Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal-Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3 mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3 mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.

Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.

Association between Stimulation-Site Pain and Clinical Improvement during Repetitive Transcranial Magnetic Stimulation for Patients with Major Depressive Disorders: A Prospective Observational Study at Two Sites.

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.

Yoga as an Add-on Therapy in Parkinson's Disease: A Single Group Open-label Trial.

OBJECTIVE: We aimed to evaluate the effect of yoga on motor and non-motor symptoms and cortical excitability in patients with Parkinson's disease (PD). METHODS: We prospectively evaluated 17 patients with PD at baseline, after one month of conventional care, and after one month of supervised yoga sessions. The motor and non-motor symptoms were evaluated using the Unified Parkinson's disease Rating Scale (motor part III), Hoehn and Yahr stage, Montreal Cognitive Assessment, Hamilton depression rating scale, Hamilton anxiety rating scale, non-motor symptoms questionnaire and World Health Organization quality of life questionnaire. Transcranial magnetic stimulation was used to record resting motor threshold, central motor conduction time, ipsilateral silent period (iSP), contralateral silent period (cSP), short interval intracortical inhibition (SICI), and intracortical facilitation. RESULTS: The mean age of the patients was 55.5 ± 10.8 years, with a mean duration of illness of 4.0 ± 2.5 years. The postural stability of the patients significantly improved following yoga (0.59 ± 0.5 to 0.18 ± 0.4, p = 0.039). There was a significant reduction in the cSP from baseline (138.07 ± 27.5 ms) to 4 weeks of yoga therapy (116.94 ± 18.2 ms, p = 0.004). In addition, a significant reduction in SICI was observed after four weeks of yoga therapy (0.22 ± 0.10) to (0.46 ± 0.23), p = 0.004). CONCLUSION: Yoga intervention can significantly improve postural stability in patients with PD. A significant reduction of cSP and SICI suggests a reduction in GABAergic neurotransmission following yoga therapy that may underlie the improvement observed in postural stability. CLINICALTRIALSGOV IDENTIFIER: CTRI/2019/02/017564.

Non-invasive Transcutaneous Spinal Cord Stimulation Programming Recommendations for the Treatment of Upper Extremity Impairment in Tetraplegia.

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.

The effects of transcutaneous auricular vagal nerve stimulation on cortical GABAergic and cholinergic circuits: A transcranial magnetic stimulation study.

Neurophysiological evidence that transcutaneous auricular vagal nerve stimulation (taVNS) affects neuronal signalling at the cortical level is sparse. We used transcranial magnetic stimulation to assess the effect of taVNS on the excitability of intracortical GABAergic and cholinergic circuits. In this within-subject, double-blind study on 30 healthy participants, we used TMS paradigms to assess the effect of a single session of taVNS at 100 Hz and sham earlobe VNS (sVNS) on short-interval intracortical inhibition (SICI) curve and short-latency afferent inhibition (SAI). Control experiment was performed on additional 15 participants using the same experimental settings, but delivering no stimulation (xVNS). Bayesian statistics were used to assess the differences, producing % values that reflect the certainty that the values of interest were decreased during or after stimulation compared with baseline. taVNS increased SICI (96.3%), whereas sVNS decreased SICI (1.2%). SAI was not affected by taVNS, although it was decreased during sVNS (1.34% and 9.1%, for interstimulus intervals 20 and 24 ms, respectively). The changes in TMS parameters detected during sVNS were present in the same direction in the control experiment with no stimulation. Our study provides evidence that taVNS increases the activity of cortical GABAAergic system, leaving cortical cholinergic circuits unaffected. Changes in intracortical cortical excitability during sVNS, which were also observed in the control experiment with no stimulation were likely the effect of expectation related to participation in an interventional study.

Corticospinal and intracortical responses from both motor cortices following unilateral concentric versus eccentric contractions.

Cross-education is the phenomenon where training of one limb can cause neuromuscular adaptations in the opposite untrained limb. This effect has been reported to be greater after eccentric (ECC) than concentric (CON) strength training; however, the underpinning neurophysiological mechanisms remain unclear. Thus, we compared responses to transcranial magnetic stimulation (TMS) in both motor cortices following single sessions of unilateral ECC and CON exercise of the elbow flexors. Fourteen healthy adults performed three sets of 10 ECC and CON right elbow flexor contractions at 75% of respective maximum on separate days. Elbow flexor maximal voluntary isometric contraction (MVIC) torques were measured before and after exercise, and responses to single- and paired-pulse TMS were recorded from the non-exercised left and exercised right biceps brachii. Pre-exercise and post-exercise responses for ECC and CON were compared by repeated measures analyses of variance (ANOVAs). MVIC torque of the exercised arm decreased (p < 0.01) after CON (-30 ± 14%) and ECC (-39 ± 13%) similarly. For the non-exercised left biceps brachii, resting motor threshold (RMT) decreased after CON only (-4.2 ± 3.9% of maximum stimulator output [MSO], p < 0.01), and intracortical facilitation (ICF) decreased (-15.2 ± 20.0%, p = 0.038) after ECC only. For the exercised right biceps, RMT increased after ECC (8.6 ± 6.2% MSO, p = 0.014) but not after CON (6.4 ± 8.1% MSO, p = 0.066). Thus, unilateral ECC and CON elbow flexor exercise modulated excitability differently for the non-exercised hemisphere. These findings suggest that responses after a single bout of exercise may not reflect longer term adaptations.

Electrically Evoked Compound Action Potentials in Spinal Cord Stimulation: Implications for Preclinical Research Models.

OBJECTIVES: The study aimed to assess the feasibility of recording electrically evoked compound action potentials (ECAPs) from the rat spinal cord. To achieve this, we characterized electrophysiological responses of dorsal column (DC) axons from electrical stimulation and quantified the relationship between ECAP and motor thresholds (ECAPTs and MTs). MATERIAL AND METHODS: Naïve, anesthetized, and freely behaving rats were implanted with a custom-made epidural spinal cord stimulation (SCS) lead. Epidural stimulation and recordings were performed on the same lead using specifically designed equipment. RESULTS: The ECAPs recorded from the rat spinal cord demonstrated the expected triphasic morphology. Using 20 µsec pulse duration and 2 Hz frequency rate, the current required in anesthetized rats to generate ECAPs was 0.13 ± 0.02 mA, while the average current required to observe MT was 1.49 ± 0.14 mA. In unanesthetized rats, the average current required to generate ECAPs was 0.09 ± 0.02 mA, while the average current required to observe MT was 0.27 ± 0.04 mA. Thus, there was a significant difference between the ECAPT and MT in both anesthetized and unanesthetized rats (MT was 13.39 ± 2.40 and 2.84 ± 0.33 times higher than ECAPT, respectively). Signal analysis revealed average conduction velocities (CVs) suggesting that predominantly large, myelinated fibers were activated. In addition, a morphometric evaluation of spinal cord slices indicated that the custom-made lead may preferentially activate DC axons. CONCLUSIONS: This is the first evidence demonstrating the feasibility of recording ECAPs from the rat spinal cord, which may be more useful in determining parameters of SCS in preclinical SCS models than MTs. Thus, this approach may allow for the development of a novel model of SCS in rats with chronic pain that will translate better between animals and humans.

Efficient high-resolution TMS mapping of the human motor cortex by nonlinear regression.

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.

Effect of Lumbar Drainage on Cortical Excitability in Normal Pressure Hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the clinical triad of gait disturbance, urinary incontinence, and memory impairment with normal cerebrospinal fluid (CSF) pressure. Transcranial magnetic stimulation (TMS) has been used to assess the corticospinal motor pathways in patients with iNPH with conflicting results. METHODS: Our study included 11 patients with iNPH and 13 healthy controls. All the subjects underwent TMS and resting motor threshold (RMT), central motor conduction time (CMCT), short-interval intracortical inhibition (SICI), intracortical facilitation, and silent period (SP) were recorded in the upper limb. Besides, RMT and CMCT in lower limb were also recorded. Cognitive assessments were done using mini-mental status examination, Montreal cognitive assessment (MoCA), and Addenbrooke's cognitive evaluation III (ACE III). Same parameters were recorded 24 h of CSF (lumbar puncture, LP) drainage. RESULTS: Mean age of the iNPH patients was 69.00 ± 6.71 years with age at onset being 66.64 ± 7.10 years. Duration of disease was 1.80 ± 1.25 years. A significant difference was noted in CMCT for the lower limb (CMCT-LL), SICI, and ipsilateral SP between pre-LP NPH and controls. Also, there was a significant difference in MoCA and ACE III between pre-LP NPH and controls. A significant reduction was observed in lower limb RMT between pre- and post-LP NPH patients. Post LP, there was a reduction in the lower limb CMCT and improvement in SICI. CONCLUSION: A significant prolongation of CMCT-LL was observed in NPH patients. Lumbar CSF drainage in them resulted in a significant reduction in lower limb RMT thereby suggesting an increase in cortical excitability.

Cortical Excitability in Temporal Lobe Epilepsy with Bilateral Tonic-Clonic Seizures.

OBJECTIVE: We investigated motor cortical excitability (CE) in unilateral temporal lobe epilepsy (TLE) and its relationship to bilateral tonic-clonic seizure (BTCS) using paired-pulse transcranial magnetic stimulation (TMS). METHODS: In this cross-sectional study, we enrolled 46 unilateral TLE patients and 16 age-and sex-matched healthy controls. Resting motor thresholds (RMT); short-interval intracortical inhibition (SICI, GABAA receptor-mediated); facilitation (ICF, glutamatergic-mediated) with interstimulus intervals (ISIs) of 2, 5, 10, and 15 ms; and long-interval intracortical inhibition (LICI, GABAB receptor-mediated) with ISIs of 200-400 ms were measured via paired-pulse TMS. Comparisons were made between controls and patients with TLE, and then among the TLE subgroups (no BTCS, infrequent BTCS and frequent BTCS subgroup). RESULTS: Compared with controls, TLE patients had higher RMT, lower SICI and higher LICI in both hemispheres, and higher ICF in the ipsilateral hemisphere. In patients with frequent BTCS, cortical hyperexcitability in the ipsilateral hemisphere was found in a parameter-dependent manner (SICI decreased at a stimulation interval of 5 ms, and ICF increased at a stimulation interval of 15 ms) compared with patients with infrequent or no BTCS. CONCLUSIONS: Our results demonstrate that motor cortical hyper-excitability in the ipsilateral hemisphere underlies the epileptogenic network of patients with active BTCS, which is more extensive than those with infrequent or no BTCS.

Resting motor threshold in the course of hand motor recovery after stroke: a systematic review.

BACKGROUND: Resting motor threshold is an objective measure of cortical excitability. Numerous studies indicate that the success of motor recovery after stroke is significantly determined by the direction and extent of cortical excitability changes. A better understanding of this topic (particularly with regard to the level of motor impairment and the contribution of either cortical hemisphere) may contribute to the development of effective therapeutical strategies in this cohort. OBJECTIVES: This systematic review collects and analyses the available evidence on resting motor threshold and hand motor recovery in stroke patients. METHODS: PubMed was searched from its inception through to 31/10/2020 on studies investigating resting motor threshold of the affected and/or the non-affected hemisphere and motor function of the affected hand in stroke cohorts. RESULTS: Overall, 92 appropriate studies (including 1978 stroke patients and 377 healthy controls) were identified. The analysis of the data indicates that severe hand impairment is associated with suppressed cortical excitability within both hemispheres and with great between-hemispheric imbalance of cortical excitability. Favorable motor recovery is associated with an increase of ipsilesional motor cortex excitability and reduction of between-hemispheric imbalance. The direction of change of contralesional motor cortex excitability depends on the amount of hand motor impairment. Severely disabled patients show an increase of contralesional motor cortex excitability during motor recovery. In contrast, recovery of moderate to mild hand motor impairment is associated with a decrease of contralesional motor cortex excitability. CONCLUSIONS: This data encourages a differential use of rehabilitation strategies to modulate cortical excitability. Facilitation of the ipsilesional hemisphere may support recovery in general, whereas facilitation and inhibition of the contralesional hemisphere may enhance recovery in severe and less severely impaired patients, respectively.

A novel approach to localize cortical TMS effects.

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.

Prognostic value of a bilateral motor threshold criterion for facial corticobulbar MEP monitoring during cerebellopontine angle tumor resection.

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.

Repetitive transcranial magnetic stimulation for treatment of tardive syndromes: double randomized clinical trial.

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.

Clinical Utility of Longitudinal Measurement of Motor Threshold in Wilson's Disease.

This study describes the longitudinal changes of resting motor threshold (RMT) and central motor conduction time (CMCT) in 18 patients with Wilson's disease (WD). The RMT, CMCT, and Global Assessment Scale for Wilson Disease (GAS-WD) were measured at baseline and at follow-up after 12.94 ± 7.23 months. There was a significant decrease in the RMT (72.11 ± 18.62 vs. 63.7 ± 15.52%; p-value = 0.002) and GAS-WD scores (14.38 ± 5.35 vs. 9.77 ± 6.47 ms; p-value = 0.04). CMCT did not improve despite chelation therapy. Hence, RMT may serve as a marker of chelation efficacy in WD.

When imaging meets neurophysiology: the value of navigated transcranial magnetic stimulation for preoperative neurophysiological mapping prior to brain tumor surgery.

Maximal safe resection is the modern goal for surgery of intrinsic brain tumors located in or close to brain eloquent areas. Nowadays different neuroimaging techniques provide important anatomical and functional information regarding the brain functional organization that can be used to plan a customized surgical strategy to preserve functional networks, and to increase the extent of tumor resection. Among these techniques, navigated transcranial magnetic stimulation (nTMS) has recently gained great favor among the neurosurgical community for preoperative mapping and planning prior to brain tumor surgery. It represents an advanced neuroimaging technique based on the neurophysiological mapping of the functional cortical brain organization. Moreover, it can be combined with other neuroimaging techniques such as diffusion tensor imaging tractography, thus providing a reliable reconstruction of brain eloquent networks. Consequently, nTMS mapping may provide reliable noninvasive brain functional mapping, anticipating information that otherwise may be available to neurosurgeons only in the operating theater by using direct electrical stimulation. The authors describe the reliability and usefulness of the preoperative nTMS-based approach in neurosurgical practice, and briefly discuss their experience using nTMS as well as currently available evidence in the literature supporting its clinical use. In particular, special attention is reserved for the discussion of the role of nTMS as a novel tool for the preoperative neurophysiological mapping of motor and language networks prior to surgery of intrinsic brain tumors located in or close to eloquent networks, as well as for future and promising applications of nTMS in neurosurgical practice.

TMS motor mapping in brain tumor patients: more robust maps with an increased resting motor threshold.

OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) has found widespread usage across many clinical centers as part of their surgical planning routines. NTMS offers a non-invasive approach to delineation of the motor cortex, in which the region is outlined through electromagnetic stimulation and electromyographic recordings of target muscles. Several neurophysiological parameters such as the motor evoked potential (MEP) and its derivatives, the resting motor threshold (RMT) and motor latency, are collected. The present study investigates the clinical feasibility and reproducibility of increasing the MEP threshold in brain tumor patients, with the goal to improve the robustness of the procedure. MATERIALS AND METHODS: Twenty-three subjects with peri-motor cortex tumors underwent motor mapping with nTMS. RMT was calculated with both conventional 50-µV and experimental 500-µV MEP amplitude thresholds. Motor mapping was performed with 105% of both RMTs stimulator intensity using the FDI as the target muscle. RESULTS: Motor mapping was possible in 20 patients with both the conventional and experimental thresholds. No significant differences in area size were found between motor area maps generated with a conventional 50-µV threshold in comparison to those generated with the higher 500-µV threshold (50 µV 272.56 mm2 [170.47-434.31] vs. 500 µV 240.54 mm2 [169.77-362.84], P = 0.34). Latency time was significantly reduced in 500-µV recordings relative to 50-µV recordings (50 µV 23.38 ms [22.55-24.51] vs. 500 µV 22.57 ms [21.41-23.70], P < 0.001). Both electric field intensity (50 µV 63.81 V/m [54.26-76.11] vs. 500 µV 77.83 V/m [65.21-93.94], P < 0.001) and RMT (50 µV 33 MSO% [28-36] vs. 500 µV 39.5 MSO% [32-44], P < 0.001) were significantly greater with the higher 500-µV threshold. CONCLUSIONS: Our study demonstrates the feasibility of increasing the MEP detection threshold to 500 µV in brain tumor patients for RMT determination and motor area mapping with nTMS.

Estimation of the resting motor threshold (RMT) in transcranial magnetic stimulation using relative-frequency and threshold-hunting methods in brain tumor patients.

BACKGROUND: Application of transcranial magnetic stimulation is often based on the resting motor threshold. The aim of this study was to validate recent findings on the advantage of resting motor threshold estimation using adaptive threshold-hunting algorithms over the Rossini-Rothwell method in a clinical sample and healthy subjects. METHODS: Resting motor thresholds in 115 patients with a brain tumor and 10 healthy subjects were assessed using the Rossini-Rothwell method and compared to an adaptive threshold-hunting algorithm. In healthy subjects, this measurement was repeated twice to capture test-retest reliability of both methods. Efficiency of both methods was assessed by comparing the number of pulses needed for resting motor threshold estimation. RESULTS: There was no significant difference between the Rossini-Rothwell method and the adaptive threshold-hunting algorithm in patients and healthy controls with limits of agreement between ± 12 V/m. There was a strong intraclass correlation and both methods showed a good test-retest reliability. However, the adaptive threshold-hunting algorithm was significantly faster. CONCLUSIONS: The adaptive threshold-hunting algorithm was more efficient in assessing the resting motor threshold, while reaching comparable results as the Rossini-Rothwell method. Thus, our results support the advantage of adaptive threshold-hunting algorithms to determine the resting motor threshold also in a clinical sample.

Comparison of Rossini-Rothwell and adaptive threshold-hunting methods on the stability of TMS induced motor evoked potentials amplitudes.

Several methods can be used to determine the resting motor threshold (RMT) and by that recording transcranial magnetic stimulation (TMS) induced motor evoked potentials (MEPs). However, no research has compared the test retest reliability of these methods. Thus, the aim of this study was to determine intra- and inter-session reliability of Rossini-Rothwell (R-R) and parameter estimation by sequential testing (PEST) methods on TMS-induced MEPs and comparison of these two methods on RMT. Twelve healthy individuals participated in this study three times (T1, T2 and T3) over two days. TMS was applied using both R-R and PEST to estimate RMT and average of 25 MEPs were acquired at each of the three time points. The intra-class correlation coefficient indicated high intra-session reliability in the MEP amplitudes for both methods (0.79 and 0.88, R-R and PEST respectively). The RMT and MEP amplitudes had higher inter-session reliability in both methods (0.99 and 0.998, R-R and PEST respectively; 0.84 and 0.76, R-R and PEST respectively). There was no significant difference between methods for RMT at both T1 (maximum stimulator output of R-R vs. PEST, 33.7% ± 7.7% vs. 33.8% ± 7.6%, p = 0.75) and T3 (maximum stimulator output of R-R vs. PEST, 33.5% ± 7.3% vs. 33.7% ± 7.3%, p = 0.19). There was a significant positive correlation between the methods' estimates of RMT, with PEST requiring significantly fewer stimuli. This study shows that the R-R and PEST methods have high intra-and inter-session reliability and the same precision, with PEST having the advantage over R-R in speed of estimation of RMT.