PT - JOURNAL ARTICLE AU - Chang, Yi-Ting AU - Finkel, Eric A. AU - Xu, Duo AU - O’Connor, Daniel H. TI - Rule-based modulation of a sensorimotor transformation across cortical areas AID - 10.1101/2023.08.21.554194 DP - 2024 Jan 01 TA - bioRxiv PG - 2023.08.21.554194 4099 - http://biorxiv.org/content/early/2024/03/09/2023.08.21.554194.short 4100 - http://biorxiv.org/content/early/2024/03/09/2023.08.21.554194.full AB - Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic environment. However, it remains unclear how the brain encodes rule information and uses this information to guide behavioral responses to sensory stimuli. Here, we made single-unit recordings while head-fixed mice performed a cross-modal sensory selection task in which they switched between two rules in different blocks of trials: licking in response to tactile stimuli applied to a whisker while rejecting visual stimuli, or licking to visual stimuli while rejecting the tactile stimuli. Along a cortical sensorimotor processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial (MM) and anterolateral (ALM) motor areas, the single-trial activity of individual neurons distinguished between the two rules both prior to and in response to the tactile stimulus. Variable rule-dependent responses to identical stimuli could in principle occur via appropriate configuration of pre-stimulus preparatory states of a neural population, which would shape the subsequent response. We hypothesized that neural populations in S1, S2, MM and ALM would show preparatory activity states that were set in a rule-dependent manner to cause processing of sensory information according to the current rule. This hypothesis was supported for the motor cortical areas by findings that (1) the current task rule could be decoded from pre-stimulus population activity in ALM and MM; (2) neural subspaces containing the population activity differed between the two rules; and (3) optogenetic disruption of pre-stimulus states within ALM and MM impaired task performance. Our findings indicate that flexible selection of an appropriate action in response to a sensory input can occur via configuration of preparatory states in the motor cortex.HIGHLIGHTSTask rules are reflected in preparatory activity in sensory and motor cortices.Neural subspaces for processing tactile signals depend on the current task rule.Motor cortical activity tracks rule switches and is required for flexible rule-guided behavior.Competing Interest StatementThe authors have declared no competing interest.