Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease
ABSTRACT Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the product of age and CAG repeat length (p < 0.0005). Dopamine D2 receptor availability measured by RAC-BP seems the most sensitive indicator of early neuronal impairment in PMC.
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ABSTRACT: Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, with neurodegeneration mainly affecting the striatum. We investigated executive functions related to response inhibition in (HD) and healthy controls by means of event-related potentials (ERP) in a simple Go/Nogo-task. In Nogo as opposed to Go trials two fronto-central ERP components are elicited: the Nogo-N2 and Nogo-P3. These components are supposed to depend on (medial) prefrontal regions, especially the anterior cingulate cortex (ACC). The results show that the Nogo-N2 did not differ between the groups, while the Nogo-P3 demonstrated a strong attenuation in the HD-group, which also showed more false alarms in the Nogo-condition. Using sLORETA it is shown that this attenuation was related to the medial frontal cortex, especially the ACC, and superior frontal cortex areas. Moreover, the attenuation was related to the underlying genetic disease load (CAG-index). The decline in inhibition is likely mediated via a dysfunction in the ACC, which is known to be dysfunctional in HD. Moreover, the results may be interpreted that the decline in response inhibition in HD is gene-associated. The differentially affected Nogo-components suggest that they rely on different neuronal circuits, even within the ACC. For HD this suggests that this structure is not entirely dysfunctional.Neuropsychologia 05/2008; 46(5):1290-7. DOI:10.1016/j.neuropsychologia.2007.12.008 · 3.45 Impact Factor
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ABSTRACT: Huntington's disease (HD) is an autosomal dominant neurological disorder, with degeneration amongst others affecting the basal ganglia dopaminergic system. Recent findings suggest compensatory as well as pathogenetic mechanisms mediated via the adenosine receptor system in the presymptomatic stage (pHD) of HD. The adenosine receptor system is functionally related to the dopaminergic system. In this study, we assessed error processing, a dopamine-dependent cognitive function, using an event-related potential the error negativity (Ne/ERN) in pHD and controls. This was done by means of a flanker task. The Ne consists of a cognitive and a motor component, expressed via different frequency bands. Time-frequency decomposition of the Ne into delta and theta sub-components was applied to assess if degeneration or compensation predominantly involve cognitive or motor processes. No parameter of the behavioral data (reaction times, error frequency, corrections, post-error slowing) differed between the groups. A selective increase in the power of the cognitive delta-Ne component was found in pHD relative to controls inversely related to the estimated age of onset (eAO). Thus, the increase in the power of the cognitive delta-Ne component was stronger in pHD with an earlier eAO. An earlier eAO implies stronger pathogenetic mechanisms. Due to the behavioral data our results speak for a solely cognitive compensating-mechanism controlling performance monitoring in pHD. In contrast, correlations with eAO suggest that the increase in delta-Ne activity is also related to pathogenesis. It is proposed that compensation is a transient effect of the whole pathogenetic dynamics of HD, with these two processes not foreclosing each other.Neuropsychologia 11/2007; 45(13):2922-30. DOI:10.1016/j.neuropsychologia.2007.06.004 · 3.45 Impact Factor
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ABSTRACT: Brain imaging of cerebral blood flow and glucose metabolism has been playing key roles in describing pathophysiology of Parkinson's disease (PD) and Huntington's disease (HD), respectively. Many biomarkers have been developed in recent years to investigate the abnormality in molecular substrate, track the time course of disease progression, and evaluate the efficacy of novel experimental therapeutics. A growing body of literature has emerged on neurobiology of these two movement disorders in resting states and in response to brain activation tasks. In this paper, we review the latest applications of these approaches in patients and normal volunteers at rest conditions. The discussions focus on brain mapping studies with univariate and multivariate statistical analyses on a voxel basis. In particular, we present data to validate the reproducibility and reliability of unique spatial covariance patterns related with PD and HD.Molecular Imaging & Biology 06/2007; 9(4):223-33. DOI:10.1007/s11307-007-0085-4 · 2.87 Impact Factor