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Episodic future thinking in semantic dementia: a cognitive and FMRI study.

ABSTRACT: Semantic dementia (SD) is characterized by gradual loss of semantic memory. While episodic autobiographical memory seems relatively preserved, behavioral studies suggest that episodic future thinking is impaired. We used fMRI to measure brain activity in four SD patients (JPL, EP, LL, EG) while they envisioned future events and remembered personal past events. Twelve healthy elders served as controls. Episodic quality, emotion, mental imagery and level of consciousness (via remember/know judgements) were checked at debriefing. We analyzed the future compared to the past for each patient. All patients presented lateral temporal atrophy, but varied in terms of frontal and anterior hippocampal atrophy. Patient JPL presented atrophy in bilateral superior medial frontal gyri and left anterior hippocampus and was unable to engage in episodic future thinking, despite hyperactivations in frontal and occipital regions. Patient EP presented no atrophy in the anterior hippocampus, but atrophy in bilateral superior medial frontal gyrus and had difficulties to engage in episodic future thinking. Patient LL presented atrophy in left anterior hippocampus, but hyperactivated its right counterpart for future compared to past thinking, permitting her to project efficiently in the future in an episodic way. Patient EG presented no atrophy in the superior medial frontal gyri or anterior hippocampi and was able to engage in episodic future thinking. Altogether, patients' future projections differed depending on the severity and localization of their atrophy. The functional integrity of bilateral superior medial frontal gyri and anterior hippocampus appear crucial for episodic future thinking: atrophy of both structures strongly impairs future projection, while integrity of these structures or hyperactivation of residual tissue normalizes episodic future projection.

SUBMITTER: Viard A

PROVIDER: S-EPMC4205092 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Multiple sclerosis (MS) is a progressive disease characterized by widespread white matter lesions in the brain and spinal cord. In addition to well-characterized motor deficits, MS results in cognitive impairments in several domains, notably in episodic autobiographical memory. Recent studies have also revealed that patients with MS exhibit deficits in episodic future thinking, i.e., our capacity to imagine possible events that may occur in our personal future. Both episodic memory and episodic future thinking have been shown to share cognitive and neural mechanisms with a related kind of hypothetical simulation known as episodic counterfactual thinking: our capacity to imagine alternative ways in which past personal events could have occurred but did not. However, the extent to which episodic counterfactual thinking is affected in MS is still unknown. The current study sought to explore this issue by comparing performance in mental simulation tasks involving either past, future or counterfactual thoughts in relapsing-remitting MS. Diffusion weighted imaging (DWI) measures were also extracted to determine whether changes in structural pathways connecting the brain's default mode network (DMN) would be associated with group differences in task performance. Relative to controls, patients showed marked reductions in the number of internal details across all mental simulations, but no differences in the number of external and semantic-based details. It was also found that, relative to controls, patients with relapsing-remitting MS reported reduced composition ratings for episodic simulations depicting counterfactual events, but not so for actual past or possible future episodes. Additionally, three DWI measures of white matter integrity-fractional anisotropy, radial diffusivity and streamline counts-showed reliable differences between patients with relapsing-remitting MS and matched healthy controls. Importantly, DWI measures associated with reduced white matter integrity in three association tracts on the DMN-the right superior longitudinal fasciculus, the left hippocampal portion of the cingulum and the left inferior longitudinal fasciculus-predicted reductions in the number of internal details during episodic counterfactual simulations. Taken together, these results help to illuminate impairments in episodic simulation in relapsing-remitting MS and show, for the first time, a differential association between white matter integrity and deficits in episodic counterfactual thinking in individuals with relapsing-remitting MS.

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Episodic future thinking in semantic dementia: a cognitive and FMRI study.

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