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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 ; Pubmed Abstract

Comments on News and Primary Papers

Primary Papers: Methamphetamine-Induced Disruption of Frontostriatal Reward Learning Signals: Relation to Psychotic Symptoms.

Comment by:  Lynn Selemon
Submitted 23 June 2013
Posted 23 June 2013

Bernacer et al. make an important contribution to the field by linking the basic neurobiologic mechanism underlying motivation and learning to psychosis in mental illness. It is particularly interesting that the potent D2 receptor antagonist amisulpride did not prevent the methamphetamine-induced disruption of incentive value signaling in the ventral prefrontal cortex. The authors discuss other possible pharmacologic sites, among them the D1 receptor, as the active site for methamphetamine in the cortex. I look forward to future studies by this group that elucidate the neurotransmitter(s) that may be involved.

View all comments by Lynn Selemon

Primary Papers: Methamphetamine-Induced Disruption of Frontostriatal Reward Learning Signals: Relation to Psychotic Symptoms.

Comment by:  J. Daniel Ragland
Submitted 25 June 2013
Posted 25 June 2013
  I recommend this paper

Phenomenologically, there can be striking similarities between acute psychotic symptoms in individuals with schizophrenia and individuals with acute methamphetamine abuse. There is also growing evidence that both conditions disrupt dopamine-rich frontostriatal brain networks, leading to similar changes in cognition, such as impaired performance on cognitive control tasks such as the Stroop (e.g., Salo et al., 2011). This current study by Bernacer and colleagues is one of the first to investigate the impact of methamphetamine on reward learning in healthy participants and uses fMRI, a methamphetamine challenge and a pharmacological intervention (the antipsychotic amisulpride) to get at putative monoaminergic mechanisms. fMRI results were convincing in linking reward prediction error to the ventral striatum and incentive value to the ventromedial prefrontal cortex. The disruptive effects of methamphetamine challenge on task performance and fMRI activation in candidate brain regions were also consistent with the notion that methamphetamine disrupts frontostriatal network function.

The links to psychosis were intriguing, but not universal. Increases in psychotic symptoms with methamphetamine challenge were associated with disruption in ventromedial prefrontal and posterior cingulate cortex, and related processing of incentive value. However, pretreatment with amisulpride did not rescue task performance or fMRI activation following drug challenge, and psychotic symptoms were not associated with reward prediction errors or related activation in the ventral striatum. The lack of an antipsychotic effect may not be surprising in retrospect, as antipsychotic efficacy depends upon sustained treatment. However, the lack of association with reward prediction errors and related brain function is more difficult to reconcile, as reward prediction errors are a central component of reward learning deficits in psychotic disorders such as schizophrenia (e.g., Morris et al., 2012). Nevertheless, this research design is an impressive way to obtain convergent data linking reinforcement learning with clinical phenomenology, and functional and pharmacological brain mechanisms. Future studies employing this approach with a patient group of first-episode psychosis patients before and after treatment would be most informative.


Salo R, Ravizza S, Fassbender C (2011). Overlapping cognitive patterns in schizophrenia and methamphetamine dependence. Cogn Behav Neurol, 24(4): 187-193. Abstract

Morris RW, Vercammen A, Lenroot R, Moore L, Langton JM, Short B, Kulkarni J, Curtis J, O'Donnell M, Weickert CS, Weickert TW (2012). Disambiguating ventral striatum fMRI-related BOLD signal during reward prediction in schizophrenia. Mol Psychiatry, 17(3):235, 280-289. Abstract

View all comments by J. Daniel Ragland