Chronic alcohol exposure during critical developmental periods differentially impacts persistence of deficits in cognitive flexibility and related circuitry

Abstract

Cognitive flexibility in decision making depends on prefrontal cortical function and is used by individuals to adapt to environmental changes in circumstances. Cognitive flexibility can be measured in the laboratory using a variety of discrete, translational tasks, including those that involve reversal learning and/or set-shifting ability. Distinct components of flexible behavior rely upon overlapping brain circuits, including different prefrontal substructures that have separable impacts on decision making. Cognitive flexibility is impaired after chronic alcohol exposure, particularly during development when the brain undergoes rapid maturation. This review examines how cognitive flexibility, as indexed by reversal and set-shifting tasks, is impacted by chronic alcohol exposure in adulthood, adolescent, and prenatal periods in humans and animal models. We also discuss areas for future study, including mechanisms that may contribute to the persistence of cognitive deficits after developmental alcohol exposure and the compacting consequences from exposure across multiple critical periods.

Keywords: Adolescent alcohol exposure; Cognition; Cognitive flexibility; Fetal alcohol spectrum disorder; Prefrontal cortex; Prenatal alcohol exposure.

Figure 1.

Brain circuitry involved in cognitive flexibility in human and rodent brains. Across species, subregions of the prefrontal cortex (PFC) and striatum are required for flexible decision-making processes. In particular, the dorsomedial striatum (DMS) and medial PFC (mPFC) guide goal-directed behaviors, and the orbitofrontal cortex (OFC), in concert with the anterior cingulate cortex (ACC), regulates positive and negative feedback to make subsequent decisions. This intricate circuitry requires sensory integration by the thalamus (THAL) and basolateral amygdala (BLA), as well as rewarding processes via the ventral tegmental area (VTA) and lateral habenula (LHb), and finally memory consolidation from the hippocampus (HIPP). Additional regions depicted: DLS=dorsolateral striatum; IL=infralimbic cortex; NAc=nucleus accumbens; PRL=prelimbic cortex; SN=substantia nigra.