Neural substrate of cognitive theory of mind impairment in amyotrophic lateral sclerosis

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Voxel-based mapping of grey matter volume and glucose metabolism profiles in amyotrophic lateral sclerosis

International audienceBACKGROUND:Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease of the nervous system involving both upper and lower motor neurons. The patterns of structural and metabolic brain alterations are still unclear. Several studies using anatomical MRI yielded a number of discrepancies in their results, and a few PET studies investigated the effect of ALS on cerebral glucose metabolism. The aim of this study was threefold: to highlight the patterns of grey matter (GM) atrophy, hypometabolism and hypermetabolism in patients with ALS, then to understand the neurobehavioral significance of hypermetabolism and, finally, to investigate the regional differences between the morphologic and functional changes in ALS patients, using a specially designed voxel-based method. Thirty-seven patients with ALS and 37 age- and sex-matched healthy individuals underwent both structural MRI and 18[F]-fluorodeoxyglucose (FDG) PET examinations. PET data were corrected for partial volume effects. Structural and metabolic abnormalities were examined in ALS patients compared with control subjects using two-sample t tests in statistical parametric mapping (SPM). Then, we extracted the metabolic values of clusters presenting hypermetabolism to correlate with selected cognitive scores. Finally, GM atrophy and hypometabolism patterns were directly compared with a one-paired t test in SPM.RESULTS:We found GM atrophy as well as hypometabolism in motor and extra motor regions and hypermetabolism in medial temporal lobe and cerebellum. We observed negative correlations between the metabolism of the right and left parahippocampal gyri and episodic memory and between the metabolism of right temporal pole and cognitive theory of mind. GM atrophy predominated in the temporal pole, left hippocampus and right thalamus, while hypometabolism predominated in a single cluster in the left frontal superior medial cortex.CONCLUSIONS:Our findings provide direct evidence of regional variations in the hierarchy and relationships between GM atrophy and hypometabolism in ALS. Moreover, the 18FDG-PET investigation suggests that cerebral hypermetabolism is deleterious to cognitive function in ALS

Retrieval mechanisms for autobiographical memories: insights from the frontal variant of frontotemporal dementia.

International audienceVery few studies have investigated autobiographical memory in the frontal variant of frontotemporal dementia (fv-FTD). The aim of this study was therefore to unravel the mechanisms of autobiographical memory disruption in general and in the anterograde and retrograde components of amnesia in particular, in patients suffering from fv-FTD. An autobiographical memory task assessing overall (AM) and strictly episodic memories (EM) from five lifetime periods covering the entire lifespan revealed the absence of a temporal gradient for both scores, suggesting the existence of a retrieval deficit. An analysis of the correlation between these two scores and a general cognitive assessment of executive function, working, episodic (i.e. new learning ability) and semantic memory, and behavioural changes highlighted the considerable involvement of executive function, semantic memory and, to a lesser degree, episodic memory and behavioural changes. Moreover, step-wise regression analyses performed on the EM score revealed that the executive function was a better predictor of the retrograde component than of the anterograde component, which was linked principally to new episodic learning ability. All these results confirm the impact of executive dysfunction on autobiographical deficits in fv-FTD, and suggest that the mechanisms at the root of autobiographical memory disruption may also involve difficulties in new episodic learning and semantic storage, though this may be due to the fact that we studied an advanced form of fv-FTD

Differential effect of age on hippocampal subfields assessed using a new high-resolution 3T MR sequence.

International audienceRecent advances in neuroimaging have highlighted the interest to differentiate hippocampal subfields for cognitive neurosciences and more notably in assessing the effects of normal and pathological aging. The main goal of the present study is to investigate the effects of normal aging onto the volume of the different hippocampal subfields. For this purpose, we developed a new magnetic resonance sequence together with reliable tracing guidelines to assess the volume of different subfields of the hippocampus using a 3 Tesla scanner, and estimated the validity of a simpler and less time-consuming method based on the widely-used automatic Voxel-Based Morphometry (VBM) technique. Three hippocampal regions of interest were delineated on the right and left hippocampi of 50 healthy subjects between 18 and 68 years old corresponding to the CA1, subiculum and other (including CA2-3-4 and Dentate Gyrus) subfields. A strong effect of age was found on the volume of the subiculum only, with a decrease paralleling that of the global gray matter volume, while CA1 and other subfields seemed relatively spared. Although less precise than the ROI-tracing technique, the VBM-based method appeared as a reliable alternative especially to distinguish CA1 and subiculum subfields. Our findings of a specific effect of age on the subiculum are consistent with the developmental hypothesis ("last-in first-out" theory). This contrasts with the predominant vulnerability of the CA1 subfield to Alzheimer's disease reported in several previous studies, suggesting that the assessment of hippocampal subfields may improve the discrimination between normal and pathological aging

Autonoetic consciousness in Alzheimer's disease: neuropsychological and PET findings using an episodic learning and recognition task.

International audienceOBJECTIVE: This study aims to map in patients with mild Alzheimer's disease (AD) the correlations between resting-state brain glucose utilization measured by FDG-PET and scores reflecting autonoetic consciousness in an episodic learning and recognition task. METHODS: Autonoetic consciousness, that gives a subject the conscious feeling to mentally travelling back in time to relive an event, was assessed using the Remember/Know (R/K) paradigm. RESULTS: AD patients provided less R responses (reflecting autonoetic consciousness) and more K ones (indicating the involvement of noetic consciousness) than healthy controls. Correct recognitions associated with a R response correlated with the metabolism of frontal areas bilaterally whereas those associated with a K response mainly correlated with the metabolism of left parahippocampal gyrus and lateral temporal cortex. CONCLUSIONS: These data show that recollection is impaired in AD and recognition is more based on a feeling of familiarity than in controls. In addition, the findings of our correlative approach indicate that the impairment of episodic memory is mainly subserved by the dysfunction of frontal areas and of the hippocampal region

Distinct neural substrates of affective and cognitive theory of mind impairment in semantic dementia

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Influence of patients' emotional state on the recovery processes after a transient global amnesia.: Emotional and memory disorders after TGA

International audienceINTRODUCTION: Currently, there is no consensus on the delay necessary to a complete recovery after a transient global amnesia (TGA). However, it seems that slight episodic memory disorders extend beyond 24h. Although this impairment is probably a consequence of the TGA attack, other factors such as patients' emotional state can intervene in the slow recovery process. METHODS: In a first experiment, we studied the dynamic of recovery processes after a TGA. Thus, we assessed the anterograde and retrograde components of episodic memory in 19 patients one day, one month and one year after the attack. In a second experiment, we examined the impact of patients' emotional state on memory disorders, in using an original neuropsychological protocol (using material with emotional features) and an assessment of anxiety and depressive mood. This protocol was carried out in 19 other patients examined four months and one year after TGA. RESULTS: In the first experiment, we highlighted mild memory disorders affecting the anterograde component of episodic memory one day after the episode. In the second experiment, we showed these mild memory disorders could be detected several months after TGA. Moreover, patients who had the more depressive tendencies recognized the fewer items and those who displayed the highest level of anxiety supplied the fewer specific remote memories. CONCLUSIONS: Our results showed that patients displayed very mild memory disorders several months after the episode of TGA, not affecting the daily routine. This impairment was influenced by patients' emotional state, which could suggest that a high level of anxiety or depression can slow down the recovery. However, we cannot be sure that the deleterious effect of patients' emotional state on their cognitive performances is specific to TGA. Other investigations are necessary to unravel this issue

Is there a specific memory signature associated with Aβ-PET positivity in patients with amnestic mild cognitive impairment?

International audienceAmnestic mild cognitive impairment (aMCI) is a clinical entity with various potential etiologies including but not limited to Alzheimer's disease. We examined whether a positive ([18F]Florbetapir) beta amyloid positron emission tomography scan, supporting underlying Alzheimer's disease pathophysiology, was associated with specific memory deficits in 48 patients with aMCI (33 beta amyloid positive, 15 beta amyloid negative). Memory was evaluated using an autobiographical fluency task and a word-list learning task with 2 different encoding types (shallow/incidental versus deep/intentional). Compared with 40 beta amyloidenegative controls, both aMCI subgroups demonstrated severe deficits in the global memory score and in most subscores of both tasks. Finer-grained analyses of memory tests showed subtle association with beta amyloid status, revealing a stronger impairment of the primacy effect in beta amyloidepositive patients. Structural magnetic resonance imaging showed that both aMCI subgroups exhibited comparable atrophy patterns, with similar degrees of medial temporal volume loss compared with controls. Specifically assessing the primacy effect might complement global memory scores in identifying beta amyloidepositive patients with aMCI

Patterns of autobiographical memory impairment according to disease severity in semantic dementia

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An impairment of prospective memory in mild Alzheimer's 2 disease: A ride in a virtual town

International audienceObjective: Research suggests that prospective memory (PM) is impaired from the very early stages of Alzheimer's disease (AD). We sought to further characterize this impairment in patients with mild AD, using a virtual reality (VR) task to provide ecological assessment of PM. Methods: Fifteen cognitively normal older individuals (76.47 years old ± 4.14, MMSE: 28.80 ± 1.21), and 17 patients with mild AD (79.29 years old ± 4.45, MMSE: 22.82 ± 2.83) were asked to recall the prospective and retrospective components of seven intentions in a virtual town task. Six intentions were event-based, where the prospective cue was either highly (three intentions) or weakly (three intentions) associated with the retrospective component. The remaining intention was time-based. All participants completed a neuropsychological assessment of episodic memory, semantic memory and executive functioning. Non-parametric tests were used to compare the two groups on the different intentions types and components. Correlations between cognition and PM scores were then realized to further understand the cognitive correlates of the PM impairment in patients with AD. Results: Overall, patients with Alzheimer disease recalled fewer intentions than controls, with the retrospective component and time-based intentions being the most challenging for them. The strength of the association between the prospective and retrospective components, however, had no effect on their performance. Event-based PM impairment, as well as deficit in the recall of prospective component correlated with memory and executive functions performance. Conclusion: PM is impaired in AD. Both automatic and controlled processes of PM retrieval are disturbed. This study also confirms the reliability of VR for assessing complex cognitive functions such as PM