Publications by authors named "Francis Eustache"

223 Publications

Temporal Cognitive and Brain Changes in Korsakoff's Syndrome.

Neurology 2021 Feb 26. Epub 2021 Feb 26.

Normandie Univ, UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000 Caen, France.

Objective: To investigate, in Korsakoff patients (KS), cognitive and brain changes over months and up to 10 years after the diagnosis.

Methods: Two groups of 8 KS patients underwent neuropsychological, motor and neuroimaging investigations including structural MRI and F-FDG-PET. The KS group was examined early after the KS diagnosis (KS-T1) and one year later (KS-T2). The KS group was evaluated 10 years after the diagnosis. Longitudinal comparisons in KS explored short-term changes while cross-sectional comparisons between KS-T1 and KS informed about long-term changes.

Results: No cognitive, motor nor brain deterioration occurred over time in KS patients. There was no clear improvement either, with only modest recovery in the frontocerebellar circuit. Compared to the norms, KS-T1 had severe episodic memory impairments, ataxia and some executive dysfunctions. They also presented widespread atrophy and hypometabolism, as well as cerebellar hypermetabolism compared to 44 healthy matched controls. Episodic memory remained significantly impaired in KS-T2 and KS. Contrary to KS at T1 and T2, KS had preserved inhibition abilities. Atrophy was similar but less extended in KS-T2, and even more limited in KS. At all times, the thalamus, hypothalamus, and fornix remained severely atrophied. Hypometabolism was still widespread in KS-T2 and KS affecting notably the diencephalon. Cerebellar metabolism decreased over time and normalized in KS, whereas motor dysfunction persisted.

Conclusion: In KS, structural and metabolic alterations of the Papez circuit persisted over time, in accordance with the irreversible nature of amnesia. There was neither significant recovery as observed in patients with alcohol use disorder nor progressive decline as in neurodegenerative diseases.
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http://dx.doi.org/10.1212/WNL.0000000000011749DOI Listing
February 2021

When affect overlaps with concept: emotion recognition in semantic variant of primary progressive aphasia.

Brain 2020 12;143(12):3850-3864

Neuropsychology and Imaging of Human Memory research unit, Caen-Normandy University-PSL Research University-EPHE-INSERM-Caen University Hospital, UMRS1077, GIP Cyceron, Caen, France.

The most recent theories of emotions have postulated that their expression and recognition depend on acquired conceptual knowledge. In other words, the conceptual knowledge derived from prior experiences guide our ability to make sense of such emotions. However, clear evidence is still lacking to contradict more traditional theories, considering emotions as innate, distinct and universal physiological states. In addition, whether valence processing (i.e. recognition of the pleasant/unpleasant character of emotions) also relies on semantic knowledge is yet to be determined. To investigate the contribution of semantic knowledge to facial emotion recognition and valence processing, we conducted a behavioural and neuroimaging study in 20 controls and 16 patients with the semantic variant of primary progressive aphasia, a neurodegenerative disease that is prototypical of semantic memory impairment, and in which an emotion recognition deficit has already been described. We assessed participants' knowledge of emotion concepts and recognition of 10 basic (e.g. anger) or self-conscious (e.g. embarrassment) facial emotional expressions presented both statically (images) and dynamically (videos). All participants also underwent a brain MRI. Group comparisons revealed deficits in both emotion concept knowledge and emotion recognition in patients, independently of type of emotion and presentation. These measures were significantly correlated with each other in patients and with semantic fluency in patients and controls. Neuroimaging analyses showed that both emotion recognition and emotion conceptual knowledge were correlated with reduced grey matter density in similar areas within frontal ventral, temporal, insular and striatal regions, together with white fibre degeneration in tracts connecting frontal regions with each other as well as with temporal regions. We then performed a qualitative analysis of responses made during the facial emotion recognition task, by delineating valence errors (when one emotion was mistaken for another of a different valence), from other errors made during the emotion recognition test. We found that patients made more valence errors. The number of valence errors correlated with emotion conceptual knowledge as well as with reduced grey matter volume in brain regions already retrieved to correlate with this score. Specificity analyses allowed us to conclude that this cognitive relationship and anatomical overlap were not mediated by a general effect of disease severity. Our findings suggest that semantic knowledge guides the recognition of emotions and is also involved in valence processing. Our study supports a constructionist view of emotion recognition and valence processing, and could help to refine current theories on the interweaving of semantic knowledge and emotion processing.
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http://dx.doi.org/10.1093/brain/awaa313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805810PMC
December 2020

Brain Substrates of Time-Based Prospective Memory Decline in Aging: A Voxel-Based Morphometry and Diffusion Tensor Imaging Study.

Cereb Cortex 2021 Jan;31(1):396-409

Normandie Université, UNICAEN, PSL Université Paris, 14000 Caen, France.

Time-based prospective memory (TBPM) allows us to remember to perform intended actions at a specific time in the future. TBPM is sensitive to the effects of age, but the neural substrates of this decline are still poorly understood. The aim of the present study was thus to better characterize the brain substrates of the age-related decline in TBPM, focusing on macrostructural gray matter and microstructural white matter integrity. We administered a TBPM task to 22 healthy young (26 ± 5.2 years) and 23 older (63 ± 5.9 years) participants, who also underwent volumetric magnetic resonance imaging and diffusion tensor imaging scans. Neuroimaging analyses revealed lower gray matter volumes in several brain areas in older participants, but these did not correlate with TBPM performance. By contrast, an age-related decline in fractional anisotropy in several white-matter tracts connecting frontal and occipital regions did correlate with TBPM performance, whereas there was no significant correlation in healthy young subjects. According to the literature, these tracts are connected to the anterior prefrontal cortex and the thalamus, 2 structures involved in TBPM. These results confirm the view that a disconnection process occurs in aging and contributes to cognitive decline.
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http://dx.doi.org/10.1093/cercor/bhaa232DOI Listing
January 2021

Long-term modulation of cardiac activity induced by inhibitory control over emotional memories.

Sci Rep 2020 09 14;10(1):15008. Epub 2020 Sep 14.

Neuropsychologie et Imagerie de la Mémoire Humaine, Normandie Université, UNICAEN, PSL Research University, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Caen, France.

Efforts to exclude past experiences from conscious awareness can lead to forgetting. Memory suppression is central to affective disorders, but we still do not really know whether emotions, including their physiological causes, are also impacted by this process in normal functioning individuals. In two studies, we measured the after-effects of suppressing negative memories on cardiac response in healthy participants. Results of Study 1 revealed that efficient control of memories was associated with long-term inhibition of the cardiac deceleration that is normally induced by disgusting stimuli. Attempts to suppress sad memories, by contrast, aggravated the cardiac response, an effect that was closely related to the inability to forget this specific material. In Study 2, electroencephalography revealed a reduction in power in the theta (3-8 Hz), alpha (8-12 Hz) and low-beta (13-20 Hz) bands during the suppression of unwanted memories, compared with their voluntary recall. Interestingly, however, the reduction of power in the theta frequency band during memory control was related to a subsequent inhibition of the cardiac response. These results provide a neurophysiological basis for the influence of memory control mechanisms on the cardiac system, opening up new avenues and questions for treating intrusive memories using motivated forgetting.
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http://dx.doi.org/10.1038/s41598-020-71858-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490349PMC
September 2020

Exploring the Event-Related Potentials' Time Course of Associative Recognition in Autism.

Autism Res 2020 11 12;13(11):1998-2016. Epub 2020 Sep 12.

Normandie Univ, UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France.

Behavioral data on episodic recollection in autism spectrum disorders (ASD) point limited relational memory functioning. However, the involvement of successive memory processes in the profile of episodic memory in ASD needs more study. Here, we used event-related potentials (ERP) to investigate the time course of episodic recollection with an associative recognition paradigm with picture pairs. Twenty-two participants with ASD and 32 with typical development (TD), all right-handed, were included. Behavioral results confirmed difficulties in correctly recognizing identical pairs in the ASD relative to TD group. We found an unexpected amplitude decrement on the P2 (220-270 msec) and FN400 (350-470 msec) potentials, suggesting diminished priming and familiarity effects in the ASD relative to TD group. However, ERP data revealed that the recognition of associative information relies on the same electrophysiological process (old/new effect in the 600-700-msec late positive component) in ASD participants as in TD ones, with a parietal extension in the ASD group. These results suggest that the electrophysiological processes of associative recognition are qualitatively similar in individuals with and without ASD but may differ quantitatively. This difference may be driven by the reduced early processing of picture pairs that may in turn lead to their diminished integration into the semantic memory system, being partially compensated by a greater involvement of associative memory during the recollection process. Other studies would be useful to go further in identifying these cognitive processes involved in atypical recognition in ASD and their neural substrates. Autism Res 2020, 13: 1998-2016. © 2020 International Society for Autism Research and Wiley Periodicals LLC LAY SUMMARY: We identified diminished performance on the associative recognition of picture pairs in adolescents and young adults with autism when compared to typical development. Electrophysiological data revealed qualitative similarities but quantitative differences between-group, with diminished priming and familiarity processes partially compensated by an enhanced parietal recollection process.
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http://dx.doi.org/10.1002/aur.2384DOI Listing
November 2020

Memory in autism spectrum disorder: A meta-analysis of experimental studies.

Psychol Bull 2020 05 19;146(5):377-410. Epub 2020 Mar 19.

Neuropsychology and Neuroimaging of Human Memory, University of Caen Normandy.

To address inconsistencies in the literature on memory in autism spectrum disorder (ASD), we report the first ever meta-analysis of short-term memory (STM) and episodic long-term memory (LTM) in ASD, evaluating the effects of type of material, type of retrieval and the role of interitem relations. Analysis of 64 studies comparing individuals with ASD and typical development (TD) showed greater difficulties in ASD compared with TD individuals in STM (Hedges' g = -0.53, 95% CI [-0.90, -0.16], = .005, I² = 96%) compared with LTM (g = -0.30, 95% CI [-0.42, -0.17], < .00001, I² = 24%), a small difficulty in verbal LTM (g = -0.21, = .01), contrasting with a medium difficulty for visual LTM (g = -0.41, = .0002) in ASD compared with TD individuals. We also found a general diminution in free recall compared with cued recall and recognition (LTM, free recall: g = -0.38, < .00001, cued recall: g = -0.08, = .58, recognition: g = -0.15, = .16; STM, free recall: g = -0.59, = .004, recognition: g = -0.33, = .07). We discuss these results in terms of their relation to semantic memory. The limited diminution in verbal LTM and preserved overall recognition and cued recall (supported retrieval) may result from a greater overlap of these tasks with semantic long-term representations which are overall preserved in ASD. By contrast, difficulties in STM or free recall may result from less overlap with the semantic system or may involve additional cognitive operations and executive demands. These findings highlight the need to support STM functioning in ASD and acknowledge the potential benefit of using verbal materials at encoding and broader forms of memory support at retrieval to enhance performance. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/bul0000225DOI Listing
May 2020

The role of metamemory on cognitive complaints in cancer patients.

Brain Behav 2020 04 10;10(4):e01545. Epub 2020 Mar 10.

Cancer & Cognition Platform, Ligue Contre le Cancer, Caen, France.

Objective: Although cancer patients frequently report cognitive disturbances, it is commonly asserted a lack of association between cognitive complaints and neuropsychological test performances. Our goal was to better understand the relationships between subjective and objective cognitive scores through a metamemory monitoring assessment.

Methods: Sixty cancer patients currently treated by chemotherapy and/or targeted therapy, and 30 healthy controls (HC) were included. Cognitive complaint was assessed by FACT-cog, QAM and DEX questionnaires. One or more z-scores ≤-1.65 among these three questionnaires defined the presence of cognitive complaints. Objective cognitive performances assessed episodic memory, processing speed and executive functions/working memory (ESR paradigm, TMT, Stroop, n-back). Metamemory was assessed with a Judgment of Learning (JOL) task.

Results: Patients with cognitive complaints had significantly more depressive and anxiety symptoms (ps < .004), and lower performances on several cognitive tests (ps < .05) than both patients without complaints and HC. More specifically, analyses of the metamemory scores revealed that HC gave significantly more overestimations ("Yes" judgment and incorrect recall) than patients with cognitive complaints (p = .036). For these patients, JOL scores correlated positively with executive functioning (ps < .01).

Conclusion: Metamemory monitoring seems to be well-preserved during cancer. What is more, patients make less overestimation than HC, and they do not underestimate their memory. An accurate self-estimation of memory abilities in cancer patients, particularly those with mild cognitive deficits, may play an adaptive function. Our results suggest that the discrepancy frequently reported between cognitive complaints and objective cognitive scores may not be related to metamemory monitoring dysfunction.
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http://dx.doi.org/10.1002/brb3.1545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177574PMC
April 2020

Resilience after trauma: The role of memory suppression.

Science 2020 02;367(6479)

Normandie Université, UNICAEN, PSL Research University, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000 Caen, France.

In the aftermath of trauma, little is known about why the unwanted and unbidden recollection of traumatic memories persists in some individuals but not others. We implemented neutral and inoffensive intrusive memories in the laboratory in a group of 102 individuals exposed to the 2015 Paris terrorist attacks and 73 nonexposed individuals, who were not in Paris during the attacks. While reexperiencing these intrusive memories, nonexposed individuals and exposed individuals without posttraumatic stress disorder (PTSD) could adaptively suppress memory activity, but exposed individuals with PTSD could not. These findings suggest that the capacity to suppress memory is central to positive posttraumatic adaptation. A generalized disruption of the memory control system could explain the maladaptive and unsuccessful suppression attempts often seen in PTSD, and this disruption should be targeted by specific treatments.
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http://dx.doi.org/10.1126/science.aay8477DOI Listing
February 2020

Collective memory shapes the organization of individual memories in the medial prefrontal cortex.

Nat Hum Behav 2020 02 16;4(2):189-200. Epub 2019 Dec 16.

Neuropsychologie et Imagerie de la Mémoire Humaine U1077, INSERM, EPHE, UNICAEN, Normandie Univ., PSL Research University, CHU de Caen, Cyceron, Caen, France.

It has long been hypothesized that individual recollection fits collective memory. To look for a collective schema, we analysed the content of 30 years of media coverage of World War II on French national television. We recorded human brain activity using functional magnetic resonance imaging as participants recalled World War II displays at the Caen Memorial Museum following an initial tour. We focused on the medial prefrontal cortex, a key region for social cognition and memory schemas. The organization of individual memories captured using the distribution of the functional magnetic resonance imaging signal in the dorsal part of the medial prefrontal cortex was more accurately predicted by the structure of the collective schema than by various control models of contextual or semantic memory. Collective memory, which exists outside and beyond individuals, can also organize individual memories and constitutes a common mental model that connects people's memories across time and space.
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http://dx.doi.org/10.1038/s41562-019-0779-zDOI Listing
February 2020

Specific cognitive theory of mind and behavioral dysfunctions in early manifest Huntington disease: a case report.

Neurocase 2020 02 26;26(1):36-41. Epub 2019 Nov 26.

Laboratoire de Psychologie des Pays de la Loire (LPPL), EA 4638, Angers, France.

Huntington's disease (HD) is a devastating illness, associated with progressive motor, behavioral and cognitive dysfunctions. However, some studies emphasized that social cognition impairment could occur prior to the onset of these other symptoms. Here, we report the case of a 47 years old patient with early manifest HD, whose complaint was mainly related to the behavioral sphere. He exhibited a significant impairment of Theory of Mind abilities as well as behavioral, and discrete motor symptoms without noticeable cognitive decline. This case study suggests that social cognition impairments and behavioral changes could be in some cases a feature of the disease and may represent a major disability, in early stages of manifest HD.
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http://dx.doi.org/10.1080/13554794.2019.1696837DOI Listing
February 2020

Prospective Memory in Adolescents with Autism: A Preliminary Study of the Impact of Memory Load.

Dev Neuropsychol 2019 11 18;44(8):543-553. Epub 2019 Nov 18.

Normandie Univ, UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France.

We evaluated event-based prospective memory (EBPM) in adolescents with Autism, varying the load of the to-be-performed intentions. We included measures of inhibition, working memory and binding. Results showed that increasing the retrospective memory load reduced performance in controls. In Autism, adolescents were impaired in the low load condition with normal performance for the ongoing task, with the reverse pattern in the high load condition. EBPM may be impacted in Autism due to difficulty to process ongoing and EBPM tasks simultaneously possibly because of restricted inhibitory control.
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http://dx.doi.org/10.1080/87565641.2019.1692020DOI Listing
November 2019

Ageing stereotypes and prodromal Alzheimer's disease (AGING): study protocol for an ongoing randomised clinical study.

BMJ Open 2019 10 7;9(10):e032265. Epub 2019 Oct 7.

Aix Marseille Univ, CNRS, LPC, Marseille, France

Introduction: The number of older people diagnosed with amnestic mild cognitive impairment (aMCI), the prodromal state of Alzheimer's disease (AD), is increasing worldwide. However, some patients with aMCI never convert to the AD type of dementia, with some remaining stable and others reverting to normal. This overdiagnosis bias has been largely overlooked and gone unexplained. There is ample evidence in the laboratory that negative ageing stereotypes (eg, the culturally shared belief that ageing inescapably causes severe cognitive decline) contribute to the deteriorating cognitive performances of healthy older adults, leading them to perform below their true abilities. The study described here is intended to test for the first time whether such stereotypes also impair patients' cognitive performances during neuropsychological examinations in memory clinics, resulting in overdiagnosis of aMCI.

Methods And Analysis: The ongoing study is a 4-year randomised clinical trial comparing patients' physiological stress and cognitive performances during neuropsychological testing in memory clinics. A total of 260 patients attending their first cognitive evaluation will be randomised to either a standard condition of test administration, assumed here to implicitly activate negative ageing stereotypes or a reduced-threat instruction condition designed to alleviate the anxiety arising from these stereotypes. Both groups will be tested with the same test battery and stress biomarkers. For 30 patients diagnosed with aMCI in each group (n=60), biomarkers of neurodegeneration and amyloidopathy will be used to distinguish between aMCI with normal versus abnormal AD biomarkers. A 9-month follow-up will be performed on all patients to identify those whose cognitive performances remain stable, deteriorate or improve.

Ethics And Dissemination: This protocol has been approved by the French National Agency for Medicines and Health Products Safety and the Sud-Est I French Ethics Committee (2017-A00946-47). Results will be published in peer-reviewed journals.

Trial Registration Number: NCT03138018.
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http://dx.doi.org/10.1136/bmjopen-2019-032265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797355PMC
October 2019

Influence of emotional complexity on the neural substrates of affective theory of mind.

Hum Brain Mapp 2020 01 30;41(1):139-149. Epub 2019 Sep 30.

Normandie Univ, UNICAEN, PSL Universités Paris, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Caen, France.

Affective theory of mind (ToM) depends on both the decoding of emotional expressions and the reasoning on emotional mental states from social situations. While previous studies characterized the neural substrates underlying these processes, it remains unclear whether the nature of the emotional state inferred from others can influence the brain activation associated with affective ToM. In the present study, we focused on two types of emotions: basic emotions (BEs) (e.g., anger and surprise), which are innate and universal and self-conscious emotions (e.g., pride and embarrassment), which correspond to a special class of emotions involving the self and including a representation of one's relative reactions to internal and external standards. Specifically, we used an ecological functional MRI paradigm, on 21 healthy young subjects, to compare brain activations during the decoding of and the reasoning on others' self-conscious, basic and neutral mental states. Our results showed that compared to neutral states, the inference of self-conscious and basic emotional states from others elicited more activation in several core regions of affective ToM. Direct comparisons between emotional conditions revealed more activation for self-conscious than BEs in the right temporoparietal junction during the reasoning process and in left middle occipital regions during the decoding process. Further analyses using a localizer task showed that the extrastriate body area was more recruited for decoding others' self-conscious versus BEs, which emphasize the importance of body clues to properly infer these emotions. Using an original task allowing for an ecological assessment of the affective ToM, these results demonstrate that the complexity of the emotion inferred to others can influence the recruitment of ToM network. This study also validates the use of our task as an ecological tool to assess the affective ToM, constituting an avenue for the characterization of ToM impairments in neurological conditions.
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http://dx.doi.org/10.1002/hbm.24794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267895PMC
January 2020

Cognitive, Emotional and Psychological Manifestations in Amyotrophic Lateral Sclerosis at Baseline and Overtime: A Review.

Front Neurosci 2019 10;13:951. Epub 2019 Sep 10.

Neuropsychology and Imaging of Human Memory, Normandy University-PSL Research University-EPHE-INSERM U1077, Caen University Hospital, Caen, France.

It is now well recognized that, in addition to motor impairment, amyotrophic lateral sclerosis (ALS) may cause extra-motor clinical signs and symptoms. These can include the alteration of certain cognitive functions, impaired social cognition, and changes in the perception and processing of emotions. Where these extra-motor manifestations occur in ALS, they usually do so from disease onset. In about 10% of cases, the cognitive and behavioral changes meet the diagnostic criteria for frontotemporal dementia. The timecourse of behavioral and cognitive involvement in ALS is unclear. Whereas longitudinal studies have failed to show cognitive decline over time, some cross-sectional studies have demonstrated poorer cognitive performances in the advanced stages of the disease. Neuroimaging studies show that in ALS, extra-motor signs and symptoms are associated with specific brain lesions, but little is known about how they change over time. Finally, patients with ALS appear less depressed than might be expected, given the prognosis. Moreover, many patients achieve satisfactory psychosocial adjustment throughout the course of the disease, regardless of their degree of motor disability. There are scant longitudinal data on extra-motor impairment in ALS, and to our knowledge, no systematic review on this subject has yet been published. Even so, a better understanding of patients' clinical trajectory is essential if they are to be provided with tailored care and given the best possible support. We therefore undertook to review the evidence for extra-motor changes and their time course in ALS, in both the cognitive, emotional and psychological domains, with a view to identifying mechanisms that may help these patients cope with their disease.
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http://dx.doi.org/10.3389/fnins.2019.00951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746914PMC
September 2019

Neurocognitive determinants of theory of mind across the adult lifespan.

Brain Cogn 2019 11 13;136:103588. Epub 2019 Aug 13.

Normandie Univ, UNICAEN, PSL Research University, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000 Caen, France. Electronic address:

Although theory of mind (ToM) has been extensively explored in aging, few studies have used the same tool to simultaneously assess and compare its cognitive and affective components. When we administered the Movie for Assessment of Social Cognition, a dynamic sequence of social scenes, to 60 healthy participants (20-75 years), we observed no different age-related decreases in both cognitive and affective ToM. While each component was associated with cognitive measures (i.e., episodic memory and processing speed were predictive of cognitive ToM, and recognition of facial emotion expressions and inhibition were predictive of affective ToM), mediation analyses showed that these measures only mediated the effect of age on affective ToM. Voxelwise regressions with grey-matter volume showed that the components partly rely on the same neural substrates, reflecting either ToM per se or other cognitive processes elicited by this multi-determinant task. We discuss the specific substrates of each ToM component, emphasising the importance of considering the impact of other aspects of cognition, present in more ecological situations, on ToM functioning.
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http://dx.doi.org/10.1016/j.bandc.2019.103588DOI Listing
November 2019

Cerebellar Hypermetabolism in Alcohol Use Disorder: Compensatory Mechanism or Maladaptive Plasticity?

Alcohol Clin Exp Res 2019 10 5;43(10):2212-2221. Epub 2019 Sep 5.

Neuropsychologie et Imagerie de la Mémoire Humaine, CHU de Caen, U1077, INSERM, EPHE, PSL Research University, UNICAEN, Normandie Univ, Caen, France.

Background: Despite severe structural brain abnormalities within the frontocerebellar circuit (FCC), cerebellar metabolism studied with F-2-fluoro-deoxy-glucose-positron emission tomography (FDG-PET) is relatively preserved in patients with alcohol use disorder (AUD). The compensatory role of the cerebellum has been explored mainly through fMRI examination of AUD patients with the preserved level of performance. The present study aims at examining cerebellar metabolism and its relationship with regional brain metabolism and neuropsychological functioning in AUD patients.

Methods: Thirty-two recently detoxified AUD patients and 23 controls underwent an FDG-PET examination at rest. Participants also performed a neuropsychological battery assessing executive functions, verbal memory, and ataxia.

Results: Compared to controls, AUD patients had higher glucose uptake in the cerebellar lobule VIII, in association with hypometabolism, notably in several nodes of the FCC. Cerebellar hypermetabolism correlated negatively with regional hypometabolism in the premotor and frontal cortices. This pattern of regional hypermetabolism and hypometabolism related to ataxia and working memory deficits.

Conclusions: These specific brain-behavior relationships do not fulfill the criteria for brain compensatory processes. Cerebellar hypermetabolism may rather reflect the involvement of different pathological mechanisms, leading to a maladaptive plasticity phenomenon within the FCC in AUD patients who are early in abstinence. Further studies are required to examine the contributions of structural and functional connectivity alterations in the cerebellar hypermetabolism and the changes in these pathological mechanisms with abstinence or relapse.
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http://dx.doi.org/10.1111/acer.14158DOI Listing
October 2019

Positive Effect of Visual Cuing in Episodic Memory and Episodic Future Thinking in Adolescents With Autism Spectrum Disorder.

Front Psychol 2019 9;10:1513. Epub 2019 Jul 9.

Normandie Université, UNICAEN, PSL Universités Paris, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France.

Cognitive studies generally report impaired autobiographical memory in individuals with autism spectrum disorder (ASD), but mostly using verbal paradigms. In the present study, we therefore investigated the properties of both past and future autobiographical productions using visual cues in 16 boys with ASD and 16 typically developing (TD) participants aged between 10 and 18 years. We focused on sensory properties, emotional properties, and recollection, probing past and future productions for both near and distant time periods. Results showed that the ASD group performed more poorly than controls on free recall for recent periods, but performed like them when provided with visual cues. In addition, the ASD group reported fewer sensory details than controls and exhibited difficulties in the experience of recollection for the most remote events. These data suggest a combination of consolidation and binding deficits. Finally, our findings reveal the relevance of using visual cues to probe autobiographical memory, with possible perspectives for memory rehabilitation.
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http://dx.doi.org/10.3389/fpsyg.2019.01513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629950PMC
July 2019

Effects of Sleep and Age on Prospective Memory Consolidation: A Walk in a Virtual Museum.

Clocks Sleep 2019 Sep 17;1(3):332-351. Epub 2019 Jul 17.

Normandie Univ, UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, GIP Cyceron, 14000 Caen, France.

Prospective memory (PM) refers to our ability to perform actions at the appropriate moment, either when a predetermined event occurs (event-based, EB) or after a predetermined amount of time (time-based, TB). Sleep favors the consolidation of both EB and TB intentions, but whether this benefit is preserved during ageing is still subject to debate. PM was assessed in 28 young and 27 older healthy volunteers using a virtual environment. Participants had to learn and execute intentions after intervals filled with either daytime wakefulness or nighttime sleep. Intentions consisted of four TB, four EB with a strong link between the cue triggering retrieval and the action to be performed (EB-link) and four with no link (EB-nolink). PM was not affected by age, whatever the type of intention and the nature of the retention interval. While sleep reinforced all types of intentions in young participants, this benefit was only observed for TB and EB-link intentions in older adults. Sleep also reinforced the intrinsic PM components in both groups. Thus, when assessed using complex realistic situations, PM is not impaired in ageing. Results are discussed in the light of memory schema theory and the possible impact of cognitive reserve on sleep and memory.
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http://dx.doi.org/10.3390/clockssleep1030028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445809PMC
September 2019

Dissociating thalamic alterations in alcohol use disorder defines specificity of Korsakoff's syndrome.

Brain 2019 05;142(5):1458-1470

Normandie Univ, UNICAEN, PSL Research University, EPHE, INSERM, U1077, CHU de Caen, Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France.

The thalamus, a relay organ consisting of several nuclei, is shared between the frontocerebellar circuit and the Papez circuit, both particularly affected in alcohol use disorder. Shrinkage of the thalamus is known to be more severe in alcoholics with Korsakoff's syndrome than in those without neurological complications (uncomplicated alcoholics). While thalamic atrophy could thus be a key factor explaining amnesia in Korsakoff's syndrome, the loci and nature of alterations within the thalamic nuclei in uncomplicated alcoholics and alcoholics with Korsakoff's syndrome remains unclear. Indeed, the literature from animal and human models is disparate regarding whether the anterior thalamic nuclei, or the mediodorsal nuclei are particularly affected and would be responsible for amnesia. Sixty-two participants (20 healthy controls, 26 uncomplicated alcoholics and 16 patients with Korsakoff's syndrome) underwent a diffusion tensor imaging sequence and T1-weighted MRI. State-of-the-art probabilistic tractography was used to segment the thalamus according to its connections to the prefrontal cortex and cerebellar Cruses I and II for the frontocerebellar circuit's executive loop, the precentral gyrus and cerebellar lobes IV-VI for the frontocerebellar circuit's motor loop, and hippocampus for the Papez circuit. The connectivity and volumes of these parcellations were calculated. Tractography showed that the hippocampus was principally connected to the anterior thalamic nuclei while the prefrontal cortex was principally connected to the mediodorsal nuclei. The fibre pathways connecting these brain regions and their respective thalamic nuclei have also been validated. ANCOVA, with age and gender as covariates, on connectivity measures showed abnormalities in both patient groups for thalamic parcellations connected to the hippocampus only [F(2,57) = 12.1; P < 0.0001; η2 = 0.2964; with graded effects of the number of connections from controls to uncomplicated alcoholics to Korsakoff's syndrome]. Atrophy, on the other hand, was observed for the prefrontal parcellation in both patient groups and to the same extent compared to controls [F(2,56) = 18.7; P < 0.0001; η2 = 0.40]. For the hippocampus parcellation, atrophy was found in the Korsakoff's syndrome group only [F(2,56) = 5.5; P = 0.006; η2 = 0.170, corrected for multiple comparisons using Bonferroni, P < 0.01]. Post hoc Tukey's test for unequal sample sizes, healthy controls > patients with Korsakoff's syndrome (P = 0.0036). Two different mechanisms seem to affect the thalamus. In the frontocerebellar circuit, atrophy of the mediodorsal nuclei may lead to the alterations, whereas in the Papez circuit, disconnection between the anterior nuclei and hippocampus may be the leading factor. Shrinkage of the anterior nuclei could be specific to patients with Korsakoff's syndrome, hence a potential neuroimaging marker of its pathophysiology, or more generally of thalamic amnesia for which Korsakoff's syndrome has historically been used as a model.
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http://dx.doi.org/10.1093/brain/awz056DOI Listing
May 2019

Neuropsychological and Neuroimaging Examinations of Self-Reported Sleep Quality in Alcohol Use Disorder With and Without Korsakoff's Syndrome.

Alcohol Clin Exp Res 2019 05 29;43(5):952-964. Epub 2019 Mar 29.

U1077, CHU de Caen , GIP Cyceron, Neuropsychologie et Imagerie de la Mémoire Humaine, Normandy Univ, UNICAEN, PSL Université, EPHE, INSERM, Caen, France.

Background: Alcohol use disorder (AUD) patients without Korsakoff's syndrome (KS) report a variable self-rated sleep quality. Their ability to accurately judge their sleep quality may be related to their alcohol-related cognitive deficits and brain damage. KS patients, who present severe brain dysfunction, may be cognitively unable to judge their sleep quality. The aim of the present study is to examine, in AUD and KS patients, whether the absence of sleep complaint is associated with altered brain structure and impaired cognitive abilities within specific cerebral networks.

Methods: An assessment of subjective sleep quality was conducted in 20 healthy controls, 37 AUD patients, and 17 KS patients. Patients were first pooled together and then classified into 2 groups (no-complaint and complaint ) according to the total Pittsburg Sleep Quality Index score. Cognitive scores, gray matter (GM) volume, and white matter (WM) integrity were compared between these 2 groups, and then in AUD and KS patients separately.

Results: Poor sleep quality was reported by 70% of AUD and 18% of KS patients. Compared to controls, both no-complaint and complaint presented cortical and subcortical alterations as well as episodic memory deficits, which were more severe in patients without sleep complaint. Only no-complaint presented executive deficits. Then, considering the clinical diagnosis, GM volume in frontotemporal regions, WM integrity, and executive functions were affected to the same extent in AUD and KS patients without sleep complaint.

Conclusions: Our results confirm the high prevalence of sleep complaint in AUD patients and the rare complaint in KS patients. In AUD and KS patients, the absence of sleep complaint may not indicate good sleep quality but rather reflect executive deficits and frontothalamic damage. Alcohol-related cognitive deficits may indeed alter the ability to self-evaluate sleep quality, suggesting that the use of sleep questionnaire should be considered with caution in patients with executive deficits.
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http://dx.doi.org/10.1111/acer.13997DOI Listing
May 2019

Altered default mode network connectivity in adolescents with post-traumatic stress disorder.

Neuroimage Clin 2019 22;22:101731. Epub 2019 Feb 22.

Normandie Univ, UNICAEN, PSL Research University, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000 Caen, France.

Post-traumatic stress disorder (PTSD) is characterized by intrusions, re-experiencing, avoidance and hyperarousal. These symptoms might be linked to dysfunction in core neurocognitive networks subserving self-referential mental processing (default mode network, DMN), detection of salient stimuli (salience network, SN) and cognitive dysfunction (central executive network, CEN). Resting state studies in adolescent PTSD are scarce and findings are inconsistent, probably due to differences in patient symptom severity. Resting state brain activity was measured in 14 adolescents with severe PTSD and 24 age-matched controls. Seed-based connectivity analyses were used to examine connectivity between the DMN and the whole brain, including regions from other networks (SN and CEN). The relationships of network properties with symptom dimensions (severity, anxiety and depression) and episodic memory were also examined. Analyses revealed decreased within-DMN connectivity (between PCC and occipital cortex) in patients compared to controls. Furthermore, within-DMN connectivity (between PCC and hippocampus) correlated negatively with symptom dimensions (severity and anxiety), while increased connectivity (DMN-SN and DMN-CEN) correlated positively with episodic memory measures. These abnormal network properties found in adolescent PTSD corroborate those previously reported in adult PTSD. Decreased within-DMN connectivity and disrupted DMN-SN and DMN-CEN coupling could form the basis for intrusive trauma recollection and impaired episodic autobiographical recall in PTSD.
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http://dx.doi.org/10.1016/j.nicl.2019.101731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402428PMC
December 2019

An Impairment of Prospective Memory in Mild Alzheimer's Disease: A Ride in a Virtual Town.

Front Psychol 2019 12;10:241. Epub 2019 Feb 12.

Normandie Université, UNICAEN, PSL Universités Paris, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France.

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. 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. Overall, patients with Alzheimer disease recalled fewer intentions than controls, with the retrospective component and 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. 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.
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http://dx.doi.org/10.3389/fpsyg.2019.00241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379453PMC
February 2019

Brain and cognitive correlates of sleep fragmentation in elderly subjects with and without cognitive deficits.

Alzheimers Dement (Amst) 2019 Dec 8;11:142-150. Epub 2019 Feb 8.

Normandie Univ, UNICAEN, PSL Université, EPHE, INSERM, U1077, CHU de Caen, GIP Cyceron, NIMH, Caen, France.

Introduction: Sleep disturbances are increasingly recognized as a risk factor for Alzheimer's disease. However, no study has assessed the relationships between objective sleep fragmentation (SF) and brain and cognitive integrity across different cognitive stages, from cognitively unimpaired elderly subjects to patients with subjective cognitive decline and/or mild cognitive impairment.

Methods: 30 cognitively unimpaired elderly participants and 36 patients with subjective cognitive decline and/or mild cognitive impairment underwent a neuropsychological evaluation, structural MRI, F-fluorodeoxyglucose, and F-florbetapir-PET scans, and an actigraphy recording over a minimum of six consecutive nights. Multiple regression and mediation analyses were performed between SF parameters, neuroimaging data, and cognitive scores.

Results: In cognitively unimpaired elderly participants, SF intensity mediated the association between frontohippocampal hypometabolism and lower executive functioning. Moreover, to a lower extent, increased SF variability was related to thalamic atrophy and ventromedial prefrontal amyloid burden. However, in patients with subjective cognitive decline and/or mild cognitive impairment, SF no longer contributed to the expression of cognitive deficits.

Discussion: These findings suggest that SF may directly contribute to lower cognitive performance in cognitively unimpaired elderly subjects. Therefore, treating sleep disturbances before the onset of cognitive deficits may help to cope with brain alterations and maintain cognitive functioning.
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http://dx.doi.org/10.1016/j.dadm.2018.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369144PMC
December 2019

Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level.

Brain Imaging Behav 2020 Feb;14(1):226-241

Normandie Univ, UNICAEN, PSL University, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000, Caen, France.

Cognitive deficits are a major complaint in breast cancer patients, even before chemotherapy. Comprehension of the cerebral mechanisms related to cognitive impairment in breast cancer patients remains difficult due to the scarcity of studies investigating both cognitive and anatomical imaging changes. Furthermore, only some of the patients experienced cognitive decline following chemotherapy, yet few studies have identified risk factors for cognitive deficits in these patients. It has been shown that education level could impact cognitive abilities during the recovery phase following chemotherapy. Our main aim was to longitudinally evaluate cognitive and anatomical changes associated with cancer and chemotherapy in breast cancer patients. Our secondary aim was to assess the impact of education level on cognitive performances and gray matter (GM) atrophy in these patients. Twenty patients were included before chemotherapy (T1), 1 month (T2) and 1 year (T3) after chemotherapy. Twenty-seven controls without a history of cancer were assessed at T1 and T3 only. Cluster groups based on education level were defined for both groups and were further compared. Comparison between patients and controls revealed deficits in patients on verbal episodic memory retrieval at T1 and T3 and on executive functions at T3. After chemotherapy, breast cancer patients had GM atrophy that persisted or recovered 1 year after chemotherapy depending on the cortical areas. Increase in GM volumes from T1 to T3 were also found in both groups. At T2, patients with a higher level of education compared to lower level exhibited higher episodic memory retrieval and state anxiety scores, both correlating with cerebellar volume. This higher level of education group exhibited hippocampal atrophy. Our results suggest that, before chemotherapy, cancer-related processes impact cognitive functioning and that this impact seems exacerbated by the effect of chemotherapy on certain brain regions. Increase in GM volumes after chemotherapy were unexpected and warrant further investigations. Higher education level was associated, 1 month after the end of chemotherapy, with greater anxiety and hippocampal atrophy despite a lack of cognitive deficits. These results suggest, for the first time, the occurrence of compensation mechanisms that may be linked to cognitive reserve in relationship to state anxiety. This identification of factors, which may compensate cognitive impairment following chemotherapy, is critical for patient care and quality of life.
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http://dx.doi.org/10.1007/s11682-018-9991-0DOI Listing
February 2020

Hippocampal subfields alterations in adolescents with post-traumatic stress disorder.

Hum Brain Mapp 2019 03 27;40(4):1244-1252. Epub 2018 Oct 27.

Normandie Univ, UNICAEN, PSL Université Paris, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000 Caen, France.

Reexperiencing symptoms in adolescent Post-Traumatic Stress Disorder (PTSD) are characterized by the apparition of vivid intrusive images of the traumatic event. The emergence of these intrusions is thought to be related to a deficiency in context processing and could then be related to hippocampal alterations. The hippocampus is a complex structure which can be divided into several subfields, namely, the Cornu Ammonis (CA1, CA2, and CA3), the subiculum, and the dentate gyrus (DG). As each subfield presents different histological characteristics and functions, it appears more relevant to consider hippocampal subfields, instead of only assessing the whole hippocampus, to understand the neurobiology of PTSD. Hence, this study presents the first investigation of structural alterations within hippocampal subfields and their links to reexperiencing symptoms in adolescent PTSD. Hippocampal subfields were manually delineated on high-resolution MRI images in 15 adolescents (13-18 years old) with PTSD and 24 age-matched healthy controls. The volume of the region CA2-3/DG region was significantly smaller in the PTSD group compared to controls in both hemispheres. No other significant difference was found for other subfields. Moreover, the volume of the left CA2-3/DG was negatively correlated with the intrusion score (as measured by the Impact of Events Scale-Revised) in the PTSD group. To conclude, an alteration in the hippocampal subregion CA2-3/DG, known to resolve interferences between new and similar stored memories, could participate in the apparition of intrusive trauma memories in adolescents with PTSD.
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http://dx.doi.org/10.1002/hbm.24443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865506PMC
March 2019

Impact of breast cancer on prospective memory functioning assessed by virtual reality and influence of sleep quality and hormonal therapy: PROSOM-K study.

BMC Cancer 2018 Sep 3;18(1):866. Epub 2018 Sep 3.

Normandie Université, UNICAEN, PSL Université, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000, Caen, France.

Background: Breast cancer (BC) is the most frequent cancer in women with more than 70% of BC patients being treated with hormonal therapy (HT). Among these patients, some report difficulties in remembering what they are supposed to do at the right moment, referring to prospective memory (PM). PM is essential for autonomy and medical adherence of patients, and requires an ecological assessment. Virtual reality, that recreates naturalistic environment, seems to be a promising method to evaluate PM. Several BC patients also report sleep disturbances. Given the role of sleep on memory consolidation, it is imperative to explore the influence of sleep quality on PM in BC patients treated with HT. The purpose of PROSOM-K study is to assess PM functioning using virtual reality and sleep quality in BC treated or not with HT.

Methods: PROSOM-K is a prospective study including post-menopausal BC patients ≤70 years old treated with radiotherapy (n = 25) or with radiotherapy and HT (n = 25), and healthy post-menopausal women (n = 25) matched for age and education. PM will be assessed using a virtual reality based task. Other cognitive functions and psychosocial factors will be assessed with validated questionnaires and neuropsychological tests. The study is divided in 3 sessions: a session of familiarisation with the virtual environment and the PM task: a day-time session during which participants learn intentions during the morning and recall them in the evening; and a night-time session during which participants learn intentions in the evening and recall them the following morning. Women will be monitored by wrist actigraphy; during the night-time session, objective sleep quality and quantity will be measured by polysomnography.

Discussion: This is a novel study aiming to assess PM using virtual reality, coupled with the evaluation of other cognitive functions. Polysomnographic study of sleep will provide further information about architectural sleep disturbances in BC. Association between sleep architecture parameters and PM mechanism in BC women treated with HT will be described in detail. We expect our results will provide knowledge for patients and clinicians and further help to improve patient care and cognitive therapy.

Trial Registration: NCT03420105 , registered: January 10, 2018.
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http://dx.doi.org/10.1186/s12885-018-4762-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122719PMC
September 2018

Role of context in affective theory of mind in Alzheimer's disease.

Neuropsychologia 2018 10 31;119:363-372. Epub 2018 Aug 31.

Normandie Univ, UNICAEN, PSL Recherche Université, EPHE, INSERM, U1077, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, 14000 Caen, France. Electronic address:

Affective theory of mind (ToM) is defined as the ability to deal with affective mental states. Attributing an affective mental state from a facial expression relies mainly on processes that allow information in the environment to be perceived and decoded. Reasoning processes are required when information is not directly available in the environment (e.g., when making an affective mental state attribution in a social situation where there is no visible facial expression of emotion). Although facial emotion decoding deficits have been reported in Alzheimer's disease (AD), few studies have assessed emotional reasoning processes. Long-term social knowledge may also contribute to mental state attribution, given its involvement in social situations, but the links between these two domains have not yet been properly explored. The aim of the present study was therefore to assess both decoding and reasoning processes in AD, as well as the effect of context on emotion attribution (i.e., whether prior presentation of a congruent vs. noncongruent social situation influences emotion recognition from faces). We also aimed to improve current understanding of the relationship between ToM processes and social knowledge. Participants were 20 patients with AD, 20 healthy older individuals, and 20 healthy young individuals. They performed three tasks testing ToM: a context task (emotion attribution in a social situation); a face task (facial emotion recognition); and a context-face task (determining whether the facial emotion was consistent with the emotion inferred from the social situation, e.g., an embarrassing situation followed by a proud face). All participants underwent a neuropsychological battery that included an assessment of social norm knowledge (e.g., determining whether it is socially acceptable to phone in a church). Results showed deficits in the patients with AD for decoding emotions from faces and for reasoning about emotions inferred from a social context. Patients were found to consider contextual information in such a way that congruency either helped or hindered the decoding of stimuli in the environment. As expected, we found that ToM abilities were linked to social norm knowledge. Overall, our findings suggest that patients with AD have difficulty attributing emotional mental states, and deficits in social norm knowledge and the presence of incongruent information may heighten this difficulty.
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http://dx.doi.org/10.1016/j.neuropsychologia.2018.08.025DOI Listing
October 2018

Alexithymia in Amyotrophic Lateral Sclerosis and Its Neural Correlates.

Front Neurol 2018 24;9:566. Epub 2018 Jul 24.

Neuropsychology and Imaging of Human Memory, Caen-Normandy University, PSL Research University, EPHE, INSERM, Caen University Hospital, Caen, France.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes progressive and extensive motor deficits. Patients may also have cognitive impairments or alteration of emotional processing. Very few studies, however, have looked at deficits in how they experience their own feelings (alexithymia). We assessed alexithymia in 28 patients with ALS using the 20-item Toronto Alexithymia Scale (TAS-20), comparing them with a control group matched for sex, age, and education level. We took into account both the total score of the TAS-20 and its three subscores corresponding to the three dimensions of alexithymia: Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Patients also underwent a neuropsychological assessment and anatomical magnetic resonance imaging (MRI) in order to correlate cognitive performances and gray matter volume and level of alexithymia. On average, ALS subjects had a significantly higher total score and DIF sub-score of the TAS-20 than controls indicating an increased alexithymia in patients. Total and DIF Scores correlated significantly and negatively to gray matter volume of the prefrontal cortex, right superior temporal pole and parahippocampal gyri. No correlations were found between scores on executive functions and those on the TAS-20. The first stage of one's own emotional processing seems to be affected in ALS independently of executive dysfunction. This trouble seems to be underpinned by cerebral regions that are well known to be both implicated in alexithymia in healthy subjects and altered in ALS.
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http://dx.doi.org/10.3389/fneur.2018.00566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066614PMC
July 2018

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

Oncologist 2019 01 22;24(1):62-68. Epub 2018 Jun 22.

INSERM, U1086, ANTICIPE, Caen, France

Background: Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls.

Patients And Methods: Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status.

Results: The sample consisted of women newly diagnosed with EBC ( = 118) and healthy controls ( = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline.

Conclusion: This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC.

Implications For Practice: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy.
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http://dx.doi.org/10.1634/theoncologist.2017-0570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324624PMC
January 2019

Neuropsychology and neuroimaging profiles of amyloid-positive versus amyloid-negative amnestic mild cognitive impairment patients.

Alzheimers Dement (Amst) 2018 17;10:269-277. Epub 2018 Mar 17.

Inserm, Inserm UMR-S U1237, Université de Caen-Normandie, GIP Cyceron, Boulevard H. Becquerel, Caen, France.

Introduction: Patients with amnestic mild cognitive impairment (aMCI) are heterogeneous as regard to their amyloid status. The present study aimed at highlighting the neuropsychological, brain atrophy, and hypometabolism profiles of amyloid-positive (Aβpos) versus amyloid-negative (Aβneg) aMCI patients.

Methods: Forty-four aMCI patients and 24 Aβneg healthy controls underwent neuropsychological, structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography scans. Data were compared between groups in specific regions of interest and voxelwise with statistical parametric mapping.

Results: When directly comparing Aβpos to Aβneg aMCI, the former had lower performances in episodic memory tests ( = .02 to  < .001) while the latter had worse scores in working memory ( = .01) and language ( < .005). Compared to Aβneg healthy controls, both aMCI subgroups showed similar profiles of atrophy and hypometabolism, with no difference between both aMCI subgroups.

Conclusion: In a sample of aMCI patients recruited and scanned in the same center, the main difference at baseline between Aβpos and Aβneg aMCI concerned the neuropsychological profile, but not the structural magnetic resonance imaging or 18F-fluorodeoxyglucose positron emission tomography profiles of brain alterations.
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http://dx.doi.org/10.1016/j.dadm.2018.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956939PMC
March 2018