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International audience; BACKGROUND: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.

Some studies highlight similarities between Autism Spectrum Disorder (ASD) and healthy aging. Indeed, the decline in older individuals' ability to create a unified representation of the individual features of an event is thought to arise from a disruption of binding within the episodic buffer of working memory (WM) as the same way as observed in ASD. In both cases, this deficit may result from an abnormal engagement of a frontohippocampal network. The objective of the present study is to identify both cognitive processes and neural substrates associated with the deficit of binding in WM in healthy aging. We studied the capacity of binding and the cognitive processes that might subtend its decline in 72 healthy participants aged 18-84 years. We examined the behavioral data in relation to the changes in brain metabolism associated with the age-related decline in a subgroup of 34 healthy participants aged 20-77 years using the resting-state [(18)F] fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). Forward stepwise regression analyses showed that the age-related decline in binding was partially explained by a decline in inhibition and processing speed. PET correlation analyses indicated that metabolism of the frontal regions, anterior and middle cingulate cortices is implicated in this phenomenon. These data suggest that executive functions and processing speed may play a crucial role in the capacity to integrate unified representations in memory in aging. Possible implications are discussed in ASD.

International audience; Autobiographical memory is commonly impaired in Alzheimer's disease (AD). However, little is known about the very recent past which is though highly important in daily life adaptation. In addition, the impact of sleep disturbances, also frequently reported in AD, on the consolidation and retrieval of autobiographical memories remains to be assessed. Using an adaptation of the TEMPau task, we investigated the neural substrates of autobiographical memory for recent events and the potential relationship with sleep in 14 patients with mild AD. On day 1, autobiographical memory was explored across 3 periods: remote (18-30 years), the last two years and the last month. After testing, sleep was recorded using polysomnography. The next day, AD patients benefited a resting state 18FDG-PET scan and a second exploration of autobiographical memory, focusing on the very recent past (today and yesterday). Total recall and episodic recall scores were obtained. In addition, for all events recalled, Remember responses justified by specific factual, spatial and temporal details were measured using the Remember/Know paradigm. Retrieval of autobiographical memories was impaired in AD, but recall of young adulthood and very recent events was relatively better compared to the two intermediate periods. Recall of recent events (experienced the day and the day preceding the assessment) was correlated with brain glucose consumption in the precuneus and retrosplenial cortex, the calcarine region, the angular gyrus and lateral temporal areas. AD patients also provided more Justified Remember responses for events experienced the previous day than for those experienced the day of the assessment. Moreover, Justified Remember responses obtained for events experienced before sleep were positively correlated with the amount of slow-wave sleep. These data provide the first evidence of an association between the ability to retrieve recent autobiographical memories and sleep in mild AD patients.

International audience; Autobiographical memory is commonly impaired in Alzheimer's disease (AD). However, little is known about the very recent past which is though highly important in daily life adaptation. In addition, the impact of sleep disturbances, also frequently reported in AD, on the consolidation and retrieval of autobiographical memories remains to be assessed. Using an adaptation of the TEMPau task, we investigated the neural substrates of autobiographical memory for recent events and the potential relationship with sleep in 14 patients with mild AD. On day 1, autobiographical memory was explored across 3 periods: remote (18-30 years), the last two years and the last month. After testing, sleep was recorded using polysomnography. The next day, AD patients benefited a resting state 18FDG-PET scan and a second exploration of autobiographical memory, focusing on the very recent past (today and yesterday). Total recall and episodic recall scores were obtained. In addition, for all events recalled, Remember responses justified by specific factual, spatial and temporal details were measured using the Remember/Know paradigm. Retrieval of autobiographical memories was impaired in AD, but recall of young adulthood and very recent events was relatively better compared to the two intermediate periods. Recall of recent events (experienced the day and the day preceding the assessment) was correlated with brain glucose consumption in the precuneus and retrosplenial cortex, the calcarine region, the angular gyrus and lateral temporal areas. AD patients also provided more Justified Remember responses for events experienced the previous day than for those experienced the day of the assessment. Moreover, Justified Remember responses obtained for events experienced before sleep were positively correlated with the amount of slow-wave sleep. These data provide the first evidence of an association between the ability to retrieve recent autobiographical memories and sleep in mild AD patients.

Autobiographical memory is commonly impaired in Alzheimer's disease (AD). However, little is known about the very recent past which is though highly important in daily life adaptation. In addition, the impact of sleep disturbances, also frequently reported in AD, on the consolidation and retrieval of autobiographical memories remains to be assessed. Using an adaptation of the TEMPau task, we investigated the neural substrates of autobiographical memory for recent events and the potential relationship with sleep in 14 patients with mild AD. On day 1, autobiographical memory was explored across 3 periods: remote (18-30 years), the last two years and the last month. After testing, sleep was recorded using polysomnography. The next day, AD patients benefited a resting state 18FDG-PET scan and a second exploration of autobiographical memory, focusing on the very recent past (today and yesterday). Total recall and episodic recall scores were obtained. In addition, for all events recalled, Remember responses justified by specific factual, spatial and temporal details were measured using the Remember/Know paradigm. Retrieval of autobiographical memories was impaired in AD, but recall of young adulthood and very recent events was relatively better compared to the two intermediate periods. Recall of recent events (experienced the day and the day preceding the assessment) was correlated with brain glucose consumption in the precuneus and retrosplenial cortex, the calcarine region, the angular gyrus and lateral temporal areas. AD patients also provided more Justified Remember responses for events experienced the previous day than for those experienced the day of the assessment. Moreover, Justified Remember responses obtained for events experienced before sleep were positively correlated with the amount of slow-wave sleep. These data provide the first evidence of an association between the ability to retrieve recent autobiographical memories and sleep in mild AD patients.

International audience; INTRODUCTION: The aim of this study was to study cognitive procedural learning in early Alzheimer's disease (AD). Methods: Cognitive procedural learning was assessed using the Tower of Hanoi (TH) task. In order to take account of possible interactions between different systems during cognitive procedural learning, we also measured non-verbal intellectual functions, working memory, and declarative memory. RESULTS: Our results showed an apparent preservation of cognitive procedural learning in AD and a deleterious effect of the disease on verbal intelligence and declarative memory. Correlational analyses revealed a difference between AD patients and control participants in the type of processing they applied to the task. CONCLUSION: The non-involvement of declarative memory would appear to be partly responsible for a slowdown in the cognitive procedural dynamics of AD patients. As the AD patients were unable to use their declarative memory, they were still in a problem-solving mode at the end of the learning protocol and had to implement higher order cognitive processes (i.e., compensatory mechanisms) to perform the procedural task.

International audience; INTRODUCTION: The aim of this study was to study cognitive procedural learning in early Alzheimer's disease (AD). Methods: Cognitive procedural learning was assessed using the Tower of Hanoi (TH) task. In order to take account of possible interactions between different systems during cognitive procedural learning, we also measured non-verbal intellectual functions, working memory, and declarative memory. RESULTS: Our results showed an apparent preservation of cognitive procedural learning in AD and a deleterious effect of the disease on verbal intelligence and declarative memory. Correlational analyses revealed a difference between AD patients and control participants in the type of processing they applied to the task. CONCLUSION: The non-involvement of declarative memory would appear to be partly responsible for a slowdown in the cognitive procedural dynamics of AD patients. As the AD patients were unable to use their declarative memory, they were still in a problem-solving mode at the end of the learning protocol and had to implement higher order cognitive processes (i.e., compensatory mechanisms) to perform the procedural task.

International audience; Transient global amnesia (TGA) is a clinical syndrome characterized by the abrupt onset of a massive episodic memory deficit that spares other cognitive functions. If the anterograde dimension is known to be impaired in TGA, researchers have yet to investigate prospective memory (PM)-which involves remembering to perform an intended action at some point in the future-in this syndrome. Furthermore, as executive functions are thought to be spared in this syndrome, TGA provides an opportunity to examine the impact of a massive "pure" memory impairment on PM. We assessed 38 patients with a newly designed protocol that distinguished between the prospective (remembering to do something at the appropriate time) and retrospective (remembering what has to be done) components of PM. Moreover, we investigated episodic memory with an anterograde memory task and assessed executive functions, anxiety and mood, as well as their links with PM. We demonstrated that PM is impaired during TGA, with a greater deficit for the retrospective component than for the prospective component. Furthermore, we highlighted a strong link between these two components. Anterograde episodic memory impairments were correlated with retrospective component deficits in TGA patients, although we were able to confirm that executive functions are globally spared. We discuss this pattern of results within the theoretical framework of PM, putting forward new arguments in favor of the idea that PM deficits can occur mainly because of a massive anterograde memory deficit. The clinical consequences of PM impairment in TGA are examined.

International audience; BACKGROUND AND PURPOSE: To provide guidance regarding the most appropriate voxel-based morphometry (VBM)-derived method for assessing hippocampal atrophy in early Alzheimer's disease (AD). METHODS: T1-MRI volume data were collected in 23 patients with amnestic mild cognitive impairment (aMCI) and 18 controls. Three types of data (unmodulated and 2 types of modulated MRI) and 2 extraction methods (with reference to the hippocampal peak of atrophy identified from a preliminary whole-brain analysis, or using a template region of interest-ROI-approach) were compared to the gold-standard individual ROI (ROI-i) method through 2 statistical approaches (ANOVA and Pearson's R). RESULTS: First, whole-brain analyses performed on modulated data are as sensitive as the ROI-i approach in detecting aMCI patients' hippocampal atrophy. Second, values extracted from the ROI-template applied to modulated data provide measures of hippocampal volume comparable to those obtained using the ROI-i approach. CONCLUSIONS: This study provides guidance on how to extract accurate hippocampal measures from VBM-derived data in early AD, as a time-saving and easy alternative to the reference ROI-i method.

International audience; BACKGROUND AND PURPOSE: To provide guidance regarding the most appropriate voxel-based morphometry (VBM)-derived method for assessing hippocampal atrophy in early Alzheimer's disease (AD). METHODS: T1-MRI volume data were collected in 23 patients with amnestic mild cognitive impairment (aMCI) and 18 controls. Three types of data (unmodulated and 2 types of modulated MRI) and 2 extraction methods (with reference to the hippocampal peak of atrophy identified from a preliminary whole-brain analysis, or using a template region of interest-ROI-approach) were compared to the gold-standard individual ROI (ROI-i) method through 2 statistical approaches (ANOVA and Pearson's R). RESULTS: First, whole-brain analyses performed on modulated data are as sensitive as the ROI-i approach in detecting aMCI patients' hippocampal atrophy. Second, values extracted from the ROI-template applied to modulated data provide measures of hippocampal volume comparable to those obtained using the ROI-i approach. CONCLUSIONS: This study provides guidance on how to extract accurate hippocampal measures from VBM-derived data in early AD, as a time-saving and easy alternative to the reference ROI-i method.

International audience; INTRODUCTION: 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.

International audience; Prospective memory (PM) is the ability to remember to perform an action at a specific point in the future. Regarded as multidimensional, PM involves several cognitive functions that are known to be impaired in normal ageing. In the present study we set out to investigate the cognitive correlates of PM impairment in normal ageing. Manipulating cognitive load, we assessed event- and time-based PM, as well as several cognitive functions, including executive functions, working memory, and retrospective episodic memory, in healthy participants covering the entire adulthood. We found that normal ageing was characterised by PM decline in all conditions and that event-based PM was more sensitive to the effects of ageing than time-based PM. Whatever the conditions, PM was linked to inhibition and processing speed. However, while event-based PM was mainly mediated by binding and retrospective memory processes, time-based PM was mainly related to inhibition. The only distinction between high- and low-load PM cognitive correlates lies in an additional, but marginal, correlation between updating and the high-load PM condition. The association of distinct cognitive functions, as well as shared mechanisms with event- and time-based PM, confirm that each type of PM relies on a different set of processes.

International audience; Transient global amnesia (TGA) is a clinical syndrome characterized by the abrupt onset of a massive episodic memory deficit that spares other cognitive functions. If the anterograde dimension is known to be impaired in TGA, researchers have yet to investigate prospective memory (PM)-which involves remembering to perform an intended action at some point in the future-in this syndrome. Furthermore, as executive functions are thought to be spared in this syndrome, TGA provides an opportunity to examine the impact of a massive "pure" memory impairment on PM. We assessed 38 patients with a newly designed protocol that distinguished between the prospective (remembering to do something at the appropriate time) and retrospective (remembering what has to be done) components of PM. Moreover, we investigated episodic memory with an anterograde memory task and assessed executive functions, anxiety and mood, as well as their links with PM. We demonstrated that PM is impaired during TGA, with a greater deficit for the retrospective component than for the prospective component. Furthermore, we highlighted a strong link between these two components. Anterograde episodic memory impairments were correlated with retrospective component deficits in TGA patients, although we were able to confirm that executive functions are globally spared. We discuss this pattern of results within the theoretical framework of PM, putting forward new arguments in favor of the idea that PM deficits can occur mainly because of a massive anterograde memory deficit. The clinical consequences of PM impairment in TGA are examined.

International audience; Recognizing a musical excerpt without necessarily retrieving its title typically reflects the existence of a memory system dedicated to the retrieval of musical knowledge. The functional distinction between musical and verbal semantic memory has seldom been investigated. In this fMRI study, we directly compared the musical and verbal memory of 20 nonmusicians, using a congruence task involving automatic semantic retrieval and a familiarity task requiring more thorough semantic retrieval. In the former, participants had to access their semantic store to retrieve musical or verbal representations of melodies or expressions they heard, in order to decide whether these were then given the right ending or not. In the latter, they had to judge the level of familiarity of musical excerpts and expressions. Both tasks revealed activation of the left inferior frontal and posterior middle temporal cortices, suggesting that executive and selection processes are common to both verbal and musical retrievals. Distinct patterns of activation were observed within the left temporal cortex, with musical material mainly activating the superior temporal gyrus and verbal material the middle and inferior gyri. This cortical organization of musical and verbal semantic representations could explain clinical dissociations featuring selective disturbances for musical or verbal material.

International audience; Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and white-matter tract disruption are well described early macroscopic events in Alzheimer's disease. The relationships between these three types of alterations have been documented in previous studies, but their chronology still remains to be established. The present study used multi-modal fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging longitudinal data to address this question in patients with amnestic mild cognitive impairment. We found unidirectional, specific sequential relationships between: (i) baseline hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 × 10⁻³) and uncinate fasciculus (r = 0.75; P = 7 × 10⁻⁴) rate of atrophy; (ii) baseline cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 × 10⁻³); and anterior (r = 0.74; P = 1 × 10⁻³) cingulate metabolism; and (iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r = 0.65; P = 6 × 10⁻³). Baseline local grey matter atrophy was not found to contribute to hypometabolism progression within the posterior and anterior cingulate as well as subgenual cortices. These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively. This study reinforces the relevance of remote mechanisms above local interactions to account for the pattern of metabolic brain alteration observed in amnestic mild cognitive impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.

International audience; Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and white-matter tract disruption are well described early macroscopic events in Alzheimer's disease. The relationships between these three types of alterations have been documented in previous studies, but their chronology still remains to be established. The present study used multi-modal fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging longitudinal data to address this question in patients with amnestic mild cognitive impairment. We found unidirectional, specific sequential relationships between: (i) baseline hippocampal atrophy and both cingulum bundle (r = 0.70; P = 3 × 10⁻³) and uncinate fasciculus (r = 0.75; P = 7 × 10⁻⁴) rate of atrophy; (ii) baseline cingulum bundle atrophy and rate of decline of posterior (r = 0.72; P = 2 × 10⁻³); and anterior (r = 0.74; P = 1 × 10⁻³) cingulate metabolism; and (iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r = 0.65; P = 6 × 10⁻³). Baseline local grey matter atrophy was not found to contribute to hypometabolism progression within the posterior and anterior cingulate as well as subgenual cortices. These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively. This study reinforces the relevance of remote mechanisms above local interactions to account for the pattern of metabolic brain alteration observed in amnestic mild cognitive impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.

International audience; Recognizing a musical excerpt without necessarily retrieving its title typically reflects the existence of a memory system dedicated to the retrieval of musical knowledge. The functional distinction between musical and verbal semantic memory has seldom been investigated. In this fMRI study, we directly compared the musical and verbal memory of 20 nonmusicians, using a congruence task involving automatic semantic retrieval and a familiarity task requiring more thorough semantic retrieval. In the former, participants had to access their semantic store to retrieve musical or verbal representations of melodies or expressions they heard, in order to decide whether these were then given the right ending or not. In the latter, they had to judge the level of familiarity of musical excerpts and expressions. Both tasks revealed activation of the left inferior frontal and posterior middle temporal cortices, suggesting that executive and selection processes are common to both verbal and musical retrievals. Distinct patterns of activation were observed within the left temporal cortex, with musical material mainly activating the superior temporal gyrus and verbal material the middle and inferior gyri. This cortical organization of musical and verbal semantic representations could explain clinical dissociations featuring selective disturbances for musical or verbal material.

International audience; In early Alzheimer's disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural magnetic resonance imaging and 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity, and gray matter metabolism by means of a whole-brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the middle cingulate gyrus, thalamus, mammillary bodies, parahippocampal gyrus, and hippocampus (all part of Papez's circuit), as well as the right temporoparietal associative cortex. These results provide the first direct evidence supporting the disconnection hypothesis as a major factor contributing to the early posterior hypometabolism in AD. Disruption of the cingulum bundle also appears to relate to hypometabolism in a large connected network over and above the posterior cingulate cortex, encompassing the whole memory circuit of Papez (consistent with the key location of this white matter tract within this loop) and also, but indirectly, the right posterior association cortex.

Patients suffering from frontal variant of frontotemporal dementia (fv-FTD) undergo autobiographical amnesia encompassing all time periods. We previously demonstrated in a group of 20 fv-FTD patients that this impairment involved deficits in executive function and semantic memory for all periods as well as new episodic learning and behavioural changes for the most recent period covering the last 12 months [Matuszewski, V., Piolino, P., de la Sayette, V., Lalev? C., P?rin, A., Dupuy, B., et al. (2006). Retrieval mechanisms for autobiographical memories: Insights from the frontal variant of frontotemporal dementia, Neuropsychologia, 44, 2386-2397]. The aim of the present study was to unravel the neural bases of this impairment by mapping in a subgroup of patients correlations between resting-state brain glucose utilization measured by FDG-PET and measures of autobiographical memory (AM) using the TEMPau task which is designed to gauge personal event recollection across five life time periods. Like in our previous report, the group of patients was impaired regardless of time periods compared to healthy subjects providing generic memories instead of event specific sensory-perceptual-affective details, i.e., episodic memories. New data showed that the patients were also impaired in sense of reliving and self-perspective during retrieval. The cognitivo-metabolic correlations between the AM score and resting normalized FDG-Uptake were computed using statistical parametric mapping (SPM2) and controlling for age and dementia severity. They revealed that AM deficits were mainly subserved by the dysfunction of left-sided orbitofrontal and also temporal neocortical areas whatever the period. Additional analysis showed that specific memories were associated with left orbitofrontal areas whereas generic memories were mainly associated with the left temporal pole. This study supports the view that fv-FTD patients undergo a breakdown of generative processes which relies regardless of the remoteness on the left orbitofrontal cortex and temporal neocortex to gain access to AM.

Patients suffering from frontal variant of frontotemporal dementia (fv-FTD) undergo autobiographical amnesia encompassing all time periods. We previously demonstrated in a group of 20 fv-FTD patients that this impairment involved deficits in executive function and semantic memory for all periods as well as new episodic learning and behavioural changes for the most recent period covering the last 12 months [Matuszewski, V., Piolino, P., de la Sayette, V., Lalev? C., P?rin, A., Dupuy, B., et al. (2006). Retrieval mechanisms for autobiographical memories: Insights from the frontal variant of frontotemporal dementia, Neuropsychologia, 44, 2386-2397]. The aim of the present study was to unravel the neural bases of this impairment by mapping in a subgroup of patients correlations between resting-state brain glucose utilization measured by FDG-PET and measures of autobiographical memory (AM) using the TEMPau task which is designed to gauge personal event recollection across five life time periods. Like in our previous report, the group of patients was impaired regardless of time periods compared to healthy subjects providing generic memories instead of event specific sensory-perceptual-affective details, i.e., episodic memories. New data showed that the patients were also impaired in sense of reliving and self-perspective during retrieval. The cognitivo-metabolic correlations between the AM score and resting normalized FDG-Uptake were computed using statistical parametric mapping (SPM2) and controlling for age and dementia severity. They revealed that AM deficits were mainly subserved by the dysfunction of left-sided orbitofrontal and also temporal neocortical areas whatever the period. Additional analysis showed that specific memories were associated with left orbitofrontal areas whereas generic memories were mainly associated with the left temporal pole. This study supports the view that fv-FTD patients undergo a breakdown of generative processes which relies regardless of the remoteness on the left orbitofrontal cortex and temporal neocortex to gain access to AM.

International audience