Elsevier

Biological Psychiatry

Volume 59, Issue 10, 15 May 2006, Pages 898-907
Biological Psychiatry

Review
Molecular Imaging of the Dopaminergic System and its Association with Human Cognitive Function

https://doi.org/10.1016/j.biopsych.2006.03.004Get rights and content

Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) has recently been used to examine dopamine (DA) function and its relationship with cognition in human subjects. This article will review PET and SPECT studies that have explored the relationship between cognitive processes and components of the DA system (pre-, intra-, and postsynaptic) in healthy and patient populations such as Parkinson’s disease (PD), schizophrenia, Huntington’s disease, and aging. It is demonstrated that DA activity modulates a range of frontal executive-type cognitive processes such as working memory, attentional functioning, and sequential organization, and alterations of DA within the fronto–striato–thalamic circuits might contribute to the cognitive impairments observed in PD, schizophrenia, and normal aging. Although associations between DA and cognitive measures need to be considered within the context of fronto–striato–thalamic circuitry, it is suggested that striatal (especially caudate) DA activity, particularly via D2 receptors, might be important for response inhibition, temporal organization of material, and motor performance, whereas cortical DA transmission via D1 receptors might be important for maintaining and representing on-going behavior.

Section snippets

Assessment of Pre-, Intra-, and Postsynaptic Components of the DA System

Molecular imaging with PET and SPECT is a nuclear medicine technique that uses radiopharmaceuticals to image the regional distribution and kinetics of chemical compounds within the brain. A wide range of PET and SPECT radiotracers have become available that can assess presynaptic, postsynaptic, and intrasynaptic components of the DA system (see Figure 1). Presynaptic markers of DA neurons include [18F]FDOPA and radioligands of the DA transporter (DAT). Postsynaptic components of the DA system

Striatal [18F]FDOPA Studies in Parkinson’s Disease

[18F]FDOPA PET is a useful tool to quantify the loss of nigrostriatal DA terminal function in PD and has been used to monitor disease severity and progression, detect preclinical disease states, and differentiate idiopathic PD from other parkinsonian syndromes (for review, see Heiss and Hilker 2004); however, the clinical manifestations of PD are not only restricted to motor deterioration. Cognitive impairment, usually described as subcortical-frontal in nature, and dementia are common in PD (

Dopamine D2 Receptors

Experimental and blood flow studies in animals and humans have demonstrated some relationships between D2 receptors, presumably acting within the striatum, and cognitive processes, particularly in switching behavior and aspects of working memory and planning (Arnsten et al 1995, Mehta et al 1999, Mehta et al 2003). Molecular imaging studies have recently explored the influence of striatal D2 receptor changes on cognition in aging and certain neurological and psychiatric disorders (Table 2).

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Dopamine Release and Cognitive Function

Neuroreceptor imaging with PET can not only be used to measure the specific molecular target but also to estimate synaptic concentration of endogenous neurotransmitters. The basis of this approach is that radioligands compete with the endogenous neurotransmitter for binding to receptors. Thus, higher synaptic neurotransmitter concentrations are associated with lower radioligand binding and vice versa.

Since the late 1980s, this technique has been used to estimate the concentration of endogenous

Summary

In recent years, molecular imaging with PET and SPECT has provided a new approach to examining DA and its role in a variety of cognitive processes, particularly those subserved by the fronto–striato–thalamic circuitry. In light of the reviewed molecular imaging studies, it seems that a range of cognitive tasks are associated with changes in pre- and postsynaptic components of the DA system within the fronto–striato–thalamic circuitry. The fact that correlations between DA indices and cognitive

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