An Electric Circuit Model of Central Auditory Processing that Replicates Low-level Features of the Mouse Mismatch Response.

Abstract

Neurophysiology research using animals is often necessary to further our understanding of particular areas of medical interest. Human mismatch negativity (MMN) is one such area, where animal models are used to explore underlying mechanisms more invasively and with greater precision than typically possible with human subjects. Computational models can supplement these efforts by providing abstractions that lead to new insights and drive hypotheses. This study aims to establish whether a mouse mismatch response (MMR) analogous to human MMN can be modelled using electric circuit theory. Input to the auditory cortex was modelled as a step function multiplied by a frequency-dependent weighting designed to reflect spectral hearing sensitivity. Afferent sensory responses were modelled using a resistor-capacitor (RC) network, while bidirectional (bottom-up and top-down) responses were modelled using a resistor-inductor-capacitor (RLC) network. Synthetic EEG was combined with RC and RLC circuit currents in response to simulated sequences of auditory input, which comprised duration and frequency oddball paradigms. Two different states of awareness were considered: i) anaesthetized, including only the RC circuit, and ii) conscious, including both RC and RLC circuits. Event-related potential waveforms were obtained from ten simulated experiments for each oddball paradigm and state. These were qualitatively and quantitatively compared with data from a previous in-vivo study, and the model was deemed to successfully replicate low-level features of the mouse central auditory response. Clinical Relevance - Abnormal MMN is believed to reflect pathological changes associated with psychiatric disease. Maximizing the effectiveness of this biomarker will require a greater understanding of the specific cause(s) of these abnormalities. This study presents a computational model that can account for differences between responses to duration and frequency oddball paradigms, which is particularly significant for clinical MMN research.