Dorsolateral Frontal Cortex, Inferior Frontal Cortex, Hippocampus: Cognitive Control, Delayed Gratification, and Memory

Addiction also entails perturbations in cortically regulated cognitive and emotional processes, which cause the overvaluing of drug reinforcers at the expense of the undervaluing of natural reinforcers, and deficits in inhibitory control of drug responses (Goldstein and Volkow, 2002). As a result, an underperforming prefrontal system is widely believed to be crucial to the addiction process.

One of the components in such a system is impulse control, which is among the most robust cognitive risk factors for substance use disorders. Cocaine appears to have a direct effect on the neurobiology underlying impulse control. After an intravenous injection of cocaine, cocaine users actually showed an improvement in a motor response inhibition task and concomitant increased activation in their right dorsolateral and inferior frontal cortices (Garavan et al, 2008). Because these areas are considered to be important in impulse control, this observation suggests that some of the acute effects of cocaine could in fact mediate a transient reversal of the chronic hypofunction in impulse control circuitry.

Another important function that resides in frontocortical areas is the ability to choose between small and immediate rewards compared to large but deferred rewards, which can be measured using a delayed discounting task. A recent study found that both the dorsolateral and inferolateral frontal cortex gray matter volumes inversely correlated with preference for immediate gratification during decision-making (Bjork et al, 2009). This finding suggests that abnormalities in frontocortical regions may underlie the inability to delay gratification, a trait that is characteristic of addiction and other psychiatric disorders.

The neural substrates of memory and conditioned learning are among the major circuits undergoing aberrant neuroadaptations in response to chronic drug exposure (Volkow et al, 2004a). Different memory systems have been proposed to be involved in drug addiction, including conditioned-incentive learning (via the nucleus accumbens and amygdala), habit learning (via the caudate and putamen), and declarative memory (via the hippocampus; White, 1996), which is the focus of this section.

Over the past decade, many provocative animal studies have suggested that addictive drugs can disrupt neurogenesis in the adult hippocampus (Canales, 2007). Damage to the ventral subiculum of the hippocampus was shown to affect cocaine self-administration in rats (Caine et al, 2001). Such observations have provided insights into the possible involvement of a dysregulated hippocampus in human addiction. This hypothesis is an extension of current knowledge because the hippocampus is broadly viewed as important in contextual conditioning, namely in the processing of contextual cues by which memories can be accessed and retrieved. In fact, declarative memory has been long recognized to be involved in learning and the linking of affective conditions or circumstances with drug-taking experiences. Studies with PET and functional magnetic resonance imaging have shown that cue-elicited craving, as well as acute intoxication, activates the hippocampus and amygdala (Volkow et al, 2004a). For example, the craving that cocaine users experience while exposed to drug-related stimuli is accompanied by blood flow increases in a distributed region implicated in several forms of memory, including the amygdala (Childress et al, 1999; Grant et al, 1996; Kilts et al, 2001) and hippocampus (Kilts et al, 2001).

Therefore, new approaches to disrupt memory reconsolidation may help erode the strong associations between context and drug (Lee, 2008; Lee et al, 2005). Interestingly, β-blockers have already shown a promising capacity to inhibit conditioned responses to both natural reinforcers and aversive stimuli (Miranda et al, 2003). Moreover, results from a more recent study suggest that drug-induced conditioned responses may also be sensitive to β-blockade treatment (Milton et al, 2008). Similarly, further research on GABA-enhancing drugs also seems warranted. GABAergic stimulation, which can attenuate Pavlovian conditioning, appears to disrupt the response to drugs of abuse in animals (Volkow et al, 2004a) and may be a useful strategy to treat addiction in humans (Dewey et al, 1998).

Date: 2016-06-12; view: 270