Top-down connections from ACC to V1 contribute to mismatch negativity

Schizophrenia is a neuropsychiatric disorder that is strongly associated with impairments in both basic sensory processing and higher cognitive functions. One of the most robust findings is that Schizophrenia patients have deficient sensory processing and impairment can be captured by the reduced “mismatch negativity” (MMN), which is an event-related potential that occurs when a sequence of repetitive stimuli is interrupted by occasional oddball stimuli. Although MMN is the biomarker of Schizophrenia and robustly translational across species, the underlying mechanisms of MMN are not clear. To investigate the role of top-down processing in MMN, we conduct the visual oddball task in the wild-type mice and 22q11DS mouse model, and record neural activity in the visual cortex while optogenetically manipulating ACC input. Our data shows that in the visual cortex of wild-type mice, the MMN is present. However, as seen in Schizophrenia patients, MMN is diminished in our 22q11DS mouse model. In wild-type mice, ACC input suppression decreases each unit’s deviant detection modulation as well as MMN in local field potential. In the 22q11DS mouse model, ACC input activation increases each unit’s deviant detection modulation. These results indicate that reduced MMN in V1 is due to weakened top-down processing and can be recovered by activating the top-down input, suggesting that abnormalities of top-down cortical processing are the leading cause of altered sensory processing in schizophrenia.