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Objective: Transcranial ultrasound stimulation (TUS) is a promising noninvasive brain stimulation technique with advantages of high spatial precision and ability to target deep brain regions. This study aimed to develop a TUS protocol to effectively induce brain plasticity in human subjects., Methods: An 80-second train of theta burst patterned TUS (tbTUS), regularly patterned TUS (rTUS) with the same sonication duration, and sham tbTUS was delivered to the motor cortex in healthy subjects. Transcranial magnetic stimulation (TMS) was used to examine changes in corticospinal excitability, intracortical inhibition and facilitation, and the site of plasticity induction. The effects of motor cortical tbTUS on a visuomotor task and the effects of occipital cortex tbTUS on motor cortical excitability were also tested., Results: The tbTUS produced consistent increase in corticospinal excitability for at least 30 minutes, whereas rTUS and sham tbTUS produced no significant change. tbTUS decreased short-interval intracortical inhibition and increased intracortical facilitation. The effects of TMS in different current directions suggested that the site of the plastic changes was within the motor cortex. tbTUS to the occipital cortex did not change motor cortical excitability. Motor cortical tbTUS shortened movement time in a visuomotor task., Interpretation: tbTUS is a novel and efficient paradigm to induce cortical plasticity in humans. It has the potential to be developed for neuromodulation treatment for neurological and psychiatric disorders, and to advance neuroscience research. ANN NEUROL 2022;91:238-252., (© 2021 American Neurological Association.)

Background and Objective: Near-infrared low-level laser (NIR-LLL) irradiation penetrates scalp and skull and can reach superficial layers of the cerebral cortex. It was shown to improve the outcome of acute stroke in both animal and human studies. In this study we evaluated whether transcranial laser stimulation (TLS) with NIR-LLL can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS)., Methods: TLS was applied for 5 minutes over the representation of the right first dorsal interosseal muscle (FDI) in left primary motor cortex (M1), in 14 healthy subjects. Motor evoked potentials (MEPs) from the FDI, elicited by single-pulse TMS, were measured at baseline and up to 30 minutes after the TLS., Results: The average MEP size was significantly reduced during the first 20 minutes following the TLS. The pattern was present in 10 (71.5%) of the participants. The MEP size reduction correlated negatively with the motor threshold at rest., Conclusions: TLS with NIR-LLL induced transitory reduction of the excitability of the stimulated cortex. These findings give further insights into the mechanisms of TLS effects in the human cerebral cortex, paving the way for potential applications of TLS in treatment of stroke and in other clinical settings., (© 2013 Wiley Periodicals, Inc.)

The aim of the present study was to assess the potential effects of intermittent Universal Mobile Telecommunications System electromagnetic fields (UMTS-EMF) on blood circulation in the human head (auditory region) using near-infrared spectroscopy (NIRS) on two different timescales: short-term (effects occurring within 80 s) and medium-term (effects occurring within 80 s to 30 min). For the first time, we measured potential immediate effects of UMTS-EMF in real-time without any interference during exposure. Three different exposures (sham, 0.18 W/kg, and 1.8 W/kg) were applied in a controlled, randomized, crossover, and double-blind paradigm on 16 healthy volunteers. In addition to oxy-, deoxy-, and total haemoglobin concentrations ([O(2) Hb], [HHb], and [tHb], respectively), the heart rate (HR), subjective well-being, tiredness, and counting speed were recorded. During exposure to 0.18 W/kg, we found a significant short-term increase in Δ[O(2) Hb] and Δ[tHb], which is small (≈17%) compared to a functional brain activation. A significant decrease in the medium-term response of Δ[HHb] at 0.18 and 1.8 W/kg exposures was detected, which is in the range of physiological fluctuations. The medium-term ΔHR was significantly higher (+1.84 bpm) at 1.8 W/kg than for sham exposure. The other parameters showed no significant effects. Our results suggest that intermittent exposure to UMTS-EMF has small short- and medium-term effects on cerebral blood circulation and HR., (Copyright © 2011 Wiley Periodicals, Inc.)

Dysfunction of the basal ganglia-thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson's disease (PD). Using high-frequency repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA), we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD. In this double-blind placebo-controlled study, 99 patients were enrolled and assigned randomly to SMA-stimulation and sham-stimulation groups. For SMA stimulation, 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110% active motor threshold for leg muscles in one session. The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS. Each session of intervention was carried out once a week for the first 8 weeks. The SMA stimulation, in contrast to the sham stimulation, engendered significant improvements in total scores and motor scores of the Unified Parkinson's Disease Rating Scale. Mean improvements in motor scores were 4.5 points in the SMA-stimulation group and -0.1 points in the sham-stimulation group. Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients; SMA is a potential stimulation site for PD treatment., ((c) 2008 Movement Disorder Society.)

We investigated whether the pulsed high frequency electromagnetic field (EMF) emitted by a mobile phone has short term effects on the human motor cortex. We measured motor evoked potentials (MEPs) elicited by single pulse transcranial magnetic stimulation (TMS), before and after mobile phone exposure (active and sham) in 10 normal volunteers. Three sites were stimulated (motor cortex (CTX), brainstem (BST) and spinal nerve (Sp)). The short interval intracortical inhibition (SICI) of the motor cortex reflecting GABAergic interneuronal function was also studied by paired pulse TMS method. MEPs to single pulse TMS were also recorded in two patients with multiple sclerosis showing temperature dependent neurological symptoms (hot bath effect). Neither MEPs to single pulse TMS nor the SICI was affected by 30 min of EMF exposure from mobile phones or sham exposure. In two MS patients, mobile phone exposure had no effect on any parameters of MEPs even though conduction block occurred at the corticospinal tracts after taking a bath. As far as available methods are concerned, we did not detect any short-term effects of 30 min mobile phone exposure on the human motor cortical output neurons or interneurons even though we can not exclude the possibility that we failed to detect some mild effects due to a small sample size in the present study. This is the first study of MEPs after electromagnetic exposure from a mobile phone in neurological patients., ((c) 2007 Wiley-Liss, Inc.)

We treated a patient with levodopa-resistant akinesia with motor cortex stimulation (MCS), and she showed dramatic improvement more than 1 year. On admission, the patient presented severe akinesia and gait disturbance without tremor and rigidity, and did not respond to levodopa test. The patient was suspected pure akinesia and progressive supranuclear palsy. First, high-frequency rTMS of primary motor cortex was examined, and showed the dramatic improvement. Next, chronic subdural electrodes were implanted over the motor cortex bilaterally. One year after surgery, the Unified Parkinson's Disease Rating Scale had improved remarkably, and she could walk four times faster than before. The H2 15O PET study showed a significant increase of rCBF in the left SMA and right dorsolateral prefrontal cortex after bilateral MCS. MCS may be an alternative treatment for patients with akinesia, including those with PD, and particularly for levodopa-resistant patients, who respond well to rTMS., (Copyright (c) 2007 Movement Disorder Society.)

Extradural motor cortex stimulation (EMCS) is a surgical procedure proposed for patients with advanced Parkinson's disease (PD) who cannot undergo deep brain stimulation (DBS). Five PD patients with motor fluctuations and dyskinesia underwent EMCS of the left hemisphere. All fulfilled CAPSIT criteria for DBS, with the exception of age > 70 years. Patients were assessed preoperatively and 6 months after surgery on and off medications, with stimulator on, and 2 weeks later with stimulator off. Outcome measures included changes in mean medication dosage (levodopa and dopamine agonists), Unified Parkinson's Disease Rating Scale (UPDRS Parts II-III and Item 39), and dyskinesias (Abnormal Involuntary Movements Scale [AIMS]). We found no significant mean changes following EMCS. However, there was a trend for a reduction of mean daily medication intake (-30%) and AIMS (-19%). There were 3 patients who reported reduced OFF time (UPDRS Item 39) and 4 of 5 who felt a subjective benefit in stability and gait. In our PD cohort, EMCS induced no objective benefit, although some subjective improvement was reported mostly on axial symptoms., (Copyright 2006 Movement Disorder Society.)

A mutation in the DYT1 gene causes dominantly inherited childhood-onset primary dystonia, but intriguingly, only 30 to 40% of those who carry the mutation ever develop symptoms. We have used the unique model provided by this group of patients to investigate the hypothesis that abnormalities in brain plasticity underlie the pathophysiology of primary dystonia. We recruited 8 DYT1 gene carriers with dystonia, 6 DYT1 gene carriers without dystonia, 6 patients with sporadic primary dystonia (torticollis), and 10 healthy control subjects. Groups were age-matched. We compared the effect in these groups of subjects of repetitive transcranial magnetic stimulation (rTMS) delivered to the motor cortex, by assessing changes in corticospinal excitability following rTMS. rTMS was given in the form of theta burst stimulation (TBS) using the inhibitory protocol "cTBS" (total of 300 pulses in 50-Hz bursts given every 5Hz). DYT1 gene carriers with dystonia and subjects with torticollis had a significantly prolonged response to rTMS in comparison with healthy subjects. In contrast, DYT1 gene carriers without dystonia had no significant response to rTMS. These data demonstrate an excessive response to an experimental "plasticity probing protocol" in subjects with dystonia, but a lack of response in genetically susceptible individuals who have not developed dystonia. These preliminary data suggest that the propensity to undergo plastic change may affect the development of symptoms in genetically susceptible individuals and that this may be an important mechanism in the pathogenesis of primary dystonia in general., (Copyright 2006 Movement Disorder Society.)

We used the paired associative stimulation (PAS) technique to investigate associative plasticity of the sensorimotor cortex in 16 Parkinson's disease (PD) patients off and on therapy and in 10 age-matched controls. After PAS, motor evoked potential (MEP) amplitudes increased more and the cortical silent period showed a reduced prolongation in patients off therapy than in controls. These changes lasted for at least 30 minutes. In addition, MEP amplitudes increased in a less focal manner in patients off therapy than in controls. After patients received dopaminergic therapy, these abnormalities normalized. The abnormal responsiveness of sensorimotor cortex neurons to PAS in PD patients off therapy probably reflects disordered plasticity within the motor cortex., (Copyright (c) 2005 Movement Disorder Society.)

Purpose: To establish the repeatability of functional magnetic resonance imaging (fMRI) examinations in order to develop an appropriate margin for functional organs at risk (fOAR) in the radiotherapy planning process., Materials and Methods: This work investigates the variability of motor cortex activation in the left and right hemispheres of 15 normal subjects. The uncertainty of the absolute position and volume of the activation was determined for each volunteer by repeating the fMRI examination three times in a single scan session., Results: Our study proposes the use of 2.9 mm and 2.2 mm margins for the left and right motor cortices, respectively., Conclusion: From the sample of 15 volunteers we established an appropriate planning margin that is considered to represent the uncertainty in spatially measuring the fOAR for a single fMRI examination. The work will be of interest to anyone investigating the clinical robustness of fMRI., ((c) 2006 Wiley-Liss, Inc.)

Transcranial magnetic stimulation of the dorsolateral prefrontal cortex by single pulses of varying field intensities was used to measure thresholds of individual perception and motor response in three groups of subjects: subjectively electrosensitive people, general population controls with a high burden of complaints related to electromagnetic field (EMF) exposure in the literature (highest decile in complaint burden), and general population controls with a low burden of complaints (lowest decile in complaint burden). The major study endpoint was the ability of the subjects to differentiate between real magnetic stimulation and a sham condition. There were no significant differences between groups in the thresholds, neither of detecting the real magnetic stimulus nor in motor response. But the three groups differed significantly in differentiating between stimulation and sham condition, with the subjectively electrosensitive people having the lowest ability to differentiate and the control group with high level of EMF-related complaints having the best ability to differentiate. Differences between groups were mostly due to false alarm reactions in the sham condition reported by subjectively electrosensitives (SES). We found no objective correlate of the self perception of being "electrosensitive." Overall, our experiment does not support the hypothesis that subjectively electrosensitive patients suffer from a physiological hypersensitivity to EMFs or stimuli. Further research should focus on disposing factors explaining the unspecific sensory hyperresponsiveness of subjectively electrosensitive subjects., (Copyright 2005 Wiley-Liss, Inc.)

Patients with writer's cramp (WC) show abnormalities of sensorimotor integration possibly contributing to their motor deficit. We studied sensorimotor integration by determining short-latency afferent inhibition (SAI) in 12 WC patients and 10 age-matched healthy controls. A conditioning electrical median nerve stimulus was followed 14 to 36 msec later by transcranial magnetic stimulation of the contralateral primary motor cortex, and motor evoked potentials (MEP) were recorded from the relaxed or contracting abductor pollicis brevis muscle (APB). SAI was normal in WC but during APB relaxation SAI was followed by abnormal MEP facilitation, which was absent during APB contraction and in the controls. These findings suggest that somatosensory short-latency inhibitory input into the primary motor cortex is normal in WC, whereas a later excitatory input, which very likely reflects the long-latency reflex II, is exaggerated., (Copyright 2004 Movement Disorder Society.)