Artifact correction and source analysis of early electroencephalographic responses evoked by transcranial magnetic stimulation over primary motor cortex.

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.

Excitation threshold of the motor cortex estimated with transcranial magnetic stimulation electroencephalography.

The excitation threshold of the human motor cortex was estimated on the basis of electroencephalographic responses evoked by transcranial magnetic stimulation. The hand area of the primary motor cortex was stimulated at 10 intensities, for seven healthy individuals. The four dominant peaks of the overall brain response could be reliably determined when stimulation was intense enough to induce a cortical electric field of approximately 33-44 mV/mm. This may be estimated as the threshold for evoking measurable brain activity by motor-cortex transcranial magnetic stimulation. The remarkably low threshold reflects the excellent sensitivity of the combination of transcranial magnetic stimulation and electroencephalography for the study of neuronal function of the cortex.

Spatial dynamics of population activities at S1 after median and ulnar nerve stimulation revisited: an MEG study.

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.

The novelty value of the combined use of electroencephalography and transcranial magnetic stimulation for neuroscience research.

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.

Prefrontal TMS produces smaller EEG responses than motor-cortex TMS: implications for rTMS treatment in depression.

RATIONALE: 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. METHODS: 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. RESULTS: 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<0.01) was found between GMFAs of motor- and prefrontal-cortex TMS across the experiments. However, when correlation between the responses of motor and prefrontal cortices was examined, significant positive correlations were found at 80 and 100% intensities only. CONCLUSIONS: This study provides further evidence that the prefrontal and motor cortices have different reactivity to TMS, but the MT may be used for determining the stimulus intensity of prefrontal rTMS treatment in depression, at least at motor threshold intensities or near to it.

Distinct differences in cortical reactivity of motor and prefrontal cortices to magnetic stimulation.

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.

The effect of stimulus intensity on brain responses evoked by transcranial magnetic stimulation.

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.

Ipsi- and contralateral EEG reactions to transcranial magnetic stimulation.

OBJECTIVES: Transcranial magnetic stimulation (TMS) and high-resolution electroencephalography (EEG) were used to study the spreading of cortical activation in 6 healthy volunteers. METHODS: Five locations in the left sensorimotor cortex (within 3cm(2)) were stimulated magnetically, while EEG was recorded with 60 scalp electrodes. A frameless stereotactic method was applied to determine the anatomic locus of stimulation and to superimpose the results on magnetic resonance images. Scalp potential and cortical current-density distributions were derived from averaged electroencephalographic (EEG) data. RESULTS: The maxima of the ipsilateral activation were detected at the gyrus precentralis, gyrus supramarginalis, and lobulus parietalis superior, depending on the subject. Activation over the contralateral cortex was observed in all subjects, appearing at 22plus minus2ms (range 17--28); the maxima were located at the gyrus precentralis, gyrus frontalis superior, and the lobulus parietalis inferior. Contralateral EEG waveforms showed consistent changes when different sites were stimulated: stimulation of the two most medial points evoked the smallest responses fronto-parietally. CONCLUSIONS: With the combination of TMS, EEG, and magnetic resonance imaging, an adequate spatiotemporal resolution may be achieved for tracing the intra- and interhemispheric spread of activation in the cortex caused by a magnetic pulse.