No abstract

Responding to a stimulus requires transforming an internal sensory representation into an internal motor representation. Where and how this sensory-motor transformation occurs is a matter of vigorous debate. Here, we trained male and female mice in a whisker detection go/no-go task in which they learned to respond (lick) following a transient whisker deflection. Using single unit recordings, we quantified sensory-related, motor-related, and choice-related activities in whisker primary somatosensory cortex (S1), whisker region of primary motor cortex (wMC), and anterior lateral motor cortex (ALM), three regions that have been proposed to be critical for the sensory-motor transformation in whisker detection. We observed strong sensory encoding in S1 and wMC, with enhanced encoding in wMC, and a lack of sensory encoding in ALM. We observed strong motor encoding in all three regions, yet largest in wMC and ALM. We observed the earliest choice probability in wMC, despite earliest sensory responses in S1. Based on the criteria of having both strong sensory and motor representations and early choice probability, we identify whisker motor cortex as the cortical region most directly related to the sensory-motor transformation. Our data support a model of sensory encoding originating in S1, sensory amplification and sensory-motor transformation occurring within wMC, and motor signals emerging in ALM after the sensory-motor transformation.

Stuttering is a neurodevelopmental speech disorder with a phenotype characterized by speech sound repetitions, prolongations and silent blocks during speech production. Developmental stuttering affects 1% of the population and 5% of children. Neuroanatomical abnormalities in the major white matter tracts, including the arcuate fasciculus, corpus callosum, corticospinal, and frontal aslant tracts (FAT), are associated with the disorder in adults who stutter but are less well studied in children who stutter (CWS). We used deterministic tractography to assess the structural connectivity of the neural network for speech production in CWS and controls. CWS had higher fractional anisotropy and axial diffusivity in the right FAT than controls. Our findings support the involvement of the corticostriatal network early in persistent developmental stuttering.

Suppressing behavioral responses to distractor stimuli is a fundamental cognitive process, essential for performing goal-directed tasks. A common framework for the neuronal implementation of distractor suppression is the attenuation of distractor stimuli from early sensory to higher-order processing. However, details of the localization and mechanisms of attenuation are poorly understood. In this study, we trained mice to selectively respond (lick) to whisker deflections from one whisker field and ignore identical deflections from the opposite whisker field. We found that suppression of frontal cortex, aligned to the target stimulus or the distractor stimulus, increases responses to distractors (false alarms). By simultaneously recording spiking activity in the mouse whisker region of primary somatosensory cortex (S1), we found that frontal cortex selectively suppresses the neuronal encoding of distractor stimuli in target-aligned S1. Frontal cortex decorrelates the encoding of target and distractor stimuli in single units, thereby increasing stimulus selectivity across the population of target-aligned S1 neurons. Even before stimulus onset, effects of frontal cortex on S1 were robust and context-dependent, indicating proactive modulation. Overall, our study provides important mechanistic details about the roles of frontal cortex in gating sensory responses in sensory cortex.

Spontaneous neuronal activity strongly impacts stimulus encoding and behavioral responses. We sought to determine the effects of neocortical prestimulus activity on stimulus detection. We trained mice in a selective whisker detection task, in which they learned to respond (lick) to target stimuli in one whisker field and ignore distractor stimuli in the contralateral whisker field. During expert task performance, we used widefield Ca2+ imaging to assess prestimulus and post-stimulus neuronal activity broadly across frontal and parietal cortices. We found that lower prestimulus activity correlated with enhanced stimulus detection: lower prestimulus activity predicted response versus no response outcomes and faster reaction times. The activity predictive of trial outcome was distributed through dorsal neocortex, rather than being restricted to whisker or licking regions. Using principal component analysis, we demonstrate that response trials are associated with a distinct and less variable prestimulus neuronal subspace. For single units, prestimulus choice probability was weak yet distributed broadly, with lower than chance choice probability correlating with stronger sensory and motor encoding. These findings support low amplitude and low variability as an optimal prestimulus cortical state for stimulus detection that presents globally and predicts response outcomes for both target and distractor stimuli.