Juha Wilenius

Prefrontal transcranial magnetic stimulation produces intensity-dependent EEG responses in humans

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.

A novel approach for documenting naming errors induced by navigated transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is widely used both in basic research and in clinical practice. TMS has been utilized in studies of functional organization of speech in healthy volunteers. Navigated TMS (nTMS) allows preoperative mapping of the motor cortex for surgical planning. Recording behavioral responses to nTMS in the speech-related cortical network in a manner that allows off-line review of performance might increase utility of nTMS both for scientific and clinical purposes, e.g., for a careful preoperative planning. Four subjects participated in the study. The subjects named pictures of objects presented every 2-3s on a computer screen. One-second trains of 5 pulses were applied by nTMS 300ms after the presentation of pictures. The nTMS and stimulus presentation screens were cloned. A commercial digital camera was utilized to record the subjects performance and the screen clones. Delays between presentation, audio and video signals were eliminated by carefully tested combination of displays and camera. An experienced neuropsychologist studied the videos and classified the errors evoked by nTMS during the object naming. Complete anomias, semantic, phonological and performance errors were observed during nTMS of left fronto-parieto-temporal cortical regions. Several errors were detected only in the video classification. nTMS combined with synchronized video recording provides an accurate monitoring tool of behavioral TMS experiments. This experimental setup can be particularly useful for high-quality cognitive paradigms and for clinical purposes.

Alcohol Reduces Prefrontal Cortical Excitability in Humans: A Combined TMS and EEG Study

The effects of alcohol (0.8 g/kg) on the prefrontal cortex were studied in nine healthy subjects using the technique of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG). A total of 120 magnetic pulses were delivered with a figure-of-eight coil to the left prefrontal cortex at the rate of 0.4–0.7 Hz. The EEG was recorded simultaneously with 60 scalp electrodes (41 electrodes were used for analysis); the TMS-evoked activation was estimated by the area under the global mean field amplitude (GMFA) time curve. TMS caused changes in EEG activity lasting up to 270 ms poststimulus. Alcohol decreased GMFA at 30–270 ms poststimulus (713±303 vs 478±142 μV ms; p=0.007). Alcohol-induced differences were most pronounced at anterior electrodes. These results suggest that alcohol reduces the excitability in the prefrontal cortex.

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.

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

RationaleThe 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.MethodsMagnetic 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.ResultsGlobal mean-field amplitudes (GMFAs) reflecting overall cortical activity were significantly smaller after prefrontal- than after motor-cortex TMS. A significant positive correlation (rs=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.ConclusionsThis 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.

Effects of alcohol on TMS-evoked N100 responses.

TMS combined with simultaneous EEG is a novel brain imaging tool allowing investigation local excitability of human cortex. As alcohol acts through increasing function of A-type gamma-aminobutyric acid receptors and attenuating the function of glutaminergic NMDA-receptors-related excitation, we tested whether TMS-evoked N100 response which is thought to reflect cortical inhibitory processes, might be affected by alcohol. Ten healthy subjects ingested alcohol (0.8 g/kg) and EEG responses from 60 channels before and after alcohol ingestion were recorded after left motor-cortex stimulation. Alcohol almost abolished TMS-evoked N100 response. Control experiments with a piece of plastic placed between the head and coil to exclude auditory artefacts were conducted. Alcohol effects were similar when EEG responses from control experiments were subtracted from real-TMS. Alcohol-induced decrease was similar at ipsilateral, contralateral and frontal EEG sites suggesting that alcohol may change cortico-cortical connectivity of motor cortex. Alternative explanation is that alcohol has overall suppression effect on motor cortex. N100 may provide a useful marker of neural inhibition of human cortex for drug research.

Interictal MEG reveals focal cortical dysplasias: special focus on patients with no visible MRI lesions.

PURPOSE To investigate the value of interictal magnetoencephalography (MEG) in localizing epileptogenic cortex in epilepsy surgery patients with focal cortical dysplasias (FCD), particularly in patients having no visible MRI lesions. METHODS Thirty-four patients with FCD and preoperative MEG were retrospectively evaluated. Interictal MEG spike source localizations in respect to the resected area were studied using postoperative MR imaging. The possible predictive value of MEG-findings in respect to the clinical outcome was evaluated. Results from intracranial recordings were also compared with the MEG localizations. RESULTS Interictal MEG spikes were observed in all but one patient. 17 of the 34 (50%) patients became seizure free (Engel class I). In patients with MEG dipole clusters (n=20) and Engel class I or II (n=15) 49% of the source clusters were removed on the average; the corresponding value in patients with Engel class III or IV (n=5) was 5.5% (p=0.02). Seven (54%) of the 13 patients with an MRI-negative lesion achieved Engel class I; the outcomes did not differ from patients having a visible MRI lesion (n=21; p=0.82). The concordance between MEG localizations and the invasive studies was good in nine of the 13 patients with no visible MRI lesions CONCLUSION MEG is particularly useful in finding small FCDs not visible on MRI. A more complete removal of MEG source cluster area is associated with better clinical outcome These features make it a valuable tool in pre-surgical evaluation of patients with intractable focal-type epilepsy and normal MRI.

Sensitivity and specificity of seizure-onset zone estimation by ictal magnetoencephalography

Purpose:  Ictal video–electroencephalography (EEG) is commonly used to establish ictal onset‐zone location. Recently software development has enabled systematic studies of ictal magnetoencephalography (MEG). In this article, we evaluate the ability of ictal MEG signals to localize the seizure‐onset zone.

Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report

IntroductionNavigated transcranial magnetic stimulation (nTMS) is increasingly used for preoperative mapping of motor function, and clinical evidence for its benefit for brain tumor patients is accumulating. In respect to language mapping with repetitive nTMS, literature reports have yielded variable results, and it is currently not routinely performed for presurgical language localization. The aim of this project is to define a common protocol for nTMS motor and language mapping to standardize its neurosurgical application and increase its clinical value.MethodsThe nTMS workshop group, consisting of highly experienced nTMS users with experience of more than 1500 preoperative nTMS examinations, met in Helsinki in January 2016 for thorough discussions of current evidence and personal experiences with the goal to recommend a standardized protocol for neurosurgical applications.ResultsnTMS motor mapping is a reliable and clinically validated tool to identify functional areas belonging to both normal and lesioned primary motor cortex. In contrast, this is less clear for language-eloquent cortical areas identified by nTMS. The user group agreed on a core protocol, which enables comparison of results between centers and has an excellent safety profile. Recommendations for nTMS motor and language mapping protocols and their optimal clinical integration are presented here.ConclusionAt present, the expert panel recommends nTMS motor mapping in routine neurosurgical practice, as it has a sufficient level of evidence supporting its reliability. The panel recommends that nTMS language mapping be used in the framework of clinical studies to continue refinement of its protocol and increase reliability.

Quantifying the contribution of video in combined video-magnetoencephalographic ictal recordings of epilepsy patients

INTRODUCTION Magnetoencephalography (MEG) measures magnetic fields generated by neuronal currents. MEG is complementary to EEG. Considerable body of evidence indicates that ictal MEG recordings can provide useful information for pre-surgical evaluation of epilepsy patients alongside the more established long-term ictal video-EEG. Ictal MEG is recorded in some epilepsy surgery centers. However, a wider adoption of ictal MEG is hampered by lack of tools for synchronized video-MEG recording similar to those of video-EEG. METHODS We have augmented MEG with a synchronized behavioral video-recording system. To estimate its additional value in ictal recordings, we retrospectively analyzed recordings of 10 epilepsy patients with and without the video. RESULTS In six patients out of ten, adding the video substantially changed the resulting interpretations. In all six cases the effect was considerable: the number of detected seizures changed by more than 50%. CONCLUSIONS Synchronized video and audio recording capabilities are important for effective ictal MEG recordings of epilepsy patients.