Stimulus-Specific Adaptation in Auditory Cortex Is an NMDA-Independent Process Distinct from the Sensory Novelty Encoded by the Mismatch Negativity

Abstract

The significance of the mismatch negativity (MMN), an event-related potential measured in humans which indexes novelty in the auditory environment, has motivated a search for a cellular correlate of this process. A leading candidate is stimulus-specific adaptation (SSA) in auditory cortex units, which shares several characteristics with the MMN. Whether auditory cortex responses encode sensory novelty, a defining property of the MMN, however, has not been resolved. To evaluate this key issue, we used several variations of the auditory oddball paradigm from the human literature and examined psychophysical and pharmacological properties of multiunit activity in the auditory cortex of awake rodents. We found converging evidence dissociating SSA from sensory novelty and the MMN. First, during an oddball paradigm with frequency deviants, neuronal responses showed clear SSA but failed to encode novelty in a manner analogous to the human MMN. Second, oddball paradigms using intensity or duration deviants revealed a pattern of unit responses that showed sensory adaptation, but again without any measurable novelty correlates aligning to the human MMN. Finally NMDA antagonists, which are known to disrupt the MMN, suppressed the magnitude of multiunit responses in a nonspecific manner, leaving the process of SSA intact. Together, our results suggest that auditory novelty detection as indexed by the MMN is dissociable from SSA at the level of activity encoded by auditory cortex neurons. Further, the NMDA sensitivity reported for the MMN, which models the disruption of MMN observed in schizophrenia, may occur at a mechanistic locus outside of SSA.

A Neuronal Model of Predictive Coding Accounting for the Mismatch Negativity

“…Recent human MEEG recordings indicate that the omission response observed when an expected sound fails to occur conforms to the predictions of hierarchical predictive coding models (Wacongne et al, 2011). In rodents, Farley et al (2010) showed that stimulus-specific adaptation is indeed observed in auditory cortex but that its properties differ sharply from those of the MMN, in terms of sensitivity to NMDA antagonists or elicitation of a novelty response. Together, these results provide strong evi- Experimental test of the model using magnetoencephalography.…”

Stimulus-specific adaptation, habituation and change detection in the gaze control system

“…In SSA, we expect a stronger response every time the sequence is switched from one stimulus to the other (lower histogram in (c)) et al 2006), and auditory (Perez-Gonzalez et al 2005) pathways. In the auditory system, neurons sensitive to deviations were found at different levels of the pathway: in the inferior colliculus, the auditory thalamus and the auditory cortex (Malmierca et al 2009;Anderson et al 2009;Farley et al 2010;Antunes et al 2010;Ulanovsky et al 2004). Detailed characterization of SSA in the auditory system revealed that it is highly sensitive to minute deviations from the standard frequency.…”

“…Other sensory features were either not studied or gave rise to poor SSA (Farley et al 2010;Ulanovsky et al 2003). In nature, a stimulus can differ from what has been in the past along multiple features, i.e., frequency, amplitude, duration, location, etc., or combinations of features.…”

Disruption of hierarchical predictive coding during sleep

“…Within this framework, the P300 is considered a high-level prediction error signal associated with conscious novelty detection, which is strongly reduced in various nonconscious conditions, such as coma and anesthesia (17,(19)(20)(21), whereas the MMN is considered a lower-level preattentive prediction error signal (22)(23)(24)(25)(26) that may be generated nonconsciously (15). In fact, two distinct mechanisms are involved during the MMN time window: an active predictive mechanism (MMN proper) and a passive habituation phenomenon known as stimulus-specific adaptation (SSA).…”

“…Inasmuch as SSA reduces the impact of redundant sensory inputs, it might be considered a primitive predictive device, yet one that rests only on neurotransmission mechanisms local to each neuron (27). It was initially thought that passive SSA may account for the MMN (28,29), but there is now evidence that the latter involves active predictive coding mechanisms (22)(23)(24)(25)(26). To summarize, at least three successive brain responses to novelty exist: recovery from sensory adaptation, MMN in the proper sense, and P300.…”