Target Site of Prepulse Inhibition of the Trigeminal Blink Reflex in Humans.

Despite the clinical significance of prepulse inhibition (PPI), the mechanisms are not well understood. Herein, we present our investigation of PPI in the R1 component of electrically induced blink reflexes. The effect of a prepulse was explored with varying prepulse test intervals (PTIs) of 20-600 ms in 4 females and 12 males. Prepulse-test combinations included the following: stimulation of the supraorbital nerve (SON)-SON [Experiment (Exp) 1], sound-sound (Exp 2), the axon of the facial nerve-SON (Exp 3), sound-SON (Exp 4), and SON-SON with a long trial-trial interval (Exp 5). Results showed that (1) leading weak SON stimulation reduced SON-induced ipsilateral R1 with a maximum effect at a PTI of 140 ms, (2) the sound-sound paradigm resulted in a U-shaped inhibition time course of the auditory startle reflex (ASR) peaking at 140 ms PTI, (3) facial nerve stimulation showed only a weak effect on R1, (4) a weak sound prepulse facilitated R1 but strongly inhibited SON-induced late blink reflexes (LateRs) with a similar U-shaped curve, and (5) LateR in Exp 5 was almost completely absent at PTIs >80 ms. These results indicate that the principal sensory nucleus is responsible for R1 PPI. Inhibition of ASR or LateR occurs at a point in the startle reflex circuit where auditory and somatosensory signals converge. Although the two inhibitions are different in location, their similar time courses suggest similar neural mechanisms. As R1 has a simple circuit and is stable, R1 PPI helps to clarify PPI mechanisms.SIGNIFICANCE STATEMENT Prepulse inhibition (PPI) is a phenomenon in which the startle response induced by a startle stimulus is suppressed by a preceding nonstartle stimulus. This study demonstrated that the R1 component of the trigeminal blink reflex shows clear PPI despite R1 generation within a circuit consisting of the trigeminal and facial nuclei, without startle reflex circuit involvement. Thus, PPI is not specific to the startle reflex. In addition, PPI of R1, the auditory startle reflex, and the trigeminal late blink reflex showed similar time courses in response to the prepulse test interval, suggesting similar mechanisms regardless of inhibition site. R1 PPI, in conjunction with other paradigms with different prepulse-test combinations, would increase understanding of the underlying mechanisms.

Mechanisms of Short- and Long-Latency Sensory Suppression: Magnetoencephalography Study.

Prepulse inhibition (PPI) is sensory suppression whose mechanism (i.e., whether PPI originates from specific inhibitory mechanisms) remains unclear. In this study, we applied the combination of short-latency PPI and long-latency paired pulse suppression in 17 healthy subjects using magnetoencephalography to investigate the mechanisms of sensory suppression. Repeats of a 25-ms pure tone without a blank at 800 Hz and 70 dB were used for a total duration of 1600 ms. To elicit change-related cortical responses, the sound pressure of two consecutive tones in this series at 1300 ms was increased to 80 dB (Test). For the conditioning stimuli, the sound pressure was increased to 73 dB at 1250 ms (Pre 1) and 80 dB at 700 ms (Pre 2). Six stimuli were randomly presented as follows: (1) Test alone, (2) Pre 1 alone, (3) Pre 1 + Test, (4) Pre 2 + Test, (5) Pre 2 + Pre 1, and (6) Pre 2 + Pre 1 + Test. The inhibitory effects of the conditioning stimuli were evaluated using N100m/P200m components. The results showed that both Pre 1 and Pre 2 significantly suppressed the Test response. Moreover, the inhibitory effects of Pre 1 and Pre 2 were additive. However, when both prepulses were present, Pre 2 significantly suppressed the Pre 1 response, suggesting that the Pre 1 response amplitude was not a determining factor for the degree of suppression. These results suggested that the suppression originated from a specific inhibitory circuit independent of the excitatory pathway.

Relationship of loudness-dependent auditory evoked potentials with change-related cortical responses.

Previous studies have suggested that change-related cortical responses are phenomena similar to the onset response and could be applied to the loudness dependence of auditory evoked potential (LDAEP) paradigm. In the present study, we examined the relationship between LDAEP and the change-related response using electroencephalography findings in 50 healthy subjects. There were five conditions (55, 65, 75, 85, and 95 dB) for LDAEP and five similar conditions (abrupt sound pressure increase from 70 to 75, 80, 85, 90, and 95 dB) for the change-related response. Both the onset and abrupt sound pressure increase evoked a triphasic response with peaks at approximately 50 (P50), 100 (N100), and 200 (P200) ms. We calculated the peak-to-peak amplitudes for P50/N100 and N100/P200. Medians and slopes for P50/N100 and N100/P200 amplitudes were calculated and compared between the two measures. Results revealed a significant correlation for both the slope and median for P50/N100 (r = 0.36, 0.37, p = 1.0 × 10-2, 7.9 × 10-3), N100/P200 (r = 0.40, 0.34, p = 4.0 × 10-3, 1.6 × 10-2), and P50/N100/P200 (r = 0.36, 0.35, p = 1.0 × 10-2, 1.3 × 10-2). These results suggested that the change-related response and LDAEP shared generation mechanisms at least partially.

Mechanisms of Long-Latency Paired Pulse Suppression: MEG Study.

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.

Suppression of Low-Frequency Gamma Oscillations by Activation of 40-Hz Oscillation.

Gamma oscillations have received considerable attention owing to their association with cognitive function and various neuropsychiatric disorders. However, interactions of gamma oscillations at different frequency bands in humans remain unclear. In the present magnetoencephalographic study, brain oscillations in a wide frequency range were examined using a time-frequency analysis during the 20-, 30-, 40-, and 50-Hz auditory stimuli in 21 healthy subjects. First, dipoles for auditory steady-state response (ASSR) were estimated and interaction among oscillations at 10-60 Hz was examined using the source strength waveforms. Results showed the suppression of ongoing low-gamma oscillations at approximately 30 Hz during stimulation at 40 Hz. Second, multi-dipole analyses suggested that the main dipole for ASSR and dipoles for suppressed low-frequency gamma oscillations were distinct. Third, an all-sensor analysis was performed to clarify the distribution of the 40-Hz ASSR and suppression of low-frequency gamma oscillations. Notably, the area of suppression surrounded the center of the 40-Hz ASSR and showed a trend of extending to the vertex, indicating that different groups of neurons were responsible for these two gamma oscillations and that the 40-Hz oscillation circuit have specific inhibitory innervation to the low-gamma circuit.

Conditioned Pain Modulation: Comparison of the Effects on Nociceptive and Non-nociceptive Blink Reflex.

Although conditioned pain modulation (CPM) is considered to represent descending pain inhibitory mechanisms triggered by noxious stimuli applied to a remote area, there have been no previous studies comparing CPM between pain and tactile systems. In this study, we compared CPM between the two systems objectively using blink reflexes. Intra-epidermal electrical stimulation (IES) and transcutaneous electrical stimulation (TS) were applied to the right skin area over the supraorbital foramen to evoke a nociceptive or a non-nociceptive blink reflex, respectively, in 15 healthy males. In the test session, IES or TS were applied six times and subjects reported the intensity of each stimulus on a numerical rating scale (NRS). Blink reflexes were measured using electromyography (R2). The first and second sessions were control sessions, while in the third session, the left hand was immersed in cold water at 10 °C as a conditioning stimulus. The magnitude of the R2 blink and NRS scores were compared among the sessions by 2-way ANOVA. Both the NRS score and nociceptive R2 were significantly decreased in the third session for IES, with a significant correlation between the two variables; whereas, TS-induced non-nociceptive R2 did not change among the sessions. Although the conditioning stimulus decreased the NRS score for TS, the CPM effect was significantly smaller than that for IES (p = 0.002). The present findings suggest the presence of a pain-specific CPM effect to a heterotopic noxious stimulus.

Synaptic Effect of Aδ-Fibers by Pulse-Train Electrical Stimulation.

Electrical stimulation of specific small fibers (Aδ- and C-fibers) is used in basic studies on nociception and neuropathic pain and to diagnose neuropathies. For selective stimulation of small fibers, the optimal stimulation waveform parameters are an important aspect together with the study of electrode design. However, determining an optimal stimulation condition is challenging, as it requires the characterization of the response of the small fibers to electrical stimulation. The perception thresholds are generally characterized using single-pulse stimulation based on the strength-duration curve. However, this does not account for the temporal effects of the different waveforms used in practical applications. In this study, we designed an experiment to characterize the effects of multiple pulse stimulation and proposed a computational model that considers electrostimulation of fibers and synaptic effects in a multiscale model. The measurements of perception thresholds showed that the pulse dependency of the threshold was an exponential decay with a maximum reduction of 55%. In addition, the frequency dependence of the threshold showed a U-shaped response with a reduction of 25% at 30 Hz. Moreover, the computational model explained the synaptic effects, which were also confirmed by evoked potential recordings. This study further characterized the activation of small fibers and clarified the synaptic effects, demonstrating the importance of waveform selection.

Test-retest reliability of paired pulse suppression paradigm using auditory change-related response.

BACKGROUND: Sensory suppression is an important brain function for appropriate processing of information and is known to be impaired in patients with various types of mental illness. Long latency suppression which is a paradigm using change-related cortical response with repeated paired pulses embedded in a train of conditioning pulses is a factor used to measure sensory suppression. NEW METHOD: The present study assessed the test-retest reliability of long-latency suppression in latency, amplitude, and suppression rate of the P50, N100, and P200 components of auditory evoked potentials in 35 healthy adults. The sound stimulus was repeats of a 25-ms pure tone at 65 dB and 2000 ms in total duration, during which the sound pressure level was increased to 80 dB twice at 1100 ms and 1700 ms. Measurements were performed twice and the validity of the findings was evaluated using intra-class correlations. RESULTS: The results showed high intra-class correlation (ICC) values (>0.7) for the amplitude of all components, except for P50 (0.44), while latency also showed high ICC values (>0.66), except for P50 (0.20). In addition, the suppression rate showed good reproducibility for the N100-P200 component (0.60). COMPARISON WITH EXISTING METHOD: The method can be performed with a short inspection time of approximately 5 min and provides high ICC values. In addition, it may reflect suppression mechanisms different from those relating to existing methods. CONCLUSION: These results support the use of long latency suppression as a biomarker in clinical settings.

Weaker prepulse exerts stronger suppression of a change-detecting neural circuit.

Change-N1 peaking 90-180 ms after changes in a sound feature of a continuous sound is clearly attenuated by a preceding change stimulus (called a "prepulse"). Here, we investigated the effects of a preceding decrease in sound pressure on the degree of inhibition of the subsequent Change-N1 amplitude. Using 100-Hz click train sounds, we obtained Change-N1s from 11 healthy volunteers. The two types of test stimuli were an abrupt 10-dB increase from the baseline (70 dB) and the insertion of a 0.45-ms inter-aural time difference in the middle of the sound. Three consecutive clicks at 30, 40, and 50 ms before the change onset that was used as a prepulse were weaker than the background by 5 or 10 dB. The Change-N1 elicited by the two test stimuli was attenuated more strongly by the weaker prepulse, which was not congruent with the theory that the inhibition of the subsequent sensory/sensory-motor processing depends on the sound pressure level of a prepulse. These results suggest that a change in any type of sound feature elicits a change-related response that is inhibited by any type of preceding change stimulus, which reflects auto-inhibition of the change-responding circuit.

Test-retest reliability of prepulse inhibition paradigm using auditory evoked potentials.

Prepulse inhibition (PPI) is a neurological phenomenon in which a weak initial stimulus reduces the level of responses to a subsequent stronger stimulus. Although acoustic startle reflexes are usually used for PPI examinations, recent studies have observed similar phenomena with event-related cortical potentials. In the present study, test-retest reliability of PPI measured using auditory change-related cortical responses was assessed in 35 healthy adults. Four sound stimuli were randomly presented at an even probability; Standard, Test alone, Prepulse alone, and Test + Prepulse. The Standard stimulus was a train of 25-ms tone pulses at 70 dB for 650 ms, while for Test alone and Prepulse alone, the sound pressure was increased to 80 dB at 350 ms and 73 dB at 300 ms, respectively. Measurements were performed twice with at least 7 days separation, and validity was evaluated using intra-class correlation (ICC) for latency, amplitude, and suppression rate of the P50, N100, and P200 components. The results showed high ICC values for the latency and amplitude of nearly all components, except for response to Prepulse alone (0.3-0.6). Furthermore, ICC for suppression rate was greater than 0.5 for the peak-to-peak amplitude. Good reproducibility for N100 and P200 components was obtained with this method. The present results support the PPI paradigm as a reliable tool for clinical measurements of inhibitory functions.

Electrical Characterisation of Aδ-Fibres Based on Human in vivo Electrostimulation Threshold.

Electrical stimulation of small fibres is gaining attention in the diagnosis of peripheral neuropathies, such as diabetes mellitus, and pain research. However, it is still challenging to characterise the electrical characteristics of axons in small fibres (Aδ and C fibres). In particular, in vitro measurement for human Aδ-fibre is difficult due to the presence of myelin and ethical reason. In this study, we investigate the in vivo electrical characteristics of the human Aδ-fibre to derive strength-duration (S-D) curves from the measurement. The Aδ-fibres are stimulated using coaxial planar electrodes with intraepidermal needle tip. For human volunteer experiments, the S-D curve of Aδ-fibre is obtained in terms of injected electrical current. With the computational analysis, the standard deviation of the S-D curve is mostly attributed to the thickness of the stratum corneum and depth of the needle tip, in addition to the fibre thickness. Then, we derive electrical parameters of the axon in the Aδ-fibre based on a conventional fibre model. The parameters derived here would be important in exploring the optimal stimulation condition of Aδ-fibres.

Effect of acceleration of auditory inputs on the primary somatosensory cortex in humans.

Cross-modal interaction occurs during the early stages of processing in the sensory cortex; however, its effect on neuronal activity speed remains unclear. We used magnetoencephalography to investigate whether auditory stimulation influences the initial cortical activity in the primary somatosensory cortex. A 25-ms pure tone was randomly presented to the left or right side of healthy volunteers at 1000 ms when electrical pulses were applied to the left or right median nerve at 20 Hz for 1500 ms because we did not observe any cross-modal effect elicited by a single pulse. The latency of N20 m originating from Brodmann's area 3b was measured for each pulse. The auditory stimulation significantly shortened the N20 m latency at 1050 and 1100 ms. This reduction in N20 m latency was identical for the ipsilateral and contralateral sounds for both latency points. Therefore, somatosensory-auditory interaction, such as input to the area 3b from the thalamus, occurred during the early stages of synaptic transmission. Auditory information that converged on the somatosensory system was considered to have arisen from the early stages of the feedforward pathway. Acceleration of information processing through the cross-modal interaction seemed to be partly due to faster processing in the sensory cortex.

Long-latency suppression of auditory and somatosensory change-related cortical responses.

Sensory suppression is a mechanism that attenuates selective information. As for long-latency suppression in auditory and somatosensory systems, paired-pulse suppression, observed as 2 identical stimuli spaced by approximately 500 ms, is widely known, though its mechanism remains to be elucidated. In the present study, we investigated the relationship between auditory and somatosensory long-latency suppression of change-related cortical responses using magnetoencephalography. Somatosensory change-related responses were evoked by an abrupt increase in stimulus strength in a train of current-constant square wave pulses at 100 Hz to the left median nerve at the wrist. Furthermore, auditory change-related responses were elicited by an increase in sound pressure by 15 dB in a continuous sound composed of a train of 25-ms pure tones. Binaural stimulation was used in Experiment 1, while monaural stimulation was used in Experiment 2. For both somatosensory and auditory stimuli, the conditioning and test stimuli were identical, and inserted at 2400 and 3000 ms, respectively. The results showed clear suppression of the test response in the bilateral parisylvian region, but not in the postcentral gyrus of the contralateral hemisphere in the somatosensory system. Similarly, the test response in the bilateral supratemporal plane (N100m) was suppressed in the auditory system. Furthermore, there was a significant correlation between suppression of right N100m and right parisylvian activity, suggesting that similar mechanisms are involved in both. Finally, a high test-retest reliability for suppression was seen with both modalities. Suppression revealed in the present study is considered to reflect sensory inhibition ability in individual subjects.

Prepulse Inhibition of the Auditory Off-Response: A Magnetoencephalographic Study.

A weak preceding sound stimulus attenuates the startle response evoked by an intense sound stimulus. Like startle reflexes, change-related auditory responses are suppressed by a weak leading stimulus (ie, a prepulse). We aim to examine whether a prepulse inhibits cerebral responses to the sound offset and how the prepulse magnitude affects the degree of the prepulse inhibition (PPI). Using magnetoencephalography, we recorded the Off-P50m elicited by an offset of a train sound of 100-Hz clicks in 12 healthy subjects. A single click slightly louder (+1.5, +3, or +5 dB) than the background sound of 80 dB was inserted 50 ms before the sound offset as a prepulse. We performed a dipole source analysis of the Off-P50m, and we measured its latency and amplitude using the source strength waveforms. The origin of the Off-P50m was estimated to be the auditory cortex on both hemispheres. The Off-P50m was clearly attenuated by the prepulses, and the degree of PPI was greater with a louder prepulse. The Off-P50m is considered to be a simple change-related response, which does not overlap with a processing of incoming sounds. Thus, the Off-P50m and its PPI comprise a valuable tool for investigating the neural inhibitory system.

New paradigm for auditory paired pulse suppression.

Sensory gating is a mechanism of sensory processing used to prevent an overflow of irrelevant information, with some indexes, such as prepulse inhibition (PPI) and P50 suppression, often utilized for its evaluation. In addition, those are clinically important for diseases such as schizophrenia. In the present study, we investigated long-latency paired-pulse suppression of change-related cortical responses using magnetoencephalography. The test change-related response was evoked by an abrupt increase in sound pressure by 15 dB in a continuous sound composed of a train of 25-ms pure tones at 65 dB. By inserting a leading change stimulus (prepulse), we observed suppression of the test response. In Experiment 1, we examined the effects of conditioning-test intervals (CTI) using a 25-ms pure tone at 80 dB as both the test and prepulse. Our results showed clear suppression of the test response peaking at a CTI of 600 ms, while maximum inhibition was approximately 30%. In Experiment 2, the effects of sound pressure on prepulse were examined by inserting prepulses 600 ms prior to the test stimulus. We found that a paired-pulse suppression greater than 25% was obtained by prepulses larger than 77 dB, i.e., 12 dB louder than the background, suggesting that long latency suppression requires a relatively strong prepulse to obtain adequate suppression, different than short-latency paired-pulse suppression reported in previous studies. In Experiment 3, we confirmed similar levels of suppression using electroencephalography. These results suggested that two identical change stimuli spaced by 600 ms were appropriate for observing the long-latency inhibition. The present method requires only a short inspection time and is non-invasive.

Why intra-epidermal electrical stimulation achieves stimulation of small fibres selectively: a simulation study.

The in situ electric field in the peripheral nerve of the skin is investigated to discuss the selective stimulation of nerve fibres. Coaxial planar electrodes with and without intra-epidermal needle tip were considered as electrodes of a stimulator. From electromagnetic analysis, the tip depth of the intra-epidermal electrode should be larger than the thickness of the stratum corneum, the electrical conductivity of which is much lower than the remaining tissue. The effect of different radii of the outer ring electrode on the in situ electric field is marginal. The minimum threshold in situ electric field (rheobase) for free nerve endings is estimated to be 6.3 kV m(-1). The possible volume for electrostimulation, which can be obtained from the in situ electric field distribution, becomes deeper and narrower with increasing needle depth, suggesting that possible stimulation sites may be controlled by changing the needle depth. The injection current amplitude should be adjusted when changing the needle depth because the peak field strength also changes. This study shows that intra-epidermal electrical stimulation can achieve stimulation of small fibres selectively, because Aß-, Aδ-, and C-fibre terminals are located at different depths in the skin.

Inhibition in the Human Auditory Cortex.

Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI) in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms) prepulse. The time course of the inhibition evaluated by prepulses presented at 10-800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20-60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful.

Echoic memory: investigation of its temporal resolution by auditory offset cortical responses.

Previous studies showed that the amplitude and latency of the auditory offset cortical response depended on the history of the sound, which implicated the involvement of echoic memory in shaping a response. When a brief sound was repeated, the latency of the offset response depended precisely on the frequency of the repeat, indicating that the brain recognized the timing of the offset by using information on the repeat frequency stored in memory. In the present study, we investigated the temporal resolution of sensory storage by measuring auditory offset responses with magnetoencephalography (MEG). The offset of a train of clicks for 1 s elicited a clear magnetic response at approximately 60 ms (Off-P50m). The latency of Off-P50m depended on the inter-stimulus interval (ISI) of the click train, which was the longest at 40 ms (25 Hz) and became shorter with shorter ISIs (2.5∼20 ms). The correlation coefficient r2 for the peak latency and ISI was as high as 0.99, which suggested that sensory storage for the stimulation frequency accurately determined the Off-P50m latency. Statistical analysis revealed that the latency of all pairs, except for that between 200 and 400 Hz, was significantly different, indicating the very high temporal resolution of sensory storage at approximately 5 ms.

Effects of acute nicotine on prepulse inhibition of auditory change-related cortical responses.

Prepulse inhibition (PPI) of startle is a measure of inhibitory function in which a weak leading stimulus suppresses the startle response to an intense stimulus. Usually, startle blink reflexes to an intense sound are used for measuring PPI. A recent magnetoencephalographic study showed that a similar phenomenon is observed for auditory change-related cortical response (Change-N1m) to an abrupt change in sound features. It has been well established that nicotine enhances PPI of startle. Therefore, in the present magnetoencephalographic study, the effects of acute nicotine on PPI of the Change-N1m were studied in 12 healthy subjects (two females and 10 males) under a repeated measures and placebo-controlled design. Nicotine (4 mg) was given as nicotine gum. The test Change-N1m response was elicited with an abrupt increase in sound pressure by 6 dB in a continuous background sound of 65 dB. PPI was produced by an insertion of a prepulse with a 3-dB-louder or 6-dB-weaker sound pressure than the background 75 ms before the test stimulus. Results show that nicotine tended to enhance the test Change-N1m response and significantly enhanced PPI for both prepulses. Therefore, nicotine's enhancing effect on PPI of the Change-N1m was similar to that on PPI of the startle. The present results suggest that the two measures share at least some mechanisms.

Prepulse inhibition of auditory change-related cortical responses.

BACKGROUND: Prepulse inhibition (PPI) of the startle response is an important tool to investigate the biology of schizophrenia. PPI is usually observed by use of a startle reflex such as blinking following an intense sound. A similar phenomenon has not been reported for cortical responses. RESULTS: In 12 healthy subjects, change-related cortical activity in response to an abrupt increase of sound pressure by 5 dB above the background of 65 dB SPL (test stimulus) was measured using magnetoencephalography. The test stimulus evoked a clear cortical response peaking at around 130 ms (Change-N1m). In Experiment 1, effects of the intensity of a prepulse (0.5 ~ 5 dB) on the test response were examined using a paired stimulation paradigm. In Experiment 2, effects of the interval between the prepulse and test stimulus were examined using interstimulus intervals (ISIs) of 50 ~ 350 ms. When the test stimulus was preceded by the prepulse, the Change-N1m was more strongly inhibited by a stronger prepulse (Experiment 1) and a shorter ISI prepulse (Experiment 2). In addition, the amplitude of the test Change-N1m correlated positively with both the amplitude of the prepulse-evoked response and the degree of inhibition, suggesting that subjects who are more sensitive to the auditory change are more strongly inhibited by the prepulse. CONCLUSIONS: Since Change-N1m is easy to measure and control, it would be a valuable tool to investigate mechanisms of sensory gating or the biology of certain mental diseases such as schizophrenia.