Thursday, April 13, 2006

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.

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At March 11, 2011 10:30 PM, Anonymous Murfomurf said...

I'm glad you put a plug in for Bob Oades! I've thought others were "rediscovering" work closely related to his over the years, but I've not been knowledgable enough to comment in journals. I worked with Bob for a few years in Adelaide, South Australia, where he was "forced" to help out on a project trialling fenfluramine with autistic kids- there was some sort of Jewish brotherhood between my boss Dr Leon Stern and Bob's bosses, Laurie & Gina Geffen, which Bob had been sucked into.

At May 01, 2011 1:08 AM, Anonymous Kay Walker said...

Here I am again- I have seen so many articles recently nibbling around the edges of the PhD I started in 1976 but never finished. I was trying to discover, by means of fine-grained observations via video, what was salient in the environment for ordinary babies vs. autistic kids (who ave a lot in common with psychotic adults in some aspects). I think I've found a place for Bob Oades work on tuning/switching in my own old work in psychology/cognitive science. I was sure that babies had to go through stages of finding facial features, then finding them interesting, then concentrating on them for information. Then babies go on to joint attention with adults and finally following what adults point towards. Whole books came out on the normal babies, but no one else looked at the autistic kids. My videos showed that autistic kids attended to very little except things they were obsessed with. The more intelligent & verbally able had some inclination to get information from faces and a few could follow a point, but usually just the hand. I interpreted all this as autistic kids not being "pre-programmed" properly to find the same things important as ordinary humans. To them the world would be confusing and anxiety provoking- as to animals that didn't know what other animals might prey on them vs. which things were food (or safe, eg. mum). I think something has gone wrong with neural fibres or function around the fusiform gyrus which has been found vital to face recognition. I think something never got tuned by whatever nor-adrenaline process and that their attentional switches [dopamine/serotonin] don't flip easily to allow transfer of attention from one thing to the next. So, if they find it feels safer to flick their fingers beside their eyes and get a constant stream of perfectly flickering light, they won't be easily distracted/switched to paying attention to another person's eyes or eye direction [which normal babies find very interesting]. Changing input to whatever sense is felt as very anxiety-provoking so autistic people may concentrate on their own input, as well as create it in the form of flicking or screaming- it blocks out the fearful stimuli [they don't have to switch]. I don't know if you look at this blog anymore, but thought you might be interested! Alternately, you may agree with the people who were supervising me and think I'm a bit nutty and don't know what I'm talking about! Meanwhile, I'm contacting Bob Oades and asking if he might like to do the necessary experimental studies to say if I am "on the right track" with the salience theme.


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