title: Aberrant connectivity of lateral prefrontal networks in presymptomatic Huntington's disease.
abstract: In clinically presymptomatic individuals with the Huntington's disease (HD) gene mutation, functional neuroimaging data have suggested a dysfunction of multiple cortical and subcortical regions including the prefrontal and parietal cortex, as well as the striatum. Although it has been hypothesized that these activation differences most likely reflect aberrant corticostriatal circuits, the functional coupling of neural networks associated with cognitive performance has not been investigated so far. In this study, we used functional magnetic resonance imaging (fMRI) and multivariate analytic techniques to investigate memory-related patterns of functional connectivity in healthy controls (n=16) and pre-HD individuals (n=16). Independent component analyses (ICA) revealed distinct bilateral frontostriatal and frontoparietal networks that were activated during a verbal working memory paradigm in both healthy controls and pre-HD subjects. Compared with healthy controls, pre-HD individuals exhibited lower functional connectivity in left lateral prefrontal and parietal regions as well as in the bilateral putamen. Functional connectivity indices in the left putamen were negatively correlated with the CAG repeat size and the UHDRS behavioral score, and positively correlated with the predicted years to manifest symptom onset. The connectivity of the right putamen was negatively correlated with the UHDRS motor score. In pre-HD individuals, these results suggest an early frontostriatal and frontoparietal deficit of dissociable functional networks associated with executive processing.
authors.affiliation: Department of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12-14 89075 Ulm, Germany. christian.wolf@uni-ulm.de
authors.forename: Robert Christian
authors.initials: RC
authors.lastname: Wolf
authors.forename: Fabio
authors.initials: F
authors.lastname: Sambataro
authors.forename: Nenad
authors.initials: N
authors.lastname: Vasic
authors.forename: Carlos
authors.initials: C
authors.lastname: Schönfeldt-Lecuona
authors.forename: Daniel
authors.initials: D
authors.lastname: Ecker
authors.forename: Bernhard
authors.initials: B
authors.lastname: Landwehrmeyer
mesh_terms: D000328:Adult; D017668:Age of Onset; D001931:Brain Mapping; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D003342:Corpus Striatum / Q000503:physiopathology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009483:Neuropsychological Tests; D009687:Nuclear Proteins / Q000235:genetics; D010296:Parietal Lobe / Q000503:physiopathology; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011699:Putamen / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins