23 research outputs found
Brain connectivity changes in autosomal recessive Parkinson Disease: a model for the sporadic form
Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients' cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptom
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Phonological dyslexia without phonological impairment?
RG, a patient with probable Alzheimer's disease, showed a severe impairment in nonword reading. RG's word reading was intact, for example, as demonstrated by her scores in standardised reading tasks, which were comparable to those of normal controls. No phonological impairment was apparent in speech production and comprehension. Moreover, RG performed well in a series of phonological tasks (e.g., production of a rhyming word, phoneme identification) on which patients with a reading deficit selective for nonwords have been reported to encounter problems. RG's data severely constrain reading models proposing that nonword reading deficits are caused by phonological deficits. However, RG's data are compatible with dual-route reading models, which do not propose a link between nonword reading deficits and phonological impairment
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Where do Perseverations Come From?
RB, a patient with probable Alzheimer’s disease, makes continuous perseverations of single letters when writing (e.g. fruit ! fruuit), particularly on high frequency letters. An analysis of her errors reveals that her perseverations do not reflect letter substitutions or transpositions, nor do they suggest difficulty with geminates. No continuous perseverations were found in oral production, in graphic and simple motor tasks, and in oral spelling. RB’s data do not support an attention deficit as the basis of her continuous perseverations. It is proposed that a deficit at the level of abstract letter representations is the source of RB’s perseverations. The implications of this conclusion for accounts of perseveration and of spelling models are discussed