Anne Botzung

The neural bases of the constructive nature of autobiographical memories studied with a self-paced fMRI design.

In Conway and Pleydell-Pearces model (2000), autobiographical memories are viewed as transitory mental representations, more often generated in an effortful way. An important claim of the model concerns the dynamic process that evolves over time, from the left prefrontal areas to posterior regions, to retrieve specific memories. The present work aims at investigating, using fMRI, the temporal distribution of effortful autobiographical memory construction. In addition, a self-paced design was implemented to elucidate the question of the timing window required to evoke recollections. The results showed a large pattern of brain regions, which included the two major poles of activation predicted by Conway and Pleydell-Pearces model. Likewise, we were able to detect the earlier implication of the left dorso-lateral prefrontal cortex, by comparison with posterior structures, which seemed to confirm its involvement in the effortful retrieval process. Finally, the self-paced procedure allowed us to refine the timing window necessary to construct past events.

Induced Brain Plasticity after a Facilitation Programme for Autobiographical Memory in Multiple Sclerosis: A Preliminary Study

This preliminary study tackles the assessment and treatment of autobiographical memory (AbM) in relapsing-remitting multiple sclerosis (RR-MS) patients. Our aim was to investigate cerebral activation changes, following clinical improvement of AbM due to a cognitive training based on mental visual imagery (MVI). We assessed AbM using the Autobiographical Interview (AI) in eight patients and 15 controls. The latter subjects established normative data. The eight patients showed selective defective performance on the AI. Four patients were trained cognitively and underwent pre- and post-AI and fMRI. The remaining four patients took a second AI, at the same interval, but with no intervention in between. Results showed a significant improvement of AbM performance after the facilitation programme that could not be explained by learning effects since the AI scores remained stable between the two assessments in the second group of patients. As expected, AbM improvement was accompanied by an increased cerebral activity in posterior cerebral regions in post-facilitation fMRI examination. We interpret this activation changes in terms of reflecting the emphasis made on the role of MVI in memory retrieval through the facilitation programme. These preliminary significant clinical and neuroimaging changes suggest the beneficial effects of this technique to alleviate AbM retrieval deficit in MS patients.

MRI-based volumetry correlates of autobiographical memory in Alzheimer's disease.

The aim of the present volumetric study was to explore the neuro-anatomical correlates of autobiographical memory loss in Alzheimers patients and healthy elderly, in terms of the delay of retention, with a particular interest in the medial temporal lobe structures. Fifteen patients in early stages of the disease and 11 matched control subjects were included in the study. To assess autobiographical memory and the effect of the retention delay, a modified version of the Crovitz test was used according to five periods of life. Autobiographical memory deficits were correlated to local atrophy via structural MRI using Voxel Based Morphometry. We used a ‘lateralized index’ to compare the relative contribution of hippocampal sub-regions (anterior vs posterior, left vs right) according to the different periods of life. Our results confirm the involvement of the hippocampus proper in autobiographical memory retrieval for both recent and very remote encoding periods, with larger aspect for the very remote period on the left side. Contrary to the prominent left-sided involvement for the young adulthood period, the implication of the right hippocampus prevails for the more recent periods and decreases with the remotness of the memories, which might be associated with the visuo-spatial processing of the memories. Finally, we suggest the existence of a rostrocaudal gradient depending on the retention duration, with left anterior aspects specifically related to retrieval deficits of remote memories from the young adulthood period, whereas posterior aspects would result of simultaneous encoding and/or consolidation and retrieval deficit of more recent memories.

Brain perfusion in dementia with Lewy bodies and Alzheimer’s disease: an arterial spin labeling MRI study on prodromal and mild dementia stages

BackgroundWe aimed to describe specific changes in brain perfusion in patients with dementia with Lewy bodies (DLB) at both the prodromal (also called mild cognitive impairment) and mild dementia stages, relative to patients with Alzheimer’s disease (AD) and controls.MethodsAltogether, 96 participants in five groups (prodromal DLB, prodromal AD, DLB with mild dementia, AD with mild dementia, and healthy elderly controls) took part in an arterial spin labeling MRI study. Three analyses were performed: a global perfusion value comparison, a voxel-wise analysis of both absolute and relative perfusion, and a linear discriminant analysis. These were used to assess the global decrease in perfusion, regional changes, and the sensitivity and specificity of these changes.ResultsPatterns of perfusion in DLB differed from AD and controls in both the prodromal stage and dementia, DLB having more deficits in frontal, insular, and temporal cortices whereas AD showed reduced perfusion in parietal and parietotemporal cortices. Decreases but also increases of perfusion in DLB relative to controls were observed in both absolute and relative measurements. All these regional changes of perfusion classified DLB patients with respect to either healthy controls or AD with sensitivity from 87 to 100 % and specificity from 90 to 96 % depending on the stage of the disease.ConclusionsOur results are consistent with previous studies. We extend the scope of those studies by integrating prodromal DLB patients and by describing both hypo- and hyperperfusion in DLB. While decreases in perfusion may relate to functional impairments, increases might suggest a functional compensation of some brain areas.

Material-independent cerebral network of re-experiencing personal events: evidence from two parallel fMRI experiments.

Two parallel fMRI experiments were conducted with the aim to clarify the lateralisation issue of the cerebral network underlying autobiographical memory retrieval independently of the stimulus material and the refreshment of the memory trace. The verbal experiment required a pre-scanning interview, while the nonverbal version tested the subjects directly during the fMRI session. Both experiments were constructed using the same experimental design to eliminate methodological variables in order to render comparisons possible. We found a predominantly left-lateralised cerebral network independently of material and regardless of whether or not memory traces were reactivated prior to the scanning session. We discuss the results in the context of neuroimaging studies of autobiographical memory (AbM).

Impaired emotional autobiographical memory associated with right amygdalar-hippocampal atrophy in Alzheimer's disease patients.

We studied the influence of emotions on autobiographical memory (AbM) in patients with Alzheimer’s disease (AD), characteristically triggering atrophy in the hippocampus and the amygdala, two crucial structures sustaining memory and emotional processing. Our first aim was to analyze the influence of emotion on AbM in AD patients, on both the proportion and the specificity of emotional memories. Additionally, we sought to determine the relationship of emotional AbM to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18 age-matched healthy controls were included. We obtained 30 autobiographical memories per participant using the modified Crovitz test (MCT). Analyses were performed on global scores, rates and specificity scores of the emotional vs. neutral categories of memories. Amygdalar-hippocampal volumes were extracted from 3D T1-weighted MRI scans and tested for correlations with behavioral data. Overall, AD patients displayed a deficit in emotional AbMs as they elicited less emotional memories than the controls, however, the specificity of those memories was preserved. The deficit likely implied retrieval or storage as it was extended in time and without reminiscence bump effect. Global scores and rates of emotional memories, but not the specificity scores, were correlated to right amygdalar and hippocampal volumes, indicating that atrophy in these structures has a central role in the deficit observed. Conversely, emotional memories were more specific than neutral memories in both groups, reflecting an enhancement effect of emotion that could be supported by other brain regions that are spared during the early stages of the disease.

Different Temporal Patterns of Specific and General Autobiographical Memories across the Lifespan in Alzheimer’s Disease

We compared specific (i.e., associated with a unique time and space) and general (i.e., extended or repeated events) autobiographical memories (AbM) in Alzheimers disease (AD). The comparison aims at investigating the relationship between these two components of AbM across the lifespan and the volume of cerebral regions of interest within the temporal lobe. We hypothesized that the ability to elicit specific memories would correlate with hippocampal volume, whereas evoking general memories would be related to lateral temporal lobe. AbM was assessed using the modified Crovitz test in 18 patients with early AD and 18 matched controls. The proportions of total memories—supposed to reflect the ability to produce general memories—and specific memories retrieved were compared between AD patients and controls. Correlations to MRI volumes of temporal cortex were tested. We found different temporal patterns for specific and general memories in AD patients, with (i) relatively spared general memories, according to a temporal gradient that preserved remote memories, predominantly associated with right lateral temporal cortex volume. (ii) Conversely, the retrieval of specific AbMs was impaired for all life periods and correlated with bilateral hippocampal volumes. Our results highlight a shift from an initially episodic to a semantic nature of AbMs during AD, where the abstracted form of memories remains.

NEURAL CORRELATES OF COGNITIVE FLUCTUATIONS IN DEMENTIA WITH LEWY BODIES AND ALZHEIMER’S DISEASE: A MULTIMODAL MRI STUDY

P3-341 NEURAL CORRELATES OF COGNITIVE FLUCTUATIONS IN DEMENTIAWITH LEWY BODIES AND ALZHEIMER’S DISEASE: A MULTIMODAL MRI STUDY Elena Chabran, Anne Botzung, Vincent Noblet, Frederic Blanc, University of Strasbourg and CNRS, ICube Laboratory (UMR 7357), Strasbourg, France; University Hospital of Strasbourg, Geriatrics, Neurology and CMRR, Strasbourg, France. Contact e-mail: anne.botzung@ chru-strasbourg.fr

Henry, where have you lost your Self?

The Self is a complex construct encompassing distinct components, including episodic and semantic autobiographical memory, the Self-concept, and the subjective sense of Self, which highest level consists of Self-awareness. The neuro-anatomical correlates are complex, and it is debated as to whether a common region could support these different components of the Self, with a particular interest for the cortical midline structures and the medial prefrontal cortex (MPFC). Alzheimers disease (AD) constitutes an interesting model for the study of Self as autobiographical memory typically deteriorates as the disease progresses. Here, we report the unexpected case of Henry, a patient with MCI due to AD who was unable to produce any personal autobiographical memories, nor describe his Self-concept, had a poor personal semantic memory, and disclosed unusual anosognosia for this stage of the disease. His cognitive performance was compared to a group of matched AD patients and a group of healthy controls confirming that the main components of his Self were degraded. We hypothesized that it was due to a marked atrophy within the cortical midline, as visually assessed on his MRI. We further elucidated these findings through Voxel-based morphometry analysis, which confirmed a significant atrophy of the MPFC that was specific to this patient. Moreover, this revealed significant atrophy within the bilateral insular cortex. Given the stage of the disease, the degradation of the Self is unlikely to be accounted for by deficient mnemonic processes, especially as the presence of discrete temporal atrophy was noted. We suggest that this specific pattern of MPFC and insular atrophy is responsible for the systematic collapse of the patients Self, through the breakdown of the subjective sense of Self, which is proposed as a prerequisite to all other components, according to the model proposed by Prebble, Addis, and Tippett (2013).

THE MEDIAL PREFRONTAL CORTEX SUPPORTS OF THE SENSE OF SELF IN ALZHEIMER’S DISEASE

differences in ultrastructure of capillary basal lamina (CBL) in humans (normal and diseased, <50 years) compared with mouse (young to middle age). Methods: Human autopsy brains without or with neurodegeneration, including Parkinson’s disease, frontotemporal degeneration and amyotrophic lateral sclerosis, and mouse models of tauopathy were evaluated. Brain tissues were fixed in formaldehyde and/or glutaraldehyde and processed for electron microscopy (EM) or post-embedding immunogold EM. Antibodies to types I, III and IV collagen and to fibronectin were used. Results: Mouse CBL is a thin and uniformly amorphous structure that is labeled with anti-type IV collagen in both normal mice and models of neurodegenerative disease at all ages. In contrast, the CBL in normal and diseased human brains has the amorphous BL, but also banded collagens. In addition, the BL frequently shows segmental splitting between endothelial and astrocytic sides of the BL. The split creates an expanded space that contains banded fibrils of type I and III collagen, but not type IV collagen. The expansion and splitting of BL increase with age and in diseased brains. The CBL in diseased human brains often extends into the pericapillary space. Anti-fibronectin co-localizes with collagens. These ultrastructural features are rarely observed in mice, but are detected in the youngest human brains studied. Conclusions: Human CBL has ageand disease-related alternations including split BL and accumulation of banded type I and III collagen fibrils associated with fibronectin. This BL “fibrosis” is rarely observed in mice brains. If these structural BL alterations are associated with capillary dysfunction, the lack of these changes inmicewarrants caution about use of mouse models for neurovascular studies.