Localization of Sensorimotor Cortex Using Navigated Transcranial Magnetic Stimulation and Magnetoencephalography.

The mapping of the sensorimotor cortex gives information about the cortical motor and sensory functions. Typical mapping methods are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG). The differences between these mapping methods are, however, not fully known. TMS center of gravities (CoGs), MEG somatosensory evoked fields (SEFs), corticomuscular coherence (CMC), and corticokinematic coherence (CKC) were mapped in ten healthy adults. TMS mapping was performed for first dorsal interosseous (FDI) and extensor carpi radialis (ECR) muscles. SEFs were induced by tactile stimulation of the index finger. CMC and CKC were determined as the coherence between MEG signals and the electromyography or accelerometer signals, respectively, during voluntary muscle activity. CMC was mapped during the activation of FDI and ECR muscles separately, whereas CKC was measured during the waving of the index finger at a rate of 3-4 Hz. The maximum CMC was found at beta frequency range, whereas maximum CKC was found at the movement frequency. The mean Euclidean distances between different localizations were within 20 mm. The smallest distance was found between TMS FDI and TMS ECR CoGs and longest between CMC FDI and CMC ECR sites. TMS-inferred localizations (CoGs) were less variable across participants than MEG-inferred localizations (CMC, CKC). On average, SEF locations were 8 mm lateral to the TMS CoGs (p < 0.01). No differences between hemispheres were found. Based on the results, TMS appears to be more viable than MEG in locating motor cortical areas.

Correction to: Extent and Location of the Excitatory and Inhibitory Cortical Hand Representation Maps: A Navigated Transcranial Magnetic Stimulation Study.

The original version of this article unfortunately contained an error. An error in the transformation between coordinate systems used to derive part of the results has been noticed.

Efficient Mapping of the Motor Cortex with Navigated Biphasic Paired-Pulse Transcranial Magnetic Stimulation.

Navigated transcranial magnetic stimulation (nTMS) can be applied to locate cortical muscle representations. Usually, single TMS pulses are targeted to the motor cortex with the help of neuronavigation and by measuring motor evoked potential (MEP) amplitudes from the peripheral muscles. The efficacy of single-pulse TMS to induce MEPs has been shown to increase by applying facilitatory paired-pulse TMS (ppTMS). Therefore, the aim was to study whether the facilitatory ppTMS could enable more efficient motor mapping. Biphasic single-pulse TMS and ppTMS with inter-stimulus intervals (ISIs) of 1.4 and 2.8 ms were applied to measure resting motor thresholds (rMTs) as a percentage of the maximal stimulator output and to determine the cortical representation areas of the right first dorsal interosseous muscle in healthy volunteers. The areas, shapes, hotspots, and center of gravities (CoGs) of the representations were calculated. Biphasic ppTMS with ISI of 1.4 ms resulted in lower rMTs than those obtained with the other protocols (p = 0.001). With ISI of 2.8 ms, rMT was lower than with single-pulse TMS (p = 0.032). The ppTMS mapping was thus performed with lower intensity than when using single-pulse TMS. The areas, shapes, hotspots, and CoGs of the muscle representations were in agreement. Hence, biphasic ppTMS has potential in the mapping of cortical hand representations in healthy individuals as an alternative for single-pulses, but with lower stimulation intensity by utilizing cortical facilitatory mechanism. This could improve application of nTMS in subjects with low motor tract excitability.

Minimum-Norm Estimation of Motor Representations in Navigated TMS Mappings.

Navigated transcranial magnetic stimulation (nTMS) can be applied to locate and outline cortical motor representations. This may be important, e.g., when planning neurosurgery or focused nTMS therapy, or when assessing plastic changes during neurorehabilitation. Conventionally, a cortical location is considered to belong to the motor cortex if the maximum electric field (E-field) targeted there evokes a motor-evoked potential in a muscle. However, the cortex is affected by a broad E-field distribution, which tends to broaden estimates of representation areas by stimulating also the neighboring areas in addition to the maximum E-field location. Our aim was to improve the estimation of nTMS-based motor maps by taking into account the E-field distribution of the stimulation pulse. The effect of the E-field distribution was considered by calculating the minimum-norm estimate (MNE) of the motor representation area. We tested the method on simulated data and then applied it to recordings from six healthy volunteers and one stroke patient. We compared the motor representation areas obtained with the MNE method and a previously introduced interpolation method. The MNE hotspots and centers of gravity were close to those obtained with the interpolation method. The areas of the maps, however, depend on the thresholds used for outlining the areas. The MNE method may improve the definition of cortical motor areas, but its accuracy should be validated by comparing the results with maps obtained with direct cortical stimulation of the cortex where the E-field distribution can be better focused.

Extent and Location of the Excitatory and Inhibitory Cortical Hand Representation Maps: A Navigated Transcranial Magnetic Stimulation Study.

Voluntary muscle action and control are modulated by the primary motor cortex, which is characterized by a well-defined somatotopy. Muscle action and control depend on a sensitive balance between excitatory and inhibitory mechanisms in the cortex and in the corticospinal tract. The cortical locations evoking excitatory and inhibitory responses in brain stimulation can be mapped, for example, as a pre-surgical procedure. The purpose of this study was to find the differences between excitatory and inhibitory motor representations mapped using navigated transcranial magnetic stimulation (nTMS). The representations of small hand muscles were mapped to determine the areas and the center of gravities (CoGs) in both hemispheres of healthy right-handed volunteers. The excitatory representations were obtained via resting motor evoked potential (MEP) mapping, with and without a stimulation grid. The inhibitory representations were mapped using the grid and measuring corticospinal silent periods (SPs) during voluntary muscle contraction. The excitatory representations were larger on the dominant hemisphere compared with the non-dominant (p < 0.05). The excitatory CoGs were more medial (p < 0.001) and anterior (p < 0.001) than the inhibitory CoGs. The use of the grid did not influence the areas or the CoGs. The results support the common hypothesis that the MEP and SP representations are located at adjacent sites. Furthermore, the dominant hemisphere seems to be better organized for controlling excitatory motor functions with respect to TMS. In addition, the inhibitory representations could provide further information about motor reorganization and aid in surgery planning when the functional cortical representations are located in abnormal cortical regions.

Respiratory event index underestimates severity of sleep apnea compared to apnea-hypopnea index.

Polygraphy (PG) is often used to diagnose obstructive sleep apnea (OSA). However, it does not use electroencephalography, and therefore cannot estimate sleep time or score arousals and related hypopneas. Consequently, the PG-derived respiratory event index (REI) differs from the polysomnography (PSG)-derived apnea-hypopnea index (AHI). In this study, we comprehensively analyzed the differences between AHI and REI. Conventional AHI and REI were calculated based on total sleep time (TST) and total analyzed time (TAT), respectively, from two different PSG datasets (n = 1561). Moreover, TAT-based AHI (AHITAT) and TST-based REI (REITST) were calculated. These indices were compared keeping AHI as the gold standard. The REI, AHITAT, and REITST were significantly lower than AHI (p < 0.0001, p ≤ 0.002, and p ≤ 0.01, respectively). The total classification accuracy of OSA severity based on REI was 42.1% and 72.8% for two datasets. Based on AHITAT, the accuracies were 68.4% and 85.9%, and based on REITST, they were 65.9% and 88.5% compared to AHI. AHI was most correlated with REITST (r = 0.98 and r = 0.99 for the datasets) and least with REI (r = 0.92 and r = 0.97). Compared to AHI, REI had the largest mean absolute errors (13.9 and 6.7) and REITST the lowest (5.9 and 1.9). REI had the lowest sensitivities (42.1% and 72.8%) and specificities (80.7% and 90.9%) in both datasets. Based on these present results, REI underestimates AHI. Furthermore, these results indicate that arousal-related hypopneas are an important measure for accurately classifying OSA severity.

Fast acquisition of resting motor threshold with a stimulus-response curve - Possibility or hazard for transcranial magnetic stimulation applications?

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 < 0.001) was detected in MEP amplitudes. No trend was observed which ISI was most excitable, as it varied between subjects. CONCLUSIONS: At the group level, the stimulus-response curves are unaffected by the short ISI. At the individual level, these curves are highly affected by the ISI. SIGNIFICANCE: Estimating rMT using stimulus-response curves with short ISIs impacts the rMT estimate and should be avoided in clinical and research TMS applications.

Minimum-Norm Estimation of TMS-Activated Motor Cortical Sites in Realistic Head and Brain Geometry.

Navigated transcranial magnetic stimulation (nTMS) is a widely used tool for motor cortex mapping. However, the full details of the activated cortical area during the mapping remain unknown due to the spread of the stimulating electric field (E-field). Computational tools, which combine the E-field with physiological responses, have potential for revealing the activated source area. We applied the minimum-norm estimate (MNE) method in a realistic head geometry to estimate the activated cortical area in nTMS motor mappings of the leg and hand muscles. We calculated the MNE also in a spherical head geometry to assess the effect of the head model on the MNE maps. Finally, we determined optimized coil placements based on the MNE map maxima and compared these placements with the initial hotspot placement. The MNE maps generally agreed well with the original motor maps: in the realistic head geometry, the distance from the MNE map maximum to the motor map center of gravity (CoG) was 8.8 ± 4.6 mm in the leg motor area and 6.6 ± 2.5 mm in the hand motor area. The head model did not have a significant effect on these distances; however, it had a significant effect on the distance between the MNE CoG and the motor map ( ). The optimized coil locations were < 1 cm from the initial hotspot in 7/10 subjects. Further research is required to determine the level of anatomical detail and the optimal mapping parameters required for robust and accurate localization.

Spatial extent of cortical motor hotspot in navigated transcranial magnetic stimulation.

BACKGROUND: Motor mapping with navigated transcranial magnetic stimulation (nTMS) requires defining a "hotspot", a stimulation site consistently producing the highest-amplitude motor-evoked potentials (MEPs). The exact location of the hotspot is difficult to determine, and the spatial extent of high-amplitude MEPs usually remains undefined due to MEP variability and the spread of the TMS-induced electric field (E-field). Therefore, here we aim to define the hotspot as a sub-region of a motor map. NEW METHOD: We analyzed MEP amplitude distributions in motor mappings of 30 healthy subjects in two orthogonal directions on the motor cortex. Based on the widths of these distributions, the hotspot extent was estimated as an elliptic area. In addition, E-field distributions induced by motor map edge stimulations were simulated for ten subjects, and the E-field attenuation was analyzed to obtain another estimate for hotspot extent. RESULTS: The median MEP-based hotspot area was 13 mm2 (95% confidence interval (CI) = [10, 18] mm2). The mean E-field-based hotspot area was 26 mm2 (95% CI = [13, 38] mm2). COMPARISON WITH EXISTING METHODS: In contrast to the conventional hotspot, the new definition considers its spatial extent, indicating the most easily excited area where subsequent nTMS stimuli should be targeted for maximal response. The E-field-based hotspot provides an estimate for the extent of cortical structures where the E-field is close to its maximum. CONCLUSIONS: The nTMS hotspot should be considered as an area rather than a single qualitatively defined spot due to MEP variability and E-field spread.

Paired-pulse navigated TMS is more effective than single-pulse navigated TMS for mapping upper extremity muscles in brain tumor patients.

OBJECTIVE: Single-pulse navigated transcranial magnetic stimulation (sp-nTMS) is used for presurgical motor mapping in patients with motor-eloquent lesions. However, recently introduced paired-pulse nTMS (pp-nTMS) with biphasic pulses could improve motor mapping. METHODS: Thirty-four patients (mean age: 56.0 ± 12.7 years, 53.0% high-grade glioma) with motor-eloquent lesions underwent motor mapping of upper extremity representations and nTMS-based tractography of the corticospinal tract (CST) by both sp-nTMS and pp-nTMS with biphasic pulses for the tumor-affected hemisphere before resection. RESULTS: In three patients (8.8%), conventional sp-nTMS did not provide motor-positive points, in contrast to pp-nTMS that was capable of generating motor maps in all patients. Good concordance between pp-nTMS and sp-nTMS in the spatial location of motor hotspots and center of gravity (CoG) as well as for CST tracking was observed, with pp-nTMS leading to similar motor map volumes (585.0 ± 667.8 vs. 586.8 ± 204.2 mm3, p = 0.9889) with considerably lower resting motor thresholds (35.0 ± 8.8 vs. 32.8 ± 7.6% of stimulator output, p = 0.0004). CONCLUSIONS: Pp-nTMS with biphasic pulses may provide motor maps even in highly demanding cases with tumor-affected motor structures or edema, using lower stimulation intensity compared to sp-nTMS. SIGNIFICANCE: Pp-nTMS with biphasic pulses could replace standardly used sp-nTMS for motor mapping and may be safer due to lower stimulation intensity.

Short-Interval Intracortical Facilitation Improves Efficacy in nTMS Motor Mapping of Lower Extremity Muscle Representations in Patients with Supra-Tentorial Brain Tumors.

Navigated transcranial magnetic stimulation (nTMS) is increasingly used for mapping of motor function prior to surgery in patients harboring motor-eloquent brain lesions. To date, single-pulse nTMS (sp-nTMS) has been predominantly used for this purpose, but novel paired-pulse nTMS (pp-nTMS) with biphasic pulse application has been made available recently. The purpose of this study was to systematically evaluate pp-nTMS with biphasic pulses in comparison to conventionally used sp-nTMS for preoperative motor mapping of lower extremity (lE) muscle representations. Thirty-nine patients (mean age: 56.3 ± 13.5 years, 69.2% males) harboring motor-eloquent brain lesions of different entity underwent motor mapping of lE muscle representations in lesion-affected hemispheres and nTMS-based tractography of the corticospinal tract (CST) using data from sp-nTMS and pp-nTMS with biphasic pulses, respectively. Compared to sp-nTMS, pp-nTMS enabled motor mapping with lower stimulation intensities (61.8 ± 13.8% versus 50.7 ± 11.6% of maximum stimulator output, p < 0.0001), and it provided reliable motor maps even in the most demanding cases where sp-nTMS failed (pp-nTMS was able to provide a motor map in five patients in whom sp-nTMS did not provide any motor-positive points, and pp-nTMS was the only modality to provide a motor map in one patient who also did not show motor-positive points during intraoperative stimulation). Fiber volumes of the tracked CST were slightly higher when motor maps of pp-nTMS were used, and CST tracking using pp-nTMS data was also possible in the five patients in whom sp-nTMS failed. In conclusion, application of pp-nTMS with biphasic pulses enables preoperative motor mapping of lE muscle representations even in the most challenging patients in whom the motor system is at high risk due to lesion location or resection.

Effect of inter-train interval on the induction of repetition suppression of motor-evoked potentials using transcranial magnetic stimulation.

Repetition suppression (RS) is evident as a weakened response to repeated stimuli after the initial response. RS has been demonstrated in motor-evoked potentials (MEPs) induced with transcranial magnetic stimulation (TMS). Here, we investigated the effect of inter-train interval (ITI) on the induction of RS of MEPs with the attempt to optimize the investigative protocols. Trains of TMS pulses, targeted to the primary motor cortex by neuronavigation, were applied at a stimulation intensity of 120% of the resting motor threshold. The stimulus trains included either four or twenty pulses with an inter-stimulus interval (ISI) of 1 s. The ITI was here defined as the interval between the last pulse in a train and the first pulse in the next train; the ITIs used here were 1, 3, 4, 6, 7, 12, and 17 s. RS was observed with all ITIs except with the ITI of 1 s, in which the ITI was equal to ISI. RS was more pronounced with longer ITIs. Shorter ITIs may not allow sufficient time for a return to baseline. RS may reflect a startle-like response to the first pulse of a train followed by habituation. Longer ITIs may allow more recovery time and in turn demonstrate greater RS. Our results indicate that RS can be studied with confidence at relatively short ITIs of 6 s and above.

Localization of cortical primary motor area of the hand using navigated transcranial magnetic stimulation, BOLD and arterial spin labeling fMRI.

BACKGROUND: Although the relationship between neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) has been widely studied in motor mapping, it is unknown how the motor response type or the choice of motor task affect this relationship. NEW METHOD: Centers of gravity (CoGs) and response maxima were measured with blood-oxygen-level dependent (BOLD) and arterial spin labeling (ASL) fMRI during motor tasks against nTMS CoGs and response maxima, which were mapped with motor evoked potentials (MEPs) and silent periods (SPs). RESULTS: No differences in motor representations (CoGs and response maxima) were observed in lateral-medial direction (p=0.265). fMRI methods localized the motor representation more posterior than nTMS (p<0.001). This was not affected by the BOLD fMRI motor task (p>0.999) nor nTMS response type (p>0.999). ASL fMRI maxima did not differ from the nTMS nor BOLD fMRI CoGs (p≥0.070), but the ASL CoG was deeper in comparison to other methods (p≤0.042). The BOLD fMRI motor task did not influence the depth of the motor representation (p≥0.745). The median Euclidean distances between the nTMS and fMRI motor representations varied between 7.7mm and 14.5mm and did not differ between the methods (F≤1.23, p≥0.318). COMPARISON WITH EXISTING METHODS: The relationship between fMRI and nTMS mapped excitatory (MEP) and inhibitory (SP) responses, and whether the choice of motor task affects this relationship, have not been studied before. CONCLUSIONS: The congruence between fMRI and nTMS is good. The choice of nTMS motor response type nor BOLD fMRI motor task had no effect on this relationship.

Onset Latency of Motor Evoked Potentials in Motor Cortical Mapping with Neuronavigated Transcranial Magnetic Stimulation.

Cortical motor mapping in pre-surgical applications can be performed using motor evoked potential (MEP) amplitudes evoked with neuronavigated transcranial magnetic stimulation. The MEP latency, which is a more stable parameter than the MEP amplitude, has not so far been utilized in motor mapping. The latency, however, may provide information about the stress in damaged motor pathways, e.g. compression by tumors, which cannot be observed from the MEP amplitudes. Thus, inclusion of this parameter could add valuable information to the presently used technique of MEP amplitude mapping. In this study, the functional cortical representations of first dorsal interosseous (FDI), abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles were mapped in both hemispheres of ten healthy righthanded volunteers. The cortical muscle representations were evaluated by the area and centre of gravity (CoG) by using MEP amplitudes and latencies. As expected, the latency and amplitude CoGs were congruent and were located in the centre of the maps but in a few subjects, instead of a single centre, several loci with short latencies were observed. In conclusion, MEP latencies may be useful in distinguishing the cortical representation areas with the most direct pathways from those pathways with prolonged latencies. However, the potential of latency mapping to identify stressed motor tract connections at the subcortical level will need to be verified in future studies with patients.

Input-Output Characteristics of Late Corticospinal Silent Period Induced by Transcranial Magnetic Stimulation.

PURPOSE: Corticospinal silent period (SP) may be interrupted by a burst of muscle activity followed by a second (late) SP, generally assumed to be a continuation from the primary SP. Our objective was to characterize the input-output behavior of the late SP. METHODS: Transcranial magnetic stimulation was applied on the cortical representation area of the right-hand muscles of 12 healthy subjects. Single-pulse transcranial magnetic stimulation was given with varying stimulation intensities normalized to the individual resting motor threshold (60% to 130% of the resting motor threshold) during voluntary muscle contraction. Electromyogram was recorded from first dorsal interosseous and abductor pollicis brevis muscles. Primary and late SPs were analyzed as absolute SPs, and input-output characteristics were assessed. RESULTS: The late SP exhibited fundamentally different input-output characteristics from that of the primary SP. The late SP most likely presented itself at stimulation intensities of 90% to 100% of the resting motor threshold. CONCLUSIONS: Different input-output characteristics of the late SP compared with the primary SP indicate that the late SP possess mechanisms different from the primary SP. The exact origin of the late SP remains unclear. Understanding the origins of the late SP could provide valuable insight on corticospinal inhibitory processes.