BMI Distinguished Seminar // Tom Mrsic-Flogel: Decision Making: From Brain-Wide Dynamics to Multi-regional Circuit Mechanisms

Throughout our lives we make countless decisions based on learned associations between sensory inputs and beneficial actions. However, flexible behaviour requires that these learned associations only influence our actions when they serve our current goals. While frontal cortex is known to be critical for this behavioural flexibility by representing internal goals and context-dependent rules, and the basal ganglia are essential for implementing learned sensorimotor associations, the mechanisms by which frontal regions exert control over these action selection circuits remain poorly understood. Using brain-wide recordings in mice, we demonstrate that learning establishes distributed sensorimotor transformations, enabling sustained representations of relevant sensory information in premotor regions of frontal-motor cortex, thalamus, basal ganglia, midbrain and cerebellum. Neural dynamics in these regions couple sensory evidence to movement preparation while remaining distinct from movement execution. At the circuit level, targeted activity manipulations and recordings reveal that the anterior tip of secondary motor cortex (atMOs) implements “cognitive control” through an activity 'state clamping' mechanism, dynamically controlling population dynamics in the striatum to enable goal-directed sensorimotor mapping. This mechanism operates in a neural dimension orthogonal to evidence accumulation, allowing precise control over whether sensory evidence leads to action. Together, these findings reveal how brain-wide dynamics coordinate with multi-regional circuit mechanisms to selectively engage learned sensorimotor transformations according to current behavioral goals.