Auditory brainstem mechanisms likely compensate for self-imposed peripheral inhibition

Abstract

Feedback networks in the brain regulate downstream auditory function as peripheral as the cochlea. However, the upstream neural consequences of this peripheral regulation are less understood. For instance, the medial olivocochlear reflex (MOCR) in the brainstem causes putative attenuation of responses generated in the cochlea and cortex, but those generated in the brainstem are perplexingly unaffected. Based on known neural circuitry, we hypothesized that the inhibition of peripheral input is compensated for by positive feedback in the brainstem over time. We predicted that the inhibition could be captured at the brainstem with shorter (1.5 s) than previously employed long duration (240 s) stimuli where this inhibition is likely compensated for. Results from 16 normal-hearing human listeners support our hypothesis in that when the MOCR is activated, there is a robust reduction of responses generated at the periphery, brainstem, and cortex for short-duration stimuli. Such inhibition at the brainstem, however, diminishes for long-duration stimuli suggesting some compensatory mechanisms at play. Our findings provide a novel non-invasive window into potential gain compensation mechanisms in the brainstem that may have implications for auditory disorders such as tinnitus. Our methodology will be useful in the evaluation of efferent function in individuals with hearing loss.

Figure 1

Schematic of a compensatory circuit in the brainstem. Known neural connections between the cochlea and the brainstem and between neuron types within the brainstem are schematically shown. Green lines indicate excitatory and red lines indicate inhibitory inputs. Axon terminals on their synaptic targets are indicated by filled circles implying the direction of information flow. Inputs from the inner hair cells (IHC) are distributed in the cochlear nucleus to T-stellate (T) cells, D-stellate (D) cells, and small (S) cells by the auditory nerve (AN). D-stellate cells provide inhibitory inputs to the T-stellate cells, and pairs (possibly more) of the T-stellate cells are interconnected via an unknown excitatory interneuron (i). Both T-stellate and small cells project to the MOC (M) neurons at the level of the superior olivary complex. Both T-stellate and small cells in turn receive excitatory collaterals (dashed lines) from the MOC en route to the outer hair cells (OHC)—the putative efference copy circuit.

Figure 2

Response amplitude change with contralateral noise. ASSR in the top four panels and OAEs in the bottom four panels. Columns separate long- and short-duration conditions and rows separate 40 and 80 Hz click rates. Black circles (40 Hz click rate) and black triangles (80 Hz click rate) indicate group means and grey lines represent individual participants. Error bars represent ± one standard deviation. Asterisks denote a significant difference in amplitude between with- (WiN) and no-noise (NoN) conditions.

Figure 3

ASSRs vs. OAE amplitude change. (A) 40 Hz click-rate, long stimulus duration (B) 40 Hz click-rate, short stimulus duration (C) 80 Hz click-rate, long stimulus duration (D) 80 Hz click-rate, short stimulus duration. Open circles represent individual participants. A black solid fit line represents a significant relationship between variables. A black dashed fit line represents a nonsignificant relationship between variables.

Figure 4

Long vs. short duration. Amplitude changes in the long stimulus durations as a function of amplitude change in the short stimulus durations are plotted for (A) 40 Hz click-rate, ASSRs (B) 40 Hz click-rate, OAEs (C) 80 Hz click-rate, ASSRs (D) 80 Hz click-rate, OAEs. Open circles represent individual participants. A black solid regression line indicates a significant relationship between the two variables. A black dashed regression line indicates a non-significant relationship between the two variables. An outlier in panel-A, not included in the correlation, is indicated with an additional ‘X’ symbol.

Figure 5

40 Hz vs. 80 Hz. Amplitude changes at 80 Hz click-rate as a function of amplitude change at 40 Hz click-rate for (A) ASSRs, long stimulus duration (B) ASSRs, short stimulus duration (C) OAEs, long stimulus duration (D) ASSRs, short stimulus duration. Open circles represent individual participants. A black solid regression line indicates a significant relationship between the two variables. A black dashed regression line indicates a non-significant relationship between the two variables.

Figure 6

Schematic of the experimental protocol. Both 40 and 80 Hz clicks were presented in short (1.5 s) and long durations (4 min) at 65 dB ppSPL, with and without a 60 dB SPL broadband noise in the contralateral ear. Clicks were presented in positive and negative polarities to facilitate ASSR averaging. Each stimulus duration was separated by 0.5 s of silence.

Figure 7

Stimulus vs. OAE change. Stimulus amplitude change as a function of OAE amplitude change for (A) 40 Hz click-rate, long stimulus duration (B) 40 Hz click-rate, short stimulus duration (C) 80 Hz click-rate, long stimulus duration (D) 80 Hz click-rate, short stimulus duration. Open circles represent individual participants. Colors indicate 1, 2, and 4 kHz 1/3^rd octave-band absolute stimulus change. A solid regression line represents a significant relationship between variables. A dashed regression line represents a non-significant relationship between variables. The resulting correlation coefficient (r) and p-value are presented in each panel.