Neural circuitry associated with risk for alcohol use disorders.
- Authors
- Tessner, Kevin D; Hill, Shirley Y
- Year
- 2010
- Journal
- Neuropsychology review
- PMID
- 19685291
- DOI
- 10.1007/s11065-009-9111-4
- PMCID
- PMC3580188
The core features of risk for alcohol use disorders (AUD), including behavioral disinhibition, affective dysregulation, and executive dysfunction, map onto distinct neural circuits that have been found to be abnormal in the offspring of alcohol dependent individuals. Components of the cerebellothalamocortical system and the extended limbic network may provide the underpinnings for the behavioral and emotional dysfunction observed in individuals at heightened risk for AUD. In addition, abnormalities in these structures appear to be altered in individuals with the predisposition for other psychiatric conditions that may share a similar genetic diathesis. This review proposes several neurobehavioral mechanisms of genetic vulnerability that may account for phenotypic characteristics in individuals at risk for AUD.
According to Schmahmann and Pandya (1997), the cerebrocerebellar circuit is composed of a feedforward limb that includes the corticopontine and pontocerebellar mossy fiber projections, and a feedback loop that contains the cerebellothalamic and thalamocortical pathways. The corticopontine pathway originates in the Vb layer of cerebral cortex and carries associative, sensory, and motor information from cortical neurons to neurons in the ventral pons. This information is directed to the cerebellum, and then projected to the thalamus through midbrain neurons of the red nucleus. Afferent pathways originating in the thalamus and projecting to the cortex complete the feedback loop
The extended limbic network consists of the basal forebrain, extended amygdala, and limbic lobe as described by Heimer and Van Hoesen (2006). To aid in visualization, not all structures or established projections are displayed. Regions of the basal forebrain, which includes areas usually referred to as the ventral striatum and nucleus accumbens, receive input from the extended amygdala, limbic lobe, and dopaminergic neurons of the ventral tegmental area. The extended amygdala includes the central and medial nuclei of the amygdala, their extensions to the bed nucleus of the stria terminalis, as well as downstream projections to the ventral striatum and nucleus accumbens. The extended amygdala has abundant associative connections with the hypothalamus as well as greater limbic lobe, including the hippocampus, cingulate and insular cortex, lateral basal cortical amygdala, and OFC
A schematic representation of the hypothalamic-pituitary-adrenocortical (HPA) system. Cortisol acts on the brain through binding to glucocorticoid receptors (GRs). Binding to these receptors in some regions of the brain, including the hippocampus, cingulate, and frontal cortex triggers a negative feedback system that dampens release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), thus modulating HPA activity
A schematic of the pathways that are of primary relevance to the core features of risk for alcohol dependence, particularly behavioral and affective dysfunction. The pathways are color coded to assist in visualization. The externalizing pathway to alcohol dependence (yellow) is associated with deficits in executive function and in inhibition and may share a common genetic diathesis with ADHD and conduct disorder. The brain regions of the externalizing pathway consist of the cerebellum (Crb), thalamus (Tha), and prefrontal cortex (PFC) which comprise the cerebellothalamocortical feedback system. The internalizing pathway to alcohol dependence (green) is associated with affective dysregulation (i.e. depression and anxiety-related traits), deficient mechanisms of motivation and reward (i.e. impulsivity and dysfunction in decision-making), and autonomic hyperarousal (i.e. harm avoidance and stress reactivity) through overlapping pathways of the HPA system (shown in red). The internalizing pathway includes the amygdala (Amy), orbitofrontal cortex (OFC), and hypothalamus (Hyp) and pituitary (Pit) of the HPA axis, as well as the brain regions of the mesolimbic dopamine pathway (NAc = nucleus accumbens; VTA = ventral tegmental area). The cingulate gyrus (CG) connects these pathways
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