Pharmacological MRI mapping of age-associated changes in basal ganglia circuitry of awake rhesus monkeys

Zhiming Zhang, Anders Andersen, Richard Grondin, Tracy Barber, Robin Avison, Greg Gerhardt, Don Gash

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


While the pathophysiological changes induced by the loss of dopamine innervation in the basal ganglia by Parkinson's disease (PD) are well studied, little is known about functional changes in the neural circuitry of this area during normal aging. Here we report the first survey of age-associated changes in the basal ganglia of behaviorally characterized, awake rhesus monkeys, using pharmacological MRI to map responses to dopaminergic stimulation. Apomorphine, a mixed D1/D2 dopamine receptor agonist, evoked little change in the substantia nigra (SN) of aged animals while significantly reducing activation in young adult monkeys. Compared to young animals, both apomorphine and D-amphetamine (which increases synaptic dopamine levels) significantly increased activation of the aged rhesus globus pallidus externa (GPe). In addition, the aged animals showed decreased activity in the putamen in response to D-amphetamine administration. Although the responses in the SN and putamen of the aged monkeys differed from those in animal models of PD, the apomorphine-evoked activation of their GPe corresponded with apomorphine-induced increases in neuronal activity seen in Parkinson's patients and animal models. Given the major role of the GPe in regulating motor behavior, the altered responses in the aged GPe may contribute significantly to the motor slowing and movement dysfunctions characterizing advanced age.

Original languageEnglish
Pages (from-to)1159-1167
Number of pages9
Issue number5
StatePublished - 2001

Bibliographical note

Funding Information:
We thank Liya Liu, Sheila McLean, Agnes Bognar, Peter Hardy, William Rayens, and Xia Wang for their assistance. The research in this report was supported by USPHS NIH Grants AG13494, NS39787, and MH01245.


  • Aging
  • Amphetamine
  • Apomorphine
  • Caudate nucleus
  • Globus pallidus externa
  • Globus pallidus interna
  • MRI
  • Putamen
  • Rhesus monkey
  • Substantia nigra

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


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