Somatosensory Evoked Spikes in Normal Adults Detected by Magnetoencephalography

Research Background and Motivation

Since 1949, clinical neurophysiology research has discovered that high-voltage cortical somatosensory evoked potentials (SEPs) can be detected in patients with reflex epilepsy, where seizures are triggered by somatosensory stimulation (Forster et al., 1949; Green, 1971). In 1971, contralateral parietal spikes were first detected in a child with behavioral disorders and named “somatosensory evoked spikes (SESs)” (De Marco, 1971). This phenomenon has since been reported in patients with various conditions, such as focal or generalized epilepsy syndromes, febrile convulsions, head trauma, headaches, etc. (Dalla Bernardina et al., 1991; De Marco, 1980; De Marco and Calzolari, 1999; Fonseca and Tedrus, 1994, 2000, 2012; Langill and Wong, 2003). However, SESs have only been detected in normal children under the age of 14, not observed in normal adults, leading to the belief that it is an age-dependent phenomenon that disappears as the central nervous system further matures (Fonseca and Tedrus, 2012; Langill and Wong, 2003).

Motivation of This Study

Previously, SESs were detected by magnetoencephalography (MEG) in three adult patients with epilepsy during spontaneous MEG measurements (Ishida et al., 2015). Hence, this study hypothesizes that MEG can detect SESs in normal adults, even though they may be invisible in scalp electroencephalography (EEG) due to the sensitivity limitations of EEG (Agari et al., 2021; Iwasaki et al., 2005; Kakisaka et al., 2017; Knake et al., 2006; Park et al., 2004, 2012; Zillgitt et al., 2022). This study, therefore, proceeds to explore whether MEG can detect SESs in normal adults.

Source of Study

This study was written by Makoto Ishida, Yosuke Kakisaka, Kazutaka Jin, Akitake Kanno, and Nobukazu Nakasato, all from the Department of Epilepsy, Tohoku University School of Medicine in Japan. The paper was published in the journal “Clinical Neurophysiology” and accepted in May 2024.

Research Process

1. Subjects

The study included 30 healthy adult volunteers, consisting of 20 males and 10 females, aged from 20 to 27 years (mean age 22.6 years). All subjects had not taken any medication before the experiment and had no sleep disorders or sleep deprivation. They were instructed not to consume caffeine within 12 hours before the experiment. The study was approved by the Ethics Committee of Tohoku University School of Medicine, and all participants signed informed consent forms, complying strictly with the guidelines of the Helsinki Declaration.

2. Research Method

2.1 MEG Recording and Median Nerve Stimulation

The study was conducted in a controlled magnetically shielded room, using a 200-channel whole-head MEG system. The system was equipped with a set of sensors, each being a first-order axial gradiometer with a 50 mm baseline length and a 15.5 mm coil diameter. The sensors were evenly distributed, with the head position determined by placing five fiducial marker coils on known positions on the scalp. The shape of the head and coil positions of each participant were determined using a three-dimensional digitizing device, based on three-dimensional magnetic resonance images (MRI) acquired using a 3 Tesla MRI system.

The study used a constant current stimulator for independent stimulation of the left and right median nerves at the wrist of the subjects. The stimulation parameters complied with the standards of the International Federation of Clinical Neurophysiology. The MEG data acquisition conditions for each subject were a sampling rate of 2000 Hz and a low-pass filter frequency of 500 Hz.

2.2 Detection and Analysis of SES and SEF

During standard spontaneous MEG recording, electrical stimulation was applied to the left and right median nerve independently for each subject for 10 minutes. SESs were identified by an experienced neurophysiologist as clearly visible single stimulus-locked evoked responses superimposed on the background brain activity. Data from 20 ms before to 100 ms after the stimulus for all subjects were averaged 398 times to analyze SEFs. The peak latencies of SES and SEFs, isofield maps, and equivalent current dipole (ECD) position information were compared and analyzed.

2.3 Statistical Analysis

All statistical analyses were conducted using GraphPad Prism 9 software. SEFs between the subjects with and without SES were compared using a two-sided Mann-Whitney U test, and gender differences were calculated using Fisher’s exact test. The significance level for statistical assumptions was set at p < 0.05.

Main Research Results

SES was detected in 10 out of 30 healthy adults (8 men and 2 women out of 20 men and 10 women, respectively), while the remaining 20 subjects did not show SES phenomena. No gender differences were observed. The occurrence rate of SES was 24.0% ± 15.0% (mean ± standard deviation). SESs consisted of one or two peaks, with the latency of the first peak consistent with the second peak (M2) latency of SEFs. The ECD of the first peak of SES was consistent in location and direction with the M2 isofield map. The ECD strength of the first peak of SES was significantly higher in subjects with SES (p < 0.0001) than in those without SES.

Figure 1 shows the comparison of SESs and SEFs detected by MEG in the same healthy adult subjects. The main peak of SES at 26.5 ms was consistent with the latency of the second SEFs peak (M2), and the isofield map pattern and ECD position and direction of the SES first peak were consistent with M2. The ECD strength of SES peaks was significantly greater in subjects with SES than in those without SES.

Research Discussion

The study found that 10 out of 30 normal adults exhibited bilateral SES through MEG research, whereas the other 20 subjects did not. The first peak of SES synchronized with the M2 of SEFs, showing consistency in latency, ECD position, and direction. The bilateral M2 ECD strength was significantly greater in subjects with SES compared to those without SES.

1. Discussion on the Age-Dependence of SES

Previous studies suggested that SESs were phenomena that only appeared in children. However, this study successfully detected SESs in one-third of 20-27-year-old adults using MEG. Since simultaneous parallel recordings of MEG and EEG were not conducted, no direct conclusion can be drawn that MEG sensitivity exceeds EEG in detecting SES. However, it is speculated that MEG has higher sensitivity, capable of detecting tangential components of somatosensory evoked responses surpassing spontaneous brain activity.

2. Advantages of MEG in Detecting Focal Cortical Activities

Consistent with many previous studies, this study further demonstrates the advantages of MEG in detecting focal cortical activities, though MEG cannot detect radial currents to the scalp (which can be detected by EEG). In this study, no unilateral SES phenomenon appeared in all subjects, suggesting that the detection of bilateral SES is an all-or-none phenomenon, directly related to the symmetrical SEFs and the signal-to-noise ratio of background brain activity.

In summary, this study first detected SES in normal adults through MEG. The results not only deepen the understanding of SES as a non-epileptic single unaveraged SEF phenomenon but also suggest the significant advantage of MEG in detecting cortical activities, laying the foundation for future applications in relevant brain function detection and diagnosis.

Research Significance

The important findings of this study include: - First evidence of somatosensory evoked spikes in adult cortical activity. - Highlighting the superiority of MEG in detecting cortical activities, aiding in integrating multiple neurophysiological detection methods for clinical diagnosis. - Providing new opportunities and directions for further research on adult brain activities and their potential pathological phenomena.

This study holds significant academic and clinical application value in the field of neurophysiology, helping to reveal more complex brain activity mechanisms and propelling further development in the field.