Publications by authors named "Jeremie Pariente"

89 Publications

Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis.

Brain Commun 2021 26;3(3):fcab185. Epub 2021 Aug 26.

French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, 69677 Bron, France.

In this study, we report the clinical features of Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome, design and validate a clinical score to facilitate the identification of patients that should be tested for Kelch-like protein 11 antibodies, and examine in detail the nature of the immune response in both the brain and the tumour samples for a better characterization of the immunopathogenesis of this condition. The presence of Kelch-like protein 11 antibodies was retrospectively assessed in patients referred to the French Reference Center for paraneoplastic neurological syndrome and autoimmune encephalitis with (i) antibody-negative paraneoplastic neurological syndrome [limbic encephalitis ( = 105), cerebellar degeneration ( = 33)] and (ii) antibody-positive paraneoplastic neurological syndrome [Ma2-Ab encephalitis ( = 34), antibodies targeting N-methyl-D-aspartate receptor encephalitis with teratoma ( = 49)]. Additionally, since 1 January 2020, patients were prospectively screened for Kelch-like protein 11 antibodies as new usual clinical practice. Overall, Kelch-like protein 11 antibodies were detected in 11 patients [11/11, 100% were male; their median (range) age was 44 (35-79) years], 9 of them from the antibody-negative paraneoplastic neurological syndrome cohort, 1 from the antibody-positive (Ma2-Ab) cohort and 1 additional prospectively detected patient. All patients manifested a cerebellar syndrome, either isolated (4/11, 36%) or part of a multi-system neurological disorder (7/11, 64%). Additional core syndromes were limbic encephalitis (5/11, 45%) and myelitis (2/11, 18%). Severe weight loss (7/11, 64%) and hearing loss/tinnitus (5/11, 45%) were common. Rarer neurologic manifestations included hypersomnia and seizures (2/11, 18%). Two patients presented phenotypes resembling primary neurodegenerative disorders (progressive supranuclear palsy and flail arm syndrome, respectively). An associated cancer was found in 9/11 (82%) patients; it was most commonly (7/9, 78%) a spontaneously regressed ('burned-out') testicular germ cell tumour. A newly designed clinical score (MATCH score: male, ataxia, testicular cancer, hearing alterations) with a cut-off ≥4 successfully identified patients with Kelch-like protein 11 antibodies (sensitivity 78%, specificity 99%). Pathological findings (three testicular tumours, three lymph node metastases of testicular tumours, one brain biopsy) showed the presence of a T-cell inflammation with resulting anti-tumour immunity in the testis and one chronic, exhausted immune response-demonstrated by immune checkpoint expression-in the metastases and the brain. In conclusion, these findings suggest that Kelch-like protein 11 antibody paraneoplastic neurological syndrome is a homogeneous clinical syndrome and its detection can be facilitated using the MATCH score. The pathogenesis is probably T-cell mediated, but the stages of inflammation are different in the testis, metastases and the brain.
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http://dx.doi.org/10.1093/braincomms/fcab185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453430PMC
August 2021

Taking the A Train? Limited Consistency of Aβ42 and the Aβ42/40 Ratio in the AT(N) Classification.

J Alzheimers Dis 2021 ;83(3):1033-1038

Toulouse Neuroimaging Center, Toulouse, France.

The consistency of cerebrospinal fluid amyloid-β (Aβ)42/40 ratio and Aβ42 has not been assessed in the AT(N) classification system. We analyzed the classification changes of the dichotomized amyloid status (A+/A-) in 363 patients tested for Alzheimer's disease biomarkers after Aβ42 was superseded by the Aβ42/40 ratio. The consistency of Aβ42 and the Aβ42/40 ratio was very low. Notably, the proportions of "false" A+T-patients were considerable (74-91%) and corresponded mostly to patients not clinically diagnosed with Alzheimer's disease. Our results suggest that the interchangeability of Aβ42/40 ratio and Aβ42 is limited for classifying patients in clinical setting using the AT(N) scheme.
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http://dx.doi.org/10.3233/JAD-210236DOI Listing
January 2021

Plasma NfL levels and longitudinal change rates in and -associated diseases: from tailored references to clinical applications.

J Neurol Neurosurg Psychiatry 2021 Aug 4. Epub 2021 Aug 4.

Sorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Inserm U1127, CNRS UMR 7225, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France

Objective: Neurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in and cohorts from presymptomatic to clinical stages.

Methods: We analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of and patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical-genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index.

Results: pNfL levels increased with age in controls, from ~5 to~18 pg/mL (p<0.0001), progressing over time (mean annualised rate of change (ARC): +3.9%/year, p<0.0001). Patients displayed higher levels and greater longitudinal progression (ARC: +26.7%, p<0.0001), with gene-specific trajectories. patients had higher levels than (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades.

Conclusions: This study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression.

Trial Registration Numbers: NCT02590276 and NCT04014673.
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http://dx.doi.org/10.1136/jnnp-2021-326914DOI Listing
August 2021

A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.

Nat Med 2021 Jul 21;27(7):1187-1196. Epub 2021 Jun 21.

University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA.

Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years. The primary outcome was a cognitive end point; secondary outcomes included clinical, cognitive, imaging and fluid biomarker measures. Fifty-two participants carrying a mutation were assigned to receive gantenerumab, 52 solanezumab and 40 placebo. Both drugs engaged their Aβ targets but neither demonstrated a beneficial effect on cognitive measures compared to controls. The solanezumab-treated group showed a greater cognitive decline on some measures and did not show benefits on downstream biomarkers. Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain. Amyloid-related imaging abnormalities edema was observed in 19.2% (3 out of 11 were mildly symptomatic) of the gantenerumab group, 2.5% of the placebo group and 0% of the solanezumab group. Gantenerumab and solanezumab did not slow cognitive decline in symptomatic DIAD. The asymptomatic groups showed no cognitive decline; symptomatic participants had declined before reaching the target doses.
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http://dx.doi.org/10.1038/s41591-021-01369-8DOI Listing
July 2021

Language Network Connectivity Increases in Early Alzheimer's Disease.

J Alzheimers Dis 2021 ;82(1):447-460

Toulouse NeuroImaging Center, Toulouse University, Inserm, UPS, France.

Background: Language production deficits occur early in the course of Alzheimer's disease (AD); however, only a few studies have focused on language network's functional connectivity in mild cognitive impairment (MCI) due to AD.

Objective: The current study aims to uncover the extent of language alteration at the MCI stage, at a behavioral and neural level, using univariate and multivariate analyses of structural MRI and resting-state fMRI.

Methods: Twenty-four MCI due to AD participants and 24 matched healthy controls underwent a comprehensive language evaluation, a structural T1-3D MRI, and resting-state fMRI. We performed seed-based analyses, using the left inferior frontal gyrus and left posterior temporal gyrus as seeds. Then, we analyzed connectivity between executive control networks and language network in each group. Finally, we used multivariate pattern analyses to test whether the two groups could be distinguished based on the pattern of atrophy within the language network; within the executive control networks, as well as the pattern of functional connectivity within the language network and within the executive control networks.

Results: MCI due to AD participants had language impairment during standardized language tasks and connected-speech production. Regarding functional connectivity, univariate analyses were not able to discriminate participants, while multivariate pattern analyses could significantly predict participants' group. Language network's functional connectivity could discriminate MCI due to AD participants better than executive control networks. Most notably, they revealed an increased connectivity at the MCI stage, positively correlated with language performance.

Conclusion: Multivariate analyses represent a useful tool for investigating the functional and structural (re-)organization of the neural bases of language.
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http://dx.doi.org/10.3233/JAD-201584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293644PMC
September 2021

Primary Progressive Aphasia Associated With Mutations: New Insights Into the Nonamyloid Logopenic Variant.

Neurology 2021 07 12;97(1):e88-e102. Epub 2021 May 12.

From Sorbonne Université (D.S., M.H., L.S., S.E., A.C., S.B., D.R., A.M., R.L., B.D., A.B., O.C., M.T., R.M., I.L.B.), Paris Brain Institute-Institut du Cerveau (ICM), Inserm U1127, CNRS UMR 7225, AP-HP-Hôpital Pitié-Salpêtrière; Reference Centre for Rare or Early Dementias (D.S., S.F., M.N.-L., M.H., A.F., L.S., S.E., D.R., A.M., R.L., B.D., M.T., R.M., I.L.B.), IM2A, Département de Neurologie, AP-HP-Hôpital Pitié-Salpêtrière; Aramis Project Team (D.S., S.E., S.B., A.M., O.C.), Inria Research Center of Paris; Centre of Excellence of Neurodegenerative Disease (CoEN) (M.H.), ICM, CIC Neurosciences, Département de Neurologie, AP-HP-Hôpital Pitié-Salpêtrière, Sorbonne Université; FrontLab (A.F., R.L., B.D., M.T., R.M., I.L.B.), Paris Brain Institute-Institut du Cerveau (ICM); Université Lille (V.D., F.P.), Inserm U1171, CHU Lille, DistAlz, LiCEND, CNR-MAJ; CMRR Service de Neurologie (P.C.), CHU de Limoges; Department of Neurology (J.P., A.G.), Toulouse University Hospital; ToNIC (J.P., A.G.), Toulouse NeuroImaging Centre, Inserm, UPS, University of Toulouse; Normandie Université (D.W., D.H.), UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Neurology and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine; Rouen University Hospital (O.M.), Department of Neurology; Normandie Université (O.M.), UNICAEN, PSL Research University, EPHE, INSERM, U1077, CHU de Caen Normandie, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen; UF de Neurogénétique Moléculaire et Cellulaire (F.C.), Département de Génétique, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix; EPHE (A.C.), PSL Research University, Paris; CMRR Nouvelle Aquitaine/Institut des Maladies Neurodégénératives clinique (IMNc) (S.A.), CHU de Bordeaux Hôpital Pellegrin; Unit of Neurology of Memory and Language (M.S., J.L., C.R.-J.), GHU Paris Psychiatry and Neurosciences, University of Paris, Hôpital Sainte Anne; Université Paris-Saclay (M.S., J.L., C.R.-J.), CEA, CNRS, Inserm, BioMaps, Orsay; Aix Marseille Université (M.D.), INSERM, Institut de Neurosciences des Systèmes, Marseille; APHM (M.D.), Timone, Service de Neurologie et Neuropsychologie, APHM Hôpital Timone Adultes, Marseille; CHU Nantes (C.B.-B.), Inserm CIC04, Department of Neurology, Centre Mémoire de Ressources et Recherche, Nantes; Centre de génétique (C.T.-R.), Hôpital d'Enfants, CHU Dijon Bourgogne; CMRR Département de Neurologie (F.S.), Hôpitaux Civils, Colmar, INSERM U1118, Université de Strasbourg, Faculté de Médecine, 67085 Strasbourg; CMRR (A.G.), Département de Neurologie, CHU de Montpellier, Inserm U1061, Université de Montpellier i-site MUSE; Department of Neurology (F.E.-B.), CMRR Angers University Hospital, Angers, France; Department of Advanced Medical and Surgical Sciences (C.C.), University of Campania Luigi Vanvitelli, Naples, Italy; and Department of Neurology (M.L.G.-T.), Memory and Aging Center, University of California, San Francisco.

Objective: To determine relative frequencies and linguistic profiles of primary progressive aphasia (PPA) variants associated with (progranulin) mutations and to study their neuroanatomic correlates.

Methods: Patients with PPA carrying mutations (PPA-) were selected among a national prospective research cohort of 1,696 patients with frontotemporal dementia, including 235 patients with PPA. All patients with amyloid-positive CSF biomarkers were excluded. In this cross-sectional study, speech/language and cognitive profiles were characterized with standardized evaluations, and gray matter (GM) atrophy patterns using voxel-based morphometry. Comparisons were performed with controls and patients with sporadic PPA.

Results: Among the 235 patients with PPA, 45 (19%) carried mutations, and we studied 32 of these. We showed that logopenic PPA (lvPPA) was the most frequent linguistic variant (n = 13, 41%), followed by nonfluent/agrammatic (nfvPPA; n = 9, 28%) and mixed forms (n = 8, 25%). Semantic variant was rather rare (n = 2, 6%). Patients with lvPPA, qualified as nonamyloid lvPPA, presented canonical logopenic deficit. Seven of 13 had a pure form; 6 showed subtle additional linguistic deficits not fitting criteria for mixed PPA and hence were labeled as logopenic-spectrum variant. GM atrophy involved primarily left posterior temporal gyrus, mirroring neuroanatomic changes of amyloid-positive-lvPPA. Patients with nfvPPA presented agrammatism (89%) rather than apraxia of speech (11%).

Conclusions: This study shows that the most frequent PPA variant associated with mutations is nonamyloid lvPPA, preceding nfvPPA and mixed forms, and illustrates that the language network may be affected at different levels. testing is indicated for patients with PPA, whether familial or sporadic. This finding is important for upcoming gene-specific therapies.
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http://dx.doi.org/10.1212/WNL.0000000000012174DOI Listing
July 2021

Increased functional connectivity supports language performance in healthy aging despite gray matter loss.

Neurobiol Aging 2021 02 28;98:52-62. Epub 2020 Sep 28.

Octogone-Lordat Interdisciplinary Research Unit (EA 4156), University of Toulouse II-Jean Jaurès, Toulouse, France.

Although language is quite preserved from aging, it remains unclear whether age-related differences lead to a deterioration or reorganization in language functional networks, or to different dynamics with other domains (e.g., the multiple-demand system). The present study is aimed at examining language networks, using resting-state functional magnetic resonance imaging in typical aging in relation to language performance. Twenty-three (23) younger adults and 24 healthy older adults were recruited. Volumetric gray matter differences between the 2 groups were assessed using voxel-based morphometry. Then, seed-based analyses, integrated local correlations in core regions of the language network, and within- and between-network connectivity were performed. We expected less extended connectivity maps, local coherence diminution, and higher connectivity with the multiple-demand system in older adults. On the contrary, analyses showed language network differences in healthy aging (i.e., increased connectivity with areas inside and outside language network), but no deterioration, despite widespread atrophy in older adults. Integrated local correlation revealed alterations that were unnoticeable with other analyses. Although gray matter loss was not correlated with language performance, connectivity differences were positively correlated with fluency performance in the older group. These results differ from the literature concerning other cognitive networks in aging in that they show extra internetwork connections without a decrease in intranetwork language connections. This reorganization could explain older adults' good language performance and could be interpreted in accordance with the scaffolding theory of aging and cognition.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.09.015DOI Listing
February 2021

The Rise of the GRN C157KfsX97 Mutation in Southern Italy: Going Back to the Fall of the Western Roman Empire.

J Alzheimers Dis 2020 ;78(1):387-394

Division of Neurology V - Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Background: Frontotemporal lobar degeneration (FTLD) designates a group of neurodegenerative diseases with remarkable clinical, pathological, and genetic heterogeneity. Mutations in progranulin gene (GRN) are among the most common causes of familial FTLD. The GRN C157KfsX97 mutation is the most frequent mutation occurring in Southern Italy and has been already described in a previous work.

Objective: In this study, we reported on additional cases carrying the same mutation and performed a genetic study on the whole cohort, aiming at demonstrating the existence of a founder effect and estimating the age of this mutation.

Methods/results: Based on the haplotype sharing analysis, a founder effect was highly probable, while the age of the mutation, estimated by means of DMLE+ software, resulted in a range between 52 and 82 generations, with the highest frequency at about 62 generations, 1,550 years ago.

Conclusion: This is the first study that reports the age estimation of the most recent common ancestor for the GRN C157KfsX97 mutation recurring in Southern Italy. Mutation dating in a geographically restricted population may be useful in order to plan genetic counseling and screening programs in the field of public health.
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http://dx.doi.org/10.3233/JAD-200924DOI Listing
September 2021

Plasma progranulin levels for frontotemporal dementia in clinical practice: a 10-year French experience.

Neurobiol Aging 2020 07 21;91:167.e1-167.e9. Epub 2020 Feb 21.

Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France.

GRN mutations are frequent causes of familial frontotemporal degeneration. Although there is no clear consensual threshold, plasma progranulin levels represent an efficient biomarker for predicting GRN mutations when decreased. We evaluated plasma levels to determine whether it could also predict age at onset, clinical phenotype, or disease progression in 160 GRN carriers. Importantly, progranulin levels were influenced by gender, with lower levels in male than in female patients in our study. Although we found no correlation with age at onset or with clinical phenotype, we confirmed that decreased level predicts GRN mutations, even in presymptomatic carriers more than four decades before disease onset. We also provided first evidence for the stability of levels throughout longitudinal trajectory in carriers, over a 4-year time span. Finally, we confirmed that progranulin levels constitute a reliable, cost-effective marker, suitable as a screening tool in patients with familial frontotemporal degeneration, and more broadly in patients without family history or with atypical presentations who are less likely to be referred for molecular diagnosis.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.02.014DOI Listing
July 2020

Two Cases of Late-Onset Anti-NMDAr Auto-Immune Encephalitis After Herpes Simplex Virus 1 Encephalitis.

Front Neurol 2020 18;11:38. Epub 2020 Feb 18.

Département de Neurologie, Hôpital Pierre Paul Riquet, CHU de Toulouse, Toulouse, France.

Encephalitis due to herpes simplex virus 1 (HSV-1) was described as a potential trigger for the development of anti-N-methyl-D-aspartate receptor (NMDAr) auto-immune encephalitis (AIE) within a few days to a few weeks after the infection. We assessed clinical, radiological, and biological diagnoses process, treatment response, and evolution. We report here cases of a 71-year-old man and a 57-year-old woman presenting anti-NMDAr AIE, respectively, 12 and 7 months after HSV-1 encephalitis. In both cases, the onset was brisk, and the symptoms were mainly neuropsychiatric (paranoid delirium, Capgras, and Cotard syndromes) and cognitive, with anterograde amnesia. Relapse of HSV encephalitis, epilepsy, and paraneoplastic neurologic syndromes were excluded. The clinical response to first-line treatments composed of intravenous immunoglobulins and high-dose corticosteroids was poor, whereas significant improvement was noticed after rituximab induction. Post-herpetic anti-NMDAr AIE could arise several months after infection. Clinicians must be aware of this possibility, particularly if cognitive and/or psychiatric symptoms occurred after a remitting period. In our two cases, only rituximab was associated with clinical improvement.
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http://dx.doi.org/10.3389/fneur.2020.00038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040193PMC
February 2020

Amyloid-β transmission through cardiac surgery using cadaveric dura mater patch.

J Neurol Neurosurg Psychiatry 2020 04 20;91(4):440-441. Epub 2020 Jan 20.

Department of Neurology, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse (University Hospital Centre), Toulouse, France.

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http://dx.doi.org/10.1136/jnnp-2019-321927DOI Listing
April 2020

Florbetapir Regional Distribution in Cerebral Amyloid Angiopathy and Alzheimer's Disease: A PET Study.

J Alzheimers Dis 2020 ;73(4):1607-1614

Department of Neurology, Toulouse University Hospital, Toulouse, France.

Background: Sporadic cerebral amyloid angiopathy shows progressive amyloid-β deposition in the wall of small arterioles and capillaries of the leptomeninges and cerebral cortex.

Objective: To investigate whether amyloid load and distribution, assessed by florbetapir positron emission tomography (PET), differs between patients with probable CAA-related intracerebral hemorrhage (CAA-ICH) and mild cognitive impairment due to Alzheimer's disease (MCI-AD).

Methods: We assessed [18F]florbetapir uptake in 15 patients with probable CAA-ICH and 20 patients with MCI-AD patients. Global and regional florbetapir retention were assessed using standard uptake values ratio (SUVr) in region-based and voxel-wise approaches. Visual reading of florbetapir scans was performed for all participants. Group comparisons were performed using univariate and multivariate analysis.

Results: Global florbetapir retention was lower in patients with CAA-ICH than MCI-AD (median SUVr, 1.33 [1.21-1.41] versus 1.44 [1.35-1.66]; p = 0.032). In the region-based analysis, regional florbetapir distribution was similar between the two groups. There was a trend for an increased occipital/global ratio in CAA-ICH patients compared to MCI-AD (p = 0.060). In the voxel-wise approach, two clusters, one in parietal regions and the other in temporal regions, had higher uptake in MCI-AD relative to CAA patients.

Conclusions: Patients with CAA-ICH had a lower global florbetapir PET burden than patients with MCI-AD. Relative florbetapir retention in the posterior regions tended to be higher in CAA patients in region-based analysis but was not statistically different between groups. Investigation on differences in amyloid deposits distribution between groups required a fine-grained voxel-wise analysis. In future studies, selective amyloid tracers are needed to differentiate vascular from parenchymal amyloid.
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http://dx.doi.org/10.3233/JAD-190625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081105PMC
May 2021

Awake Craniotomy and Memory Induction Through Electrical Stimulation: Why Are Penfield's Findings Not Replicated in the Modern Era?

Neurosurgery 2020 08;87(2):E130-E137

Centre de Recherche Cerveau et Cognition CerCo, CNRS, UMR5549, Toulouse, France.

From the 1930s through the early 1960s, Wilder Penfield12 collected a large number of memories induced by electrical brain stimulation (EBS) during awake craniotomy. As a result, he was a major contributor to several neuroscientific and neuropsychological concepts of long-term memory. His 1963 paper, which recorded all the cases of memories he induced in his operating room, remains a substantial point of reference in neuroscience in 2019, although some of his interpretations are now debatable.  However, it is highly surprising that, since Penfield's12 reports, there has been no other surgical publication on memories induced during awake surgery. In this review, we explore this phenomenon and analyze some of the reasons that might explain it. We hypothesize that the main reasons for lack of subsequent reports are related to changes in operative procedures (ie, use of anesthetics, time constraints, and insufficient debriefings) and changes in EBS parameters, rather than to the sites that are stimulated, the pathology treated, or the tasks used. If reminiscences are still induced, they should be reported in detail to add valuable contributions to the understanding of long-term memory networks, especially memories that are difficult to reproduce in the laboratory, such as autobiographical memories.
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http://dx.doi.org/10.1093/neuros/nyz553DOI Listing
August 2020

Underlying Small Vessel Disease Associated With Mixed Cerebral Microbleeds.

Front Neurol 2019 23;10:1126. Epub 2019 Oct 23.

Neurology Department, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Whether patients with both lobar and deep cerebral microbleeds (mixed CMB) have advanced cerebral amyloid angiopathy (CAA), hypertensive angiopathy (HA) or both is uncertain. To get insight into the underlying small vessel disease (SVD) associated with mixed CMB, we explored its association with cortical superficial siderosis (cSS), a key marker of CAA and other MRI markers of SVD in patients with intracerebral hemorrhage (ICH). Of 425 consecutive patients with acute ICH who had received brain MRIs, 260 had ≥1 CMB and were included in the analysis. They were categorized as strictly lobar CMB (suggesting CAA), strictly deep CMB (suggesting HA) or mixed CMB. Clinical and imaging characteristics were compared (1) between the three CMB groups and (2) within mixed CMB patients according to the symptomatic ICH location. Overall, 111 (26%) patients had mixed CMB. Compared to strictly lobar CMB ( = 111) and strictly deep CMB ( = 38), patients with mixed CMB had a more severe burden of lacune, white matter hyperintensities and CMB. cSS was observed in 24.3% of patients with mixed CMB compared to 44.1% in strictly lobar CMB and 10.5% in strictly deep CMB ( < 0.0001). Among patients with mixed CMB, 44 (39.6%) had a lobar symptomatic ICH and 67 (60.4%) had a non-lobar ICH. Patients with non-lobar ICH were more likely to have hypertension, whereas those with lobar ICH were more likely to have cSS and chronic lobar ICH and had higher ratio lobar CMB count/total CMB count. Mixed CMB is frequently encountered in patients with ICH and appears as a heterogeneous group, suggesting that both CAA and HA may be contributing to mixed CMB. Neuroimaging markers including ICH location, cSS, and CMB distribution may indicate the predominant underlying vasculopathy, with potential prognostic implications.
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http://dx.doi.org/10.3389/fneur.2019.01126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819505PMC
October 2019

Posterior Cortical Atrophy: Does Complaint Match the Impairment? A Neuropsychological and FDG-PET Study.

Front Neurol 2019 20;10:1010. Epub 2019 Sep 20.

ToNIC, Toulouse NeuroImaging Centre, University of Toulouse, Inserm, UPS, Toulouse, France.

Posterior Cortical Atrophy (PCA) is a neurodegenerative disease characterized predominantly by visual impairment. However, diagnosis of PCA remains complicated with an interval of several years between initial reporting of symptoms and diagnosis. The aim of the present study is to define if patients' visual and gestural complaints are consistent with their clinical profile. An evaluation of daily visual problems as well as a full neuropsychological assessment and FDG-PET were performed in 15 PCA patients. We compared glucose metabolism between these PCA patients and 18 healthy controls. Correlation analyses were conducted in PCA patients between visual and gestural complaint, clinical impairments, and brain glucose metabolism. Major impairment of cognitive functions was detected in PCA patients specifically in visual domains. Positive correlations were found between visual impairments and hypometabolism in the right temporo-parieto-occipital cortices. However, no correlation was found between complaint and visual impairment in PCA patients. Our main results suggest a consistent relationship between clinical impairment and brain metabolism. However, the patient's complaint and visual performance are not linked. Combining the literature and our results, it seems that patients are generally aware of difficulties but misinterpret them. This misinterpretation may be responsible for the delayed diagnosis.
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http://dx.doi.org/10.3389/fneur.2019.01010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764288PMC
September 2019

Déjà vu and prescience in a case of severe episodic amnesia following bilateral hippocampal lesions.

Memory 2021 08 6;29(7):843-858. Epub 2019 Oct 6.

Centre de Recherche Cerveau et Cognition, Université de Toulouse, Université Paul Sabatier Toulouse, Toulouse, France.

Several studies pertaining to déjà vu have consistently made a connection with the perirhinal region, a region located below the hippocampus. This idea is strengthened by the fact that déjà vu is an erroneous sense of familiarity and that familiarity appears to largely depend on the perirhinal region in healthy subjects. In this context, the role of the hippocampus is particularly unclear as it is unknown whether or not it plays a role in the genesis of déjà vu. We report on the case of OHVR, an epileptic patient who suffers from severe episodic amnesia related to massive isolated bilateral damage to the hippocampus. In contrast, the perirhinal region is intact structurally and functionally. This patient reports frequent déjà vu but also another experiential phenomenon with a prominent feeling of prescience, which shows some of the characteristics of déjà vécu. She clearly distinguishes both. She also developed a form of synaesthesia by attributing affective valence to numbers. This study shows that déjà vu can occur in cases of amnesia with massively damaged hippocampi and confirms that the perirhinal region is a core region for déjà vu, using a different approach from previous reports. It also provides clues about a potential influence of hippocampal alterations in déjà vécu.
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http://dx.doi.org/10.1080/09658211.2019.1673426DOI Listing
August 2021

Déjà vu and prescience in a case of severe episodic amnesia following bilateral hippocampal lesions.

Memory 2021 08 6;29(7):843-858. Epub 2019 Oct 6.

Centre de Recherche Cerveau et Cognition, Université de Toulouse, Université Paul Sabatier Toulouse, Toulouse, France.

Several studies pertaining to déjà vu have consistently made a connection with the perirhinal region, a region located below the hippocampus. This idea is strengthened by the fact that déjà vu is an erroneous sense of familiarity and that familiarity appears to largely depend on the perirhinal region in healthy subjects. In this context, the role of the hippocampus is particularly unclear as it is unknown whether or not it plays a role in the genesis of déjà vu. We report on the case of OHVR, an epileptic patient who suffers from severe episodic amnesia related to massive isolated bilateral damage to the hippocampus. In contrast, the perirhinal region is intact structurally and functionally. This patient reports frequent déjà vu but also another experiential phenomenon with a prominent feeling of prescience, which shows some of the characteristics of déjà vécu. She clearly distinguishes both. She also developed a form of synaesthesia by attributing affective valence to numbers. This study shows that déjà vu can occur in cases of amnesia with massively damaged hippocampi and confirms that the perirhinal region is a core region for déjà vu, using a different approach from previous reports. It also provides clues about a potential influence of hippocampal alterations in déjà vécu.
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http://dx.doi.org/10.1080/09658211.2019.1673426DOI Listing
August 2021

Grey Matter changes in treatment-resistant depression during electroconvulsive therapy.

J Affect Disord 2019 11 31;258:42-49. Epub 2019 Jul 31.

ToNIC, Toulouse NeuroImaging Center, University of Toulouse, Inserm, UPS, Toulouse, France.

Introduction: 20-30% of depressed patients experience Treatment Resistant Depression (TRD). Electroconvulsive Therapy (ECT) remains the treatment of choice for TRD. However, the exact mechanism of ECT remains unclear. We aim to assess grey matter changes in patients with TRD undergoing bilateral ECT treatment at different points during and after treatment.

Methods: Patients are recruited at the University Hospital of Toulouse. Eligibility criteria include a diagnosis of TRD and an age between 50 and 70 years old. Patients received clinical assessments (Hamilton Depression Rating Scale) and structural scans (MRI) at three points: baseline (within 48 h before the first ECT); V2 (after the first ECT considered effective); and V3 (within 1 week of completing ECT).

Results: At baseline, controls had significantly higher cortical thickness than patients in the fusiform gyrus, the inferior, middle and superior temporal gyrus, the parahippocampal gyrus and the transverse temporal gyrus (respectively: t(35)=2.7, p = 0.02; t(35)=2.89, p = 0.017; t(35)=3.1, p = 0.015; t(35)=3.6, p = 0.009; t(35)=2.37, p = 0.031; t(35)=2.46, p = 0.03). This difference was no longer significant after ECT. We showed an increase in cortical thickness in superior temporal gyrus between (i) baseline and V3 (t(62)=-3.43 p = 0.009) and (ii) V2 and V3 (t(62)=-3.42 p = 0.009). We showed an increase in hippocampal volume between (i) baseline and V3 (t(62)=-5.23 p < 0.001) and (ii) V2 and V3 (t(62)=-5.3 p < 0.001).

Conclusion: We highlight that there are grey matter changes during ECT treatment in a population with TRD compared to a healthy control population. These changes seem to occur after several rounds of ECT.
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http://dx.doi.org/10.1016/j.jad.2019.07.075DOI Listing
November 2019

Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer's Disease Before 51 Years.

J Alzheimers Dis 2019 ;71(1):227-243

CMRR Department of Neurology, Toulouse University Hospital, Toulouse, France.

Background: Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer's disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants.

Objective: To describe the proportion of each genetic variation among patients with very young-onset sporadic AD.

Methods: We first screened PSEN1, PSEN2, and APP in 154 EOAD patients with an onset before 51 years and a negative family history. Among 99 patients with no mutation (NMC), whole exome sequencing (WES) was performed. We analyzed the APOE genotype and rare protein-truncating or missense predicted damaging variants of TREM2, SORL1, and ABCA7. Neurological examination and cerebrospinal fluid (CSF) biomarkers were systematically retrieved.

Results: Nineteen (12.3%) mutation carriers (MC) harbored an APP or PSEN1 pathogenic or likely pathogenic variant. Among the NMC, 54/99 carried at least one genetic risk factor, including 9 APOE4/E4 homozygous, 37 APOE4 heterozygous, and 14 with a rare variant in another risk factor gene: 3 SORL1, 4 TREM2, and 9 ABCA7. MC presented an earlier disease onset (p < 0.0001) and associated neurologic symptoms more frequently (p < 0.002). All but one patient had at least 2 CSF biomarkers in abnormal ranges.

Conclusion: The genetic component of very early sporadic EOAD gathers a substantial proportion of pathogenic variants in autosomal dominant genes and an even higher proportion of patients carrying genetic risk factors, suggesting an oligogenic determinism, even at this range of ages.
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http://dx.doi.org/10.3233/JAD-190193DOI Listing
October 2020

Enlarged perivascular spaces and florbetapir uptake in patients with intracerebral hemorrhage.

Eur J Nucl Med Mol Imaging 2019 Oct 29;46(11):2339-2347. Epub 2019 Jul 29.

Department of Neurology, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse, Place Baylac, 31059, Toulouse Cedex 9, France.

Purpose: Enlarged perivascular spaces in the centrum semiovale (CSO-EPVS) have been linked to cerebral amyloid angiopathy (CAA). To get insight into the underlying mechanisms of this association, we investigated the relationship between amyloid-β deposition assessed by 18F-florbetapir PET and CSO-EPVS in patients with acute intracerebral hemorrhage (ICH).

Methods: We prospectively enrolled 18 patients with lobar ICH (suggesting CAA) and 20 with deep ICH (suggesting hypertensive angiopathy), who underwent brain MRI and 18F-florbetapir PET. EPVS were assessed on MRI using a validated 4-point visual rating scale in the centrum semiovale and the basal ganglia (BG-EPVS). PET images were visually assessed, blind to clinical and MRI data. We evaluated the association between florbetapir PET positivity and high degree (score> 2) of CSO-EPVS and BG-EPVS.

Results: High CSO-EPVS degree was more common in patients with lobar ICH than deep ICH (55.6% vs. 20.0%; p = 0.02). Eight (57.1%) patients with high CSO-EPVS degree had a positive florbetapir PET compared with 4 (16.7%) with low CSO-EPVS degree (p = 0.01). In contrast, prevalence of florbetapir PET positivity was similar between patients with high vs. low BG-EPVS. In multivariable analysis adjusted for age, hypertension, and MRI markers of CAA, florbetapir PET positivity (odds ratio (OR) 6.44, 95% confidence interval (CI) 1.32-38.93; p = 0.03) was independently associated with high CSO-EPVS degree.

Conclusions: Among patients with spontaneous ICH, high degree of CSO-EPVS but not BG-EPVS is associated with amyloid PET positivity. The findings provide further evidence that CSO-EPVS are markers of vascular amyloid burden that may be useful in diagnosing CAA.
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http://dx.doi.org/10.1007/s00259-019-04441-1DOI Listing
October 2019

Risk of Intracerebral Hemorrhage and Mortality After Convexity Subarachnoid Hemorrhage in Cerebral Amyloid Angiopathy.

Stroke 2019 09 24;50(9):2562-2564. Epub 2019 Jul 24.

From the Department of Neurology, Hôpital Pierre-Paul Riquet (L.C., A.V., J.-F.A., M.P., J.P., J.-M.O., N.R.), Centre Hospitalier Universitaire de Toulouse, France.

Background and Purpose- Convexity subarachnoid hemorrhage (cSAH) is an increasingly recognized presentation of cerebral amyloid angiopathy (CAA), usually revealed by transient symptoms, but data on its outcome are limited. We compared the risk of future intracerebral hemorrhage (ICH), cSAH, and death in patients with CAA after cSAH and after lobar ICH. Methods- Consecutive patients with probable CAA, based on the Boston criteria, presenting with cSAH (CAA-cSAH) or lobar ICH (CAA-ICH) were included. We obtained baseline clinical and magnetic resonance imaging data and follow-up information. Univariable and multivariable analyses were used to compare incidence rate for symptomatic ICH, symptomatic cSAH, and late-death (beyond 30 days) between patients with CAA-cSAH and CAA-ICH. Results- Among 105 patients (mean age, 76.7±7.5 years) enrolled, 44 participants presented with CAA-cSAH and 61 with CAA-ICH. The median follow-up was 22.2 months (interquartile range, 12.6-34.4). The symptomatic ICH rate (per person-year) was 10.5% (95% CI, 5.6-19.4) in patients with CAA-cSAH compared with 8.5% (95% CI, 4.4-16.4) in those with CAA-ICH (adjusted hazard ratio, 1.05; 95% CI, 0.32-3.43). The annual incidence rates of symptomatic cSAH (9.9% versus 3.8%; adjusted hazard ratio, 1.77; 95% CI, 0.43-7.28) and death (9.5% versus 17.8%; adjusted hazard ratio, 0.56; 95% CI, 0.22-1.43) were not significantly different between patients with CAA-cSAH and those with CAA-ICH. Conclusions- Patients with CAA-related cSAH have a poor outcome, with similar high risk of future ICH and long-term mortality than CAA patients after lobar ICH. Our findings may have important prognostic implication and guide management of patients with cSAH in CAA.
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http://dx.doi.org/10.1161/STROKEAHA.119.026244DOI Listing
September 2019

Biallelic MYORG mutation carriers exhibit primary brain calcification with a distinct phenotype.

Brain 2019 06;142(6):1573-1586

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, F, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Primary familial brain calcification (PFBC) is a rare neurogenetic disorder with diverse neuropsychiatric expression. Mutations in four genes cause autosomal dominant PFBC: SLC20A2, XPR1, PDGFB and PDGFRB. Recently, biallelic mutations in the MYORG gene have been reported to cause PFBC with an autosomal recessive pattern of inheritance. We screened MYORG in 29 unrelated probands negatively screened for the autosomal dominant PFBC genes and identified 11 families with a biallelic rare or novel predicted damaging variant. We studied the clinical and radiological features of 16 patients of these 11 families and compared them to that of 102 autosomal dominant PFBC patients carrying a mutation in one of the four known autosomal dominant PFBC genes. We found that MYORG patients exhibited a high clinical penetrance with a median age of onset of 52 years (range: 21-62) with motor impairment at the forefront. In particular, dysarthria was the presenting sign in 11/16 patients. In contrast to patients with autosomal dominant PFBC, 12/15 (80%) symptomatic patients eventually presented at least four of the following five symptoms: dysarthria, cerebellar syndrome, gait disorder of any origin, akinetic-hypertonic syndrome and pyramidal signs. In addition to the most severe clinical pattern, MYORG patients exhibited the most severe pattern of calcifications as compared to the patients from the four autosomal dominant PFBC gene categories. Strikingly, 12/15 presented with brainstem calcifications in addition to extensive calcifications in other brain areas (lenticular nuclei, thalamus, cerebellar hemispheres, vermis, ±cortex). Among them, eight patients exhibited pontine calcifications, which were observed in none of the autosomal dominant PFBC patients and hence appeared to be highly specific. Finally, all patients exhibited cerebellar atrophy with diverse degrees of severity on CT scans. We confirmed the existence of cerebellar atrophy by performing MRI voxel-based morphometry analyses of MYORG patients with autosomal dominant PFBC mutation carriers as a comparison group. Of note, in three families, the father carried small pallido-dentate calcifications while carrying the mutation at the heterozygous state, suggesting a putative phenotypic expression in some heterozygous carriers. In conclusion, we confirm that MYORG is a novel major PFBC causative gene and that the phenotype associated with such mutations may be recognized based on pedigree, clinical and radiological features.
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http://dx.doi.org/10.1093/brain/awz095DOI Listing
June 2019

Progressive Dementia Revealing an Atypical Encephalitis: Neuroimaging Aspects.

J Neuropsychiatry Clin Neurosci Summer 2019;31(3):268-271. Epub 2019 Mar 8.

The Department of Neurology and Neuropsychology, Pierre-Paul Riquet Hospital, Site Purpan, Place du Docteur Baylac, Toulouse, France (Makhtar Ba, Benaiteau, Rigal, Salleles, Pariente); INSERM UMR TONIC-Toulouse NeuroImaging Centre, Purpan University Hospital, Pavillon Baudot, Toulouse, France (Makhtar Ba, Guerrier, Rigal, Mirabel, Pariente); the Neurology Department, Albi Hospital, Albi, France (Perez); the Department of Infectious and Tropical Diseases, Purpan University Hospital, Toulouse, France (Martin-Blondel); and INSERM, Centre de Physiopathologie Toulouse-Purpan, Toulouse, France (Martin-Blondel).

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http://dx.doi.org/10.1176/appi.neuropsych.18050100DOI Listing
March 2020

Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

Alzheimers Dement (Amst) 2019 Dec 22;11:180-190. Epub 2019 Feb 22.

The University of Melbourne and the Florey Institute, Parkville, VIC, Australia.

Introduction: Quantitative measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.

Methods: Pittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.

Results: Global amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.

Discussion: Although the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.
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http://dx.doi.org/10.1016/j.dadm.2018.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389727PMC
December 2019

Neuronal spiking activity highlights a gradient of epileptogenicity in human tuberous sclerosis lesions.

Clin Neurophysiol 2019 04 30;130(4):537-547. Epub 2019 Jan 30.

Centre de Recherche Cerveau et Cognition, Université de Toulouse, Université Paul Sabatier Toulouse, Toulouse F-31330, France; Centre National de la Recherche Scientifique, CerCo, UMR 5549, Toulouse F-31052, France.

Objective: The mechanisms underlying epileptogenicity in tuberous sclerosis complex (TSC) are poorly understood.

Methods: We analysed neuronal spiking activity (84 neurons), fast ripples (FRs), local field potentials and intracranial electroencephalogram during interictal epileptiform discharges (IEDs) in the tuber and perituber of a patient using novel hybrid electrodes equipped with tetrodes.

Results: IEDs were recorded in the tuber and perituber. FRs were recorded only in the tuber and only with the microelectrodes. A larger proportion of neurons in the tuber (57%) than in the perituber (17%) had firing-rates modulated around IEDs.

Conclusions: A multi-scale analysis of neuronal activity, FRs and IEDs indicates a gradient of epileptogenicity running from the tuber to the perituber.

Significance: We demonstrate, for the first time in vivo, a gradient of epileptogenicity from the tuber to the perituber, which paves the way for future models of epilepsy in TSC. Our results also question the extent of the neurosurgical resection, including or not the perituber, that needs to be made in these patients.
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http://dx.doi.org/10.1016/j.clinph.2018.12.013DOI Listing
April 2019

An Analysis of Famous Person Semantic Memory in Aging.

Exp Aging Res 2019 Jan-Feb;45(1):74-93. Epub 2019 Jan 31.

c Centre de Recherche Cerveau et Cognition (CNRS, Cerco, UMR5549) , UPS , Toulouse , France.

Background: In contrast to most memory systems that decline with age, semantic memory tends to remain relatively stable across the life span. However, what exactly is stable remains unclear. Is it the quantity of information available or the organization of semantic memory, i.e., the connections between semantic items? Even less is known about semantic memory for celebrities, a subsystem of semantic memory. In the present study, we studied the organization of person-specific semantic memory and its stability in aging.

Methods: We designed a word association task based on a previous study, which consisted in providing the first word that came to the mind of the participants (15 participants for each age group 20-30, 40-50 and 60-70 years old) for 144 celebrities. We developed a new taxonomy of associated responses as the responses associated with celebrities name could in principle be very varied.

Results: We found that most responses (>90%) could be grouped into five categories (subjective; superordinate general; superordinate specific; imagery and activities). The elderly group did not differ from the other two groups in term of errors or reaction time suggesting they performed the task well. However, they also provided associations that were less precise and less based on imagery. In contrast, the middle-age group provided the most precise associations.

Conclusion: These results support the idea of a durable person-specific semantic memory in aging but show changes in the type of associations that elders provide. Future work should aim at studying patients with early semantic impairment, as they could be different from the healthy elders on such semantic association task.
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http://dx.doi.org/10.1080/0361073X.2018.1560118DOI Listing
April 2019

Structural, Microstructural, and Metabolic Alterations in Primary Progressive Aphasia Variants.

Front Neurol 2018 18;9:766. Epub 2018 Sep 18.

Institut du Cerveau et de la Moelle épinière, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, FrontLab, Paris, France.

Neuroimaging studies have described the brain alterations in primary progressive aphasia (PPA) variants (semantic, logopenic, nonfluent/agrammatic). However, few studies combined T1, FDG-PET, and diffusion MRI techniques to study atrophy, hypometabolism, and tract alterations across the three PPA main variants. We therefore explored a large early-stage cohort of semantic, logopenic and nonfluent/agrammatic variants ( = 86) and of 23 matched healthy controls with anatomical MRI (cortical thickness), FDG PET (metabolism) and diffusion MRI (white matter tracts analyses), aiming at identifying cortical and sub-cortical brain alterations, and confronting these alterations across imaging modalities and aphasia variants. In the semantic variant, there was cortical thinning and hypometabolism in anterior temporal cortices, with left-hemisphere predominance, extending toward posterior temporal regions, and affecting tracts projecting to the anterior temporal lobes (inferior longitudinal fasciculus, uncinate fasciculus) and tracts projecting to or running nearby posterior temporal cortices: (superior longitudinal fasciculus, inferior frontal-occipital fasciculus). In the logopenic variant metabolic alterations were more extensive than atrophy affecting mainly the left temporal-parietal junction and extending toward more anterior temporal cortices. Metabolic and tract data were coherent given the alterations of the left superior and inferior longitudinal fasciculus and the left inferior frontal-occipital fasciculus. In the nonfluent/agrammatic variant cortical thinning and hypometabolism were located in the left frontal cortex but Broca's area was only affected on metabolic measures. Metabolic and tract alterations were coherent as reflected by damage to the left uncinate fasciculus connecting with Broca's area. Our findings provide a full-blown statistically robust picture of brain alterations in early-stage variants of primary progressive aphasia which has implications for diagnosis, classification and future therapeutic strategies. They demonstrate that in logopenic and semantic variants patterns of brain damage display a non-negligible overlap in temporal regions whereas they are substantially distinct in the nonfluent/agrammatic variant (frontal regions). These results also indicate that frontal networks (combinatorial syntax/phonology) and temporal networks (lexical/semantic representations) constitute distinct anatomo-functional entities with differential vulnerability to degenerative processes in aphasia variants. Finally, the identification of the specific damage patterns could open an avenue for trans-cranial stimulation approaches by indicating the appropriate target-entry into the damaged language system.
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http://dx.doi.org/10.3389/fneur.2018.00766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153366PMC
September 2018

The Regulatory Role of the Human Mediodorsal Thalamus.

Trends Cogn Sci 2018 Nov 17;22(11):1011-1025. Epub 2018 Sep 17.

Centre de recherche Cerveau et Cognition, UMR5549, Université de Toulouse - CNRS, Toulouse 31000, France; Equivalent contribution as last authors.

The function of the human mediodorsal thalamic nucleus (MD) has so far eluded a clear definition in terms of specific cognitive processes and tasks. Although it was at first proposed to play a role in long-term memory, a set of recent studies in animals and humans has revealed a more complex, and broader, role in several cognitive functions. The MD seems to play a multifaceted role in higher cognitive functions together with the prefrontal cortex and other cortical and subcortical brain areas. Specifically, we propose that the MD is involved in the regulation of cortical networks especially when the maintenance and temporal extension of persistent activity patterns in the frontal lobe areas are required.
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http://dx.doi.org/10.1016/j.tics.2018.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198112PMC
November 2018
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