Figure 2. Temporally-precise uncertainty-related modulation of wide-scale cortical computations by the basal forebrain (BF).

(A-C) BF broadcasts the timing and predictions of behaviorally salient, aversive, valuable, and uncertain events [44, 45, 63, 64]. (A) Location of the basal forebrain shown on sagittal MRI of a macaque monkey brain. Red arrows represent the wide projections of BF neurons to the cortical mantle. MR image is reproduced from reference [45]. (B) Two functional classes of BF neurons: “Type 1” neurons (top), which predict uncertain salient events, and “Type 2” neurons (bottom) that encode these events’ salience and timing, after they occur. The neurons’ average activity is separated to trials in which five distinct probabilistic reward predictions were made with five distinct visual cues. The outcomes (reward or no reward) occurred 2.5 seconds after each prediction. Both ramping (Type 1) and phasic (Type 2) neurons are found in the medial and lateral regions of the BF, though the medial BF is particularly enriched with ramping (Type 1, top) neurons (reproduced from [45]). (C) Temporally precise modulation and coordination of cortical activity by the BF, constrained by anatomical biases in BF connectivity to distinct functional regions of the cortical mantle [60, 65]. Thickness of red arrows from the medial and lateral BF denotes connectivity strength (red arrows, on left). Cartoon of example cells’ responses in sensory and higher-order cortices (top square) with (red) and without (gray) BF-mediated gain modulation to external events that predict behaviorally/motivationally salient outcomes. This temporally precise gain enhancement across distinct cortical subregions may be crucial for rapid control of cognitive functions under uncertainty (Figure 1), such as prediction-mediated control of sensory processing resembling attention (black arrows on the right in top square). Furthermore, wide-scale temporally precise gain modulation may mediate spike-timing across many cortical areas to impact slower time scale changes for learning and memory (e.g. by enhancing prediction error or external salient event responses by ramping activity of Type 1 neurons).