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The Journal of Neuroscience, October 15, 2002, 22(20):9099-9103

Dopamine Modulates the Response of the Human Amygdala: A Study in Parkinson's Disease

Alessandro Tessitore¹, Ahmad R. Hariri¹, Francesco Fera¹, William G. Smith¹, Thomas N. Chase², Thomas M. Hyde¹, Daniel R. Weinberger¹, and Venkata S. Mattay¹

¹ Clinical Brain Disorders Branch, National Institute of Mental Health, and ² Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892

In addition to classic motor signs and symptoms, Parkinson's disease (PD) is characterized by neuropsychological and emotional deficits, including a blunted emotional response. In the present study, we explored both the neural basis of abnormal emotional behavior in PD and the physiological effects of dopaminergic therapy on the response of the amygdala, a central structure in emotion processing. PD patients and matched normal controls (NCs) were studied with blood oxygenation level-dependent functional magnetic resonance imaging during a paradigm that involved perceptual processing of fearful stimuli. PD patients were studied twice, once during a relatively hypodopaminergic state (i.e., 12 hr after their last dose of dopamimetic treatment) and again during a dopamine-replete state. The imaging data revealed a robust bilateral amygdala response in NCs that was absent in PD patients during the hypodopaminergic state. Dopamine repletion partially restored this response in PD patients. Our results demonstrate an abnormal amygdala response in PD that may underlie the emotional deficits accompanying the disease. Furthermore, consistent with findings in experimental animal paradigms, our results provide in vivo evidence of the role of dopamine in modulating the response of the amygdala to sensory information in human subjects.

Key words: Parkinson's disease; dopamine; amygdala; modulating emotions; BOLD fMRI; depression

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22209099-05$05.00/0

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