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Abstract Evoked compound action potential (ECAP) is an important parameter in close-loop spinal cord stimulation (SCS). The recording electrode is typically positioned proximal to the stimulation electrode to capture the antegrade ECAP signals generated by ascending fibers. However, relatively little research has been conducted on retrograde ECAPs. This study investigated retrograde ECAPs using custom-made epidural electrodes in 11 adult male Sprague–Dawley rats. Results show that the average motor threshold (MT) and ECAP threshold (ECAPT) for 11 anesthetized rats were 218.18 ± 69.54 μA and 107.27 ± 27.96 μA, respectively. The ECAP amplitudes increased with increasement of the stimulation current and pulse width (PW), and were larger in awake rats than in anesthetized rats. Additionally, aside from ECAPs recorded by a commercial electrophysiological recorder, ECAPs were also recorded by a custom-made amplifier for the purpose of future long-term implantation, but the custom-made amplifier showed lower signal to noise ratio than the commercial amplifier. In conclusion, this study illustrates that retrograde ECAP may also be considered as a feedback signal for close-loop SCS and more sophisticated ECAP recording circuits are needed to form a close-loop system.

AbstractObjectivesMethodsResultsConclusionsMagnetic seizure therapy (MST) is more benign than electroconvulsive therapy (ECT) in terms of cognitive impairment. However, whether these two ‘artificial seizures’ facilitate the central motor neural pathway and the motor cortical effects have not been investigated. The study aimed to compare the effects of ECT and MST on motor-evoked potential (MEP) in patients with mental disorders.Forty-nine patients with mental disorders (major depressive disorder, bipolar disorder type II and schizophrenia [SCZ]) received 6 treatment sessions of vertex MST versus 6 bifrontal ECT treatments in a nonrandomized comparative clinical design. Data on the duration of motor seizures were collected for each treatment. MEP latency and the resting motor threshold (rMT) were measured at baseline and after every two treatments. Comparisons were performed between or within the groups.Seizure durations were significantly longer in the ECT group compared to the MST group across multiple sessions. Both MST and ECT demonstrated a significant reduction in rMT in the left and right hemispheres after the fourth (T3) and sixth treatments (T4) compared to baseline (T1). However, there were no significant changes in MEP latency within or between the groups throughout the treatment sessions. The only difference was that the rMT in the left cerebral hemisphere was significantly lower after T4 than after the second treatment (T2). There was no difference in rMT between the ECT and MST groups.Both ECT and MST facilitate the central motor pathway, with a shared mechanism of increased motor cortex excitability. [ABSTRACT FROM AUTHOR]

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]

ObjectiveWe 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.MethodsIn 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.ResultsHigher 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.ConclusionPhysical 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.

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]

Objective: This study aimed to assess the efficacy and safety of quadripulse transcranial magnetic stimulation-50 (QPS-50) in patients with intractable epilepsy. Methods: Four patients were included in the study. QPS-50, which induces long-term depression in healthy subjects, was administered for 30 min on a weekly basis for 12 weeks. Patients’ clinical symptoms and physiological parameters were evaluated before, during, and after the repeated QPS-50 period. We performed two control experiments: the effect in MEP (Motor evoked potential) size after a single QPS-50 session with a round coil in nine healthy volunteers, and a follow-up study of physiological parameters by repeated QPS-50 sessions in four other healthy participants. Results: Motor threshold (MT) decreased during the repeated QPS-50 sessions in all patients. Epileptic symptoms worsened in two patients, whereas no clinical worsening was observed in the other two patients. In contrast, MT remained unaffected for 12 weeks in all healthy volunteers. Conclusions: QPS-50 may not be effective as a treatment for intractable epilepsy. Significance: In intractable epilepsy patients, administering repeated QPS-50 may paradoxically render the motor cortex more excitable, probably because of abnormal inhibitory control within the epileptic cortex. The possibility of clinical aggravation should be seriously considered when treating intractable epilepsy patients with non-invasive stimulation methods.

Background: The effects of transcranial magnetic stimulation (TMS) on brain activity depend on the design of the stimulation coil. A wide range of coils from different vendors are currently used with different stimulation properties. This decreases the comparability of study results. Objective: To systematically compare widely used commercial TMS coils concerning their focality, stimulation depth and efficacy. To provide validated models and data of these coils for accurate simulations of the induced electric fields. Methods: We reconstructed the magnetic vector potential of 25 commercially available TMS coils of different vendors from measurements of their magnetic fields. Most coils had a figure-of-eight configuration. We employed the reconstructed magnetic vector potential in simulations of the electric field in a spherical head model. We estimated the motor thresholds of the coil-stimulator combinations using the calculated fields, the pulse waveforms and a leaky integrator model of the neural membrane. Results: Our results confirm a previously reported systematic trade-off between focality and relative depth of stimulation. However, neither the peak field strength in the “cortex” of the sphere model nor the estimated motor thresholds were strongly related to the two former measures and need to be additionally determined. Conclusion: Our comprehensive coil characterization facilitates objective comparisons of coils of different sizes and from different vendors. The models and auxiliary data will be made available for electric field simulations in SimNIBS. Our work will support TMS users making an informed selection of a suited coil for a specific application and will help to reduce uncertainty regarding the TMS-induced electric field in the brain target region.

Objective: Previous research has suggested that transcranial magnetic stimulation (TMS) related cortical excitability measures could be estimated quickly using stimulus–response curves with short interstimulus intervals (ISIs). Here we evaluated the resting motor threshold (rMT) estimated with these curves. Methods: Stimulus-response curves were measured with three ISIs: 1.2–2 s, 2–3 s, and 3–4 s. Each curve was formed with 108 stimuli using stimulation intensities ranging from 0.75 to 1.25 times the rMTguess, which was estimated based on motor evoked potential (MEP) amplitudes of three scout responses. Results: The ISI did not affect the rMT estimated from the curves (F = 0.235, p = 0.683) or single-trial MEP amplitudes at the group level (F = 0.90, p = 0.405), but a significant subject by ISI interaction (F = 3.64; p

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]

Background: Accurate positioning and effective programming of sacral neuromodulation (SNM) relies upon the use of several acute stimulation measurements. While the clinical utility of these acute measurements including pelvic floor motor thresholds (PFMT), toe/leg motor thresholds (TMT), and sensory thresholds (ST), are widely accepted, their usefulness in quantitative research remains unclear. The purpose of this prospective study was to test these measurements and gauge their utility in future research., Methods: Eight participants received Axonics SNM, 6 Medtronic Interstim II, and 2 Medtronic Micro SNM. PFMT was measured after implantation. ST and the location of sensation (LOS) were measured immediately postoperatively (PO), at pre-release from the surgery center (PR), and during a follow-up clinic visit (FU). Thresholds were compared across contact and time using linear mixed-effects models., Results: Significant differences in PFMT were found across electrode configurations, with stimulation through proximal contacts exhibiting lower PFMT than distal configurations. ST displayed no significant differences across electrodes and showed minimal changes over time. LOS exhibited substantial variability across patients and periods., Conclusions: Results suggest that PFMT were able to differentiate differences across electrode configurations that may be useful for future quantitative research. The lack of differences in ST and LOS across electrode configurations was interesting given the focus on these measurements clinically. Future testing is to confirm these limitations., Competing Interests: Additional Declarations: No competing interests reported.

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.

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]

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]

Transcranial magnetic stimulation (TMS) is commonly delivered at an intensity defined by the resting motor threshold (rMT), which is thought to represent cortical excitability, even if the TMS target area falls outside of the motor cortex. This approach rests on the assumption that cortical excitability, as measured through the motor cortex, represents a 'global' measure of excitability. Another common approach to measure cortical excitability relies on the phosphene threshold (PT), measured through the visual cortex of the brain. However, it remains unclear whether either estimate can serve as a singular measure to infer cortical excitability across different brain regions. If PT and rMT can indeed be used to infer cortical excitability across brain regions, they should be correlated. To test this, we systematically identified previous studies that measured PT and rMT to calculate an overall correlation between the two estimates. Our results, based on 16 effect sizes from eight studies, indicated that PT and rMT are correlated (ρ = 0.4), and thus one measure could potentially serve as a measure to infer cortical excitability across brain regions. Three exploratory meta-analyses revealed that the strength of the correlation is affected by different methodologies, and that PT intensities are higher than rMT. Evidence for a PT-rMT correlation remained robust across all analyses. Further research is necessary for an in-depth understanding of how cortical excitability is reflected through TMS. • Transcranial magnetic stimulation (TMS) resting motor threshold (rMT) and phosphene threshold (PT) are correlated. • The correlation supports the use of rMT as a proxy measure for cortical excitability even for TMS outside the motor cortex. • The correlation between rMT and PT is influenced by different methodologies but remained robust across all analyses. • Future directions are provided to investigate how cortical excitability is reflected through TMS. [ABSTRACT FROM AUTHOR]

The effects of transcranial magnetic stimulation (TMS) on brain activity depend on the design of the stimulation coil. A wide range of coils from different vendors are currently used with different stimulation properties. This decreases the comparability of study results. To systematically compare widely used commercial TMS coils concerning their focality, stimulation depth and efficacy. To provide validated models and data of these coils for accurate simulations of the induced electric fields. We reconstructed the magnetic vector potential of 25 commercially available TMS coils of different vendors from measurements of their magnetic fields. Most coils had a figure-of-eight configuration. We employed the reconstructed magnetic vector potential in simulations of the electric field in a spherical head model. We estimated the motor thresholds of the coil-stimulator combinations using the calculated fields, the pulse waveforms and a leaky integrator model of the neural membrane. Our results confirm a previously reported systematic trade-off between focality and relative depth of stimulation. However, neither the peak field strength in the "cortex" of the sphere model nor the estimated motor thresholds were strongly related to the two former measures and need to be additionally determined. Our comprehensive coil characterization facilitates objective comparisons of coils of different sizes and from different vendors. The models and auxiliary data will be made available for electric field simulations in SimNIBS. Our work will support TMS users making an informed selection of a suited coil for a specific application and will help to reduce uncertainty regarding the TMS-induced electric field in the brain target region. • We present validated models of 25 TMS coils for electric field simulations. • Models are based on measurements, avoiding use of ambiguous technical coil descriptions. • Peak field strength and motor threshold are poorly related to depth and focality. • Field strength is more sensitive to details of coil design than depth and focality. [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]

Background: Transcranial magnetic stimulation (TMS) is a rapidly expanding technology utilized in research and neuropsychiatric treatments. Yet, conventional TMS configurations affect primarily neurons that are aligned parallel to the induced electric field by a fixed coil, making the activation orientation-specific. A novel method termed rotational field TMS (rfTMS), where two orthogonal coils are operated with a 90° phase shift, produces rotation of the electric field vector over almost a complete cycle, and may stimulate larger portion of the neuronal population within a given brain area. Objective: To compare the physiological effects of rfTMS and conventional unidirectional TMS (udTMS) in the motor cortex. Methods: Hand and leg resting motor thresholds (rMT), and motor evoked potential (MEP) amplitudes and latencies (at 120% of rMT), were measured using a dual-coil array based on the H7-coil, in 8 healthy volunteers following stimulation at different orientations of either udTMS or rfTMS. Results: For both target areas rfTMS produced significantly lower rMTs and much higher MEPs than those induced by udTMS, for comparable induced electric field amplitude. Both hand and leg rMTs were orientation-dependent. Conclusions: rfTMS induces stronger physiologic effects in targeted brain regions at significantly lower intensities. Importantly, given the activation of a much larger population of neurons within a certain brain area, repeated application of rfTMS may induce different neuroplastic effects in neural networks, opening novel research and clinical opportunities.

ObjectiveThe 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).MethodsIn 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.ResultsWe 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.ConclusionsThese 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.

Objectives: This study analyzes the stimulation parameters implemented during two successful trials that used non-invasive transcutaneous spinal cord stimulation (tSCS) to effectively improve upper extremity function after chronic spinal cord injury (SCI). It proposes a framework to guide stimulation programming decisions for the successful translation of these techniques into the clinic., Materials and Methods: Programming data from 60 participants who completed the Up-LIFT trial and from 17 participants who subsequently completed the LIFT Home trial were analyzed. All observations of stimulation amplitudes, frequencies, waveforms, and electrode configurations were examined. The incidence of adverse events and relatedness to stimulation parameters is reported. A comparison of parameter usage across the American Spinal Injury Association Impairment Scale (AIS) subgroups was conducted to evaluate stimulation strategies across participants with varying degrees of sensorimotor preservation., Results: Active (cathodal) electrodes were typically placed between the C3/C4 and C6/C7 spinous processes. Most sessions featured return (anodal) electrodes positioned bilaterally over the anterior superior iliac spine, although clavicular placement was frequently used by 12 participants. Stimulation was delivered with a 10-kHz carrier frequency and typically a 30-Hz burst frequency. Biphasic waveforms were used in 83% of sessions. Average stimulation amplitudes were higher for biphasic waveforms. The AIS B subgroup required significantly higher amplitudes than did the AIS C and D subgroups. Device-related adverse events were infrequent, and not correlated with specific waveforms or amplitudes. Within the home setting, participants maintained their current amplitudes within 1% of the preset values. The suggested stimulation programming framework dictates the following hierarchical order of parameter adjustments: current amplitude, waveform type, active/return electrode positioning, and burst frequency, guided by clinical observations as required., Conclusions: This analysis summarizes effective stimulation parameters from the trials and provides a decision-making framework for clinical implementation of tSCS for upper extremity functional restoration after SCI. The parameters are aligned with existing literature and proved safe and well tolerated by participants., Competing Interests: Conflict of Interest Kristen Gelenitis, Jared Pradarelli, Jenny Suggitt, Amanda Turner, and Markus Rieger are employees of ONWARD Medical. Andrea Santamaria, Jessica M D’Amico, Edelle Field-Fote, and Chet Moritz are paid consultants of ONWARD Medical. The remaining authors reported no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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]

• 687 healthy participant's TMS data were pooled across 35 studies. • Significant relationships between age and resting motor threshold. • Significant relationships between baseline MEP amplitude and SICI/ICF. This study brought together over 60 transcranial magnetic stimulation (TMS) researchers to create the largest known sample of individual participant single and paired-pulse TMS data to date, enabling a more comprehensive evaluation of factors driving response variability. Authors of previously published studies were contacted and asked to share deidentified individual TMS data. Mixed-effects regression investigated a range of individual and study level variables for their contribution to variability in response to single and paired-pulse TMS data. 687 healthy participant's data were pooled across 35 studies. Target muscle, pulse waveform, neuronavigation use, and TMS machine significantly predicted an individual's single-pulse TMS amplitude. Baseline motor evoked potential amplitude, motor cortex hemisphere, and motor threshold (MT) significantly predicted short-interval intracortical inhibition response. Baseline motor evoked potential amplitude, test stimulus intensity, interstimulus interval, and MT significantly predicted intracortical facilitation response. Age, hemisphere, and TMS machine significantly predicted MT. This large-scale analysis has identified a number of factors influencing participants' responses to single and paired-pulse TMS. We provide specific recommendations to minimise interindividual variability in single and paired-pulse TMS data. This study has used large-scale analyses to give clarity to factors driving variance in TMS data. We hope that this ongoing collaborative approach will increase standardisation of methods and thus the utility of single and paired-pulse TMS. [ABSTRACT FROM AUTHOR]

To assess by transcranial magnetic stimulation (TMS) the excitability of various cortical circuits in akinetic-rigid and tremor-dominant subtypes of Parkinson's disease (PD). The study included 92 patients with PD according to UK Brain Bank criteria, with akinetic-rigid (n = 64) or tremor-dominant (n = 28) subtype. Cortical excitability study, including resting and active motor thresholds (rMT and aMT), input—output curve of motor evoked potentials, contralateral and ipsilateral silent periods (cSP and iSP), short and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were measured. The results obtained were compared to a control group of 30 age- and sex-matched healthy subjects. The patients in the tremor group had significantly lower rMT and aMT compared to controls and akinetic-rigid patients and significantly shorter iSP duration compared to akinetic-rigid patients, while iSP latency tended to be longer in akinetic-rigid patients compared to controls. There were no significant differences between the two PD subgroups regarding other cortical excitability parameters, including paired-pulse TMS parameters. Only subtle differences of cortical excitability were found between patients with akinetic-rigid vs. tremor-dominant subtype of PD. The clinical heterogeneity of PD patients probably has an impact on cortical excitability measures, far beyond the akinetic-rigid versus tremor-dominant profile. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate causal structure-function relationships in the human brain. However, a precise delineation of the effectively stimulated neuronal populations is notoriously impeded by the widespread and complex distribution of the induced electric field.Here, we propose a method that allows rapid and feasible cortical localization at the individual subject level. The functional relationship between electric field and behavioral effect is quantified by combining experimental data with numerically modeled fields to identify the cortical origin of the modulated effect. Motor evoked potentials (MEPs) from three finger muscles were recorded for a set of random stimulations around the primary motor area. All induced electric fields were nonlinearly regressed against the elicited MEPs to identify their cortical origin.We could distinguish cortical muscle representation with high spatial resolution and localized them primarily on the crowns and rims of the precentral gyrus. A post-hoc analysis revealed exponential convergence of the method with the number of stimulations, yielding a minimum of about 180 random stimulations to obtain stable results.Establishing a functional link between the modulated effect and the underlying mode of action, the induced electric field, is a fundamental step to fully exploit the potential of TMS. In contrast to previous approaches, the presented protocol is particularly easy to implement, fast to apply, and very robust due to the random coil positioning and therefore is suitable for practical and clinical applications.

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

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.

• In 38 tobacco use disorder participants, we used electric field modeling to reexamine TMS % resting motor threshold (rMT) dosing. • Prefrontal TMS at 133.5% rMT would be required to produce equivalent electric fields as motor TMS at 100% rMT. • The wide between-subjects range of 79.9–247.5% rMT for motor equivalent prefrontal electric fields supports using personalized electric field dosing. In this study, we reexamined the use of 120% resting motor threshold (rMT) dosing for transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) using electric field modeling. We computed electric field models in 38 tobacco use disorder (TUD) participants to compare figure-8 coil induced electric fields at 100% rMT over the primary motor cortex (M1), and 100% and 120% rMT over the DLPFC. We then calculated the percentage of rMT needed for motor-equivalent induced electric fields at the DLPFC and modeled this intensity for each person. Electric fields from 100% rMT stimulation over M1 were significantly larger than what was modeled in the DLPFC using 100% rMT (p < 0.001) and 120% rMT stimulation (p = 0.013). On average, TMS would need to be delivered at 133.5% rMT (range = 79.9 to 247.5%) to produce motor-equivalent induced electric fields at the DLPFC of 158.2 V/m. TMS would have to be applied at an average of 133.5% rMT over the left DLPFC to produce equivalent electric fields to 100% rMT stimulation over M1 in these 38 TUD patients. The high interindividual variability between motor and prefrontal electric fields for each participant supports using personalized electric field modeling for TMS dosing to ensure that each participant is not under- or over-stimulated. These electric field modeling in TUD data suggest that 120% rMT stimulation over the DLPFC delivers sub-motor equivalent electric fields in many individuals (73.7%). With further validation, electric field modeling may be an impactful method of individually dosing TMS. [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.

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.

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]

• Somatosensory electrical stimulation can facilitate balance. • However, a 200% supra-sensory threshold intensity was too high to facilitate balance. • The intensity should be close to the sensory threshold to facilitate balance. • Excitomotor electrical stimulation did not disturb balance control. Somatosensory (which activates sensory neurons only) and excitomotor (which activates both motoneurons and sensory neurons) electrical stimulations applied on the musculature of the lower-limb are likely to facilitate and disturb balance control respectively. The aim of this study was to compare the possible balance control modifications induced by somatosensory (SS) and excitomotor (EX) electrical stimulations applied on the quadriceps femoris in quiet standing condition. Kinetics and kinematics parameters were recorded with a force platform (displacements of center of foot pressure) and a 3D analysis system (hip, knee and ankle angles) respectively during a postural task. Twenty healthy young male participants carried out a monopedal postural task (i.e., unilateral stance) in three conditions: SS stimulation (1ms; 10Hz; 7±2 mA i.e., twice the intensity corresponding to the sensory threshold), EX stimulation (400 µs; 50 Hz; 20 ± 5 mA i.e., twice the intensity corresponding to the motor threshold), and a control (CONT) condition without stimulation. The results showed no significant differences between the three conditions except for the knee' angle which was higher in the EX condition (167.3±11.6 vs 164.3±5.8 and 163.9±8) (p < 0.005) than in the two other conditions (SS stimulation and CONT). This means that the EX stimulation induced a postural position change (i.e., a slight knee extension) during the monopedal postural task without altering balance control. Overall, on the basis of the stimulation parameters used in the present work, neither the SS stimulation, nor the EX stimulation facilitated or disturbed postural balance. [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.

BackgroundFunctional neurological disorders are characterized by neurological symptoms that have no identifiable pathology and little is known about their underlying pathophysiology.ObjectivesTo analyze motor cortex excitability and intracortical inhibitory and excitatory circuits’ imbalance in patients with flaccid functional weakness.MethodsTwenty-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.ResultsWe 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.ConclusionThis study extends current knowledge of functional weakness, arguing for a specific central nervous system abnormality which may be involved in the symptoms’ pathophysiology.

Despite the widespread use of transcranial magnetic stimulation (TMS), the precise cortical locations underlying the resulting physiological and behavioral effects are still only coarsely known. To date, mapping strategies have relied on projection approaches (often termed “center of gravity” approaches) or maximum electric field value evaluation, and therefore localize the stimulated cortical site only approximately and indirectly. Focusing on the motor cortex, we present and validate a novel method to reliably determine the effectively stimulated cortical site at the individual subject level. The approach combines measurements of motor evoked potentials (MEPs) at different coil positions and orientations with numerical modeling of induced electric fields. We identify sharply bounded cortical areas, around the gyral crowns and rims of the motor hand area, as the origin of MEPs and show that the magnitude of the tangential component and the overall magnitude of the electric field are most relevant for the observed effect. To validate our approach, we identified the coil location and orientation that produces the maximal electric field at the predicted stimulation site, and then experimentally show that this location produces MEPs more efficiently than other tested locations/orientations. Moreover, we used extensive uncertainty and sensitivity analyses to verify the robustness of the method and identify the most critical model parameters. Our generic approach improves the localization of the cortical area effectively stimulated by TMS and may be transferred to other modalities such as language mapping.

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]

Accumulating evidence suggests that major depressive disorders (MDD) are associated with an imbalance of excitation–inhibition within the prefrontal cortex (PFC), generated by a deficit of inhibitory synaptic transmission onto glutamatergic principal neurons. Transcranial magnetic stimulation (TMS) protocols can be used to measure neuronal excitability and GABAergic inhibition and thus provide additional evidence to evaluate this theory. In the present study, TMS protocols were used to compare GABAergic function and cortical excitability of dominant hemisphere in unmedicated patients with MDD versus a control group of healthy individuals. The study included 43 MDD patients according to DSM-V and 20 age- and sex- matched healthy volunteers. Psychological evaluation was conducted using the Beck Depression Inventory (BDI). Resting and active motor thresholds (rMT and aMT) together with contralateral and ipsilateral cortical silent periods (cSP, and iSP) were measured for each participant. rMT and aMT were higher in MDD patients compared with the control group, while cSP and iSP were significantly shorter in duration. There were significant positive correlations between the BDI score and rMT, aMT (P = 0.001 and 0.002 respectively), and a negative correlation with cSP duration (P = 0.001). Global hypoexcitability of both pyramidal cortical neurons (elevated MTs) and GABAergic controls (shortened SPs) was evidenced within the left/dominant motor cortex in MDD. These results are consistent with previous reports of abnormal glutamate and GABA function in frontal cortex. [ABSTRACT FROM AUTHOR]

The aim of the present study was to identify neurophysiologic markers to differentiate between Alzheimer dementia (AD), Vascular dementia (VaD), and Parkinson's disease dementia (PDD), and to examine their relationship to levels of transforming growth factor β1 (TGFβ1). The study included 15 patients with each type of dementia (AD, VaD, PDD) and 25 control subjects. Dementia patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition-revised (DSM-IV-R). Modified Mini Mental State Examination (MMMSE), motor cortex excitability including resting and active motor thresholds (rMT, aMT), input-output (I/O) curve, contralateral and ipsilateral silent periods (cSP, iSP), short-interval intracortical inhibition (SICI) at 1,2 and 4 ms, and serum levels of TGFβ1 were examined. There were no significant differences between groups with regards to age, sex, education or socioeconomic level. There was significant neuronal hyperexcitability in the form of reduced rMT and aMT and a shallower I/O curve in all three groups of dementia compared with the control group. The durations of cSP and iSP were longer in AD and PDD groups compared with the control group, whereas there were no significant differences in VaD. SICI was less effective in the three dementia groups than in the control group at intervals of 4 ms. Serum levels of TGFβ1 were significantly elevated in all dementia groups in comparison with the control group. There was a significant negative correlation between serum level of TGFβ1 and cSP, iSP, and SICI across all patients and a significant negative correlation between serum level of TGFβ1 and iSP duration in AD. Although motor thresholds were reduced in all patients, measures of SICI, cSP and iSP could distinguish between dementia groups. Serum level of TGFβ1 negatively correlated with iSP specifically in the AD group. This suggests that levels of TGFβ1 may relate to GABAergic dysfunction in dementia. [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]

Transcranial magnetic stimulation (TMS) is a rapidly expanding technology utilized in research and neuropsychiatric treatments. Yet, conventional TMS configurations affect primarily neurons that are aligned parallel to the induced electric field by a fixed coil, making the activation orientation-specific. A novel method termed rotational field TMS (rfTMS), where two orthogonal coils are operated with a 90° phase shift, produces rotation of the electric field vector over almost a complete cycle, and may stimulate larger portion of the neuronal population within a given brain area. To compare the physiological effects of rfTMS and conventional unidirectional TMS (udTMS) in the motor cortex. Hand and leg resting motor thresholds (rMT), and motor evoked potential (MEP) amplitudes and latencies (at 120% of rMT), were measured using a dual-coil array based on the H7-coil, in 8 healthy volunteers following stimulation at different orientations of either udTMS or rfTMS. For both target areas rfTMS produced significantly lower rMTs and much higher MEPs than those induced by udTMS, for comparable induced electric field amplitude. Both hand and leg rMTs were orientation-dependent. rfTMS induces stronger physiologic effects in targeted brain regions at significantly lower intensities. Importantly, given the activation of a much larger population of neurons within a certain brain area, repeated application of rfTMS may induce different neuroplastic effects in neural networks, opening novel research and clinical opportunities. • The study characterizes a novel method of rotational field TMS (rfTMS). • Unique effects in both the hand and leg motor cortices are demonstrated. • RMTs and MEPs were compared to conventional TMS applied at different orientations. • rfTMS produced significantly lower RMTs and higher MEPs in both motor cortices. • Potential benefits and applications of rfTMS are discussed. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) allows exploration of the mode of action of neuroactive substances in the human brain, and allows evaluation of neuronal networks, which might be involved in the action of nicotine. The aim of the present study was to explore motor cortex excitability in chronic smokers and non-smokers using TMS. The study included 50 healthy subjects, of whom 25 were chronic smokers and 25 were age- and sex-matched non-smokers. Number of cigarettes per day and duration of smoking in years were documented. Serum level of cotinine was measured. Resting and active motor threshold (RMT, AMT) and input-output curves (I/O) were performed to assess corticospinal excitability. The duration of the contralateral silent period (cSP) at different ranges of stimulation intensities and ipsilateral silent period (iSP) were used as measures of inhibition. There were no significant differences either in RMT or AMT between groups. I/O curve showed a significant intensity × group interaction (P = 0.008). This was attributable to significantly higher amplitudes of MEP among smokers than non-smokers especially at 130, 140 and 150% of RMT (P = 0.0001 and P = 0.03 and 0.02 respectively). The mean duration of the cSP at different intensities and iSP duration were similar in both groups. Nicotine level and smoking index were correlated respectively with rMT and iSP (P = 0.03 and 0.01). The present results confirm previous findings by Grundey et al. (2013) that chronic nicotine consumption is characterized by hyperexcitability of corticospinal output. We speculate that it is a secondary adaptation to long-term nicotine use with high inter-individual variance. [ABSTRACT FROM AUTHOR]