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Objective: We investigated the longitudinal associations of cumulative motor fitness, muscular strength, and cardiorespiratory fitness (CRF) from childhood to adolescence with cortical excitability and inhibition in adolescence. The other objective was to determine cross-sectional associations of motor fitness and muscular strength with brain function in adolescence. Methods: In 45 healthy adolescents (25 girls and 20 boys) aged 16-19 years, we assessed cortical excitability and inhibition by navigated transcranial magnetic stimulation (nTMS), and motor fitness by 50-m shuttle run test and Box and block test, and muscular strength by standing long jump test. These measures of physical fitness and CRF by maximal exercise were assessed also at the ages 7-9, 9-11, and 15-17 years. Cumulative measures of physical measures were computed by summing up sample-specific z-scores at ages 7-9, 9-11, and 15-17 years. Results: Higher cumulative motor fitness performance from childhood to adolescence was associated with lower right hemisphere resting motor threshold (rMT), lower silent period threshold (SPt), and lower motor evoked potential (MEP) amplitude in boys. Better childhood-to-adolescence cumulative CRF was also associated with longer silent period (SP) duration in boys and higher MEP amplitude in girls. Cross-sectionally in adolescence, better motor fitness and better muscular strength were associated with lower left and right rMT among boys and better motor fitness was associated with higher MEP amplitude and better muscular strength with lower SPt among girls. Conclusion: Physical fitness from childhood to adolescence modifies cortical excitability and inhibition in adolescence. Motor fitness and muscular strength were associated with motor cortical excitability and inhibition. The associations were selective for specific TMS indices and findings were sex-dependent. [ABSTRACT FROM AUTHOR]

Introduction: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. Methods: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. Results: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). Conclusion: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain. [ABSTRACT FROM AUTHOR]

Objective. To investigate whether the motor threshold (MT) and the location of the motor hotspot in transcranial magnetic stimulation (TMS) can be predicted with computational models of the induced electric field. Approach. Individualized computational models were constructed from structural magnetic resonance images of ten healthy participants, and the induced electric fields were determined with the finite element method. The models were used to optimize the location and direction of the TMS coil on the scalp to produce the largest electric field at a predetermined cortical target location. The models were also used to predict how the MT changes as the magnetic coil is moved to various locations over the scalp. To validate the model predictions, the motor evoked potentials were measured from the first dorsal interosseous (FDI) muscle with TMS in the ten participants. Both computational and experimental methods were preregistered prior to the experiments. Main results. Computationally optimized hotspot locations were nearly as accurate as those obtained using manual hotspot search procedures. The mean Euclidean distance between the predicted and the measured hotspot locations was approximately 1.3 cm with a 0.8 cm bias towards the anterior direction. Exploratory analyses showed that the bias could be removed by changing the cortical target location that was used for the prediction. The results also indicated a statistically significant relationship (p < 0.001) between the calculated electric field and the MT measured at several locations on the scalp. Significance. The results show that the individual TMS hotspot can be located using computational analysis without stimulating the subject or patient even once. Adapting computational modelling would save time and effort in research and clinical use of TMS. [ABSTRACT FROM AUTHOR]

The measurement of the motor threshold (MT) is an important element in determining stimulation intensity during Transcranial Magnetic Stimulation treatment (rTMS). The current recommendations propose its realization at least once a week. The variability in this motor threshold is an important factor to consider as it could translate certain neurophysiological specificities. We conducted a retrospective naturalistic study on data from 30 patients treated for treatment-resistant depression in an rTMS-specialized center. For each patient, weekly motor-evoked potential (MEP) was performed and several clinical elements were collected as part of our clinical interviews. Regarding response to treatment (Patient Health Questionnaire-9 (PHQ-9) before and after treatment), there was a mean difference of −8.88 (−21 to 0) in PHQ9 in the Theta Burst group, of −9.00 (−18 to −1) in the High-Frequency (10 Hz) group, and of −4.66 (−10 to +2) in the Low-Frequency (1 Hz) group. The mean improvement in depressive symptoms was 47% (p < 0.001, effect-size: 1.60). The motor threshold changed over the course of the treatment, with a minimum individual range of 1 point and a maximum of 19 points (total subset), and a greater concentration in the remission group (4 to 10) than in the other groups (3 to 10 in the response group, 1 to 8 in the partial response group, 3 to 19 in the stagnation group). We also note that the difference between MT at week 1 and week 6 was statistically significant only in the remission group, with a different evolutionary profile showing an upward trend in MT. Our findings suggest a potential predictive value of MT changes during treatment, particularly an increase in MT in patients who achieve remission and a distinct "break" in MT around the 4th week, which could predict nonresponse. [ABSTRACT FROM AUTHOR]

Variability in the response of individuals to various non-invasive brain stimulation protocols is a major problem that limits their potential for clinical applications. Baseline motor-evoked potential (MEP) amplitude is the key predictor of an individual's response to transcranial magnetic stimulation protocols. However, the factors that predict MEP amplitude and its variability remain unclear. In this study, we aimed to identify the input–output curve (IOC) parameters that best predict MEP amplitude and its variability. We analysed IOC data from 75 subjects and built a general linear model (GLM) using the IOC parameters as regressors and MEP amplitude at 120% resting motor threshold (RMT) as the response variable. We bootstrapped the data to estimate variability of IOC parameters and included them in a GLM to identify the significant predictors of MEP amplitude variability. Peak slope, motor threshold, and maximum MEP amplitude of the IOC were significant predictors of MEP amplitude at 120% RMT and its variability was primarily driven by the variability of peak slope and maximum MEP amplitude. Recruitment gain and maximum corticospinal excitability are the key predictors of MEP amplitude and its variability. Inter-individual variability in motor output may be reduced by achieving a uniform IOC slope. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is widely used for therapeutic and research purposes such as cognitive studies, treatment of psychiatric disorders, and Parkinson's disease. In research, TMS is perhaps the only technique that can establish a functional connection between brain regions and task performance. In gait research, often TMS is used to identify the extent to which leg motor cortex is involved in different phases on gait cycle. However, using TMS in gait can be challenging for several technical reasons and physiological variations. The objective of this narrative review is to summarize literature in the field of TMS and gait research and present comprehensive challenges. A comprehensive literature search was conducted in PubMed and Google Scholar to identify all relevant literature on TMS and gait. Several critical challenges could potentially impact the findings. For instance, the use of different protocols to obtain motor threshold. This review presents some of the critical challenges in applying TMS during gait. It is important to be aware of these variations and utilize strategies to mitigate some challenges. [ABSTRACT FROM AUTHOR]

Cortical stimulation patterns in patients with Parkinson's disease (PD) are asymmetric and get altered over time. This study examined cortical neurophysiological markers for PD and identified neurophysiological markers for lateralization in PD. We used transcranial magnetic stimulation (TMS) to study corticospinal and intracortical excitability in 21 patients with idiopathic PD. We used the Movement Disorder Society Unified Parkinson's Disease Rating Scale for examination during on and off periods and evaluated inhibitory and facilitatory process markers using TMS, including resting motor thresholds (RMT), active motor thresholds, and motor evoked potential amplitude. The RMT in the more affected cortex was significantly shorter than in the less affected cortex, and was strongly correlated with improved motor function following medication. Patients in the tremor group exhibited significantly lower RMT compared to those in the akinetic-rigid group. Cortical electrophysiological laterality observed in patients with PD may be a useful marker for guiding treatment and identifying underlying compensatory mechanisms. [ABSTRACT FROM AUTHOR]

Objective: The time interval between transcranial magnetic stimulation (TMS) pulses affects evoked muscle responses when the targeted muscle is resting. This necessitates using sufficiently long inter-pulse intervals (IPIs). However, there is some evidence that the IPI has no effect on the responses evoked in active muscles. Thus, we tested whether voluntary contraction could remove the effect of the IPI on TMS motor evoked potentials (MEPs). Methods: In our study, we delivered sets of 30 TMS pulses with three different IPIs (2, 5, and 10 s) to the left primary motor cortex. These measurements were performed with the resting and active right hand first dorsal interosseous muscle in healthy participants (N = 9 and N = 10). MEP amplitudes were recorded through electromyography. Results: We found that the IPI had no significant effect on the MEP amplitudes in the active muscle (p = 0.36), whereas in the resting muscle, the IPI significantly affected the MEP amplitudes (p < 0.001), decreasing the MEP amplitude of the 2 s IPI. Conclusions: These results show that active muscle contraction removes the effect of the IPI on the MEP amplitude. Therefore, using active muscles in TMS motor mapping enables faster delivery of TMS pulses, reducing measurement time in novel TMS motor mapping studies. [ABSTRACT FROM AUTHOR]

Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey and white matter damage with cortical excitability abnormalities. We applied advanced diffusion imaging with 3T magnetic resonance tomography for neurite orientation dispersion and density imaging (NODDI), as well as diffusion tensor imaging (DTI) in 50 MS patients and 49 age-matched healthy controls to quantify microstructural integrity of the motor system. To assess excitability, we determined resting motor thresholds using non-invasive transcranial magnetic stimulation. As measures of cognitive-motor performance, we conducted neuropsychological assessments including the Nine-Hole Peg Test, Trail Making Test part A and B (TMT-A and TMT-B) and the Symbol Digit Modalities Test (SDMT). Patients were evaluated clinically including assessments with the Expanded Disability Status Scale. A hierarchical regression model revealed that lower neurite density index (NDI) in primary motor cortex, suggestive for axonal loss in the grey matter, predicted higher motor thresholds, i.e. reduced excitability in MS patients (p =.009, adjusted r² = 0.117). Furthermore, lower NDI was indicative of decreased cognitive-motor performance (p =.007, adjusted r² =.142 for TMT-A; p =.009, adjusted r² =.129 for TMT-B; p =.006, adjusted r² =.142 for SDMT). Motor WM tracts of patients were characterized by overlapping clusters of lowered NDI (p <.05, Cohen's d = 0.367) and DTI-based fractional anisotropy (FA) (p <.05, Cohen's d = 0.300), with NDI exclusively detecting a higher amount of abnormally appearing voxels. Further, orientation dispersion index of motor tracts was increased in patients compared to controls, suggesting a decreased fiber coherence (p <.05, Cohen's d = 0.232). This study establishes a link between microstructural characteristics and excitability of neural tissue, as well as cognitive-motor performance in multiple sclerosis. We further demonstrate that the NODDI parameters neurite density index and orientation dispersion index detect a larger amount of abnormally appearing voxels in patients compared to healthy controls, as opposed to the classical DTI parameter FA. Our work outlines the potential for microstructure imaging using advanced biophysical models to forecast excitability alterations in neuroinflammation. [ABSTRACT FROM AUTHOR]

Single-pulse and repetitive transcranial magnetic stimulation (rTMS) are used in clinical practice for diagnostic and therapeutic purposes. However, rTMS-based therapies that lead to a significant and sustained reduction in neuropsychiatric symptoms remain scarce. While it is generally accepted that the stimulation frequency plays a crucial role in producing the therapeutic effects of rTMS, less attention has been dedicated to determining the role of the electric field strength. Conventional threshold-based intensity selection approaches, such as the resting motor threshold, produce variable stimulation intensities and electric fields across participants and cortical regions. Insufficient standardization of electric field strength may contribute to the variability of rTMS effects and thus therapeutic success. Computational approaches that can prospectively optimize the electric field and standardize it across patients and cortical targets may overcome some of these limitations. Here, we discuss these approaches and propose that electric field standardization will be instrumental for translational science frameworks (e.g., multiscale modeling and basic science approaches) aimed at deciphering the subcellular, cellular, and network mechanisms of rTMS. Advances in understanding these mechanisms will be important for optimizing rTMS-based therapies in psychiatry. [ABSTRACT FROM AUTHOR]

In intraoperative neuromonitoring (IONM), facial nerve motor function (FaNMF) is assessed by facial muscle corticobulbar motor evoked potentials (FMcoMEP). Mostly only amplitude decrease is used as warning criterion. We related a refined criterion for FMcoMEP consisting of a bilateral final-to-baseline motor threshold ratio with standard criteria and postoperative FaNMF. 79 patients (45 females; 48 ± 16 years) undergoing IONM-guided cerebellopontine angle tumor surgery were retrospectively analyzed. An intraoperative final-to-baseline motor threshold increase ≥ 20% ipsi- versus contralaterally (bFBMT20) was correlated to postoperative FaNMF at day 1 (D1), 7 (D7) and 3 months (3 M). An ipsilateral-only final-to-baseline motor threshold increase ≥ 20 mA (iAMT20) and amplitude decrement ≥ 50% (iAR50) served as reference. Tumors included vestibular schwannomas (68%), meningiomas (19%) and others (13%). Mean tumor diameter was 2.7 ± 1.1 cm. Postoperatively, HB-increase ≥ 2 was seen in 27% (D1), 17% (D7), and 6% (3 M) of patients, respectively. FMcoMEP were obtained in 75/79 cases. Pathological bFBMT20, iAMT20 and iAR50 were seen in 17, 17, and 46 cases, respectively. Area under the ROC curve for bFBMT20 (iAMT20) was 0.894 (0.868) at D1; 0.903 (0.822) at D7 and 0.941 (0.959) at 3 M. iAR50 performed worse at all time points. Diagnostic odds ratios were highest for bfBMT20 compared to iAMT20 and iAR50 for D1 (172.5 vs. 8.7 vs. 0.45) and D7 (51.4 vs. 6.1 vs. 0.8). The refined parameter bFBMT20 provides a valuable contribution to the prognostic assessment of FaNMF. Due to its bihemispheric character, it might thus circumvent false-positive events which affect FMcoMEP bilaterally. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is commonly used in basic research to evaluate human brain function. Although scalp pain is a side effect, no studies have quantitatively assessed the TMS intensity threshold for inducing pain and whether sensitivity to TMS-induced pain differs between sexes. In the present study, we measured pain thresholds when single-pulse TMS was applied over either Broca's area (BA) or left primary motor cortex (M1), and compared these thresholds with the motor threshold (MT) for inducing motor evoked potentials (MEPs) through M1 stimulation. Additionally, we compared the pain thresholds for BA and M1 between males and females. We found that pain thresholds for both sites were significantly lower than the MT. Furthermore, the pain threshold for BA was much lower than that for M1. No significant difference was observed between sexes. The results suggest that TMS at an intensity equivalent to MTs, which is often used in experimental or clinical studies, causes slight scalp pain. Experimental designs using TMS to evaluate functional relationships between brain and behavior should consider scalp pain and reduce its likelihood as much as possible. [ABSTRACT FROM AUTHOR]

Background: Functional neurological disorders are characterized by neurological symptoms that have no identifiable pathology and little is known about their underlying pathophysiology. Objectives: To analyze motor cortex excitability and intracortical inhibitory and excitatory circuits' imbalance in patients with flaccid functional weakness. Methods: Twenty-one consecutive patients with acute onset of flaccid functional weakness were recruited. Single and paired-pulse transcranial magnetic stimulation (TMS) protocols were used to analyze resting motor thresholds (RMT) and intracortical inhibitory (short interval intracortical inhibition – SICI) and excitatory (intracortical facilitation – ICF) circuits' imbalance between the affected and non-affected motor cortices. Results: We observed a significant increase in RMT and SICI in the affected motor cortex (p < 0.001), but not for ICF, compared to the contralateral unaffected side. Conclusion: This study extends current knowledge of functional weakness, arguing for a specific central nervous system abnormality which may be involved in the symptoms' pathophysiology. [ABSTRACT FROM AUTHOR]

Tardive syndromes (TDS) typically manifest 3 months or later after exposure to antipsychotic drugs, and unfortunately have no satisfactory medical treatment. We explored the possibility of using therapeutic repetitive transcranial magnetic stimulation (rTMS). Twenty-six patients were allocated to receive real or sham rTMS over the hand/arm area of motor cortex (M1). Each received a daily total of 2000 rTMS pulses (20 Hz at 100% rMT: 1000 stimuli per hemisphere) for 10 consecutive days. Outcome was assessed using the Abnormal Involuntary Movement Scale (AIMS) and TMS measures of M1 excitability. Three patients in the sham group failed to complete the study. At baseline, there was no significant difference between the groups in age, sex distribution, duration of illness, AIMS score and drug treatment. rTMS improved symptoms in both groups. However, there was a greater reduction in the AIMS score of the real rTMS group compared with the sham group (real, 8.3 ± 1.7 points; sham 1.2 ± 3.3; repeated measure analysis ANOVA Time X Group interaction P = 0.001). The same trends were observed in the clinical subscales. Following treatment, MEP amplitudes at higher intensities (140, and 150%) increased more in the real treatment group than in the sham group. This is the first clinical trial study of bilateral hemispheric rTMS in patients with TDS and suggests that 20 Hz rTMS might be a feasible treatment option in patients unresponsive to "first-line" treatment.Clinical trial registration ClinicalTrials.gov Identifier: NCT03145311. [ABSTRACT FROM AUTHOR]

Purpose: The mechanisms involved in the coordination of muscle activity are not completely known: to investigate adaptive changes in human motor cortex Transcranial magnetic stimulation (TMS) was often used. The sport models are frequently used to study how the training may affect the corticospinal system excitability: Karate represents a valuable sport model for this kind of investigations for its high levels of coordination required to athletes. This study was aimed at examining possible changes in the resting motor threshold (rMT) and in the corticospinal response in karate athletes, and at determining whether athletes are characterized by a specific value of rMT. Methods: We recruited 25 right-handed young karate athletes and 25 matched non-athletes. TMS was applied to primary motor cortex (M1). Motor evoked potential (MEP) were recorded by two electrodes placed above the first dorsal interosseous (FDI) muscle. We considered MEP latencies and amplitudes at rMT, 110% of rMT, and 120% of rMT. Results: The two groups were similar for age (p > 0.05), height (p > 0.05) and body mass (p > 0.05). The TMS had a 70-mm figure-of-eight coil and a maximum output of 2.2 T, placed over the left motor cortex. During the stimulation, a mechanical arm kept the coil tangential to the scalp, with the handle at 45° respect to the midline. The SofTaxic navigator system (E.M.S. Italy, www.emsmedical.net) was used in order to correctly identifying and repeating the stimulation for every subject. Compared to non-athletes, athletes showed a lower resting motor threshold (p < 0.001). Furthermore, athletes had a lower MEP latency (p < 0.001) and a higher MEP amplitude (p < 0.001) compared to non-athletes. Moreover, a ROC curve for rMT was found significant (area: 0.907; sensitivity 84%, specificity 76%). Conclusions: As the main finding, the present study showed significant differences in cortical excitability between athletes and non-athletes. The training can improve cortical excitability inducing athletes' modifications, as demonstrated in rMT and MEP values. These finding support the hypothesis that the sport practice determines specific brain organizations in relationship with the sport challenges. [ABSTRACT FROM AUTHOR]

Background: Motor-evoked potentials (MEPs) produced by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex can be an objective measure of cortical excitability. Previously, MEP thresholds were found to be normal, increased, or even reduced in patients with migraine. In the present study, we determined whether the level of cortical excitability changes with the time interval from the last migraine attack, thereby accounting for the inconsistencies in previous reports. Methods: Twenty-six patients with untreated migraine without aura (MO) underwent a MEP study between attacks. Their data were then compared to the MEP data collected from a group of 24 healthy volunteers (HVs). During the experiment, the TMS figure-of-eight coil was positioned over the left motor area. After identifying the resting motor threshold (RMT), we delivered 10 single TMS pulses (rate: 0.1 Hz, intensity: 120% of the RMT) and averaged the resulting MEP amplitudes. Results: The mean RMTs and MEP amplitudes were not significantly different between the MO and HV groups. In patients with MO, the RMTs were negatively correlated with the number of days elapsed since the last migraine attack (rho = -0.404, p = 0.04). Conclusion: Our results suggest that the threshold for evoking MEPs is influenced by the proximity of an attack; specifically, the threshold is lower when a long time interval has passed after an attack, and is higher (within the range of normative values) when measured close to an attack. These dynamic RMT variations resemble those we reported previously for visual and somatosensory evoked potentials and may represent time-dependent plastic changes in brain excitability in relation to the migraine cycle. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) can be used as an assessment or intervention to evaluate or influence brain activity in children with hemiparetic cerebral palsy (CP) commonly caused by perinatal stroke. This communication report analyzed data from two clinical trials using TMS to assess corticospinal excitability in children and young adults with hemiparetic CP. The results of this communication revealed a higher probability of finding a motor evoked potential (MEP) on the non-lesioned hemisphere compared to the lesioned hemisphere (p = 0.005). The resting motor threshold (RMT) was lower on the non-lesioned hemisphere than the lesioned hemisphere (p = 0.013). There was a significantly negative correlation between age and RMT (rs = -0.65, p = 0.003). This communication provides information regarding MEP responses, motor thresholds (MTs) and the association with age during TMS assessment in children with hemiparetic CP. Such findings contribute to the development of future pediatric studies in neuroplasticity and neuromodulation to influence motor function and recovery after perinatal stroke. [ABSTRACT FROM AUTHOR]

The selective serotonin reuptake inhibitor fluoxetine significantly enhances adult visual cortex plasticity within the rat. This effect is related to decreased gamma-aminobutyric acid (GABA) mediated inhibition and identifies fluoxetine as a potential agent for enhancing plasticity in the adult human brain. We tested the hypothesis that fluoxetine would enhance visual perceptual learning of a motion direction discrimination (MDD) task in humans. We also investigated (1) the effect of fluoxetine on visual and motor cortex excitability and (2) the impact of increased GABA mediated inhibition following a single dose of triazolam on post-training MDD task performance. Within a double blind, placebo controlled design, 20 healthy adult participants completed a 19-day course of fluoxetine (n = 10, 20 mg per day) or placebo (n = 10). Participants were trained on the MDD task over the final 5 days of fluoxetine administration. Accuracy for the trained MDD stimulus and an untrained MDD stimulus configuration was assessed before and after training, after triazolam and 1 week after triazolam. Motor and visual cortex excitability were measured using transcranial magnetic stimulation. Fluoxetine did not enhance the magnitude or rate of perceptual learning and full transfer of learning to the untrained stimulus was observed for both groups. After training was complete, trazolam had no effect on trained task performance but significantly impaired untrained task performance. No consistent effects of fluoxetine on cortical excitability were observed. The results do not support the hypothesis that fluoxetine can enhance learning in humans. However, the specific effect of triazolam on MDD task performance for the untrained stimulus suggests that learning and learning transfer rely on dissociable neural mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To develop a pipeline for realistic head models of nonhuman primates (NHPs) for simulations of noninvasive brain stimulation, and use these models together with empirical threshold measurements to demonstrate that the models capture individual anatomical variability. Methods: Based on structural MRI data, we created models of the electric field (E-field) induced by right unilateral (RUL) electroconvulsive therapy (ECT) in four rhesus macaques. Individual motor threshold (MT) was measured with transcranial electric stimulation (TES) administered through the RUL electrodes in the same subjects. Results: The interindividual anatomical differences resulted in 57% variation in median E-field strength in the brain at fixed stimulus current amplitude. Individualization of the stimulus current by MT reduced the E-field variation in the target motor area by 27%. There was significant correlation between the measured MT and the ratio of simulated electrode current and E-field strength (r^2 = 0.95, p = 0.026). Exploratory analysis revealed significant correlations of this ratio with anatomical parameters including of the superior electrode-to-cortex distance, vertex-to-cortex distance, and brain volume (r^{2} > 0.96, p < 0.02$). The neural activation threshold was estimated to be $0.45 \pm 0.07$ V/cm for 0.2-ms stimulus pulse width. Conclusion: These results suggest that our individual-specific NHP E-field models appropriately capture individual anatomical variability relevant to the dosing of TES/ECT. These findings are exploratory due to the small number of subjects. Significance: This study can contribute insight in NHP studies of ECT and other brain stimulation interventions, help link the results to clinical studies, and ultimately lead to more rational brain stimulation dosing paradigms. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Purpose The neurophysiological characteristics of motor cortex have been well characterized in patients with Huntington's disease. We present the first data on cortical excitability in patients with Sydenham's chorea. Methods Motor cortex excitability was examined using transcranial magnetic stimulation in 16 patients in the early clinical stages of Sydenham's chorea and in 17 age- and sex-matched control subjects. Investigations included resting and active motor threshold, motor evoked potential, input-output curves, contralateral silent period, and transcallosal inhibition. Results Resting and active motor threshold were significantly higher and motor evoked potentials were significantly smaller in patients in comparison with controls. The input-output curves were shallower in both hemispheres of patients with chorea compared with controls. No significant differences were seen in silent period or transcallosal inhibition duration. Conclusion Sydenham's chorea is characterized by reduced excitability of corticospinal output similar to that observed in Huntington's disease. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background Motor cortex excitability was found to be changed after repetitive transcranial magnetic stimulation (rTMS) of the temporal cortex highlighting the occurrence of cross-modal plasticity in non-invasive brain stimulation. Here, we investigated the effects of temporal low-frequency rTMS on motor cortex plasticity in a large sample of tinnitus patients. In 116 patients with chronic tinnitus different parameters of cortical excitability were assessed before and after ten rTMS treatment sessions. Patients received one of three different protocols all including 1 Hz rTMS over the left temporal cortex. Treatment response was defined as improvement by at least five points in the tinnitus questionnaire (TQ). Variables of interest were resting motor threshold (RMT), short-interval intra-cortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). Results After rTMS treatment RMT was decreased by about 1% of stimulator output nearsignificantly in the whole group of patients. SICI was associated with significant changes with respect to treatment response. The group of treatment responders showed a decrease of SICI over the course of treatment, the group of non-responders the reverse pattern. Conclusions Minor RMT changes during rTMS treatment do not necessarily suggest the need for systematic re-examination of the RMT for safety and efficacy issues. Treatment response to rTMS was shown to be related to changes in SICI that might reflect modulation of GABAergic mechanisms directly or indirectly related to rTMS treatment effects. [ABSTRACT FROM AUTHOR]

Background: For accuracy in navigated transcranial magnetic stimulation (nTMS), determination of the hotspot location of small hand muscles is crucial because it is the basis for the resting motor threshold (RMT) and, therefore, its spatial resolution. We investigated intra- and interobserver differences of hotspot mapping to provide evidence for the reproducibility of this method. Ten subjects underwent nTMS motor mapping of the hotspot for the abductor pollicis brevis muscle (APB) three times. The first two sessions were performed by the same examiner; the third mapping was performed by a different examiner. Distances between the first and second mappings (intraobserver variability) and between the second and third mappings (interobserver variability) were measured. Results: Intraobserver variability had a mean of 8.1 ± 3.3 mm (limits of agreement (LOA) 1.7 to 14.6 mm), whereas mean interobserver variability was 10.3 ± 3.3 mm (LOA 3.8 to 16.7 mm). Concerning RMT, CCC was 0.725 (95% CI: 0.276; 0.914). The mean variability in the same cortical depth was measured as 5.7 ± 3.3 mm (LOA -0.7 to 12.2 mm) for intraobserver and 9.2 ± 3.3 mm (LOA 2.7 to 15.8 mm) for interobserver examinations. When evaluating the RMT, CCC was 0.709 (95% CI: 0.244; 0.909). Conclusions: Overall, intraobserver variability showed higher reliability than interobserver variability. Our findings show that we can achieve good reliability in hotspot determination, ranging within the calculated precision of the system. [ABSTRACT FROM AUTHOR]

Background: While cortical representations of intrinsic hand muscles have been extensively studied in healthy individuals, little is known about the representation of proximal upper limb muscles. Improving our understanding of normal shoulder function is important, given that shoulder musculoskeletal disorders affect approximately 20% of the population and are suspected to involve changes in central motor representations. The purpose of the study is to describe the motor representation (motor evoked potentials (MEP) amplitude at the hotspot, map area, normalized map volume and center of gravity) of the infraspinatus muscle in healthy individuals, and to explore the potential influence of hand dominance on this representation (i.e. symmetry of the excitability and of the location of motor map between sides), as well as the effect of age and gender on motor excitability. Results: Fifteen healthy participants took part in this study. No significant asymmetry between sides was observed for motor excitability (p = 0.14), map area (p = 0.73) and normalized map volume (p = 0.34). Moreover, no side x intensity interaction was found (p = 0.54), indicating similar stimulus response properties. No difference between sides was found in the location of infraspinatus motor representation, either in the mediolateral or anteroposterior axis (p > 0.10). Neither age nor gender influenced aMT (p > 0.58) or MEP size (p > 0.61). Conclusions: As the cortical representation of infraspinatus muscles was found to be symmetric between sides, both in terms of excitability and location, comparisons between the intact and affected side could be performed in clinical studies, regardless of whether the dominant or non-dominant side is affected. The next step will be to characterize corticospinal excitability and map parameters in populations with shoulder disorders. [ABSTRACT FROM AUTHOR]

Background/Aim: This study aimed to compare the cortical excitability of patients with generalized tonic-clonic seizures (GTCSs) and that of patients with psychogenic non-epileptic seizures (PNESs). Methods: Patients were classified into groups according to their electroencephalogram (EEC) find- ings and seizure types: group 1 = GTCS with an abnormal EEG, group 2 = GTCS with a normal EEC and group 3 = PNES with a normal EEG. The control group included healthy vol- unteers with normal EEGs. Cortical silent period (CSP) and motor threshold (MT) were measured for all groups and the results were compared. Results: CSPs were significantly pro- longed in groups 1 and 2 when compared with group 3 and the control group. No differences were found between the MT measurements of all groups. Conclusion:The prolonga- tion of CSP may demonstrate the differences between the pathophysiological mechanisms of GTCS and those of PNES. [ABSTRACT FROM AUTHOR]

Background: Clinical studies have shown that repetitive transcranial magnetic stimulation (rTMS) is effective in a certain percentage of treatment-resistant depression (TRD). The left dorsolateral prefrontal cortex (DLPFC) 10 Hz rTMS stimulation received FDA approval in 2008, although different rTMS protocols have also shown their effectiveness in reducing depressive symptoms. We investigated the clinical, cognitive and neurophysiologic effects of a 3 weeks' protocol of low-frequency rTMS applied over the right DLPFC in resistant depression. Methods: Twenty-eight patients with TRD (age range 28-55) received low-frequency rTMS (1 Hz) over the right DLPFC in a 3-week open trial. Hamilton scales for depression and anxiety, Corsi block-tapping test, phonemic verbal fluency, right and left resting motor thresholds were evaluated in each subject over the trial period. Results: At the end of the trial 42.9% of the subjects were considered as responders. A significant reduction of both HAMD (p < 0.001) and HAMA (p < 0.01) total scores was observed. At the 3rd week, the performances in Corsi test (p < 0.02) and phonemic verbal fluency (p = 0.065) were improved independently from depressive symptoms variation. At the end of the rTMS protocol, a significantly decreased left hemisphere resting motor threshold was registered (p < 0.01), while right hemisphere resting motor threshold did not show significant variation. Conclusion: Low-frequency rTMS over the right DLPFC appeared effective in 42.9% of depressive resistant subjects in this sample. A significant decrease in left hemisphere resting motor threshold was observed only in responders, while a trend for improvement in cognitive function has been found and appeared independent from clinical response. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) are well-established tools for investigating the human motor system in-vivo. We here studied the relationship between movement-related fMRI signal changes in the primary motor cortex (M1) and electrophysiological properties of the hand motor area assessed with neuronavigated TMS in 17 healthy subjects. The voxel showing the highest task-related BOLD response in the left hand motor area during right hand movements was identified for each individual subject. This fMRI peak voxel in M1 served as spatial target for coil positioning during neuronavigated TMS. We performed correlation analyses between TMS parameters, BOLD signal estimates and effective connectivity parameters of M1 assessed with dynamic causal modeling (DCM). The results showed a negative correlation between the movement-related BOLD signal in left M1 and resting as well as active motor threshold (MT) obtained for left M1. The DCM analysis revealed that higher excitability of left M1 was associated with a stronger coupling between left supplementary motor area (SMA) and M1. Furthermore, BOLD activity in left M1 correlated with ipsilateral silent period (ISP), i.e. the stronger the task-related BOLD response in left M1, the higher interhemispheric inhibition effects targeting right M1. DCM analyses revealed a positive correlation between the coupling of left SMA with left M1 and the duration of ISP. The data show that TMS parameters assessed for the hand area of M1 do not only reflect the intrinsic properties at the stimulation site but also interactions with remote areas in the human motor system. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article presents the results of a meta-analysis on transcranial magnetic stimulation (TMS) that compares the effectiveness of peripheral electromyography (EMG) and observed movement (OM) methods. A study by S. Pridmore et al found no significant differences between EMG and OM but five out of six OM subjects had lower motor threshold (MT). In a research by A. B. Conforto et. al, 13 out of 14 OM subjects had higher MT. The meta-analysis concludes that the results were conflicting and suggests adopting safety guidelines before using them.

Background and purpose: The excitability of the visual and motor cortical areas is altered in migraineurs. Controversial results of previous studies on cortical excitability may depend on the hormonal status of female subjects. The present study aimed to determine whether the different phases of the menstrual cycle influence the phosphene thresholds (PT) and resting motor thresholds (RMT) in migraineurs. Methods: Thirty-two migraine patients participated in this study. Three to six PT and RMT measurements were done in headache-free intervals during the follicular, middle and luteal phases of the female cycle, or in active dosage and withdrawal phases in patients who were taking low dosage oral contraceptives. Results: Generally, PTs showed higher individual variabilities than RMTs. Additionally, we have observed that the RMTs and PTs were significantly independent from hormonal changes. However, patients who were taking a low dosage of oral contraceptives had lower PTs compared with patients who were not taking oral contraceptives. RMTs show the opposite tendency. Conclusion: The results imply that PTs and RMTs can be reliably measured independently from the menstrual hormone status in female migraineurs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the intra-rater reliability of motor evoked potentials (MEP) obtained through transcranial magnetic stimulation (TMS). TMS was applied over the primary motor cortex of 16 healthy subjects. Motor thresholds, MEP latencies, and amplitudes were recorded from the contralateral upper limb on 6 occasions over 15 days. An intraclass correlation coefficient (ICC 2,1) was used to estimate reliability. The ICCs ranged from 0.60 to 0.92 for all MEP measures except amplitude (ICC = 0.01 to 0.34). MEPs obtained with the TMS technique described are generally reliable, although MEP amplitudes demonstrated less consistency. [ABSTRACT FROM AUTHOR]

We investigated electrophysiological correlates of fatigue in patients with multiple sclerosis (MS). Transcranial magnetic stimulation (TMS) was used to explore motor excitability in three groups of subjects: MS patients with fatigue (MS-F), MS patients without fatigue (MS-NF) and healthy control subjects. All participants had to perform a fatiguing hand-grip exercise. TMS was performed prior to and after the exercise. Prior to the motor task, MS-F patients had less inhibition in the primary motor cortex compared to both other groups. Postexercise, intracortical inhibition was still reduced in the MS-F patients compared to the MS-NF patients. In MS-F patients the postexercise time interval for normalization of the motor threshold was correlated with the fatigue severity. We conclude that MS patients with fatigue have an impairment of inhibitory circuits in their primary motor cortex. The results also indicate that fatigue severity is associated with an exercise-induced reduction of membrane excitability. [ABSTRACT FROM AUTHOR]

Dolberg OT, Dannon PN, Schreiber S, Grunhaus L. Magnetic motor threshold and response to TMS in major depressive disorder. Acta Psychiatr Scand 2002: 106: 220–223. © Blackwell Munksgaard 2002. Objective: The aim of this study was to examine motor threshold (MT) during treatment with transcranial magnetic stimulation (TMS). Method: The TMS was administered to 46 patients with depression and 13 controls. TMS was performed at 90% power of measured MT. The stimulation frequency was 10 Hz for 6 s, for 20 trains, with 30 s inter-train intervals. The trial included 20 sessions. Patients and controls were assessed on various outcome measures. Results: The MT values were comparable between patients and controls. Neither demographic nor clinical variables were factors in determining MT. MT was not shown to have any predictive value regarding outcome of treatment. Conclusion: In this study, MT at baseline or changes in MT during the treatment period were not able to discriminate between patients and controls and were not found to have any predictive value with regard to treatment outcome. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Focal cerebral cooling has been shown to reduce epileptiform activity in animals. There are, however, few reports of this phenomenon in humans. Methods: Electrocorticography was performed before resection of a right frontal tumor in a patient with partial seizures. Cold saline was applied to the interictal spike focus, and its effect on the epileptiform discharges was observed. Results: Application of cold saline to the spike focus resulted in a transient, complete cessation of spiking. This effect was reproduced with a second application of cold saline. The motor threshold for electrical stimulation remained unchanged during the application of saline. Conclusions: In this patient with tumor-related epilepsy, focal cooling of the cortex reproducibly abolished interictal epileptiform discharges without changing the motor threshold to electrical stimulation. [ABSTRACT FROM AUTHOR]

Navigated transcranial magnetic stimulation (nTMS) has developed into a reliable non-invasive clinical and scientific tool over the past decade. Specifically, it has undergone several validating clinical trials that demonstrated high agreement with intraoperative direct electrical stimulation (DES), which paved the way for increasing application for the purpose of motor mapping in patients harboring motor-eloquent intracranial neoplasms. Based on this clinical use case of the technique, in this article we review the evidence for the feasibility of motor mapping and derived models (risk stratification and prediction, nTMS-based fiber tracking, improvement of clinical outcome, and assessment of functional plasticity), and provide collected sets of evidence for the applicability of quantitative mapping with nTMS. In addition, we provide evidence-based demonstrations on factors that ensure methodological feasibility and accuracy of the motor mapping procedure. We demonstrate that selection of the stimulation intensity (SI) for nTMS and spatial density of stimuli are crucial factors for applying motor mapping accurately, while also demonstrating the effect on the motor maps. We conclude that while the application of nTMS motor mapping has been impressively spread over the past decade, there are still variations in the applied protocols and parameters, which could be optimized for the purpose of reliable quantitative mapping. [ABSTRACT FROM AUTHOR]

To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9±5.4% vs. 45.6±7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 30–40 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30–40 ms. Threshold elevation was significantly longer than the SP (220±41 vs. 151±28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation. [ABSTRACT FROM AUTHOR]

Neuromuscular electrical stimulation (NMES) is useful for muscle strengthening and for motor restoration of stroke patients. Using a portable ultrasound instrument, we developed an M-mode imaging protocol to visualize contractions elicited by NMES in the quadriceps muscle group. To quantify muscle activation, we performed digital image processing based on the Teager–Kaiser energy operator. The proposed method was applied for 35 voluntary patients (18 women and 17 men), of 63.8 ± 14.1 years and body mass index (BMI) 30.2 ± 6.70 kg/m2 (mean ± standard deviation). Biphasic, rectangular electric pulses of 350 µs duration were applied at two frequencies (60 Hz and 120 Hz), and ultrasound was used to assess the sensory threshold (ST) and motor threshold (MT) amplitude of the NMES signal. The MT was 23.4 ± 4.94 mA, whereas the MT to ST ratio was 2.69 ± 0.57. Linear regression analysis revealed that MT correlates poorly with body mass index (R2 = 0.004) or with the thickness of the subcutaneous adipose tissue layer that covers the treated muscle (R2 = 0.013). Our work suggests that ultrasound is suitable to visualize neuromuscular reactivity during electrotherapy. The proposed method can be used in the clinic, enabling the physiotherapist to establish personalized treatment parameters. [ABSTRACT FROM AUTHOR]