Academic journal article Cognitive, Affective and Behavioral Neuroscience

Individual Capacity Differences Predict Working Memory Performance and Prefrontal Activity Following Dopamine Receptor Stimulation

Academic journal article Cognitive, Affective and Behavioral Neuroscience

Individual Capacity Differences Predict Working Memory Performance and Prefrontal Activity Following Dopamine Receptor Stimulation

Article excerpt

Dopamine receptors are abundant in the prefrontal cortex (PFC), a critical region involved in working memory. This pharmacological fMRI study tested the relationships between dopamine, PFC function, and individual differences in working memory capacity. Subjects performed a verbal delayed-recognition task after taking either the dopamine receptor agonist bromocriptine or a placebo. Behavioral effects of bromocriptine treatment depended on subjects' working memory spans, with the greatest behavioral benefit for lower span subjects. After bromocriptine, PFC activity was positively correlated with a measure of cognitive efficiency (RT slope) during the probe period of the task. Less efficient subjects with slower memory retrieval rates had greater PFC activity, whereas more efficient subjects had less activity. After placebo, these measures were uncorrelated. These results support the role of dopamine in verbal working memory and suggest that dopamine may modulate the efficiency of retrieval of items from the contents of working memory. Individual differences in PFC dopamine receptor concentration may thus underlie the behavioral effects of dopamine stimulation on working memory function.

Working memory refers to those processes that support the short-term maintenance or manipulation of relevant information when it is no longer present to guide behavior. Monkey physiology and human functional neuroimaging studies support the critical involvement of the prefrontal cortex (PFC) in working memory (Curtis & D'Esposito, 2003; Fuster, 1997). The PFC is the main target of extensive dopamine projections from the midbrain. In addition, the nigrostriatal dopamincrgic pathway innervates the basal ganglia, which also have direct and extensive connections with PFC (Cooper, Bloom, & Roth, 1991 ). An early study demonstrated that depleting PFC dopamine, but not norepinephrine or serotonin, caused performance deficits equivalent to PFC lesions in monkeys performing a delayed-response task (Brozoski, Brown, Rosvold, & Goldman, 1979). Later animal work demonstrated that endogenous baseline dopamine levels and evoked release of dopamine influence performance on delayed-response tasks. For example, the amount of dopamine released in the PFC is positively correlated with accurate memory performance (Floresco & Phillips, 2001; Phillips, Ahn, & Floresco, 2004). Also, delayed-response tasks elicit increases in extracellular PFC dopamine that are not seen when performance is guided by visual cues alone (Watanabe, Kodama, & Hikosaka, 1997). Application of dopamine to the PFC increases task-related activity, and it does so by increasing the signal-to-noise ratio (Durstewitz & Seamans, 2002; Sawaguchi, Matsumura, & Kubota, 1990b).

There is also evidence suggesting that D1 and D2 receptor family activity may affect different components of working memory. Since there are currently no D1-selective agonists approved for human use, most substantiating evidence comes from neurophysiological studies of primates performing delayed-recognition tasks. Delay-related processing may be most sensitive to Dl receptor activation, because Dl agonists increase and Dl antagonists reduce delay period activity in the primate PFC (Sawaguchi, 2001; Sawaguchi, Matsumura, & Kubota, 1988). In contrast, effects of selective D2 receptor agonists and antagonists suggest that D2 receptor activation is most critical for response preparation processes (Wang, Vijayraghavan, & Goldman-Rakic, 2004). Thus, dopamine appears to play a critical role in working memory function, and activation of different receptor families may selectively influence component processes of working memory (Cohen, Braver, & Brown, 2002; Cools & Robbins, 2004).

Human studies have also provided support for a relationship between dopamine and working memory. For example, young subjects' performance on a spatial delayed-response task was improved by low doses of bromocriptine, a D2 dopamine receptor agonist (Luciana & Collins, 1997; Luciana, Depue, Arbisi, & Leon, 1992), and pergolide, a mixed D1-D2 receptor agonist (Müller, von Cramon, & Pollmann, 1998). …

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