Patterns of Laminar Engagement During Visual Mismatch Processing

Several decades of work have highlighted basic sensory processing deficits as a core feature of psychosis-related psychopathologies, such as schizophrenia. Among the most reliable deficits is that of a pre-attentive, unconscious brain response termed the “mismatch negativity” (MMN) signal, an event-related potential that is enhanced when statistical regularities in the environment, such as a repeated sight or sound, are violated. Responses to “oddball” stimuli arise early in sensory pathways, and are present across multiple modalities, suggesting (i) that the MMN may well be a generalized cortical mechanism for aligning an individual’s internal model of the world with what is, and (ii) that canonical symptoms seen in the clinic (e.g. paranoias or delusions) may ultimately have propagated forward from misaligned detection of low-level features present all around us. While the MMN is reliably evoked, cost-effective to measure, and predictive of conversion to psychotic episodes in at-risk demographics, its utility in the clinic has been hindered by an incomplete understanding of its governing mechanisms in neuronal circuits. MMN has been linked to impaired N-methyl-D-aspartate receptor (NMDAR) functioning across humans, rodents, and primates, implicating deficient excitatory neurotransmission as one major axis of dysfunction. In this work, we sought first to characterize MMN-like responses across visual cortical layers of the mouse during a visual “oddball” paradigm, and second to understand how these patterns are disrupted with exposure to a non-competitive NMDAR pore blocker (“MK-801”). We found that multi-unit spiking activity (MUA) associated with deviance detection processing was present in supragranular cortical layers, spatially segregated from reductions in neuronal firing which index adaptation to repeated, predictable stimuli. Moreover, slow and fast oscillations—specifically, theta (2-7 Hz) and high gamma (∼67-76 Hz)—were enhanced following deviant stimuli, consistent with predictive processing theories that postulate distinct frequency-specific channels for feedforward and feedback cortical communication. MK-801 caused context-selective reductions in Layer 5 MUA, and surprisingly, increased modulation during deviant stimulus contexts by the phase of top-down local field potentials, indicating augmented influence of top-down suppression during impaired bottom-up processing. Collectively, these findings suggest that impaired excitatory neurotransmission biases V1 towards a dependence on top-down inputs thought to convey sensory predictions.