Cortical Mapping of Mismatch Negativity with Deviance Detection Property in Rat

Abstract

Mismatch Negativity (MMN) is an N-methyl-d-aspartic acid (NMDA)-mediated, negative deflection in human auditory evoked potentials in response to a cognitively discriminable change. MMN-like responses have been extensively investigated in animal models, but the existence of MMN equivalent is still controversial. In this study, we aimed to investigate how closely the putative MMN (MMNp) in rats exhibited the comparable properties of human MMN. We used a surface microelectrode array with a grid of 10×7 recording sites within an area of 4.5×3.0 mm to densely map evoked potentials in the auditory cortex of anesthetized rats under the oddball paradigm. Firstly, like human MMN, deviant stimuli elicited negative deflections in auditory evoked potentials following the positive middle-latency response, termed P1. Secondly, MMNp exhibited deviance-detecting property, which could not be explained by simple stimulus specific adaptation (SSA). Thirdly, this MMNp occurred focally in the auditory cortex, including both the core and belt regions, while P1 activation focus was obtained in the core region, indicating that both P1 and MMNp are generated in the auditory cortex, yet the sources of these signals do not completely overlap. Fourthly, MMNp significantly decreased after the application of AP5 (D-(-)-2-amino-5-phosphonopentanoic acid), an antagonist at NMDA receptors. In stark contrast, AP5 affected neither P1 amplitude nor SSA of P1. These results provide compelling evidence that the MMNp we have examined in rats is functionally comparable to human MMN. The present work will stimulate translational research into MMN, which may help bridge the gap between electroencephalography (EEG)/magnetoencephalography (MEG) studies in humans and electrophysiological studies in animals.

Criteria for determining whether mismatch responses exist in animal models: Focus on rodents

“…Many report a deviance detection-like shift (positive or negative) in the ERP peaking between 50-100 ms. For positive shifts, latencies range from 29-69 ms (Ahmed et al, 2011), 50-70 ms (Nakamura et al, 2011), 60-100 ms ), 75-124.5 ms (Ruusuvirta et al, 2015 to81-125 ms (Jung et al, 2013). For negative shifts, the range is similar at 50-150 ms (Shiramatsu et al, 2013), 50-70 ms (Nakamura et al, 2011), 44-66 ms (Harms et al, 2014) and 30-60 ms (Sivarao et al, 2014).…”

“…Several laboratories have utilised the many-standards control sequence to demonstrate that rats exhibit human-like MMRs that are independent from adaptation. Adaptation-independent MMRs have been observed in awake, freely moving rats (Harms et al, 2014;Jung et al, 2013;Nakamura et al, 2011;Sivarao et al, 2014) and anesthetised (Ahmed et al, 2011;Astikainen et al, 2011;Nakamura et al, 2011;Shiramatsu et al, 2013) rats, using a variety of different anaesthetic agents (urethane, fentanyl/medetomidine and isoflurane). In addition, deviance detection was identified for a range of stimulus types, including frequency Harms et al, 2014;Jung et al, 2013;Nakamura et al, 2011;Shiramatsu et al, 2013;Sivarao et al, 2014), duration (Nakamura et al, 2011) and speech sounds (Ahmed et al, 2011).…”

“…Adaptation-independent MMRs have been observed in awake, freely moving rats (Harms et al, 2014;Jung et al, 2013;Nakamura et al, 2011;Sivarao et al, 2014) and anesthetised (Ahmed et al, 2011;Astikainen et al, 2011;Nakamura et al, 2011;Shiramatsu et al, 2013) rats, using a variety of different anaesthetic agents (urethane, fentanyl/medetomidine and isoflurane). In addition, deviance detection was identified for a range of stimulus types, including frequency Harms et al, 2014;Jung et al, 2013;Nakamura et al, 2011;Shiramatsu et al, 2013;Sivarao et al, 2014), duration (Nakamura et al, 2011) and speech sounds (Ahmed et al, 2011). Additional studies in anesthetised rats, rather than using a many-standards sequence to control for adaptation, used complex deviations that involve combinations of stimulus features such that each individual feature occurs equally often and therefore subjected to equal amounts of adaptation, such as frequency x intensity conjunctions (Astikainen et al, 2006) or frequency-intensity relationship 'rules' (Astikainen et al, 2014).…”

“…Consistent with this, rat studies indicate that adaptation-independent MMRs may be only observable on a small scale in primary auditory cortical recordings. Indeed, a study using surface microelectrode array recordings over the auditory cortex in anesthetised rats demonstrated that the adaptationindependent component of the ERP has a more broadly distributed localisation within the auditory cortex compared to the adaptation-dependent component of the ERP (Shiramatsu et al, 2013). The reason that intracortical recording methods often do not identify a larger response to deviants compared to the many-standards control, which would indicate the presence of deviance detection (Eriksson and Villa, 2005;Farley et al, 2010;Taaseh et al, 2011), could be that the neuronal populations responsible for deviance detection, may overlap with, but not exclusively contain, those with specific frequency tuning to the stimuli that are presented and those with sensitivity to adaption to the stimuli.…”

Auditory cortical and hippocampal local-field potentials to frequency deviant tones in urethane-anesthetized rats: An unexpected role of the sound frequencies themselves

“…Furthermore, similarly to MMN (Jacobsen and Schröger, 2001), differential brain responses in animals have been attributed to deviant tones as changes in the repetitiveness of a standard tone rather than as rare tones relative to the standard tone (e.g., Ruusuvirta et al, 1998;Nakamura et al, 2011;Taaseh et al, 2011;Jung et al, 2013;Shiramatsu et al, 2013;Harms et al, 2014;Malmierca et al, 2014). Together, these findings suggest that the mechanisms for automatic auditory change detection are not limited to the human brain.…”