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Altered frontostriatal coupling in pre-manifest Huntington's disease: Effects of increasing cognitive load
- Publication Year :
- 2008
-
Abstract
- Background and purpose: Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre-symptomatic individuals with the Huntington’s disease (HD) gene mutation (pre-HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre-HD individuals. Methods: Sixteen healthy controls and sixteen pre-HD subjects were studied using functional MRI and a verbal working memory task with increasing cognitive load. Load-dependent functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) was investigated by means of psychophysiological interactions. Results: In pre-HD subjects, aberrant functional connectivity of the left DLPFC was found at high working memory load levels only. Compared with healthy controls, pre-HD individuals exhibited lower connectivity strength in the left putamen, the right anterior cingulate and the left medial prefrontal cortex. Pre-HD individuals close to the onset of motor symptoms additionally exhibited lower connectivity strength in the right putamen and the left superior frontal cortex. The connectivity strength in the left putamen was associated with several clinical measures including CAG repeat length, Unified Huntington's Disease Rating Scale motor score and predicted years to manifest symptom onset. Conclusion: These findings suggest that early prefrontal connectivity abnormalities in pre-HD individuals are modulated by cognitive demand.
- Subjects :
- Adult
Male
DNA Mutational Analysis
Psychophysiological interactions
Nerve Tissue Proteins
Gene mutation
Neuropsychological Tests
Gyrus Cinguli
Prefrontal cortex
Cognition
Huntington's disease
Pre-symptomatic
Age of Onset
Brain Mapping
Cognition Disorders
Corpus Striatum
Disability Evaluation
Disease Progression
Early Diagnosis
Female
Humans
Huntingtin Protein
Huntington Disease
Magnetic Resonance Imaging
Middle Aged
Neural Pathways
Nuclear Proteins
Prefrontal Cortex
Putamen
Functional neuroimaging
medicine
Neurology (clinical)
Neurology
Working memory
business.industry
medicine.disease
Consumer neuroscience
business
Neuroscience
Cognitive load
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....2cc24b068641730c124b097ab1f63fc0