Dopa-mine and You, Dopa-mine and Me. . .

...always have a lot of fun together!





There was a symposium entitled "Dopaminergic Modulation of the Adaptive Mind" at the recent Cognitive Neuroscience meeting. Although behavioral pharmacologists have studied the effects of dopaminergic (and noradrenergic and serotonergic) drugs in animals for years, only recently has a similar (albeit much less invasive) approach come into vogue in studies of human cognition. Part of this new-found trendiness comes from functional neuroimaging -- give a person a drug (versus placebo), see what activation changes occur in the brain when the subject is doing XYZ (or CPT-AX) task. However, many neuroscientists (such as Robert Oades) have been interested in these questions for over 20 years, but their work has been mostly neglected by cognitive types:

Oades RD (1985). The role of noradrenaline in tuning and dopamine in switching between signals in the CNS. Neurosci Biobehav Rev. 9(2):261-82.

Neuronal catecholaminergic activity modulates central nervous function. Specifically noradrenaline can exert a tuning or biassing function whereby the signal to noise ratio is altered. Dopamine activity may promote switching between inputs and outputs of information to specific brain regions. It has been ten years since evidence for a tuning function was advanced for noradrenaline and in the last 5 years the switching hypothesis for dopamine has been tentatively put forward. Recent studies are reviewed to show that while catecholamine activity contributes to neural interactions in separate brain regions that give rise to the organization of different functions, their working principles may be common between species and independent of the nucleus of origin. Behavioral examples are discussed and an attempt is made to integrate this with evidence from intracellular recording studies. It is suggested that the tuning principle in noradrenergic systems is particularly important for the formation of associations and neural plasticity (interference control) and that the switching principle of dopaminergic systems modulates the timing, time-sharing and initiation of responses (program-control).

Hmm, that abstract looks remarkably similar to work published 5, 10, and 20 years later by other (computational-type) investigators, who are older than The Neurocritic¹ (and therefore should have some sense of history in the field. for shame! Anyway...)

Fortunately, Trevor Robbins (who has 431 articles listed in Pubmed) started off the morning with a review of the literature. Despite the fact that Professor Robbins has numerous publications of his own on the topic, he cited the work of the late Pat Goldman-Rakic to illustrate that the functional relationship between mesocortical DA activity and optimal cognitive function conforms to the Yerkes-Dodson law of arousal (inverted U-shaped function).

The second speaker, Roshan Cools, presented some interesting data from a small sample of "high" and "low" impulsive subjects, selected from the tails of 1200 students who were screened using the Barratt Impulsiveness Scale. The "high-impulsive" subjects performed worse than the "low-impulsive" on a switching task. Specifically, the cost of switching attention between stimulus types in a visual display was greater in the highly impulsive individuals. Bromocriptine, a dopamine D2 agonist, improved performance in the high-impulsives but impaired performance in the low-impulsive subjects.

But what differences in brain activity were observed, you may ask. Well, they saw changes in basal ganglia² activity after bromocriptine. So there we have it, presumed differences in baseline DA levels resulting in divergent patterns of performance in the two groups.

¹who was a precocious little child in 1985 but aware of that research at the time, I'll have you know.

²a member of the audience, however, asked why the basal ganglia and not the prefrontal cortex, since the study used a switching task. Hmm, could be because D2 receptors are more common in the BG than in the PFC, although the speaker did not use that as a retort. It could also be because the subjects were switching between stimuli rather than switching between abstract rules, but who knows.