS techniques are beneficial for the recovery of patients with PSD. Conclusions: NIBS has the potential to become a novel alternative treatment for PSD rehabilitation.

Low-frequency repetitive transcranial magnetic stimulation can alleviate spasticity and induce functional recovery in patients with severe chronic stroke: A prospective, non-controlled, pilot study.

Objective: Developing new therapies to improve motor function in patients with severe chronic stroke remains a major focus of neurorehabilitation. In this prospective, non-controlled, pilot study, we aimed to investigate the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy (OT) on the motor function recovery of the affected upper limb in chronic stroke patients with severe upper limb hemiparesis. Methods: Consecutive patients (n = 40) diagnosed with chronic stroke (time since stroke, ≥1 year) and upper limb hemiparesis were enrolled in this study. Patients were classified according to the Brunnstrom recovery stage (BRS) for fingers. The severity of upper limb hemiparesis was categorized as mild (BRS IV-VI) or severe (BRS I-III). Patients received low-frequency rTMS to the contralesional primary motor area (M1) followed by OT for 12 consecutive days. The primary outcome was upper limb motor recovery, as measured with the Fugl-Meyer assessment (FMA). Secondary outcomes included manual dexterity, upper limb use, spasticity of the fingers and wrist, and motor evoked potential (MEP). Results: Patients with severe hemiparesis showed a significant increase in upper limb use, significantly improved quality of movement, and significantly reduced spasticity. Those with mild hemiparesis showed significant improvements in the FMA scores and manual dexterity, a significant increase in upper limb use and MEP, and significantly reduced spasticity. Conclusions: Low-frequency rTMS applied to the contralesional M1 combined with OT was effective in the rehabilitation of chronic stroke patients with severe upper limb hemiparesis by reducing the spasticity of the fingers.

Effect of transcranial static magnetic stimulation over unilateral or bilateral motor association cortex on performance of simple and choice reaction time tasks.

Background: Transcranial static magnetic stimulation (tSMS) is a non-invasive brain stimulation technique that place a strong neodymium magnet on scalp to reduce cortical excitability. We have recently developed a new tSMS device with three magnets placed close to each other (triple tSMS) and confirmed that this new device can produce a stronger and broader static magnetic field than the conventional single tSMS. The aim of the present study was to investigate the effect of the conventional single tSMS as well as triple tSMS over the unilateral or bilateral motor association cortex (MAC) on simple and choice reaction time (SRT and CRT) task performance. Methods: There were two experiments: one involved the conventional tSMS, and the other involved the triple tSMS. In both experiments, right-handed healthy participants received each of the following stimulations for 20 min on different days: tSMS over the unilateral (left) MAC, tSMS over the bilateral MAC, and sham stimulation. The center of the stimulation device was set at the premotor cortex. The participants performed SRT and CRT tasks before, immediately after, and 15 min after the stimulation (Pre, Post 0, and Post 15). We evaluated RT, standard deviation (SD) of RT, and accuracy (error rate). Simulation was also performed to determine the spatial distribution of magnetic field induced by tSMS over the bilateral MAC. Results: The spatial distribution of induced magnetic field was centered around the PMd for both tSMS systems, and the magnetic field reached multiple regions of the MAC as well as the sensorimotor cortices for triple tSMS. SD of CRT was significantly larger at Post 0 as compared to Pre when triple tSMS was applied to the bilateral MAC. No significant findings were noted for the other conditions or variables. Discussion: We found that single tSMS over the unilateral or bilateral MAC did not affect performance of RT tasks, whereas triple tSMS over the bilateral MAC but not over the unilateral MAC increased variability of CRT. Our finding suggests that RT task performance can be modulated using triple tSMS.

Transcranial static magnetic stimulation over the motor cortex can facilitate the contralateral cortical excitability in human.

Transcranial static magnetic stimulation (tSMS) has been focused as a new non-invasive brain stimulation, which can suppress the human cortical excitability just below the magnet. However, the non-regional effects of tSMS via brain network have been rarely studied so far. We investigated whether tSMS over the left primary motor cortex (M1) can facilitate the right M1 in healthy subjects, based on the hypothesis that the functional suppression of M1 can cause the paradoxical functional facilitation of the contralateral M1 via the reduction of interhemispheric inhibition (IHI) between the bilateral M1. This study was double-blind crossover trial. We measured the corticospinal excitability in both M1 and IHI from the left to right M1 by recording motor evoked potentials from first dorsal interosseous muscles using single-pulse and paired-pulse transcranial magnetic stimulation before and after the tSMS intervention for 30 min. We found that the corticospinal excitability of the left M1 decreased, while that of the right M1 increased after tSMS. Moreover, the evaluation of IHI revealed the reduced inhibition from the left to the right M1. Our findings provide new insights on the mechanistic understanding of neuromodulatory effects of tSMS in human.

Effects of transcranial static magnetic stimulation over the primary motor cortex on local and network spontaneous electroencephalogram oscillations.

Transcranial static magnetic stimulation (tSMS) is a novel non-invasive brain stimulation technique that reduces cortical excitability at the stimulation site. We investigated the effects of tSMS over the left primary motor cortex (M1) for 20 min on the local electroencephalogram (EEG) power spectrum and interregional EEG coupling. Twelve right-handed healthy subjects participated in this crossover, double-blind, sham-controlled study. Resting-state EEG data were recorded for 3 min before the intervention and 17 min after the beginning of the intervention. The power spectrum at the left central electrode (C3) and the weighted phase lag index (wPLI) between C3 and the other electrodes was calculated for theta (4-8 Hz), alpha (8-12 Hz), and beta (12-30 Hz) frequencies. The tSMS significantly increased theta power at C3 and the functional coupling in the theta band between C3 and the parietal midline electrodes. The tSMS over the left M1 for 20 min exhibited modulatory effects on local cortical activity and interregional functional coupling in the theta band. The neural oscillations in the theta band may have an important role in the neurophysiological effects induced by tSMS over the frontal cortex.

Effects of propofol on cortico-cortical evoked potentials in the dorsal language white matter pathway.

OBJECTIVE: In order to evaluate the clinical utility even under general anesthesia, the present study aimed to clarify the effect of anesthesia on the cortico-cortical evoked potentials (CCEPs). METHODS: We analyzed 14 patients' data in monitoring the integrity of the dorsal language pathway by using CCEPs both under general anesthesia with propofol and remifentanil and awake condition, with the main aim of clarifying the effect of anesthesia on the distribution and waveform of CCEPs. RESULTS: The distribution of larger CCEP response sites, including the locus of the maximum CCEP response site, was marginally affected by anesthesia. With regard to similarity of waveforms, the mean waveform correlation coefficient indicated a strong agreement. CCEP N1 amplitude increased by an average of 25.8% from general anesthesia to waking, except three patients. CCEP N1 latencies had no correlation in changes between the two conditions. CONCLUSIONS: We demonstrated that the distribution of larger CCEP responses was marginally affected by anesthesia and that the CCEP N1 amplitude had tendency to increase from general anesthesia to the awake condition. SIGNIFICANCE: The CCEP method provides the efficiency of intraoperative monitoring for dorsal language white matter pathway even under general anesthesia.

Effects of a stable concentration of propofol on interictal high-frequency oscillations in drug-resistant epilepsy.

The aim of this study was to clarify the effect of a stable concentration of propofol on interictal high-frequency oscillations (HFOs), which may contribute to identifying the epileptogenic zone intraoperatively for resection surgery. Nine patients with drug-resistant focal epilepsy who underwent invasive pre-surgical evaluation with chronic subdural electrodes were recruited. Five-minute electrocorticograms during wakefulness, slow-wave sleep, and under a stable brain concentration of propofol were recorded with the same electrodes. In each patient, 1-10 pairs of electrodes were selected for both electrodes with EEG changes within 5 seconds from the ictal onset (ictal pattern for 5 seconds [IP5]) and those outside the area of IP5 with no interictal epileptiform discharges (non-epileptiform [nEPI]). The numbers of ripples (80-250 Hz) and fast ripples (>250 Hz) were measured semi-automatically using an established algorithm. Statistical testing was performed with a mixed effect model. Thirty-seven pairs of electrodes from nine patients were analysed for IP5 and 29 pairs from seven patients were analysed for nEPI. The numbers of HFOs differed between the areas (IP5 and nEPI) and among the conditions (wakefulness, slow-wave sleep, propofol anaesthesia) (all p <0.01). The HFO occurrence rates were significantly higher for IP5 than those for nEPI in all conditions (for both ripples and fast ripples in all conditions; p <0.01). The occurrence rates of HFOs for IP5 were significantly higher than those for nEPI under propofol anaesthesia. These are fundamental findings for intraoperative HFO analysis, however, the following limitations should be considered: physiological HFOs could not be completely differentiated from pathological HFOs; in order to apply an HFO detector, an appropriate cut-off threshold is needed; an artefact of the impulse response filter appears as an HFO; and the series was comprised of a small number of heterogeneous patients.

[A case of A3-A3 bypass and proximal clipping for a ruptured left A1 dissecting aneurysm].

A 58-year-old woman was admitted to our hospital with sudden onset of headache. CT and angiogram revealed subarachnoid hemorrhage due to a dissecting aneurysm at the left A1 segment. ACoA was not identified. We performed proximal clipping with A3-A3 bypass for preventing the recurrence of the hemorrhage and for reducing ischemia in the territory of the left ACA. After the operation, CT revealed the infarctions in the corpus callosum, the left medial frontal lobe and the genu of the internal capsule. But the postoperative angiogram demonstrated no aneurysm and the opacification of the recurrent artery of Heubner and the part of perforating branches. A3-A3 bypass was patent. The patient experienced a good recovery without recurrence of bleeding.

Effect of transcranial static magnetic stimulation on intracortical excitability in the contralateral primary motor cortex.

Transcranial static magnetic stimulation (tSMS) is a new technique of non-invasive brain stimulation using a small, high-powered neodymium magnet placed on the scalp. It can reduce cortical excitability below the magnet. The aim of this study was to investigate the effect of tSMS on the intracortical excitability of the primary motor cortex (M1) contralateral to the M1 where the magnet was placed. Fourteen right-handed healthy subjects participated in this experiment. TSMS was applied over the left M1 for 20 min. Single-pulse and paired-pulse transcranial magnetic stimulation (TMS) was applied over the right M1 to assess corticospinal excitability, short-latency intracortical inhibition (SICI), and intracortical facilitation (ICF) before and immediately after the intervention. ICF decreased significantly after tSMS, whereas corticospinal excitability and SICI did not change. This study suggests that tSMS applied over the M1 for 20 min has a remote modulatory effect on the interneuronal facilitatory circuit in the contralateral M1. The ability of tSMS to modulate neuronal activities in the remote cortex could expand the possibility of its clinical use.

Normal Variants in Magnetoencephalography.

Normal variants, although not occurring frequently, may appear similar to epileptic activity. Misinterpretation may lead to false diagnoses. In the context of presurgical evaluation, normal variants may lead to mislocalizations with severe impact on the viability and success of surgical therapy. While the different variants are well known in EEG, little has been published in regard to their appearance in magnetoencephalography. Furthermore, there are some magnetoencephalography normal variants that have no counterparts in EEG. This article reviews benign epileptiform variants and provides examples in EEG and magnetoencephalography. In addition, the potential of oscillatory configurations in different frequency bands to appear as epileptic activity is discussed.

Intraoperative Electrophysiologic Mapping of Medial Frontal Motor Areas and Functional Outcomes.

OBJECTIVE: To propose a method for intraoperative mapping and monitoring of the medial frontal motor areas (MFMA). METHODS: We estimated the location of the MFMA using the corticocortical evoked potential (CCEP) provoked by electric stimuli to the primary motor area (M1) of the upper limb. We localized or defined the MFMA by recording the motor evoked potentials (MEPs) provoked by electric stimuli to the medial frontal cortex around the estimated area. We monitored the patients' motor function during awake craniotomy and sequentially recorded the MEPs of the upper and/or lower limbs. This method was applied to 8 patients. RESULTS: Four patients who had part of the areas identified as the MFMA removed showed transient hemiparesis postoperatively (supplementary motor area [SMA] syndrome). The MEP from the M1 was preserved in the 4 patients. The resection of the identified MFMA might have caused their SMA syndrome. The CCEP showed a strong connection between the M1 and the SMA of the upper limb. Our method did not provoke any seizures. CONCLUSIONS: This is a safe and sensitive method for intraoperative mapping and monitoring of the MFMA by combining electrophysiologic monitoring and awake craniotomy. It is clinically useful for mapping the MFMA and can prevent permanent motor deficits.