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Imaging insights into basal ganglia function, Parkinson's disease, and dystonia.

ABSTRACT: Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson's disease from healthy controls, and show great promise for differentiation between Parkinson's disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson's disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson's disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression.

SUBMITTER: Stoessl AJ

PROVIDER: S-EPMC4454525 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Imaging insights into basal ganglia function, Parkinson's disease, and dystonia.

Stoessl A Jon AJ Lehericy Stephane S Strafella Antonio P AP

Lancet (London, England) 20140618 9942

Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advance ...[more]

PMID: 24954673

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Project description:Basal ganglia (BG) circuitry plays a crucial role in the control of movement. Degeneration of its pathways and imbalance of dopaminergic signalling goes along with movement disorders such as Parkinson's disease. In this study, we explore the interaction of degeneration in two BG pathways (the nigro-striatal and dentato-pallidal pathway) with D2 receptor signalling to elucidate an association to motor impairment and medication response. Included in the study were 24 parkinsonian patients [male, 62?years (± 9.3 SD)] compared to 24 healthy controls [male, 63?years (± 10.2 SD)]; each participant passed through three phases of the study (i) acquisition of metadata/clinical testing, (ii) genotyping and (iii) anatomical/diffusion MRI. We report a decline in nigro-striatal (p?<?.003) and dentato-pallidal (p?<?.0001) connectivity in the patients compared to controls, which is associated with increasing motor impairment (relating to nigro-striatal, r?=?-0.48; p?<?.001 and dentato-pallidal connectivity, r?=?-0.36; p?=?.035). Given, that variations of the ANKK1 Taq1 (rs 1,800,497) allele alters dopamine D2-dependent responses, all participants were genotyped respectively. By grouping patients (and controls) according to their ANKK1 genotype, we demonstrate a link between D2 receptor signalling and decline in connectivity in both investigated pathways for the A1- variant (nigro-striatal pathway: r?=?-0.53; p?=?.012, dentato-pallidal pathway: r?=?-0.62; p?=?.0012). In patients with the A1+ variant, we only found increased brain connectivity in the dentato-pallidal pathway (r?=?0.71; p?=?.001) correlating with increasing motor impairment, suggesting a potentially compensatory function of the cerebellum. Related to medication response carriers of the A1+ variant had a better drug effect associated with stronger brain connectivity in the nigro-striatal pathway (r?=?0.54; p?<?.02); the A1- group had a good medication response although nigro-striatal connectivity was diminished (r?=?-0.38; p?<?.05); these results underscore differences in receptor availability between both groups in the nigro-striatal pathway. No effect onto medication response was found in the dentato-pallidal pathway (p?>?.05). Interplay between basal ganglia connectivity and D2 receptor availability influence the clinical presentation and medication response of parkinsonian patients. Furthermore, while current models of basal-ganglia function emphasize that balanced activity in the direct and indirect pathways is required for normal movement, our data highlight a role of the cerebellum in compensating for physiological imbalances in this respect.

Dataset Information

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia.

Publications

Imaging insights into basal ganglia function, Parkinson's disease, and dystonia.

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