1292 Circuitry of the Preparatory Period: A Role for Thalamocortical Circuit Dynamics in Optimizing Spontaneous Attentional Control Prior to Cognitive Engagement

INTRODUCTION: Human cognition involves the complex coordination of interconnected networks, where pre-task spontaneous network states can prime brain performance. Thalamocortical communication is known to be a crucial element of attentional processes. METHODS: We employed a temporal expectancy task in 24 humans and 6 wild-type mice, consisting of an initial cue followed by a go cue separated by a variable time interval, and a response to the go cue. Human subjects were implanted with iEEG, and mice were injected with a fluorescent Ca2+ indicator (GCAMP6m) in the mediodorsal thalamus (MD), with neural activity subsequently recorded using fiber photometry in MD and prefrontal cortex (PFC). RESULTS: In humans, spectral power and graph communicability (Qexp) were calculated for each of four canonical frequency bands within 500 ms before the initial cue or the go cue. We streamlined the feature space by bootstrapping univariate linear regressions 1000 times, selecting features significantly correlated to reaction time (RT) in over 35% of iterations. A rank-sum test identified anatomical regions consistently predicting RT across subjects by comparing selected and non-selected features. Low frequency TC white matter Qexp predicted upcoming RT in the preparatory period while high frequency spectral activity predicted RT in the anticipatory period. In mice, activity in MD-PFC projections correlated strongly with RT. In trials with the fastest RTs (0-20ms), TC activity surged approximately 4s prior to initial cue onset as well prior to the go cue, compared to other trials (20-500ms) (p<0.001). When comparing the fastest vs. the slowest third of trials with RT<100ms, activity significantly increased for the fastest trials in the preparatory period but not the anticipatory period (p<0.001). CONCLUSIONS: These findings indicate that enhanced TC communication primes mammalian neural circuitry during the preparatory period for optimal performance.