July 10, 2013. Disruptions in how the brain assigns value to a stimulus or memory may underlie features of psychosis, according to a study published online June 4 in the American Journal of Psychiatry. Led by Graham Murray of the University of Cambridge, U.K., the study examined the effects of a low dose of methamphetamine, which boosts dopamine as well as norepinephrine and serotonin, on reward-learning tasks in 18 healthy controls. Using functional magnetic resonance imaging (fMRI), the researchers found that the drug attenuated signals in the ventromedial prefrontal cortex (also called the orbitofrontal cortex) and that these reductions correlated with the degree of psychotic symptoms experienced.
The results support the idea that symptoms of schizophrenia can stem from reward learning, in which associations are made between a stimulus or action and an outcome. Faulty reward learning could lead people to misjudge the relevance of something or to mistakenly associate unconnected ideas or events—processes that could build delusional beliefs (Kapur et al., 2003) or the profound apathy characteristic of negative symptoms (see SRF related news story). Typically, reward learning involves connections between the ventral striatum, which encodes prediction error signals, and the ventromedial prefrontal cortex, which represents value. In the new study, the researchers used methamphetamine to tweak how the circuitry worked and to see if anything resembling psychosis resulted.
When subjects were under the influence of methamphetamine, first author Javier Bernacer and colleagues write, the learning paradigm produced attenuated signals in both the ventral striatum and the cortex relative to placebo, but only the cortical value signals varied according to degree of psychosis. The researchers also found that reduced signals in the posterior cingulate cortex, a region also implicated in encoding value, correlated with greater psychosis symptoms. Methamphetamine also slowed the rate of learning, though it did not make a difference in what was ultimately learned. Amisulpride, a selective dopamine D2 receptor blocker, did not alter the effects of methamphetamine. This suggests that other neuromodulatory pathways impinge on reward-learning circuitry and parsing these may offer a fuller picture of the mechanisms of psychosis.—Michele Solis.
Bernacer J, Corlett PR, Ramachandra P, McFarlane B, Turner DC, Clark L, Robbins TW, Fletcher PC, Murray GK. Methamphetamine-Induced Disruption of Frontostriatal Reward Learning Signals: Relation to Psychotic Symptoms. Am J Psychiatry. 2013 Jun 4. Abstract