Contextual processing in unpredictable auditory environments: the limited resource model of auditory refractoriness in the rhesus

Abstract

Auditory refractoriness refers to the finding of smaller electroencephalographic (EEG) responses to tones preceded by shorter periods of silence. To date, its physiological mechanisms remain unclear, limiting the insights gained from findings of abnormal refractoriness in individuals with schizophrenia. To resolve this roadblock, we studied auditory refractoriness in the rhesus, one of the most important animal models of auditory function, using grids of up to 32 chronically implanted cranial EEG electrodes. Four macaques passively listened to sounds whose identity and timing was random, thus preventing animals from forming valid predictions about upcoming sounds. Stimulus onset asynchrony ranged between 0.2 and 12.8 s, thus encompassing the clinically relevant timescale of refractoriness. Our results show refractoriness in all 8 previously identified middle- and long-latency components that peaked between 14 and 170 ms after tone onset. Refractoriness may reflect the formation and gradual decay of a basic sensory memory trace that may be mirrored by the expenditure and gradual recovery of a limited physiological resource that determines generator excitability. For all 8 components, results were consistent with the assumption that processing of each tone expends ∼65% of the available resource. Differences between components are caused by how quickly the resource recovers. Recovery time constants of different components ranged between 0.5 and 2 s. This work provides a solid conceptual, methodological, and computational foundation to dissect the physiological mechanisms of auditory refractoriness in the rhesus. Such knowledge may, in turn, help develop novel pharmacological, mechanism-targeted interventions.

Loudness- and time-dependence of auditory evoked potentials is blunted by the NMDA channel blocker MK-801

“…In addition, we also report results from other previously identified AEP components referred to by polarity and latency as P14, P21, P31, N43, P55, N85, P135 and N170 (27). Earlier work has shown that all 8 components exhibit TDAEP (Teichert et al, 2016), and that TDAEP can be blunted by non-competitive NMDA antagonists such as ketamine and MK-801 (under review). The aim of the current experiments was to determine whether components also show LDAEP, and whether MK-801 would simultaneously blunt both LDAEP and TDAEP.…”

“…All methods were approved by the Institutional Animal Care and Use Committee at the University of Pittsburgh. All animals have previously been exposed to similar passive listening paradigms in previous studies (Teichert, 2016; Teichert et al, 2016). …”

“…Details of the EEG recording system were reported previously (Teichert, 2016; Teichert et al, 2016). Briefly, animals had 33 electrodes implanted into 1 mm deep holes in the cranium covering roughly the same anatomy as the international 10-20 system (Teichert, 2016).…”

“…The auditory paradigm was a modification of a paradigm we used previously (Teichert, 2016; Teichert et al, 2016). In this variant of the paradigm, animals passively listened to 0.1 ms long bi-phasic clicks of 5 different intensities (62, 68, 74, 80, 86 dB SPL) (Fig 1).…”

“…The filtered data was cut into short epochs around the onset of each sound (−150 to 750 ms). A subtraction method was used to reduce AEP superposition for tones with short SOAs (Teichert et al, 2016). The data was then exported for use with the statistics software R (R Development Core Team, 2009).…”