Nobuyuki Takeuchi

Wind-up is a nociceptive-specific phenomenon in which pain sensations are facilitated, in a frequency-dependent manner, by the repeated application of noxious stimuli of constant intensity, with invariant tactile sensations. Thus, cortical activities during wind-up could be an alteration associated with pain potentiation. We aimed to investigate somatosensory-evoked cortical responses and induced brain oscillations during wind-up by recording magnetoencephalograms. Wind-up was produced by the application of 11 consecutive electrical stimuli to the sural nerve, repeated at a frequency of 1 Hz without varying the intensity. The augmentation of flexion reflexes and pain rating scores were measured simultaneously as an index of wind-up. In the time-frequency analyses, the γ-band late event-related synchronization and the β-band event-related desynchronization were observed in the primary somatosensory region and the bilateral operculo-insular region, respectively. Repetitive exposure to the stimuli enhanced these activities, along with an increase in the flexion reflex magnitude. The evoked cortical activity reflected novelty, with no alteration to these repetitive stimuli. Observed oscillations enhanced by repetitive stimulation at a constant intensity could reflect a pain mechanism associated with wind-up.

Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains unclear whether the suppression comes from specific inhibitory mechanisms, refractoriness, or fatigue. In the present study, to investigate mechanisms of suppression induced by an auditory paired pulse paradigm in 19 healthy subjects, magnetoencephalography was employed. The control stimulus was a train of 25-ms pure tones of 65 dB SPL for 2500 ms. In order to evoke a test response, the sound pressure of two consecutive tones at 2200 ms in the control sound was increased to 80 dB (Test stimulus). Similar sound pressure changes were also inserted at 1000 (CS2) and 1600 (CS1) ms as conditioning stimuli. Four stimulus conditions were used; (1) Test alone, (2) Test + CS1, (3) Test + CS1 + CS2, and (4) Test + CS2, with the four sound stimuli randomly presented and cortical responses averaged at least 100 times for each condition. The baseline-to-peak and peak-to-peak amplitudes of the P50m, N100m, and P200m components of the test response were compared among the four conditions. In addition, the response to CS1 was compared between conditions (2) and (3). The results showed significant test response suppression by CS1. While the response to CS1 was significantly suppressed when CS2 was present, it did not affect suppression of the test response by CS1. It was thus suggested that the amplitude of the response to a conditioning stimulus is not a factor to determine the inhibitory effects of the test response, indicating that suppression is due to an external influence on the excitatory pathway.

Haptic memory briefly retains somatosensory information for later use; however, how and which cortical areas are affected by haptic memory remain unclear. We used change‐related cortical responses to investigate the relationship between the somatosensory cortex and haptic memory objectively. Electrical pulses, at 50 Hz with a duration of 500 ms, were randomly applied to the second, third, and fourth fingers of the right and left hands at an even probability every 800 ms. Each stimulus was labeled as D (preceded by a different side) or S (preceded by the same side). The D stimuli were further classified into 1D, 2D, and 3D, according to the number of different preceding stimuli. The S stimuli were similarly divided into 1S and 2S. The somatosensory‐evoked magnetic fields obtained were divided into four components via a dipole analysis, and each component's amplitudes were measured using the source strength waveform. The results showed that the preceding event did not affect the amplitude of the earliest 20–30 ms response in the primary somatosensory cortex. However, in the subsequent three components, the cortical activity amplitude was largest in 3D, followed by 2D, 1D, and S. These results indicate that such modulatory effects occurred somewhere in the somatosensory processing pathway higher than Brodmann's area 3b. To the best of our knowledge, this is the first study to demonstrate the existence of haptic memory for somatosensory laterality and its impact on the somatosensory cortex using change‐related cortical responses without contamination from peripheral effects.

We used auditory-evoked magnetic fields to investigate the properties of echoic memory. The sound stimulus was a repeated 1-ms click at 100 Hz for 500 ms, presented every 800 ms. The phase of the sound was shifted by inserting an interaural time delay of 0.49 ms to each side. Therefore, there were two sounds, lateralized to the left and right. According to the preceding sound, each sound was labeled as D (preceded by a different sound) or S (by the same sound). The D sounds were further grouped into 1D, 2D, and 3D, according to the number of preceding different sounds. The S sounds were similarly grouped to 1S and 2S. The results showed that the preceding event significantly affected the amplitude of the cortical response; although there was no difference between 1S and 2S, the amplitudes for D sounds were greater than those for S sounds. Most importantly, there was a significant amplitude difference between 1S and 1D. These results suggested that sensory memory was formed by a single sound, and was immediately replaced by new information. The constantly-updating nature of sensory memory is considered to enable it to act as a real-time monitor for new information.

Paired-pulse suppression refers to attenuation of neural activity in response to a second stimulus and has a pivotal role in inhibition of redundant sensory inputs. Previous studies have suggested that cortical responses to a somatosensory stimulus are modulated not only by a preceding same stimulus, but also by stimulus from a different submodality. Using magnetoencephalography, we examined somatosensory suppression induced by three different conditioning stimuli. The test stimulus was a train of electrical pulses to the dorsum of the left hand at 100 Hz lasting 1500 ms. For the pulse train, the intensity of the stimulus was abruptly increased at 1200 ms. Cortical responses to the abrupt intensity change were recorded and used as the test response. Conditioning stimuli were presented at 600 ms as pure tones, either innocuous or noxious electrical stimulation to the right foot. Four stimulus conditions were used: (1) Test alone, (2) Test + auditory stimulus, (3) Test + somatosensory stimulus, and (4) Test + nociceptive stimulus. Our results showed that the amplitude of the test response was significantly smaller for conditions (3) and (4) in the secondary somatosensory cortex contralateral (cSII) and ipsilateral (iSII) to the stimulated side as compared to the response to condition (1), whereas the amplitude of the response in the primary somatosensory cortex did not differ among the conditions. The auditory stimulus did not have effects on somatosensory change-related response. These findings show that somatosensory suppression was induced by not only a conditioning stimulus of the same somatosensory submodality and the same cutaneous site to the test stimulus, but also by that of a different submodality in a remote area.