期刊
BRAIN
卷 131, 期 -, 页码 1646-1657出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awn082
关键词
frontotemporal lobar degeneration; Alzheimer's disease; emotion; fear conditioning
资金
- NCRR NIH HHS [M01 RR00079, M01 RR000079] Funding Source: Medline
- NIA NIH HHS [1K08AG020760-01, K08 AG020760, AG10129, P01 AG019724-050002, P01 AG019724, P50-AG05142, P50 AG016570, P50 AG005142, P30 AG010129, AG16570] Funding Source: Medline
- NINDS NIH HHS [R56 NS050915, NS050915, R01 NS050915] Funding Source: Medline
Emotional blunting and abnormal processing of rewards and punishments represent early features of frontotemporal lobar degeneration (FTLD). Better understanding of the physiological underpinnings of these emotional changes can be facilitated by the use of classical psychology approaches. Fear conditioning (FC) is an extensively used paradigm for studying emotional processing that has rarely been applied to the study of dementia. We studied FC in controls (n = 25), Alzheimer's disease (n = 25) and FTLD (n = 25). A neutral stimulus (coloured square on a computer screen) was repeatedly paired with a 1 s burst of 100 db white noise. Change in skin conductance response to the neutral stimulus was used to measure conditioning. Physiologicalanatomical correlations were examined using voxel-based morphometry (VBM). Both patient groups showed impaired acquisition of conditioned responses. However, the basis for this deficit appeared to differ between groups. In Alzheimer's disease, impaired FC occurred despite normal electrodermal responses to the aversive stimulus. In contrast, FTLD patients showed reduced skin conductance responses to the aversive stimulus, which contributed significantly to their FC deficit. VBM identified correlations with physiological reactivity in the amygdala, anterior cingulate cortex, orbitofrontal cortex and insula. These data indicate that Alzheimer's disease and FTLD both show abnormalities in emotional learning, but they suggest that in FTLD this is associated with a deficit in basic electrodermal response to aversive stimuli, consistent with the emotional blunting described with this disorder. Deficits in responses to aversive stimuli could contribute to both the behavioural and cognitive features of FTLD and Alzheimer's disease. Further study of FC in humans and animal models of dementia could provide a valuable window into these symptoms.
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