Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 23, Pages 5976-5982Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1153-08.2008
Keywords
methylphenidate; dopamine; striatum; prefrontal cortex; reversal learning; fMRI
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Funding
- Medical Research Council [G0001354] Funding Source: Medline
- Wellcome Trust [076274/4/Z/04/Z] Funding Source: Medline
- Medical Research Council [G0001354, G0001354B] Funding Source: researchfish
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Complete understanding of the neural mechanisms by which stimulants such as methylphenidate ameliorate attention deficit hyperactivity disorder is lacking. Theories of catecholamine function predict that the neural effects of stimulant drugs will vary according to task requirements. We used event-related, pharmacological functional magnetic resonance imaging to investigate the effects of 60 mg of methylphenidate, alone and in combination with 400 mg of sulpiride, on blood oxygenation level-dependent ( BOLD) signal in a group of 20 healthy participants during probabilistic reversal learning, in a placebo-controlled design. In a whole-brain analysis, methylphenidate attenuated BOLD signal in the ventral striatum during response switching after negative feedback but modulated activity in the prefrontal cortex when subjects maintained their current response set. The results show that the precise neural site of modulation by methylphenidate depends on the nature of the cognitive subprocess recruited.
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