Purpose The basic principle of sensorimotor gating (SMG) relies on the ability of a weak lead stimulus (such as a pre-pulse) to inhibit a startling effect of a following, more intense, abrupt stimulus—the so-called pre-pulse inhibition (PPI) paradigm. PPI has been used for near half a century as a means to investigate psychiatric disorders in which its disruption is a surrogate for altered SMG in schizophrenia. However, the blinking response is very variable, making it a poor outcome measure at the individual level. Unlike PPI, which is regulated in the lateral globus pallidus from the basal ganglia, inhibition of the startle reflex by preceding silent gaps embedded in continuous background noise is processed in the auditory cortex, making it particularly suitable for measuring cortical responses. Methods Here, based on the behavioral gap-pre-pulse inhibition of acoustic startle (GPIAS) stemming from animal research in tinnitus research, we present a new sensory gating (SG) paradigm using source-localized magnetoencephalography (MEG) in 26 normal hearing healthy participants (13 females, 12 males, 1 other) with a mean age of 28.4 (SD <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="10162_2025_999_Article_IEq1.gif" Format="GIF" Height="14" Rendition="HTML" Resolution="72" Type="Linedraw" Width="37" /> </InlineMediaObject> <EquationSource Format="TEX">$\pm 5.8$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mo>±</mo> <mn>5.8</mn> </mrow> </math></EquationSource> </InlineEquation>), where we expose them to various levels of sound pulses in presence or absence of preceding silent gaps embedded in broadband carrier noises of either 60 or 70 dB SPL, using various interstimulus intervals (ISI: 0, 60, 120, 240 ms). Results We evidence a near 72.5% (SD <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="10162_2025_999_Article_IEq2.gif" Format="GIF" Height="14" Rendition="HTML" Resolution="72" Type="Linedraw" Width="44" /> </InlineMediaObject> <EquationSource Format="TEX">$\pm 15.9$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mo>±</mo> <mn>15.9</mn> </mrow> </math></EquationSource> </InlineEquation>) suppression of N1 evoked response to a pulse as high as 90 dB(A) sound pressure level (SPL) when preceded by a 50 ms long silent gap in a 60 dB(A) SPL broadband carrier noise. Cortical inhibition was greatest with 240 ms ISI between gap and pulses, and about 1.5 times larger in the right transverse temporal gyrus when compared to the left hemisphere. While merely 68% of the individuals blinked at the highest pulse levels, cortical evoked responses were found in all participants. Conclusion Overall, we provide evidence that SG, measured by N1 cortical response to sound pulses, is reliably inhibited by preceding gaps. We propose this paradigm as an effective method to assess auditory SG through development and aging, and potentially as a method for the diagnosis of hearing disorders like tinnitus or hyperacusis.

Inhibition of Cortical Evoked Responses to Sound Pulses by Preceding Silent Gaps

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2025年7月23日

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Payam S. Shabestari,
Niklas K. Edvall,
Mikkel C. Vinding,
Sven Vanneste,
Daniel Lundqvist,
Patrick Neff,
Christopher R. Cederroth

摘要

Purpose

The basic principle of sensorimotor gating (SMG) relies on the ability of a weak lead stimulus (such as a pre-pulse) to inhibit a startling effect of a following, more intense, abrupt stimulus—the so-called pre-pulse inhibition (PPI) paradigm. PPI has been used for near half a century as a means to investigate psychiatric disorders in which its disruption is a surrogate for altered SMG in schizophrenia. However, the blinking response is very variable, making it a poor outcome measure at the individual level. Unlike PPI, which is regulated in the lateral globus pallidus from the basal ganglia, inhibition of the startle reflex by preceding silent gaps embedded in continuous background noise is processed in the auditory cortex, making it particularly suitable for measuring cortical responses.

Methods

Here, based on the behavioral gap-pre-pulse inhibition of acoustic startle (GPIAS) stemming from animal research in tinnitus research, we present a new sensory gating (SG) paradigm using source-localized magnetoencephalography (MEG) in 26 normal hearing healthy participants (13 females, 12 males, 1 other) with a mean age of 28.4 (SD $\pm 5.8$ $\pm 5.8$ ), where we expose them to various levels of sound pulses in presence or absence of preceding silent gaps embedded in broadband carrier noises of either 60 or 70 dB SPL, using various interstimulus intervals (ISI: 0, 60, 120, 240 ms).

Results

We evidence a near 72.5% (SD $\pm 15.9$ $\pm 15.9$ ) suppression of N1 evoked response to a pulse as high as 90 dB(A) sound pressure level (SPL) when preceded by a 50 ms long silent gap in a 60 dB(A) SPL broadband carrier noise. Cortical inhibition was greatest with 240 ms ISI between gap and pulses, and about 1.5 times larger in the right transverse temporal gyrus when compared to the left hemisphere. While merely 68% of the individuals blinked at the highest pulse levels, cortical evoked responses were found in all participants.

Conclusion

Overall, we provide evidence that SG, measured by N1 cortical response to sound pulses, is reliably inhibited by preceding gaps. We propose this paradigm as an effective method to assess auditory SG through development and aging, and potentially as a method for the diagnosis of hearing disorders like tinnitus or hyperacusis.