Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism.
In this study, we tested the hypotheses that (1) the acquisition of sequential information is related to the integrity of dopaminergic input to the caudate nucleus; and (2) the integrity of dopaminergic input to the caudate nucleus correlates significantly with brain activation during sequence acquisition. Twelve early stage Parkinson's disease (PD) patients and six age-matched healthy volunteers were scanned using a dual tracer PET imaging design. All subjects were scanned with [(18)F]fluoropropyl-betaCIT (FPCIT) to measure striatal dopamine transporter (DAT) binding and with [(15)O]water to assess activation during a sequence learning task where movements were made to a repeating sequence of eight targets. Caudate and putamen DAT binding in the PD cohort was reduced by 15% and 43%, respectively. In PD, caudate DAT binding correlated with target acquisition (R = 0.57, P < 0.05), while putamen DAT binding did not correlate with performance. In volunteers, caudate DAT binding correlated with learning-related activation (P < 0.05, corrected for multiple comparisons) in the left dorsolateral and ventral prefrontal cortices, the anterior cingulate and premotor regions, and the right cerebellum. A significant correlation with caudate DAT binding was additionally detected in the right anteromedial thalamus, extending into the rostral midbrain. By contrast, in the PD cohort, most of these regional relationships were lost: Only ventral and dorsolateral prefrontal cortex activation correlated with caudate dopaminergic tone. Our findings suggest that sequence learning is normally associated with tight coupling between dopaminergic input to the caudate and thalamo-cortical functional activity. Despite minimal reductions in nigro-caudate input, PD patients demonstrate a loss of this coupling early in the disease.
Carbon
Maren
M
Center for Neurosciences, North Shore-Long Island Jewish Research Institute, New York, NY 11030, USA.
Ma
Yilong
Y
Barnes
Anna
A
Dhawan
Vijay
V
Chaly
Thomas
T
Ghilardi
Maria Felice
MF
Eidelberg
David
D
D000368:Aged; D001143:Arousal / Q000502:physiology*; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000000981:diagnostic imaging* / Q000503:physiopathology; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000503:physiopathology; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004292:Dominance, Cerebral / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007699:Kinesthesis / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000502:physiology*; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology; D011699:Putamen / Q000000981:diagnostic imaging / Q000503:physiopathology; D012691:Serial Learning / Q000502:physiology*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000503:physiopathology; D014055:Tomography, Emission-Computed; D014326:Tropanes
D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D004298:Dopamine