Publications by authors named "Grégory Operto"

28 Publications

  • Page 1 of 1

Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer's continuum.

Alzheimers Res Ther 2021 08 5;13(1):135. Epub 2021 Aug 5.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.

Background: Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer's disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and these pathophysiological mechanisms remains unknown.

Objective: We aimed to investigate the association between ePVS and CSF biomarkers of several pathophysiological mechanisms for AD. We hypothesized that ePVS will be associated to CSF biomarkers early in the AD continuum (i.e., amyloid positive cognitively unimpaired individuals). Besides, we explored associations between ePVS and demographic and cardiovascular risk factors.

Methods: The study included 322 middle-aged cognitively unimpaired participants from the ALFA + study, many within the Alzheimer's continuum. NeuroToolKit and Elecsys® immunoassays were used to measure CSF Aβ42, Aβ40, p-tau and t-tau, NfL, neurogranin, TREM2, YKL40, GFAP, IL6, S100, and α-synuclein. PVS in the basal ganglia (BG) and centrum semiovale (CS) were assessed based on a validated 4-point visual rating scale. Odds ratios were calculated for associations of cardiovascular and AD risk factors with ePVS using logistic and multinomial models adjusted for relevant confounders. Models were stratified by Aβ status (positivity defined as Aβ42/40 < 0.071).

Results: The degree of PVS significantly increased with age in both, BG and CS regions independently of cardiovascular risk factors. Higher levels of p-tau, t-tau, and neurogranin were significantly associated with ePVS in the CS of Aβ positive individuals, after accounting for relevant confounders. No associations were detected in the BG neither in Aβ negative participants.

Conclusions: Our results support that ePVS in the CS are specifically associated with tau pathophysiology, neurodegeneration, and synaptic dysfunction in asymptomatic stages of the Alzheimer's continuum.
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http://dx.doi.org/10.1186/s13195-021-00878-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340485PMC
August 2021

Cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF biomarker profile.

Alzheimers Res Ther 2021 07 27;13(1):134. Epub 2021 Jul 27.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Wellington 30, 08005, Barcelona, Spain.

Background: Understanding the changes that occur in the transitional stage between absent and overt amyloid-β (Aβ) pathology within the Alzheimer's continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF, structural, and functional neuroimaging biomarker profile.

Methods: Cross-sectional study of 318 middle-aged, cognitively unimpaired individuals from the ALFA+ cohort. We measured CSF Aβ42/40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100B, and α-synuclein. Participants also underwent cognitive assessments, APOE genotyping, structural MRI, [F]-FDG, and [F]-flutemetamol PET. To ensure the robustness of our results, we used three definitions of low burden of Aβ pathology: (1) positive CSF Aβ42/40 and < 30 Centiloids in Aβ PET, (2) positive CSF Aβ42/40 and negative Aβ PET visual read, and (3) 20-40 Centiloid range in Aβ PET. We tested CSF and neuroimaging biomarker differences between the low burden group and the corresponding Aβ-negative group, adjusted by age and sex.

Results: The prevalence and demographic characteristics of the low burden group differed between the three definitions. CSF p-tau and t-tau were increased in the low burden group compared to the Aβ-negative in all definitions. CSF neurogranin was increased in the low burden group definitions 1 and 3, while CSF NfL was only increased in the low burden group definition 1. None of the defined low burden groups showed signs of atrophy or glucose hypometabolism. Instead, we found slight increases in cortical thickness and metabolism in definition 2.

Conclusions: There are biologically meaningful Aβ-downstream effects in individuals with a low burden of Aβ pathology, while structural and functional changes are still subtle or absent. These findings support considering individuals with a low burden of Aβ pathology for clinical trials.

Trial Registration: NCT02485730.
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http://dx.doi.org/10.1186/s13195-021-00863-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314554PMC
July 2021

Brain correlates of urban environmental exposures in cognitively unimpaired individuals at increased risk for Alzheimer's disease: A study on Barcelona's population.

Alzheimers Dement (Amst) 2021 5;13(1):e12205. Epub 2021 Jul 5.

Barcelonaβeta Brain Research Center (BBRC) Pasqual Maragall Foundation Barcelona Spain.

Introduction: Urban environmental exposures might contribute to the incidence of Alzheimer's disease (AD). Our aim was to identify structural brain imaging correlates of urban environmental exposures in cognitively unimpaired individuals at increased risk of AD.

Methods: Two hundred twelve participants with brain scans and residing in Barcelona, Spain, were included. Land use regression models were used to estimate residential exposure to air pollutants. The daily average noise level was obtained from noise maps. Residential green exposure indicators were also generated. A cerebral 3D-T1 was acquired to obtain information on brain morphology. Voxel-based morphometry statistical analyses were conducted to determine the areas of the brain in which regional gray matter (GM) and white matter (WM) volumes were associated with environmental exposures.

Results: Exposure to nitrogen dioxide was associated with lower GM volume in the precuneus and greater WM volume in the splenium of the corpus callosum and inferior longitudinal fasciculus. In contrast, exposure to fine particulate matter was associated with greater GM in cerebellum and WM in the splenium of corpus callosum, the superior longitudinal fasciculus, and cingulum cingulate gyrus. Noise was positively associated with WM volume in the body of the corpus callosum. Exposure to greenness was associated with greater GM volume in the middle frontal, precentral, and the temporal pole.

Discussion: In cognitively unimpaired adults with increased risk of AD, exposure to air pollution, noise, and green areas are associated with GM and WM volumes of specific brain areas known to be affected in AD, thus potentially conferring a higher vulnerability to the disease.
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http://dx.doi.org/10.1002/dad2.12205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256622PMC
July 2021

Genetic Influences on Hippocampal Subfields: An Emerging Area of Neuroscience Research.

Neurol Genet 2021 Jun 21;7(3):e591. Epub 2021 May 21.

Barcelonaβeta Brain Research Center (BBRC) (N.V.-T., J.M.G.-d-E., J.L.M., J.D.G., G.O.), Pasqual Maragall Foundation; Centre for Genomic Regulation (CRG) (N.V.-T., R.G.), the Barcelona Institute for Science and Technology, Spain; Department of Clinical Genetics (N.V.-T., T.E.E., H.H.A.), Erasmus Medical Center, Rotterdam, the Netherlands; Universitat Pompeu Fabra (N.V.-T., J.M.G.--E., J.L.M., R.G., J.D.G.), Barcelona, Spain; Department of Radiology and Nuclear Medicine (H.H.A.), Erasmus Medical Center, Rotterdam, the Netherlands; IMIM (Hospital del Mar Medical Research Institute) (J.L.M., J.D.G., G.O.), Barcelona, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES) (J.L.M., G.O.); and Centro de Investigación Biomédica en Red Bioingeniería (J.D.G.), Biomateriales y Nanomedicina, Madrid, Spain.

There is clear evidence that hippocampal subfield volumes have partly distinct genetic determinants associated with specific biological processes. The identification of genetic correlates of hippocampal subfield volumes may help to elucidate the mechanisms of neurologic diseases, as well as aging and neurodegenerative processes. However, despite the emerging interest in this area of research, the current knowledge of the genetic architecture of hippocampal subfields has not yet been consolidated. We aimed to provide a review of the current evidence from genetic studies of hippocampal subfields, highlighting current priorities and upcoming challenges. The limited number of studies investigating the influential genetic effects on hippocampal subfields, a lack of replicated results and longitudinal designs, and modest sample sizes combined with insufficient standardization of protocols are identified as the most pressing challenges in this emerging area of research.
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http://dx.doi.org/10.1212/NXG.0000000000000591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192059PMC
June 2021

Genetic Predisposition to Alzheimer's Disease Is Associated with Enlargement of Perivascular Spaces in Centrum Semiovale Region.

Genes (Basel) 2021 05 27;12(6). Epub 2021 May 27.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, 08005 Barcelona, Spain.

This study investigated whether genetic factors involved in Alzheimer's disease (AD) are associated with enlargement of Perivascular Spaces (ePVS) in the brain. A total of 680 participants with T2-weighted MRI scans and genetic information were acquired from the ALFA study. ePVS in the basal ganglia (BG) and the centrum semiovale (CS) were assessed based on a validated visual rating scale. We used univariate and multivariate logistic regression models to investigate associations between ePVS in BG and CS with -rs744373, as well as genotypes. We found a significant association of the -rs744373 polymorphism in the CS subscale ( value = 0.019; OR = 2.564), suggesting that G allele carriers have an increased risk of ePVS in comparison with A allele carriers. In stratified analysis by - status (carriers vs. non-carriers), these results remained significant only for ε4 carriers ( value = 0.011; OR = 1.429). To our knowledge, the present study is the first suggesting that genetic predisposition for AD is associated with ePVS in CS. These findings provide evidence that underlying biological processes affecting AD may influence CS-ePVS.
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http://dx.doi.org/10.3390/genes12060825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226614PMC
May 2021

Amyloid-β positive individuals with subjective cognitive decline present increased CSF neurofilament light levels that relate to lower hippocampal volume.

Neurobiol Aging 2021 08 6;104:24-31. Epub 2021 Mar 6.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain; Present address: H. Lundbeck A/S, Denmark. Electronic address:

Neurofilament light chain (NfL) is an axonal protein that when measured in cerebrospinal fluid (CSF) serves as a biomarker of neurodegeneration. We aimed at investigating the association among CSF NfL, presence of Subjective Cognitive Decline (SCD) and hippocampal volume, and how CSF amyloid-β (Aβ) modifies these associations. We included 278 cognitively unimpaired participants from the Alfa+ cohort (78 SCD and 200 Controls). Linear models accounting for covariates (age, gender, and mood) were used to test the association between CSF NfL and SCD status, and between CSF NfL and bilateral hippocampal volumes. Interactions with Aβ were also explored. Individuals with SCD had higher CSF NfL and lower CSF Aβ42/40 than Controls. There was a significant interaction between SCD and CSF-Aβ42/40 levels. Stratified analyses showed a significant association between SCD and NfL only in Aβ+ individuals. Higher CSF NfL was significantly associated with lower hippocampal volume specifically in Aβ+ individuals with SCD. The presence of SCD in Aβ+ individuals may represent an early symptom in the Alzheimer's continuum related to incipient neurodegeneration.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.02.026DOI Listing
August 2021

Management and Quality Control of Large Neuroimaging Datasets: Developments From the Barcelonaβeta Brain Research Center.

Front Neurosci 2021 15;15:633438. Epub 2021 Apr 15.

Barcelonabeta Brain Research Center, Barcelona, Spain.

Recent decades have witnessed an increasing number of large to very large imaging studies, prominently in the field of neurodegenerative diseases. The datasets collected during these studies form essential resources for the research aiming at new biomarkers. Collecting, hosting, managing, processing, or reviewing those datasets is typically achieved through a local neuroinformatics infrastructure. In particular for organizations with their own imaging equipment, setting up such a system is still a hard task, and relying on cloud-based solutions, albeit promising, is not always possible. This paper proposes a practical model guided by core principles including user involvement, lightweight footprint, modularity, reusability, and facilitated data sharing. This model is based on the experience from an 8-year-old research center managing cohort research programs on Alzheimer's disease. Such a model gave rise to an ecosystem of tools aiming at improved quality control through seamless automatic processes combined with a variety of code libraries, command line tools, graphical user interfaces, and instant messaging applets. The present ecosystem was shaped around XNAT and is composed of independently reusable modules that are freely available on GitLab/GitHub. This paradigm is scalable to the general community of researchers working with large neuroimaging datasets.
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http://dx.doi.org/10.3389/fnins.2021.633438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081968PMC
April 2021

DHA intake relates to better cerebrovascular and neurodegeneration neuroimaging phenotypes in middle-aged adults at increased genetic risk of Alzheimer disease.

Am J Clin Nutr 2021 06;113(6):1627-1635

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.

Background: The number of APOE-ε4 alleles is a major nonmodifiable risk factor for sporadic Alzheimer disease (AD). There is increasing evidence on the benefits of dietary DHA (22:6n-3) before the onset of AD symptoms, particularly in APOE-ε4 carriers. Brain alterations in the preclinical stage can be detected by structural MRI.

Objectives: We aimed, in middle-aged cognitively unimpaired individuals at increased risk of AD, to cross-sectionally investigate whether dietary DHA intake relates to cognitive performance and to MRI-based markers of cerebral small vessel disease and AD-related neurodegeneration, exploring the effect modification by APOE-ε4 status.

Methods: In 340 participants of the ALFA (ALzheimer and FAmilies) study, which is enriched for APOE-ε4 carriership (n = 122, noncarriers; n = 157, 1 allele; n = 61, 2 alleles), we assessed self-reported DHA intake through an FFQ. We measured cognitive performance by administering episodic memory and executive function tests. We performed high-resolution structural MRI to assess cerebral small vessel disease [white matter hyperintensities (WMHs) and cerebral microbleeds (CMBs)] and AD-related brain atrophy (cortical thickness in an AD signature). We constructed regression models adjusted for potential confounders, exploring the interaction DHA × APOE-ε4.

Results: We observed no significant associations between DHA and cognitive performance or WMH burden. We observed a nonsignificant inverse association between DHA and prevalence of lobar CMBs (OR: 0.446; 95% CI: 0.195, 1.018; P = 0.055). DHA was found to be significantly related to greater cortical thickness in the AD signature in homozygotes but not in nonhomozygotes (P-interaction = 0.045). The association strengthened when analyzing homozygotes and nonhomozygotes matched for risk factors.

Conclusions: In cognitively unimpaired APOE-ε4 homozygotes, dietary DHA intake related to structural patterns that may result in greater resilience to AD pathology. This is consistent with the current hypothesis that those subjects at highest risk would obtain the largest benefits from DHA supplementation in the preclinical stage.This trial was registered at clinicaltrials.gov as NCT01835717.
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http://dx.doi.org/10.1093/ajcn/nqab016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168359PMC
June 2021

Nonlinear interaction between APOE ε4 allele load and age in the hippocampal surface of cognitively intact individuals.

Hum Brain Mapp 2021 01 5;42(1):47-64. Epub 2020 Oct 5.

BCN MedTech, Departament de Tecnologies de la Informació i les Comunicacions, Universitat Pompeu Fabra, Barcelona, Spain.

The ε4 allele of the gene Apolipoprotein E is the major genetic risk factor for Alzheimer's Disease. APOE ε4 has been associated with changes in brain structure in cognitively impaired and unimpaired subjects, including atrophy of the hippocampus, which is one of the brain structures that is early affected by AD. In this work we analyzed the impact of APOE ε4 gene dose and its association with age, on hippocampal shape assessed with multivariate surface analysis, in a ε4-enriched cohort of n = 479 cognitively healthy individuals. Furthermore, we sought to replicate our findings on an independent dataset of n = 969 individuals covering the entire AD spectrum. We segmented the hippocampus of the subjects with a multi-atlas-based approach, obtaining high-dimensional meshes that can be analyzed in a multivariate way. We analyzed the effects of different factors including APOE, sex, and age (in both cohorts) as well as clinical diagnosis on the local 3D hippocampal surface changes. We found specific regions on the hippocampal surface where the effect is modulated by significant APOE ε4 linear and quadratic interactions with age. We compared between APOE and diagnosis effects from both cohorts, finding similarities between APOE ε4 and AD effects on specific regions, and suggesting that age may modulate the effect of APOE ε4 and AD in a similar way.
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http://dx.doi.org/10.1002/hbm.25202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721244PMC
January 2021

Effect of BDNF Val66Met on hippocampal subfields volumes and compensatory interaction with APOE-ε4 in middle-age cognitively unimpaired individuals from the ALFA study.

Brain Struct Funct 2020 Nov 17;225(8):2331-2345. Epub 2020 Aug 17.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.

Background: Current evidence supports the involvement of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and the ε4 allele of APOE gene in hippocampal-dependent functions. Previous studies on the association of Val66Met with whole hippocampal volume included patients of a variety of disorders. However, it remains to be elucidated whether there is an impact of BDNF Val66Met polymorphism on the volumes of the hippocampal subfield volumes (HSv) in cognitively unimpaired (CU) individuals, and the interactive effect with the APOE-ε4 status.

Methods: BDNF Val66Met and APOE genotypes were determined in a sample of 430 CU late/middle-aged participants from the ALFA study (ALzheimer and FAmilies). Participants underwent a brain 3D-T1-weighted MRI scan, and volumes of the HSv were determined using Freesurfer (v6.0). The effects of the BDNF Val66Met genotype on the HSv were assessed using general linear models corrected by age, gender, education, number of APOE-ε4 alleles and total intracranial volume. We also investigated whether the association between APOE-ε4 allele and HSv were modified by BDNF Val66Met genotypes.

Results: BDNF Val66Met carriers showed larger bilateral volumes of the subiculum subfield. In addition, HSv reductions associated with APOE-ε4 allele were significantly moderated by BDNF Val66Met status. BDNF Met carriers who were also APOE-ε4 homozygous showed patterns of higher HSv than BDNF Val carriers.

Conclusion: To our knowledge, the present study is the first to show that carrying the BDNF Val66Met polymorphisms partially compensates the decreased on HSv associated with APOE-ε4 in middle-age cognitively unimpaired individuals.
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http://dx.doi.org/10.1007/s00429-020-02125-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544723PMC
November 2020

The relation between APOE genotype and cerebral microbleeds in cognitively unimpaired middle- and old-aged individuals.

Neurobiol Aging 2020 11 29;95:104-114. Epub 2020 Jun 29.

Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering, UCL, London, UK.

Positive associations between cerebral microbleeds (CMBs) and APOE-ε4 (apolipoprotein E) genotype have been reported in Alzheimer's disease, but show conflicting results. We investigated the effect of APOE genotype on CMBs in a cohort of cognitively unimpaired middle- and old-aged individuals enriched for APOE-ε4 genotype. Participants from ALFA (Alzheimer and Families) cohort were included and their magnetic resonance scans assessed (n = 564, 50% APOE-ε4 carriers). Quantitative magnetic resonance analyses included visual ratings, atrophy measures, and white matter hyperintensity (WMH) segmentations. The prevalence of CMBs was 17%, increased with age (p < 0.05), and followed an increasing trend paralleling APOE-ε4 dose. The number of CMBs was significantly higher in APOE-ε4 homozygotes compared to heterozygotes and non-carriers (p < 0.05). This association was driven by lobar CMBs (p < 0.05). CMBs co-localized with WMH (p < 0.05). No associations between CMBs and APOE-ε2, gray matter volumes, and cognitive performance were found. Our results suggest that cerebral vessels of APOE-ε4 homozygous are more fragile, especially in lobar locations. Co-occurrence of CMBs and WMH suggests that such changes localize in areas with increased vascular vulnerability.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.06.015DOI Listing
November 2020

Association of years to parent's sporadic onset and risk factors with neural integrity and Alzheimer biomarkers.

Neurology 2020 10 31;95(15):e2065-e2074. Epub 2020 Jul 31.

From the Barcelonaβeta Brain Research Center (E.M.A.-U., G.S., G.O., C.M., G.S.-B., M.C.-B., O.G.-R., A.S.-V, C.F., M.S.-C., J.D.G., J.L.M.), Pasqual Maragall Foundation; IMIM (Hospital del Mar Medical Research Institute) (E.M.A.-U., G.S., G.O., C.M., G.S.-B., M.C.-B., O.G.-R., A.S.-V, C.F., M.S.-C., J.D.G., J.L.M.), Barcelona; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (E.M.A.-U., G.S., G.O., C.M., G.S.-B., M.C.-B., O.G.-R., M.S.-C., J.L.M.), Madrid, Spain; Department of Epidemiology (M.C.-B.), Harvard TH Chan School of Public Health, Boston, MA; Servei de Neurologia (O.G.-R., M.S.-C.), Hospital del Mar, Barcelona; Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (C.F., J.D.G.), Madrid, Spain; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.), London; and Universitat Pompeu Fabra (J.D.G., J.L.M.), Barcelona, Spain.

Objective: To evaluate the hypothesis that proximity to parental age at onset (AAO) in sporadic Alzheimer disease (AD) is associated with greater AD and neural injury biomarker alterations during midlife and to assess the role of nonmodifiable and modifiable factors.

Methods: This observational study included 290 cognitively unimpaired (CU) participants with a family history (FH) of clinically diagnosed sporadic AD (age 49-73 years) from the Alzheimer's and Families (ALFA) study. [F]flutemetamol-PET standardized uptake value ratios, CSF β-amyloid ratio, and phosphorylated tau were used as AD biomarkers. Hippocampal volumes and CSF total tau were used as neural injury biomarkers. Mental and vascular health proxies were calculated. In multiple regression models, we assessed the effect of proximity to parental AAO and its interaction with age on AD and neural injury biomarkers. Then, we evaluated the effects of FH load (number of parents affected), sex, ε4, education, and vascular and mental health.

Results: Proximity to parental AAO was associated with β-amyloid, but not with neural injury biomarkers, and interacted with sex and age, showing that women and older participants had increased β-amyloid. FH load and ε4 showed independent contributions to β-amyloid load. Education and vascular and mental health proxies were not associated with AD biomarkers. However, lower mental health proxies were associated with decreased hippocampal volumes with age.

Conclusion: The identification of the earliest biomarker changes and modifiable factors to be targeted in early interventions is crucial for AD prevention. Proximity to parental AAO may offer a timeline for detection of incipient β-amyloid changes in women. In risk-enriched middle-aged cohorts, mental health may be a target for early interventions.

Clinicaltrialsgov Identifier: NCT02485730.

Classification Of Evidence: This study provides Class II evidence that in CU adults with FH of sporadic AD, proximity to parental AAO was associated with β-amyloid but not with neural injury biomarkers.
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http://dx.doi.org/10.1212/WNL.0000000000010527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774330PMC
October 2020

NeAT: a Nonlinear Analysis Toolbox for Neuroimaging.

Neuroinformatics 2020 10;18(4):517-530

BarcelonaBeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.

NeAT is a modular, flexible and user-friendly neuroimaging analysis toolbox for modeling linear and nonlinear effects overcoming the limitations of the standard neuroimaging methods which are solely based on linear models. NeAT provides a wide range of statistical and machine learning non-linear methods for model estimation, several metrics based on curve fitting and complexity for model inference and a graphical user interface (GUI) for visualization of results. We illustrate its usefulness on two study cases where non-linear effects have been previously established. Firstly, we study the nonlinear effects of Alzheimer's disease on brain morphology (volume and cortical thickness). Secondly, we analyze the effect of the apolipoprotein APOE-ε4 genotype on brain aging and its interaction with age. NeAT is fully documented and publicly distributed at https://imatge-upc.github.io/neat-tool/ .
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http://dx.doi.org/10.1007/s12021-020-09456-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498484PMC
October 2020

Association between insomnia and cognitive performance, gray matter volume, and white matter microstructure in cognitively unimpaired adults.

Alzheimers Res Ther 2020 01 7;12(1). Epub 2020 Jan 7.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Wellington 30, 08003, Barcelona, Spain.

Background: Mounting evidence links poor sleep quality with a higher risk of late-life dementia. However, the structural and cognitive correlates of insomnia are still not well understood. The study aims were to characterize the cognitive performance and brain structural pattern of cognitively unimpaired adults at increased risk for Alzheimer's disease (AD) with insomnia.

Methods: This cross-sectional study included 1683 cognitively unimpaired middle/late-middle-aged adults from the ALFA (ALzheimer and FAmilies) study who underwent neuropsychological assessment, T1-weighted structural imaging (n = 366), and diffusion-weighted imaging (n = 334). The World Health Organization's World Mental Health Survey Initiative version of the Composite International Diagnostic Interview was used to define the presence or absence of insomnia. Multivariable regression models were used to evaluate differences in cognitive performance between individuals with and without insomnia, as well as potential interactions between insomnia and the APOE genotype. Voxel-based morphometry and tract-based spatial statistics were used to assess between-group differences and potential interactions between insomnia and the APOE genotype in gray matter volume and white matter diffusion metrics.

Results: Insomnia was reported by 615 out of 1683 participants (36.5%), including 137 out of 366 (37.4%) with T1-weighted structural imaging available and 119 out of 334 (35.6%) with diffusion-weighted imaging. Individuals with insomnia (n = 615) performed worse in executive function tests than non-insomniacs and displayed lower gray matter volume in left orbitofrontal and right middle temporal cortex, bilateral precuneus, posterior cingulate cortex and thalamus, higher gray matter volume in the left caudate nucleus, and widespread reduction of mean and axial diffusivity in right hemisphere white matter tracts. Insomnia interacted with the APOE genotype, with APOE-ε4 carriers displaying lower gray matter volumes when insomnia was present, but higher volumes when insomnia was not present, in several gray matter regions, including the left angular gyrus, the bilateral superior frontal gyri, the thalami, and the right hippocampus.

Conclusions: Insomnia in cognitively unimpaired adults at increased risk for AD is associated to poorer performance in some executive functions and volume changes in cortical and subcortical gray matter, including key areas involved in Alzheimer's disease, as well as decreased white matter diffusivity.
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http://dx.doi.org/10.1186/s13195-019-0547-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945611PMC
January 2020

White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants.

Hum Brain Mapp 2020 04 28;41(5):1309-1322. Epub 2019 Nov 28.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.

White matter hyperintensities (WMH) have been extensively associated with cognitive impairment and reductions in gray matter volume (GMv) independently. This study explored whether WMH lesion volume mediates the relationship between cerebral patterns of GMv and cognition in 521 (mean age 57.7 years) cognitively unimpaired middle-aged individuals. Episodic memory (EM) was measured with the Memory Binding Test and executive functions (EF) using five WAIS-IV subtests. WMH were automatically determined from T2 and FLAIR sequences and characterized using diffusion-weighted imaging (DWI) parameters. WMH volume was entered as a mediator in a voxel-wise mediation analysis relating GMv and cognitive performance (with both EM and EF composites and the individual tests independently). The mediation model was corrected by age, sex, education, number of Apolipoprotein E (APOE)-ε4 alleles and total intracranial volume. We found that even at very low levels of WMH burden in the cohort (median volume of 3.2 mL), higher WMH lesion volume was significantly associated with a widespread pattern of lower GMv in temporal, frontal, and cerebellar areas. WMH mediated the relationship between GMv and EF, mainly driven by processing speed, but not EM. DWI parameters in these lesions were compatible with incipient demyelination and axonal loss. These findings lead to the reflection on the relevance of the control of cardiovascular risk factors in middle-aged individuals as a valuable preventive strategy to reduce or delay cognitive decline.
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http://dx.doi.org/10.1002/hbm.24877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267988PMC
April 2020

Interactive effect of age and APOE-ε4 allele load on white matter myelin content in cognitively normal middle-aged subjects.

Neuroimage Clin 2019 16;24:101983. Epub 2019 Aug 16.

Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain. Electronic address:

The apolipoprotein E gene (APOE) ε4 allele has a strong and manifold impact on cognition and neuroimaging phenotypes in cognitively normal subjects, including alterations in the white matter (WM) microstructure. Such alterations have often been regarded as a reflection of potential thinning of the myelin sheath along axons, rather than pure axonal degeneration. Considering the main role of APOE in brain lipid transport, characterizing the impact of APOE on the myelin coating is therefore of crucial interest, especially in healthy APOE-ε4 homozygous individuals, who are exposed to a twelve-fold higher risk of developing Alzheimer's disease (AD), compared to the rest of the population. We examined T1w/T2w ratio maps in 515 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-ε4 homozygotes, 197 heterozygotes, and 250 non-carriers). Using tract-based spatial statistics, we assessed the impact of age and APOE genotype on this ratio taken as an indirect descriptor of myelin content. Healthy APOE-ε4 carriers display decreased T1w/T2w ratios in extensive regions in a dose-dependent manner. These differences were found to interact with age, suggesting faster changes in individuals with more ε4 alleles. These results obtained with T1w/T2w ratios, confirm the increased vulnerability of WM tracts in APOE-ε4 healthy carriers. Early alterations of myelin content could be the result of the impaired function of the ε4 isoform of the APOE protein in cholesterol transport. These findings help to clarify the possible interactions between the APOE-dependent non-pathological burden and age-related changes potentially at the source of the AD pathological cascade.
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http://dx.doi.org/10.1016/j.nicl.2019.101983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742967PMC
September 2020

Prediction of amyloid pathology in cognitively unimpaired individuals using voxel-wise analysis of longitudinal structural brain MRI.

Alzheimers Res Ther 2019 08 17;11(1):72. Epub 2019 Aug 17.

Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, C/ Wellington 30, 08005, Barcelona, Spain.

Background: Magnetic resonance imaging (MRI) has unveiled specific alterations at different stages of Alzheimer's disease (AD) pathophysiologic continuum constituting what has been established as "AD signature". To what extent MRI can detect amyloid-related cerebral changes from structural MRI in cognitively unimpaired individuals is still an area open for exploration.

Method: Longitudinal 3D-T1 MRI scans were acquired from a subset of the ADNI cohort comprising 403 subjects: 79 controls (Ctrls), 50 preclinical AD (PreAD), and 274 MCI and dementia due to AD (MCI/AD). Amyloid CSF was used as gold-standard measure with established cutoffs (< 192 pg/mL) to establish diagnostic categories. Cognitively unimpaired individuals were defined as Ctrls if were amyloid negative and PreAD otherwise. The MCI/AD group was amyloid positive. Only subjects with the same diagnostic category at baseline and follow-up visits were considered for the study. Longitudinal morphometric analysis was performed using SPM12 to calculate Jacobian determinant maps. Statistical analysis was carried out on these Jacobian maps to identify structural changes that were significantly different between diagnostic categories. A machine learning classifier was applied on Jacobian determinant maps to predict the presence of abnormal amyloid levels in cognitively unimpaired individuals. The performance of this classifier was evaluated using receiver operating characteristic curve analysis and as a function of the follow-up time between MRI scans. We applied a cost function to assess the benefit of using this classifier in the triaging of individuals in a clinical trial-recruitment setting.

Results: The optimal follow-up time for classification of Ctrls vs PreAD was Δt > 2.5 years, and hence, only subjects within this temporal span are used for evaluation (15 Ctrls, 10 PreAD). The longitudinal voxel-based classifier achieved an AUC = 0.87 (95%CI 0.72-0.97). The brain regions that showed the highest discriminative power to detect amyloid abnormalities were the medial, inferior, and lateral temporal lobes; precuneus; caudate heads; basal forebrain; and lateral ventricles.

Conclusions: Our work supports that machine learning applied to longitudinal brain volumetric changes can be used to predict, with high precision, the presence of amyloid abnormalities in cognitively unimpaired subjects. Used as a triaging method to identify a fixed number of amyloid-positive individuals, this longitudinal voxel-wise classifier is expected to avoid 55% of unnecessary CSF and/or PET scans and reduce economic cost by 40%.
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http://dx.doi.org/10.1186/s13195-019-0526-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698344PMC
August 2019

Longitudinal structural cerebral changes related to core CSF biomarkers in preclinical Alzheimer's disease: A study of two independent datasets.

Neuroimage Clin 2018 16;19:190-201. Epub 2018 Apr 16.

Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Neurology Department, Hospital Clínic i Provincial de Barcelona, Barcelona, Spain; CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain. Electronic address:

Alzheimer's disease (AD) is characterized by an accumulation of β-amyloid (Aβ) accompanied by brain atrophy and cognitive decline. Several recent studies have shown that Aβ accumulation is associated with gray matter (GM) changes prior to the development of cognitive impairment, in the so-called preclinical stage of the AD (pre-AD). It also has been proved that the GM atrophy profile is not linear, both in normal ageing but, especially, on AD. However, several other factors may influence this association and may have an impact on the generalization of results from different samples. In this work, we estimate differences in rates of GM volume change in cognitively healthy elders in association with baseline core cerebrospinal fluid (CSF) AD biomarkers, and assess to what these differences are sample dependent. We report the dependence of atrophy rates, measured in a two-year interval, on Aβ, computed both over continuous and categorical values of Aβ, at voxel-level (p < 0.001; k < 100) and corrected for sex, age and education. Analyses were performed jointly and separately, on two samples. The first sample was formed of 31 individuals (22 Ctrl and 9 pre-AD), aged 60-80 and recruited at the Hospital Clinic of Barcelona. The second sample was a replica of the first one with subjects selected from the ADNI dataset. We also investigated the dependence of the GM atrophy rate on the basal levels of continuous p-tau and on the p-tau/Aβ ratio. Correlation analyses on the whole sample showed a dependence of GM atrophy rates on Aβ in medial and orbital frontal, precuneus, cingulate, medial temporal regions and cerebellum. Correlations with p-tau were located in the left hippocampus, parahippocampus and striatal nuclei whereas correlation with p-tau/Aβ was mainly found in ventral and medial temporal areas. Regarding analyses performed separately, we found a substantial discrepancy of results between samples, illustrating the complexities of comparing two independent datasets even when using the same inclusion criteria. Such discrepancies may lead to significant differences in the sample size needed to detect a particular reduction on cerebral atrophy rates in prevention trials. Higher cognitive reserve and more advanced pathological progression in the ADNI sample could partially account for the observed discrepancies. Taken together, our findings in these two samples highlight the importance of comparing and merging independent datasets to draw more robust and generalizable conclusions on the structural changes in the preclinical stages of AD.
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http://dx.doi.org/10.1016/j.nicl.2018.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050455PMC
January 2019

White matter microstructure is altered in cognitively normal middle-aged APOE-ε4 homozygotes.

Alzheimers Res Ther 2018 05 24;10(1):48. Epub 2018 May 24.

Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, C/ Wellington, 30, 08005, Barcelona, Spain.

Background: The ε4 allele of the apolipoprotein E gene (APOE-ε4) is the strongest genetic factor for late-onset Alzheimer's disease. During middle age, cognitively healthy APOE-ε4 carriers already show several brain alterations that resemble those of Alzheimer's disease (AD), but to a subtler degree. These include microstructural white matter (WM) changes that have been proposed as one of the earliest structural events in the AD cascade. However, previous studies have focused mainly on comparison of APOE-ε4 carriers vs noncarriers. Therefore, the extent and magnitude of the brain alterations in healthy ε4 homozygotes, who are the individuals at highest risk, remain to be characterized in detail.

Methods: We examined mean, axial, and radial water diffusivity (MD, AxD, and RD, respectively) and fractional anisotropy in the WM as measured by diffusion-weighted imaging in 532 cognitively healthy middle-aged participants from the ALFA study (ALzheimer and FAmilies) cohort, a single-site population-based study enriched for AD risk (68 APOE-ε4 homozygotes, 207 heterozygotes, and 257 noncarriers). We examined the impact of age and APOE genotype on these parameters using tract-based spatial statistics.

Results: Healthy APOE-ε4 homozygotes display increased WM diffusivity in regions known to be affected by AD. The effects in AxD were much smaller than in RD, suggesting a disruption of the myelin sheath rather than pure axonal damage.

Conclusions: These findings could be interpreted as the result of the reduced capacity of the ε4 isoform of the APOE protein to keep cholesterol homeostasis in the brain. Because cerebral lipid metabolism is strongly related to the pathogenesis of AD, our results shed light on the possible mechanisms through which the APOE-ε4 genotype is associated with an increased risk of AD.
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http://dx.doi.org/10.1186/s13195-018-0375-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968505PMC
May 2018

Neuroimaging Methods for MRI Analysis in CSF Biomarkers Studies.

Methods Mol Biol 2018 ;1750:165-184

Barcelonaβeta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.

Among others, the existence of pathophysiological biomarkers such as cerebrospinal fluid (CSF) Aβ-42, t-tau, and p-tau preceding the onset of Alzheimer's disease (AD) symptomatology have shifted the conceptualization of AD as a continuum. In addition, magnetic resonance imaging (MRI) enables the study of structural and functional cross-sectional correlates and longitudinal changes in vivo and, therefore, the combination of CSF data and imaging analyses emerges as a synergistic approach to understand the structural correlates related with specific AD-related biomarkers. In this chapter, we describe the methods used in neuroimaging that will allow researchers to combine data on CSF metabolites with imaging analyses.
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http://dx.doi.org/10.1007/978-1-4939-7704-8_11DOI Listing
February 2019

Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort.

Alzheimers Res Ther 2017 Aug 29;9(1):67. Epub 2017 Aug 29.

Memory Resource and Research Centre of Besançon, CHU de Besançon, Hôpital Jean Minjoz, Hôpital Saint-Jacques, F-25000, Besançon, France.

Background: The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements.

Methods: In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR] <1). Baseline data collection included neurological and physical examinations as well as extensive neuropsychological testing. To be included in the MEMENTO cohort, participants had to agree to undergo both brain magnetic resonance imaging (MRI) and blood sampling. Cerebral F-fluorodeoxyglucose positon emission tomography and lumbar puncture were optional. Automated analyses of cerebral MRI included assessments of volumes of whole-brain, hippocampal and white matter lesions.

Results: The 2323 participants, recruited from April 2011 to June 2014, were aged 71 years, on average (SD 8.7), and 62% were women. CDR was 0 in 40% of participants, and 30% carried at least one apolipoprotein E ε4 allele. We observed that more than half (52%) of participants had amnestic mild cognitive impairment (17% single-domain aMCI), 32% had non-amnestic mild cognitive impairment (16.9% single-domain naMCI) and 16% had isolated SCCs. Multivariable analyses of neuroimaging markers associations with cognitive categories showed that participants with aMCI had worse levels of imaging biomarkers than the others, whereas participants with naMCI had markers at intermediate levels between SCC and aMCI. The burden of white matter lesions tended to be larger in participants with aMCI. Independently of CDR, all neuroimaging and neuropsychological markers worsened with age, whereas differences were not consistent according to sex.

Conclusions: MEMENTO is a large cohort with extensive clinical, neuropsychological and neuroimaging data and represents a platform for studying the natural history of ADRD in a large group of participants with different subtypes of MCI (amnestic or not amnestic) or isolated SCCs.

Trial Registration: Clinicaltrials.gov, NCT01926249 . Registered on 16 August 2013.
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http://dx.doi.org/10.1186/s13195-017-0288-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576287PMC
August 2017

CATI: A Large Distributed Infrastructure for the Neuroimaging of Cohorts.

Neuroinformatics 2016 07;14(3):253-64

INSERM U708, Neuroepidemiology, CIC-EC7 & Bordeaux University, Bordeaux, France.

This paper provides an overview of CATI, a platform dedicated to multicenter neuroimaging. Initiated by the French Alzheimer's plan (2008-2012), CATI is a research project called on to provide service to other projects like an industrial partner. Its core mission is to support the neuroimaging of large populations, providing concrete solutions to the increasing complexity involved in such projects by bringing together a service infrastructure, the know-how of its expert academic teams and a large-scale, harmonized network of imaging facilities. CATI aims to make data sharing across studies easier and promotes sharing as much as possible. In the last 4 years, CATI has assisted the clinical community by taking charge of 35 projects so far and has emerged as a recognized actor at the national and international levels.
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http://dx.doi.org/10.1007/s12021-016-9295-8DOI Listing
July 2016

Structural analysis of fMRI data: a surface-based framework for multi-subject studies.

Med Image Anal 2012 Jul 28;16(5):976-90. Epub 2012 Feb 28.

LSIS Laboratory, CNRS, Marseille, France.

We present a method for fMRI data group analysis that makes the link between two distinct frameworks: surface-based techniques, which process data in the domain defined by the surface of the cortex, and structural techniques, which use object-based representations of the data as opposed to voxel-based ones. This work is a natural surface-based extension of the volume-based structural approach presented in a previous paper. A multi-scale surface-based representation of individual activation maps is first computed for each subject. Then the inter-subject matching and the activation detection decision are performed jointly by optimization of a Markovian model. Finally, a significance measure is computed in a non-parametric way for the results, in order to assess their relevance and control the risk of type I error. The method is applied on simulated and real data and the results are compared to those produced by standard analyses. The surface-based structural analysis is shown to be particularly robust to inter-subject spatial variability and to produce relevant results with good specificity and sensitivity. We also demonstrate the advantages of the surface-based approach by comparing with the results of a 3D structural analysis.
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http://dx.doi.org/10.1016/j.media.2012.02.007DOI Listing
July 2012

Two new stable anatomical landmarks on the Central Sulcus: definition, automatic detection, and their relationship with primary motor functions of the hand.

Annu Int Conf IEEE Eng Med Biol Soc 2011 ;2011:7795-8

Laboratoire des Sciences de l’Information et des Systèmes, UMR CNRS 6168, Marseille, France.

We present a method to automatically detect two new stable anatomical landmarks L(1) and L(2) on the Central Sulcus (CS). Those landmarks are shown to be representative of the Central Sulcus morphology and linked to the functional primary motor area of the hand. Detection is performed after introducing a new morphological characteristic, the sulcal profile. We show that when matching explicitly L(1) and L(2) across individuals the inter-subject matching of the central sulcus anatomy is improved, as well as the inter-subject matching of the primary motor area of the hand. This opens possibilities for morphological studies of the CS, more precise functional studies of primary motor function, and a better understanding of motor representations along the CS.
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http://dx.doi.org/10.1109/IEMBS.2011.6091921DOI Listing
May 2012

Cortical pattern of complex but not simple movements is affected in writer's cramp: a parametric event-related fMRI study.

Clin Neurophysiol 2012 Apr 7;123(4):755-63. Epub 2011 Sep 7.

Dept. of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Prague, Czech Republic.

Objective: Patients with writer's cramp (WC) were studied for differences in cortical activation during movements likely to induce WC (complex movements) and movements which rarely lead to dystonia (simple movements).

Methods: Eleven WC patients (10F, 1M, mean age 41.5 ± (SD)7.2 years) and eleven age matched controls were examined for Blood oxygenation-level dependent (BOLD) 1.5 T fMRI. The complex task consisted of writing a single letter or random drawing using an especially adapted joystick with the line of trajectory visualized or hidden. The simple task consisted of self-initiated fingers flexion/extension using the affected hand.

Results: Unlike the controls, WC patients performing complex movements exhibited a lower BOLD signal in the primary sensorimotor cortex and in the posterior parietal cortex bilaterally. A hypoactivation was also observed in the right secondary somatosensory area, in the right anterior insula and in the left premotor cortex (p < 0.05 corrected). No significant inter-group differences were found for simple movements.

Conclusions: Although WC patients' complex movements during fMRI were never associated with dystonic cramp, they exhibited an abnormally low cortical activity. This phenomenon was not observed in simple movements and was unrelated to the character of handwriting or to visual feedback.

Significance: Our results support the dualistic behavior in the sensorimotor system in WC.
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http://dx.doi.org/10.1016/j.clinph.2011.08.002DOI Listing
April 2012

Repetitive TMS of the somatosensory cortex improves writer's cramp and enhances cortical activity.

Neuro Endocrinol Lett 2010 ;31(1):73-86

Department of Neurology, 1st Medical Faculty and General Teaching Hospital, Charles University, Prague, Czech Republic.

Since the somatosensory system is believed to be affected in focal dystonia, we focused on the modulation of the primary somatosensory cortex (SI) induced by repetitive transcranial magnetic stimulation (rTMS) in order to improve symptoms of writer's cramp. Patients with writer's cramp (N=9 in the pilot study and N=11 in the advanced study) were treated with 30-minute 1 Hz real- or sham-rTMS of the SI cortex every day for 5 days. Before and after rTMS, 1.5 T fMRI was examined during simple hand movements. While in the pilot study the rTMS coil was navigated over the SI cortex with a maximum of blood oxygenation-level dependent (BOLD) signal induced by passive movement, patients in the advanced study had the coil above the postcentral sulcus. After real-rTMS, 4 pilot study patients and 10 advanced study patients experienced subjective and objective improvement in writing, while only minimal changes were observed after sham-rTMS. Patients involved in the active movement task exhibited a rTMS-induced BOLD signal increase bilaterally in the SI cortex, posterior parietal cortex and in the supplementary motor area (P<0.001 corrected). After sham-rTMS, no BOLD signal changes were observed. In conclusion, 1 Hz rTMS of the SI cortex can improve writer's cramp while increasing the cortical activity in both hemispheres. Handwriting improved in most patients, as well as the subjective benefit, and lasted for 2-3 weeks. The beneficial effects of rTMS paralleled the functional reorganization in the SI cortex and connected areas, reflecting the impact of somatosensory system on active motion control.
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May 2010

Surface-based structural group analysis of fMRI data.

Med Image Comput Comput Assist Interv 2008 ;11(Pt 1):959-66

Laboratoire LSIS, UMR CNRS 6168, Marseille, France.

As structural and surface-based analyses gain interest for activation detection, morphometry and intersubject matching purposes, this paper proposes a method to perform structural group analyses directly on the cortical surface. Scale-space blobs are extracted from surface-based functional maps and matched across subjects. The process aims at identifying activations within a population despite the various effects due to variability. Results of the method are presented with simulated activations and with data from a somatotopy protocol.
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http://dx.doi.org/10.1007/978-3-540-85988-8_114DOI Listing
December 2008

Anatomically informed convolution kernels for the projection of fMRI data on the cortical surface.

Med Image Comput Comput Assist Interv 2006 ;9(Pt 2):300-7

Laboratoire LSIS, UMR 6168, CNRS, Marseille, France.

We present here a method that aims at producing representations of functional brain data on the cortical surface from functional MRI volumes. Such representations are required for subsequent cortical-based functional analysis. We propose a projection technique based on the definition, around each node of the grey/white matter interface mesh, of convolution kernels whose shape and distribution rely on the geometry of the local anatomy. For one anatomy, a set of convolution kernels is computed that can be used to project any functional data registered with this anatomy. The method is presented together with experiments on synthetic data and real statistical t-maps.
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http://dx.doi.org/10.1007/11866763_37DOI Listing
April 2007
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