Dopamine modulates the response of the human amygdala: a study in Parkinson's disease.
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., > or =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.
Tessitore
Alessandro
A
Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1384, USA.
Hariri
Ahmad R
AR
Fera
Francesco
F
Smith
William G
WG
Chase
Thomas N
TN
Hyde
Thomas M
TM
Weinberger
Daniel R
DR
Mattay
Venkata S
VS
D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001519:Behavior; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000503:physiopathology*; D010364:Pattern Recognition, Visual; D010775:Photic Stimulation; D011930:Reaction Time; D012016:Reference Values
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D004298:Dopamine