Invited Article: Functional imaging in Parkinson disease

Abstract

Objective: Functional imaging techniques represent useful tools to assess in vivo the neurochemical alterations and functional connectivity in Parkinson disease (PD). Here, the authors review the various approaches and potential application of these imaging techniques to the study of PD.

Method: Radiotracer imaging using dopaminergic markers facilitates assessment of pre- and postsynaptic nigrostriatal integrity, while imaging with other appropriate radiotracers explores nondopaminergic neurotransmitter function, local metabolism, blood flow, and mechanisms potentially related to disease progression and pathogenesis. Activation studies using functional MRI detect blood oxygen level dependent signal, as an indirect marker of neuronal activity.

Result: Functional imaging techniques have been applied to infer the potential role of inflammation and other factors in etiopathogenesis as well as to study compensatory and regulatory mechanisms in early PD and subclinical disease in genetic forms of PD. Imaging studies also help to understand the neurobiological basis of motor and nonmotor complications. Recent reports suggest a role for striatal dopaminergic transmission in modulating neurobehavioral processes including the placebo effect in PD. Although functional imaging has been employed to monitor disease progression, the discordance between clinical outcome and imaging measures after therapeutic interventions precludes their use as surrogate end points in clinical trials. Beyond these limitations and potential challenges, imaging techniques continue to find wide application in the study of PD.

Conclusion: Functional imaging can provide meaningful insights into mechanisms underlying various aspects of motor and nonmotor dysfunction in Parkinson disease and the role of striatal dopaminergic transmission in behavioral processes beyond motor control. These modalities hold promise to study the preclinical phase and to elucidate further the benefits and complications of surgical interventions and the utility of neuroprotective strategies.

GLOSSARY: AADC = aromatic amino acid decarboxylase; AD = Alzheimer disease; BOLD = blood oxygen level dependent; DA = dopamine; DAT = DA transporter; DBS = deep brain stimulation; DLB = dementia with Lewy bodies; DLPFC = dorsolateral prefrontal area; fMRI = functional MRI; l-DOPA = l-3,4-dihydroxyphenylalanine; DRT = DA replacement therapy; PD = Parkinson disease; PDCP = PD-related cognitive pattern; PDD = PD dementia; PDRP = PD-related metabolic covariance pattern; RAC = raclopride; SMA = supplementary motor area; TH = tyrosine hydroxylase; VMAT2 = vesicular monoamine transporter type 2.