The prefrontal cortex as a critical gate of negative affect and motivation in alcohol use disorder

Abstract

The prefrontal cortex (PFC) represents and executes the highest forms of goal-directed behavior, and has thereby attained a central neuroanatomical position in most pathophysiological conceptualizations of motivational disorders, including alcohol use disorder (AUD). Excessive, intermittent exposure to alcohol produces an allostatic dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis along with heightened forebrain glucocorticoid signaling that can damage PFC architecture and function. Negative affective states intimately associated with the transition to alcohol dependence result not only from a dysregulated HPA axis, but also from the inability of a damaged PFC to regulate subcortical stress and reinforcement centers, including the ventral striatum and amygdala. Several cognitive symptoms commonly associated with severe AUD, ranging from poor risk management to the cognitive/affective dimension of pain, are likely mediated by altered function of key anatomical elements that modulate PFC executive function, including contributions from the cingulate cortex and insula. Future therapeutic strategies for severe AUD should focus on attenuating the deleterious effects of excessive stress hormone activity on cognitive/affective and motivational behaviors gated by the PFC.

Neurobiological Correlates of Pain Avoidance-Like Behavior in Morphine-Dependent and Non-Dependent Rats

“…We chose to investigate phosphoprotein-level neuroadaptations in motivation-related brain regions including the prefrontal cortex, striatum, and dorsal hippocampus. Dysregulation of signaling within these areas has been implicated in the transition to drug addiction (Edwards & Koob, 2010; Egli, et al, 2012; Pahng et al, 2017). Corticostriatal circuitry is also intimately involved in affective self-regulation (Woo et al, 2015) and behavior selection (Baliki and Apkarian, 2015) in chronic pain states, while functional impairments due to chronic pain have been reported in the prefrontal cortex (Apkarian et al, 2004; Metz et al, 2009), striatum (Baliki et al, 2012), and hippocampus (Mutso et al, 2012; Vachon-Presseau et al, 2013).…”

Sex Differences in Trauma-Related Psychopathology: a Critical Review of Neuroimaging Literature (2014–2017)

“…Most commonly, these regions have included the amygdala, limbic and salience hub linked to emotional processing and response [24, 25], hippocampus, associated with learning and memory [26], insula, a major salience hub implicated in self-referential processing [20], and prefrontal cortex (PFC). The PFC is involved in executive functions [27] and includes sub-regions such as the orbitofrontal (OFC; implicated in emotional processing [28]) and anterior cingulate (ACC; associated with monitoring [29]) cortices. More recently, the involvement of reward- and motivation-related striatal regions [30], most commonly implicated in depression [31] and substance use [32], has also been explored [33•, 34].…”

Improving cerebral oxygenation, cognition and autonomic nervous system control of a chronic alcohol abuser through a three-month running program

“…Studies have shown that alcoholic individuals have lower PFC volume, activity and oxygenation, with consequent impairment in cognitive functions ( Asensio et al, 2016 , Pahng et al, 2017 , Schecklmann et al, 2007 , Wang et al, 2016 ). This condition has been associated to compulsive behavior and greater chance for relapse ( Volkow et al, 2016 ).…”

“…Moreover, it has been widely shown to causes liver diseases and cancer ( Alcohol Consumption | Cancer Trends Progress Report, n.d. ). In the brain, deterioration of prosencephalic regions caused by alcohol abuse has been reported ( Asensio et al, 2016 , Pahng et al, 2017 ), with decreased oxygenation ( Schecklmann et al, 2007 ) and reductions of gray matter volume in the anterior cingulate and in the medial, orbitofrontal and prefrontal cortices ( Wang et al, 2016 ). Impairment in these structures has been accompanied by decreases in cognition ( Volkow, Koob, & McLellan, 2016 ) with lower control of impulsivity and emotional regulation, leading to inappropriate decision-making with further alcohol seeking behavior ( Goldstein & Volkow, 2011 ).…”