Prediction error signaling explains neuronal mismatch responses in the medial prefrontal cortex

Abstract

The mismatch negativity (MMN) is a key biomarker of automatic deviance detection thought to emerge from 2 cortical sources. First, the auditory cortex (AC) encodes spectral regularities and reports frequency-specific deviances. Then, more abstract representations in the prefrontal cortex (PFC) allow to detect contextual changes of potential behavioral relevance. However, the precise location and time asynchronies between neuronal correlates underlying this frontotemporal network remain unclear and elusive. Our study presented auditory oddball paradigms along with “no-repetition” controls to record mismatch responses in neuronal spiking activity and local field potentials at the rat medial PFC. Whereas mismatch responses in the auditory system are mainly induced by stimulus-dependent effects, we found that auditory responsiveness in the PFC was driven by unpredictability, yielding context-dependent, comparatively delayed, more robust and longer-lasting mismatch responses mostly comprised of prediction error signaling activity. This characteristically different composition discarded that mismatch responses in the PFC could be simply inherited or amplified downstream from the auditory system. Conversely, it is more plausible for the PFC to exert top-down influences on the AC, since the PFC exhibited flexible and potent predictive processing, capable of suppressing redundant input more efficiently than the AC. Remarkably, the time course of the mismatch responses we observed in the spiking activity and local field potentials of the AC and the PFC combined coincided with the time course of the large-scale MMN-like signals reported in the rat brain, thereby linking the microscopic, mesoscopic, and macroscopic levels of automatic deviance detection.

Neural Correlates of Auditory Pattern Learning in the Auditory Cortex

“…These studies, as well as our results, suggest that neural responses under anesthesia carry important information that are highly correlated with sensory perception. In the present study, the usage of urethane was chosen to minimize any adverse effect of anesthetics on brain function (Capsius and Leppelsack, 1996;Hara and Harris, 2002;Curto et al, 2009). Furthermore, our findings suggesting distinct neural traces for Ref sequences over the AC in rats under anesthesia are comparable to the findings observed from human neuroimaging study during REM sleep (Andrillon et al, 2017).…”

Cortical ensembles selective for context

“…It remains possible that this layer 6 portion of the circuitry plays a different, still uncharacterized role in V1 DD and ensemble membership. Also, it was recently reported that DD appears to increase in magnitude from sub-to primary-to frontal-cortical regions, particularly in the auditory domain (48). One intriguing possibility, which would conform well with predictive coding theories (9), is that the difference from our report lies in the type of neurons recorded; our study selectively recorded PFC neurons which send backward projections to V1 (which convey predictions, not prediction errors), while Casado-Román et al recorded indiscriminately among PFC neurons (48).…”

Corticothalamic Pathways in Auditory Processing: Recent Advances and Insights From Other Sensory Systems

“…In higher order auditory thalamus (medial and dorsal subdivisions), suppression of repeated sounds coexists with enhancement to rare, surprising sounds in single neurons, the so-called stimulus-specific adaptation (SSA; Figure 2 ; Ulanovsky et al, 2003 ) or neuronal mismatch (Parras et al, 2017 ). This property is not restricted to the thalamus but is distributed hierarchically from as early as the auditory midbrain to the auditory cortex and prefrontal cortex (some classical studies: AC, Ulanovsky et al, 2003 ; inferior colliculus, Pérez-González et al, 2005 ; TRN, Yu et al, 2009 ; MGB, Antunes et al, 2010 ; prefrontal cortex, Casado-Román et al, 2020 ). Classically, SSA is elicited using an oddball paradigm, where two tones that differ in their probability of appearance in a sequence are played (a repeated sound interrupted randomly by a deviant sound; Figure 2 ).…”

“…As we progress along the auditory hierarchy, responses to the repeated sound are suppressed, but responses to the deviant are enhanced. Responses to the deviant are maximal in prefrontal cortex (Casado-Román et al, 2020 ). Because their enhanced responses to surprising sounds cannot be explained solely by bottom-up mechanisms of neural fatigue, these neurons are believed to signal expectancy deviance that can be regarded as a prediction error signal (Parras et al, 2017 ; Malmierca et al, 2019 ; Hamm et al, 2021 ).…”

“…A gain mechanism to facilitate perceptual saliency could underlie this enhancement (Parras et al, 2017 ; Carbajal and Malmierca, 2018 ). Although SSA in the MGB is not inherited from the auditory cortex ( Figure 2 ; Antunes and Malmierca, 2011 ), it is still unknown if this error enhancement is generated by cortical influences, because Antunes and Malmierca ( 2011 ) did not use the control sequences used to discern between repetition suppression and error enhancement (for details, see Parras et al, 2017 ; Casado-Román et al, 2020 ).…”