TMS Mapping Research Articles

Brain Tumour Surgery Guided by Navigated TMS Mapping for Calculation

Brain Tumour Surgery Guided by Navigated TMS Mapping for Calculation

Multi-scale and cross-dimensional TMS mapping: A proof of principle in patients with Parkinson's disease and deep brain stimulation.

Transcranial magnetic stimulation (TMS) mapping has become a critical tool for exploratory studies of the human corticomotor (M1) organization. Here, we propose to gather existing cutting-edge TMS-EMG and TMS-EEG approaches into a combined multi-dimensional TMS mapping that considers local and whole-brain excitability changes as well as state and time-specific changes in cortical activity. We applied this multi-dimensional TMS mapping approach to patients with Parkinson's disease (PD) with Deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) ON and OFF. Our goal was to identifying one or several TMS mapping-derived markers that could provide unprecedent new insights onto the mechanisms of DBS in movement disorders. Six PD patients (1 female, mean age: 62.5 yo [59-65]) implanted with DBS-STN for 1 year, underwent a robotized sulcus-shaped TMS motor mapping to measure changes in muscle-specific corticomotor representations and a movement initiation task to probe state-dependent modulations of corticospinal excitability in the ON (using clinically relevant DBS parameters) and OFF DBS states. Cortical excitability and evoked dynamics of three cortical areas involved in the neural control of voluntary movements (M1, pre-supplementary motor area - preSMA and inferior frontal gyrus - IFG) were then mapped using TMS-EEG coupling in the ON and OFF state. Lastly, we investigated the timing and nature of the STN-to-M1 inputs using a paired pulse DBS-TMS-EEG protocol. In our sample of patients, DBS appeared to induce fast within-area somatotopic re-arrangements of motor finger representations in M1, as revealed by mediolateral shifts of corticomuscle representations. STN-DBS improved reaction times while up-regulating corticospinal excitability, especially during endogenous motor preparation. Evoked dynamics revealed marked increases in inhibitory circuits in the IFG and M1 with DBS ON. Finally, inhibitory conditioning effects of STN single pulses on corticomotor activity were found at timings relevant for the activation of inhibitory GABAergic receptors (4 and 20 ms). Taken together, these results suggest a predominant role of some markers in explaining beneficial DBS effects, such as a context-dependent modulation of corticospinal excitability and the recruitment of distinct inhibitory circuits, involving long-range projections from higher level motor centers and local GABAergic neuronal populations. These combined measures might help to identify discriminative features of DBS mechanisms towards deep clinical phenotyping of DBS effects in Parkinson's Disease and in other pathological conditions.

An efficient and easy-to-use model to determine the stimulation thresholds in transcranial brain stimulation and its application to TMS mapping

An efficient and easy-to-use model to determine the stimulation thresholds in transcranial brain stimulation and its application to TMS mapping

Multi-muscle TMS mapping: reliability, malleability, clinical aspects, and methodology

Multi-muscle TMS mapping: reliability, malleability, clinical aspects, and methodology

TMS mapping of the cerebellum as a way of understanding TMS cellular mechanisms

TMS mapping of the cerebellum as a way of understanding TMS cellular mechanisms

Combination of TMS mapping and E-field modeling reveals dissociation of language functions within the temporal gyrus

Combination of TMS mapping and E-field modeling reveals dissociation of language functions within the temporal gyrus

How does TMS “engage” the human cortex? Insights from structural and functional mapping of the precentral motor hand knob

Abstract Background: TMS of the primary motor hand area (M1-HAND) can probe the function of fast corticomotor connections to the contralateral hand. TMS gives rise to indirect (transsynaptic) excitation of large pyramidal tract (PT) neurons in M1-HAND that make monosynaptic connections with spinal motoneurons in the cervical cord. Other cell types are effectively excited by TMS as well. Yet, it is still unclear which neuronal elements (e.g. axon terminals or axon hillock), which cell types (e.g. PT neurons, intra-telencephalic (IT) neurons, or inhibitory interneurons), and which sites in the precentral hand knob (e.g. crown, lip, or sulcus region) are preferentially depolarized by the TMS-induced electrical field in the precentral gyrus. Objective: To address whether non-invasive neuroimaging in human volunteers can help to pinpoint the primary targets for TMS of M1-HAND. Methods: Structural and functional neuroimaging (MRI and PET) were employed in a series of experiments to target the M1-HAND. Structural MRI was used for shaped-based TMS mapping, electrical field modelling, and mapping of cortical myelin content. Functional MRI and PET were used to localize clusters in the precentral hand knob that are functionally activated by focal TMS of M1-HAND. Results: Inter-individual differences in precentral cortical myelin content account for interindividual differences in rostro-caudal “motor hotspot” location, linking cortical myelination to TMS target engagement. Functional brain mapping reveals different peak target sites in the precentral hand knob and indicates that PT and IT neurons as well as inhibitory interneurons are effectively excited by TMS. Discussion: Structural and functional neuroimaging can help to elucidate how TMS engages its local cortical targets in the precentral gyrus. Causal interpretation of the results needs to consider the potential and pitfalls inherent to the neuroimaging method and the physiological implications of the TMS protocol (e.g. intensity, number of stimuli, online-offline TMS). Keywords: Transcranial magnetic stimulation, Motor cortex, Magnetic resonance imaging, Positron emission tomography

The impact of rTMS on patients with dual diagnosis of depressive disorder and substance use disorders

AimsWe aim to investigate the effectiveness of repetitive Transcranial Magnetic Stimulation (rTMS) in reducing consumption and craving among patients with Substance Use Disorder (SUD) and comorbid depressive disorder.BackgroundDorsolateral prefrontal cortex (DLPFC) is greatly involved in SUD evolution (1). Research has turned to targeting this brain area with rTMS; a non-invasive brain stimulation technique that modulates cortical excitability by sending pulsatile electromagnetic fields through the skull and into the brain (2). rTMS is an FDA approved and safe treatment option for treatment-resistant depression (TRD) (3).MethodFifty-four patients were admitted over six-month period of time (June 2019- December 2019) to the inpatient unit of Erada center for treatment and rehabilitation of SUD in Dubai. All patients who fulfilled ICD-10 diagnoses of Depressive disorder and SUD were screened for further assessment.Positive drug screen was confirmed through urine analysis. Hospital Anxiety and Depression Scale (HADS) and Brief Substance Craving Scale (BSCS) were applied to all participants. Patients were contracted for 5-times weekly High frequency (10 Hz) rTMS for 4 weeks (total of 20 treatments). Those who managed to complete their contracted TMS sessions were matched for age and sex with similar number of patients who received standard treatment as usual (TAU). Stimulation was as per FDA clearance for rTMS application in TRD.ResultEight patients were excluded (previous head trauma). A total of 46 patients had TMS mapping; nine of whom completed 20 sessions.Opioids was the most commonly used drug in almost 52% of patients (n = 14), followed by amphetamines in almost 30% (n = 8) and Cannabis in 18.5% (n = 5).Among those who completed 20 rTMS sessions; HADS scores on anxiety and depression fell by 85% and 78% respectively. BSCS score fell by 98%. Relapse rate (defined by positive drug screen) at 3 months was 33%.For those who completed 10 sessions; there was only 50% reduction on BSCS scores and 66% relapse rate. There were no data available on their HADS scores (only collected at baseline and at completion of 20 sessions).Those who only had TAU; there were no reduction in their BSCS (average score of 7 at both baseline and after 2 weeks).ConclusionOur findings suggest that rTMS may be an effective and safe treatment for both depressive disorder and craving for SUD which is supported by other studies (3,4).Our study is probably the first of its kind within Middle East population with addiction problems.

Two Distinct Systems Represent Contralateral and Ipsilateral Sensorimotor Processes in the Human Premotor Cortex: A Dense TMS Mapping Study.

Animal brains contain behaviorally committed representations of the surrounding world, which integrate sensory and motor information. In primates, sensorimotor mechanisms reside in part in the premotor cortex (PM), where sensorimotor neurons are topographically clustered according to functional specialization. Detailed functional cartography of the human PM is still under investigation. We explored the topographic distribution of spatially dependent sensorimotor functions in healthy volunteers performing left or right, hand or foot, responses to visual cues presented in the left or right hemispace, thus combining independently stimulus side, effector side, and effector type. Event-related transcranial magnetic stimulation was applied to single spots of a dense grid of 10 points on the participants' left hemiscalp, covering the whole PM. Results showed: (1) spatially segregated hand and foot representations, (2) focal representations of contralateral cues and movements in the dorsal PM, and (3) distributed representations of ipsilateral cues and movements in the ventral and dorso-medial PM. The present novel causal information indicates that (1) the human PM is somatotopically organized and (2) the left PM contains sensory-motor representations of both hemispaces and of both hemibodies, but the hemispace and hemibody contralateral to the PM are mapped on a distinct, nonoverlapping cortical region compared to the ipsilateral ones.

P79-F Disrupted muscle cortical representations in amyotrophic lateral sclerosis studied by navigated TMS mapping

Background The search for biomarkers in amyotrophic lateral sclerosis (ALS) can provide pathophysiological insights and is important for early diagnosis and monitoring of the disease progression. Mapping muscle cortical representations using navigated transcranial magnetic stimulation (nTMS) is a noninvasive method for probing corticospinal excitability. We aimed at studying nTMS map parameters as potential biomarkers in ALS. Methods We examined 12 ALS patients (4 women, age median 49, quartiles 40, 55) and 7 healthy controls (5 women, age median 37, quartiles 35, 41). Navigated TMS mapping was performed at the intensity of 110% of the resting motor threshold (RMT) with motor evoked potentials (MEPs) recorded from the abductor pollicis brevis muscle (APB). We used a 7 × 7 stimulation point grid, with 5 stimuli per cell in a pseudorandom order. We analyzed the RMT, the area of cells with at least one suprathreshold MEP, the area weighted by the probability of a suprathreshold MEP, and the area weighted by the mean MEP amplitude. Results The groups were not significantly different in age. The RMT was higher in ALS (p = 0.01, Mann-Whitney). Among the studied representation parameters, only the area weighted by the mean MEP amplitude showed a significant difference, with lower values in ALS patients than in controls (p = 0.02). Conclusions The results suggest that the extent of the APB motor representation in ALS patients is not significantly altered, whereas the excitability and amplitude-weighted area are reduced. Thus, it is important to study motor representation parameters other than the extent as potential ALS biomarkers. Funding RSF17-75-10062.

P21-T The influence of the navigated TMS mapping protocol on the accuracy of motor representation characteristics

Background Navigated transcranial magnetic stimulation enables noninvasive mapping of muscle cortical representations for research and clinical purposes. Several mapping protocols are in use, with no consensus regarding the optimal one and insufficient data about their influence on the mapping accuracy. We aimed to determine this influence for protocols that employ a stimulation point grid. Methods We mapped the abductor pollicis brevis muscle representations in 8 healthy volunteers (3 women, age median 28, quartiles 24, 29) three times on consecutive days. We used a 7 × 7 stimulation grid, with 10 stimuli per cell applied in a pseudorandom order at an intensity of 110% of the resting motor threshold. The grid size was chosen to cover on average 98% of the area of 121 representations previously mapped without grid. The studied parameters were the area of cells with mean motor evoked potential (MEP) amplitude above 50 μV, the area of cells with at least one (or 6) suprathreshold MEP, the area weighted by the mean amplitude (or the probability of suprathreshold MEP), and the location of the center of gravity. Results Parameter accuracy significantly increased with the number of stimuli. The area weighted by the probability of suprathreshold MEP had the highest accuracy and differed significantly between sessions in three subjects. Conclusions The obtained accuracy dependencies can guide the choice of a sufficient number of stimuli for a given problem, e.g. the detection of significant area changes between sessions in our dataset was possible with at least 7 stimuli per cell. Funding RSF17-75-10062.

Optimization of the Navigated TMS Mapping Algorithm for Accurate Estimation of Cortical Muscle Representation Characteristics.

Navigated transcranial magnetic stimulation (nTMS) mapping of cortical muscle representations allows noninvasive assessment of the state of a healthy or diseased motor system, and monitoring changes over time. These applications are hampered by the heterogeneity of existing mapping algorithms and the lack of detailed information about their accuracy. We aimed to find an optimal motor evoked potential (MEP) sampling scheme in the grid-based mapping algorithm in terms of the accuracy of muscle representation parameters. The abductor pollicis brevis (APB) muscles of eight healthy subjects were mapped three times on consecutive days using a seven-by-seven grid with ten stimuli per cell. The effect of the MEP variability on the parameter accuracy was assessed using bootstrapping. The accuracy of representation parameters increased with the number of stimuli without saturation up to at least ten stimuli per cell. The detailed sampling showed that the between-session representation area changes in the absence of interventions were significantly larger than the within-session fluctuations and thus could not be explained solely by the trial-to-trial variability of MEPs. The results demonstrate that the number of stimuli has no universally optimal value and must be chosen by balancing the accuracy requirements with the mapping time constraints in a given problem.

Does Transcranial Magnetic Stimulation (TMS) primarily target premotor or motor cortex in precentral gyrus?

TMS can be used to map the corticomotor representations of hand muscles (HMs) in the precentral gyrus (PG), whose spatial peak is often not located in the primary motor hand area (M1HAND) but shifts towards the caudal part of dorsal premotor cortex (PMd). We used magnetic resonance imaging (MRI) to test the hypothesis that “hand-knob” of PG shows different structural properties in individuals with a “premotor” representation compared to individuals with a “primary-motor” representation of HMs. Twenty-four volunteers underwent MRI and sulcus-shape-based TMS-mapping of right PG. T1-weighted-MRIs were used for neuronavigation and to calculate cortical-thickness of the PG. We also performed quantitative multiparameter mapping of the longitudinal relaxation rate as an index of cortical myelination and simulated the electric field strength induced by TMS in the hand-knob-region. In 14 out-of 24 individuals (58%), TMS mapping disclosed a spatial peak in the PMd (“PMd-subjects”), whereas the remaining 10 subjects (42%) showed maximal motor response in M1HAND (“M1HAND-subjects”). “M1-subjects” displayed a higher electric field strength in the rostral part of the M1HAND (p = 0.01). “PMd-subjects” showed an increase of regional-myelination in the PG (p = 0.033). The results support the notion of two distinct functional-microstructural phenotypes of corticomotor hand representations in human PG.

TMSmap - Software for Quantitative Analysis of TMS Mapping Results.

The use of the MRI-navigation system ensures accurate targeting of TMS. This, in turn, results in TMS motor mapping becoming a routinely used procedure in neuroscience and neurosurgery. However, currently, there is no standardized methodology for assessment of TMS motor-mapping results. Therefore, we developed TMSmap—free standalone graphical interface software for the quantitative analysis of the TMS motor mapping results (http://tmsmap.ru/). In addition to the estimation of standard parameters (such as the size of cortical muscle representation and the center of gravity location), it allows estimation of the volume of cortical representations, excitability profile of the cortical surface map, and the overlap between cortical representations. The input data for the software includes the coordinates of the coil position (or electric field maximum) and the corresponding response in each stimulation point. TMSmap has been developed for versatile assessment and comparison of TMS maps relating to different experimental interventions including, but not limited to longitudinal, pharmacological and clinical studies (e.g., stroke recovery). To illustrate the use of TMSmap we provide examples of the actual TMS motor-mapping analysis of two healthy subjects and one chronic stroke patient.

TMS-guided physiotherapy reduces pain and induces plasticity in the motor cortex in Chronic Knee Osteoarthritis

BACKGROUND: Knee osteoarthritis (OA) is associated with chronic pain, impaired function and loss of quality of life. Brain maladaptive plasticity may be involved and prevent beneficial effects of exercises and other interventions. Neuromodulation with peripheral electrical stimulation guided by TMS mapping may specifically influence those maladaptive modifications. OBJECTIVE: To compare the cortical organization and excitability of three muscles (straight femuris, vastus lateralis and vastus medialis) in a subject with OA knee. METHODS: This single case ABA study involved a 66 yo woman with knee OA that was considering an arthroplasty. She was assessed for pain (VAS), function (WOMAC, ICOAP), and quadriceps strength one time a week, for 10 weeks (A – four weeks assessment; B – two weeks assessment and intervention; A – four weeks assessment). TMS mapping was performed at baseline, after the two-week intervention period and at the end of the study. This examination initially revealed a prominent decrease in the volume of vastus medialis portion of the quadriceps muscle over the primary motor cortex (M1), which determined a peripheral electrical stimulation protocol specifically designed to increase this muscle’s excitability. During the intervention period the participant also carried over specific exercises daily. RESULTS: WOMAC scores, and quadriceps strength were not changed during the study period. Improvements were seen in the three subscales of the ICOAP following the intervention. This clinical change was associated with an increase in vastus medialis and also Vastus lateralis, and a decrease in rectus femuris TMS map volumes, which were maintained until the last evaluation. CONCLUSION: TMS mapping may guide specific interventions to counteract motor cortex maladaptive plasticity and positively influence pain and function in knee OA.

Aphasia and cognitive impairment decrease the reliability of rnTMS language mapping

Navigated transcranial magnetic stimulation (nTMS) is a non-invasive mapping tool to locate functional areas of the brain. While gaining importance in the preoperative planning process in motor eloquent regions, its usefulness for reliably identifying language areas is still being discussed. The aim of this study was to identify biometric factors which might influence and therefore bias the results of repetitive nTMS (rnTMS) over cortex areas relevant for language. We included data of 101 patients with language eloquent brain lesions who underwent preoperative rnTMS examination bihemispherically. Prior to rnTMS mapping, all patients performed two to three baseline runs of a picture-naming paradigm without stimulation, and only promptly and correctly named objects were retained for TMS mapping. Nine biometric factors (age, gender, baseline dataset, cognitive performance score, aphasia score, histology of lesion, affected hemisphere, location of lesion on the hemisphere, pain caused by examination) were included in the statistical analysis measuring their correlation with the incidence of errors during baseline naming as well as during rnTMS mapping. The incidence of baseline errors correlated with aphasia (p < 0.0001) and cognitive impairment (p < 0.0001). No significant correlation was observed between most biometric factors and errors during rnTMS mapping. Factors significantly affecting the incidence of errors during rnTMS mapping were again aphasia (p < 0.023) and cognitive impairment (p < 0.038). Patients affected by those factors showed a significantly higher baseline error rate, starting at 28% error rate. Patients with pre-existing aphasia or severe cognitive impairment did still make significantly more mistakes during rnTMS mapping than non-aphasic patients despite baseline stratification, rendering the question of whether the procedure is reliable in those patient groups. Baseline testing revealed a cut-off point at 28% error rate. Interestingly, age or pain (caused by the examination) did not bias the results.

Multi-muscle TMS mapping using subject-specific FEA models of induced currents

Multi-muscle TMS mapping using subject-specific FEA models of induced currents

P181 tACS frequency dependent changes in corticospinal excitability revealed using TMS mapping

Transcranial alternating current stimulation (tACS) has been suggested to entrain neuronal oscillations leading to changes in motor behaviour and corticospinal excitability (CSE). Reports characterising the effect of tACS on CSE are equivocal despite tACS after-effects being ascribed to changes in synaptic plasticity. All studies to date assessing tACS-induced CSE have used single pulse TMS at a single intensity. However, this method might not reveal shifts in the corticospinal representation or unequal expansion of the cortical representation. The present study aimed to investigate the effect of tACS on CSE using TMS maps, with a stimulation frequency within (20 Hz) and outside (140 Hz) the traditional beta band for the motor system. Eleven participants visited the lab on three separate occasions to receive 10 min of sham stimulation or tACS at 1 mA and either 20 or 140 Hz. Stimulating electrodes (4 × 4 cm) were placed over the motor representation of the first dorsal interosseous (FDI) muscle and contralateral orbit. A novel rapid TMS mapping method was employed to assess the FDI motor representation before and 10–35 min after tACS. The difference in TMS map area and centre of gravity (COG) before and after stimulation were analysed. On average, map area increased after 140 Hz and decreased after 20 Hz tACS. A repeated measures ANOVA revealed no significant effect for either FREQUENCY (P = 0.07), TIME (P = 0.86) or a FREQUENCY’TIME interaction (P = 0.34). Based on variability in the baseline measures we identified five participants with increased map area following 140 Hz tACS, whilst following 20 Hz tACS map area decreased for three participants. On average COG was displaced 5 ± 3 mm in the post maps compared to the baseline map. However, COG were not systematically displaced in either the x (xDisp: FREQUENCY: P = 0.38, TIME: P = 0.83, FREQUENCY’TIME: P = 0.83) or y direction (yDisp: FREQUENCY: P = 0.23, TIME: P = 0.97, FREQUENCY’TIME: P = 0.94) In conclusion, no main effect of tACS was found on CSE using TMS mapping. Nonetheless, these pilot data suggest that 10 min of 20 Hz stimulation may inhibit excitability and 140 Hz stimulation may facilitate excitability, in line with our hypothesis. This effect is masked by significant variability in the response with only a third to a half of the participants showing a changes in CSE following tACS, which is in line with reports for tDCS.

Robotic TMS mapping of motor cortex in the developing brain

Robotic TMS mapping of motor cortex in the developing brain

P219 The variability of targets for repetitive transcranial magnetic stimulation based on navigated TMS mapping and intrinsic connectivity measures

Introduction Despite the quasi high effectiveness of the repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal cortex (lDLPFC) in treatment of major depression, the high effect size variability is noticed (Herbsman et al., 2009). One of the reasons for this variability is the imperfect targeting of stimulation point. Resting state functional MRI (rsfMRI) has become a very popular tool to measure an intrinsic connectivity. Seed-based connectivity analysis is the method to evaluate functional connectivity between a chosen region and the whole brain. This analysis could be used for rTMS point targeting (Fox et al., 2012). Objectives Our aim was to evaluate the possibilities of seed-based connectivity analysis in TMS stimulation point targeting and to measure the variability of these points compared to navigated transcranial magnetic stimulation (nTMS)-guided targeting. Materials and Methods Five patients (all females, mean age = 36.6, SD = 8.7) suffering major depression were enrolled in this study. They were clinically evaluated with Beck Depression Inventory (mean value = 28.5, SD = 12). Resting-state fMRI data was acquired on 3T MR-scanner. nTMS with Abductor pollicis brevis muscle mapping was also performed with NBS eXimia Nexstim device. Maps of functional connectivity were built using CONNtoolbox for MATLAB. Subgenual cingulated cortex area (10 mm radius sphere at MNI coordinates (6,16,-10) was taken as a seed region. Then points in lDLPFC with maximum value of negative correlation were found individually in seed maps. The second pool of points was determined as5 cmanterior to individual APB muscle hotspot. The coordinates of two pools of points were compared inter- and intra-individually. Results Maximal distance between nTMS-guided points was 13.27 mmvs.53.62 mm between rsfMRI-guided points. Mean distance to the center of points in nTMS-guided group was 5.45 mmvs 38.83 mmin rsfMRI-guided group. Mean distance between intraindividual nTMS- and rsfMRI-guided points was 40.02 mm (Fig. 1) . Conclusion The interindividual variability of rsfMRI-based points’ coordinates was much higher than in nTMS-based points. High intraindividual variability was also shown. We are starting a clinical trial comparing the effects of rTMS targeting with these two methods in major depression.