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Analyzing the brain responses to transcranial magnetic stimulation (TMS) using electroencephalography (EEG) is a promising method for the assessment of functional cortical connectivity and excitability of areas accessible to this stimulation. However, until now it has been difficult to analyze the EEG responses during the several tens of milliseconds immediately following the stimulus due to TMS-induced artifacts. In the present study we show that by combining a specially adapted recording system with software artifact correction it is possible to remove a major part of the artifact and analyze the cortical responses as early as 10 ms after TMS. We used this methodology to examine responses of left and right primary motor cortex (M1) to TMS at different intensities. Based on the artifact-corrected data we propose a model for the cortical activation following M1 stimulation. The model revealed the same basic response sequence for both hemispheres. A large part of the response could be accounted for by two sources: a source close to the stimulation site (peaking approximately 15 ms after the stimulus) and a midline frontal source ipsilateral to the stimulus (peaking approximately 25 ms). In addition the model suggests responses in ipsilateral temporo-parietal junction areas (approximately 35 ms) and ipsilateral (approximately 30 ms) and middle (approximately 50 ms) cerebellum. Statistical analysis revealed significant dependence on stimulation intensity for the ipsilateral midline frontal source. The methodology developed in the present study paves the way for the detailed study of early responses to TMS in a wide variety of brain areas.

The excitation threshold of the human motor cortex (M1) was estimated on the basis of electroencephalographic (EEG) responses evoked by transcranial magnetic stimulation (TMS). The hand area of M1 (n = 7) was stimulated at ten intensities. The four dominant peaks of the overall brain response were reliably determined when stimulation intensity was  40% of the motor threshold, the probability of identifying each peak ranging between 0.71 and 0.86. Therefore, the cortical electric field of 33–44 mV/mm, approximately being induced with this intensity, may be estimated as the threshold for evoking measurable brain activity by motor-cortex TMS. As TMS–EEG enables the assessment of cortical reactivity with excellent sensitivity, it seems justified to move over to lower stimulation intensities, for increased safety.

In a number of studies, magnetoencephalography (MEG) has been successfully employed in localizing cortical neural population activities after stimulation of peripheral nerves. Little attention has been paid, however, to the spatiotemporal dynamics of these activations within the primary somatosensory cortex (SI). Here we report on the activation sequence at the right SI after left median and ulnar nerve stimulation. The results show that at least three macroscopically separable sources within or near SI are activated within 100 ms after the stimulus, corresponding to the somatosensory evoked field (SEF) deflections N20m, P35m and P60m. As P60m was localized significantly more posteriorly and also tended to be deeper than the two earlier deflections, its underlying source may be more extensive than during N20m and P35m, and it may get contribution from the postcentral gyrus and sulcus, possibly Brodmann areas 1 and 2. The source separation between the neural populations activated by the 2 nerves was 12 mm during N20m, 6 mm during P35m and 4 mm during P60m. Thus, at longer latencies, the centers of gravity of the activations were closer to each other for the 2 nerves. We argue that this reflects spreading of the activation with time from the site of initial excitation to encompass larger and more overlapping neural populations at longer latencies.

Electroencephalographic (EEG) responses measured simultaneously with transcranial magnetic stimulation (TMS) have opened a new window into the human nervous system. The combined use of TMS and EEG (TMS-EEG) provides a means for the detailed study of the reactivity of any cortical region in the intact brain; also the reactivities of non-motor cortical areas related with higher-order functions are now appreciable. A recent epochal finding concerning cortical reactivity is that neuronal activation is induced with remarkably low stimulation intensities. This knowledge is significant when optimizing experimental set-ups for maximal patient safety. Stimulation of different cortical areas evokes different patterns of remote EEG activity, confirming the viability of TMS-EEG for the study of corticocortical connections. In this review, we expand on these and other notable findings related with TMS-EEG. We discuss the possibilities of the technique for the study of cortical reactivity and connectivity. We show that TMS-EEG allows the study of interhemispheric connections with high spatiotemporal specificity and the assessment of cortical reactivity with excellent sensitivity.

To better understand the neuronal effects of transcranial magnetic stimulation (TMS), we studied how the TMS-evoked brain responses depend on stimulation intensity. We measured electroencephalographic (EEG) responses to motor-cortex TMS, estimated the intensity dependence of the overall brain response, and compared it to a theoretical model for the intensity dependence of the TMS-evoked neuronal activity. Left and right motor cortices of seven volunteers were stimulated at intensities of 60, 80, 100, and 120% of the motor threshold (MT). A figure-of-eight coil (diameter of each loop 4 cm) was used for focal stimulation. EEG was recorded with 60 scalp electrodes. The intensity of 60% of MT was sufficient to produce a distinct global mean field amplitude (GMFA) waveform in all subjects. The GMFA, reflecting the overall brain response, was composed of four peaks, appearing at 15 +/- 5 msec (Peak I), 44 +/- 10 msec (II), 102 +/- 18 msec (III), and 185 +/- 13 msec (IV). The peak amplitudes depended nonlinearly on intensity. This nonlinearity was most pronounced for Peaks I and II, whose amplitudes appeared to sample the initial part of the sigmoid-shaped curve modeling the strength of TMS-evoked neuronal activity. Although the response amplitude increased with stimulus intensity, scalp distributions of the potential were relatively similar for the four intensities. The results imply that TMS is able to evoke measurable brain activity at low stimulus intensities, probably significantly below 60% of MT. The shape of the response-stimulus intensity curve may be an indicator of the activation state of the brain.

Invasive cortical mapping is conventionally required for preoperative identification of epileptogenic and eloquent cortical regions before epilepsy surgery. The decision on the extent and exact location of the resection is always demanding and multimodal approach is desired for added certainty. The present study describes two non-invasive preoperative protocols, used in addition to the normal preoperative work-up for localization of the epileptogenic and sensorimotor cortical regions, in two young patients with epilepsy. Magnetoencephalography (MEG) was used to determine the primary somatosensory cortex (S1) and the ictal onset zones. Navigated transcranial magnetic stimulation (nTMS) was used to determine the location and the extent of the primary motor representation areas. The localization results from these non-invasive methods were used for guiding the subdural grid deployment and later compared with the results from electrical cortical stimulation (ECS) via subdural grids, and validated by surgery outcome. The results from MEG and nTMS localizations were consistent with the ECS results and provided improved spatial precision. Consistent results of our study suggest that these non-invasive methods can be added to the standard preoperative work-up and may even hold a potential to replace the ECS in a subgroup of patients with epilepsy who have the suspected epileptogenic zone near the sensorimotor cortex and seizures frequent enough for ictal MEG.

The stimulus intensity of prefrontal repetitive transcranial magnetic stimulation (rTMS) during depression treatment is usually determined by adjusting it with respect to the motor threshold (MT). There is some evidence that reactivity of the prefrontal cortex to transcranial magnetic stimulation (TMS) is lower than that of the motor cortex at MT stimulation. However, it is unknown whether this is true when other stimulus intensities are used. We investigated whether the magnitude and shape of the overall TMS-evoked electroencephalographic (EEG) responses differ between prefrontal and motor cortices. Magnetic pulses to the left motor and prefrontal cortices (the middle frontal gyrus identified from magnetic resonance images) were delivered at four intensities (60, 80, 100, and 120% of MT of the right abductor digiti minimi muscle) for six subjects. Simultaneously, EEG was recorded with 60 scalp electrodes. Global mean-field amplitudes (GMFAs) reflecting overall cortical activity were significantly smaller after prefrontal- than after motor-cortex TMS. A significant positive correlation (r s=0.84, p

The reactivity of the prefrontal cortex (PFC) was studied by measuring electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS) with different stimulus intensities. Focal TMS at intensities of 60%, 80%, 100%, and 120% of the motor threshold was delivered to the left middle frontal gyrus identified individually from magnetic resonance images (MRI) in seven healthy subjects. EEG was simultaneously recorded with 60 scalp electrodes. Stimulation evoked clear responses at all intensities. Left prefrontal TMS evoked an averaged EEG response consisting of five deflections at 27 ± 3 ms (peak I), 39 ± 3 ms (II), 52 ± 7 ms (III), 105 ± 14 ms (IV), and 193 ± 15 ms (V) at the Fz/FCz electrodes. The slope of the almost linear dependence of the overall response on stimulus intensity varied with latency. Potential distributions were relatively similar for the four intensities, suggesting that the same cortical structures may be activated. Intensity dependence function to TMS may be an indicator of cortical activation in humans.

Objective: Dipole models, which are frequently used in attempts to solve the electromagnetic inverse problem, require explicit a priori assumptions about the cerebral current sources. This is not the case for solutions based on minimum-norm estimates. In the present study, we evaluated the spatial accuracy of the L2 minimum-norm estimate (MNE) in realistic noise conditions by assessing its ability to localize sources of evoked responses at the primary somatosensory cortex (SI). Methods: Multichannel somatosensory evoked potentials (SEPs) and magnetic fields (SEFs) were recorded in 5 subjects while stimulating the median and ulnar nerves at the left wrist. A Tikhonov-regularized L2-MNE, constructed on a spherical surface from the SEP signals, was compared with an equivalent current dipole (ECD) solution obtained from the SEFs. Results: Primarily tangential current sources accounted for both SEP and SEF distributions at around 20 ms (N20/N20m) and 70 ms (P70/P70m), which deflections were chosen for comparative analysis. The distances between the locations of the maximum current densities obtained from MNE and the locations of ECDs were on the average 12 ‐ 13 mm for both deflections and nerves stimulated. In accordance with the somatotopical order of SI, both the MNE and ECD tended to localize median nerve activation more laterally than ulnar nerve activation for the N20/N20m deflection. Simulation experiments further indicated that, with a proper estimate of the source depth and with a good fit of the head model, the MNE can reach a mean accuracy of 5 mm in 0.2-mV root-mean-square noise. Conclusions: When compared with previously reported localizations based on dipole modelling of SEPs, it appears that equally accurate localization of S1 can be obtained with the MNE. Significance: MNE can be used to verify parametric source modelling results. Having a relatively good localization accuracy and requiring minimal assumptions, the MNE may be useful for the localization of poorly known activity distributions and for tracking activity changes between brain areas as a function of time. q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Objective : The stimulus intensity of prefrontal transcranial magnetic stimulation (TMS) is usually determined with respect to the motor threshold (MT). However, the association between the excitability of the prefrontal and motor cortices is unknown. Methods : Magnetic pulses to the left motor and prefrontal cortices were delivered at the MT of the right abductor digiti minimi muscle for 9 subjects and at 4 different stimulus intensities (60, 80, 100, and 120% of MT) for two subjects. Simultaneously, EEG was recorded with 60 scalp electrodes. Results : Global mean field amplitudes of the TMS-evoked responses were significantly (32%) smaller after prefrontal than after motor cortex TMS, but they correlated positively. Conclusions : The reactivity to TMS is different between the motor and prefrontal cortices. However, an association between these reactivities suggests that MT may be used for determining the stimulus intensity of prefrontal TMS.