Inhibition in the Human Auditory Cortex

Abstract

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.

Fig 1. The change-related cortical response and its inhibition by a weak prepulse.

(A) Sound stimuli consisted of a train of 1-ms clicks at 100 Hz in repetitive frequency and 70 dB SPL in sound pressure. An abrupt increase in sound pressure of 10 dB evoked the Test response, while that for the prepulse to inhibit the Test response was 5 dB from the background (Standard). Each bar indicates a single click. (B) Superimposed MEG waveforms recorded from the 204 channels following the four sound stimuli in a single subject, Standard (a), Test alone (b), Prepulse alone presented 60 ms before the Test onset (c), and Prepulse + Test (d). (C) Difference waveforms used to analyze the data. The Test alone response was obtained by subtracting Standard-evoked waveforms (Ba) from Test-evoked waveforms (Bb). The Prepulse alone response was obtained by subtracting Standard-evoked waveforms (Ba) from Prepulse-evoked waveforms (Bc). The Prepulse + Test response was obtained by subtracting Prepulse-evoked waveforms (Bc) from waveforms for the Prepulse + Test stimulus (Bd). (D) The dipole locations estimated at approximately the peak latency of Change-N1m for the Test-evoked response (back arrow) were superimposed on each subject’s MR images. (E) Source strength waveforms obtained by applying the dipole model in D to the difference waveforms in C.

Fig 2. Time course of inhibition.

(A) The results of Experiment 1–1 (10–200 ms) and Experiment 1–2 (300–800 ms) are shown together. (B) Comparison of the time course of long-latency inhibition between a prepulse of a single click (Experiment 1–2, blue line) and that of 3 clicks (Experiment 1–3, green line). Average values between hemispheres are shown (n = 9 subjects). Although the 3-click Prepulse confirmed the time course of the inhibition by the weak prepulse in Experiment 1–2, inhibition was still weak. (C) Waveforms show the Test alone (black) and Test + Prepulse response (red) for the 600ms-Prepulse condition in Experiment 1–3. (D) Results of Experiment 1–4. Although inhibition was the greatest for the 40ms-Prepulse on average, the inhibition curve was biphasic in both hemispheres. (E) The time course of the short-latency inhibition in three representative subjects showing two peaks at 30 and 60 ms (Subject 1), and single peaks at 60 ms (Subject 2) and at 20 ms (Subject 3). %PPI, percent prepulse inhibition.

Fig 3. Effects of prepulses with a click train.

(A) The magnitude of inhibition and Prepulse-evoked excitatory responses were compared among four Prepulses, with a single 75-dB click 60 ms (1-Prepulse), two clicks 60 and 50 ms (2-Prepulse), three clicks 60, 50, and 40 ms (3-Prepulse), and four clicks 60–30 ms (4-Prepulse) before the Test onset. (B) Grand-averaged Test- and Prepulse-evoked responses across 13 subjects. (C) Black filled circles are plots of the degree of inhibition (y-axis, percent inhibition) against the amplitude of the Prepulse-evoked response (x-axis) for the four Prepulses. Orange filled circles show data for the 2-click prepulse in D and E. (D) Comparison of excitatory and inhibitory effects of two Prepulses with two clicks at 60 and 30 ms (6030 Prepulse) and 60 and 50 ms (6050 Prepulse identical with 2-Prepulse in A). (E) Grand-averaged waveforms of Test- and Prepulse-evoked responses for Test alone (black line) and with 6050 (green) or 6030 Prepulse (orange) conditions. The excitatory effect (Prepulse-evoked) was stronger for the 6050 Prepulse, whereas the inhibitory effect was stronger for the 6030 Prepulse.