Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia.

The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke's Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.

Simulation-based mentalizing generates a "proxy" self-reference effect in memory.

The self-reference effect (SRE) in memory is thought to depend on specialized mechanisms that enhance memory for self-relevant information. We investigated whether these mechanisms can be engaged "by proxy" when we simulate other people, by asking participants to interact with two virtual partners: one similar and one dissimilar to self. Participants viewed pairs of objects and picked one for themselves, for their similar partner, or their dissimilar partner. A surprise memory test followed that required participants to identify which object of each pair was chosen, and for whom. Finally, participants were shown both partners' object pairs again, and asked to indicate their personal preference. Four key findings were observed. Overlap between participants' own choice and those made for their partner was significantly higher for the similar than the dissimilar partner, revealing participants' use of their own preferences to simulate the similar partner. Recollection of chosen objects was significantly higher for self than for both partners and, critically, was significantly higher for similar than dissimilar partners. Source confusion between self and the similar partner was also higher. These findings suggest that self-reference by proxy enhances memory for non-self-relevant material, and we consider the theoretical implications for functional interpretation of the SRE.

Selective deficits in episodic feeling of knowing in ageing: a novel use of the general knowledge task.

Failure to recall an item from memory can be accompanied by the subjective experience that the item is known but currently unavailable for report. The feeling of knowing (FOK) task allows measurement of the predictive accuracy of this reflective judgement. Young and older adults were asked to provide answers to general knowledge questions both prior to and after learning, thus measuring both semantic and episodic memory for the items. FOK judgements were made at each stage for all unrecalled responses, providing a measure of predictive accuracy for semantic and episodic knowledge. Results demonstrated a selective effect of age on episodic FOK resolution, with older adults found to have impaired episodic FOK accuracy while semantic FOK accuracy remained intact. Although recall and recognition measures of episodic memory are equivalent between the two age groups, older adults may have been unable to access contextual details on which to base their FOK judgements. The results suggest that older adults are not able to accurately predict future recognition of unrecalled episodic information, and consequently may have difficulties in monitoring recently encoded memories.

Working memory and the enactment effect in early Alzheimer's disease.

This study examines the enactment effect in early Alzheimer's disease using a novel working memory task. Free recall of action-object instruction sequences was measured in individuals with Alzheimer's disease (n = 14) and older adult controls (n = 15). Instruction sequences were read out loud by the experimenter (verbal-only task) or read by the experimenter and performed by the participants (subject-performed task). In both groups and for all sequence lengths, recall was superior in the subject-performed condition than the verbal-only condition. Individuals with Alzheimer's disease showed a deficit in free recall of recently learned instruction sequences relative to older adult controls, yet both groups show a significant benefit from performing actions themselves at encoding. The subject-performed task shows promise as a tool to improve working memory in early Alzheimer's disease.