Convergent grey and white matter evidence of orbitofrontal cortex changes related to disinhibition in behavioural variant frontotemporal dementia

被引:179
|
作者
Hornberger, Michael [1 ,2 ]
Geng, John [1 ]
Hodges, John R. [1 ,2 ]
机构
[1] Neurosci Res Australia, Sydney, NSW 2031, Australia
[2] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia
基金
澳大利亚研究理事会;
关键词
behavioural variant frontotemporal dementia; disinhibition; orbitofrontal cortex; voxel-based morphometry; diffusion tensor imaging; MILD ALZHEIMERS-DISEASE; INFERIOR FRONTAL GYRUS; COGNITIVE TEST BATTERY; LOBAR DEGENERATION; PREFRONTAL CORTEX; DOUBLE DISSOCIATION; INHIBITORY CONTROL; EPISODIC MEMORY; STOP-SIGNAL; DYSFUNCTION;
D O I
10.1093/brain/awr173
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Disinhibition is a common behavioural symptom in frontotemporal dementia but its neural correlates are still debated. In the current study, we investigated the grey and white matter neural correlates of disinhibition in a sample of behavioural variant frontotemporal dementia (n = 14) and patients with Alzheimer's disease (n = 15). We employed an objective (Hayling Test of inhibitory functioning) and subjective/carer-based (Neuropsychiatric Inventory) measure of disinhibition to reveal convergent evidence of disinhibitory behaviour. Mean and overlap-based statistical analyses were conducted to investigate profiles of performance in patients with behavioural variant frontotemporal dementia, Alzheimer's disease and controls. Hayling Test and Neuropsychiatric Inventory scores were entered as covariates in a grey matter voxel-based morphometry, as well as in a white matter diffusion tensor imaging analysis to determine the underlying grey and white matter correlates. Patients with behavioural variant frontotemporal dementia showed more disinhibition on both behavioural measures in comparison to patients with Alzheimer's disease and controls. Voxel-based morphometry results revealed that atrophy in orbitofrontal/subgenual, medial prefrontal cortex and anterior temporal lobe areas covaried with total errors score of the Hayling Test. Similarly, the Neuropsychiatric Inventory disinhibition frequency score correlated with atrophy in orbitofrontal cortex and temporal pole brain regions. The orbitofrontal atrophy related to the objective (Hayling Test) and subjective (Neuropsychiatric Inventory) measures of disinhibition was partially overlapping. Diffusion tensor imaging analysis revealed that white matter integrity fractional anisotropy values of the white matter tracts connecting the identified grey matter regions, namely uncinate fasciculus, forceps minor and genu of the corpus callosum, correlated well with the total error score of the Hayling Test. Our results show that a network of orbitofrontal, anterior temporal and mesial frontal brain regions and their connecting white matter tracts are involved in inhibitory functioning. Further, we find convergent evidence for objective and subjective disinhibition measures that the orbitofrontal/subgenual brain region is critical for adapting and maintaining normal behaviour.
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页码:2502 / 2512
页数:11
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