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Montandon, M.-L., Herrmann, F. R., Garibotto, V., Rodriguez, C., Haller, S. & Giannakopoulos, P. (2020). Determinants of mesial temporal lobe volume loss in older individuals with preserved cognition: a longitudinal PET amyloid study. Neurobiology of Aging, 87, 108-114
Open this publication in new window or tab >>Determinants of mesial temporal lobe volume loss in older individuals with preserved cognition: a longitudinal PET amyloid study
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2020 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 87, p. 108-114Article in journal (Refereed) Published
Abstract [en]

Mesial temporal lobe (MTL) is prominently affected in normal aging and associated with neurodegeneration in AD. Whether or not MTL atrophy is dependent on increasing amyloid load before the emergence of cognitive deficits is still disputed. We performed a 4.5-year longitudinal study in 75 older community dwellers (48 women, mean age: 79.3 years) including magnetic resonance imaging at baseline and follow-up, positron emission tomography amyloid during follow-up, neuropsychological assessment at 18 and 55 months, and APOE genotyping. Linear regression models were used to identify predictors of the MTL volume loss. Amyloid load was negatively associated with bilateral MTL volume at baseline explaining almost 10.5% of its variability. In multivariate models including time of follow-up and demographic variables (older age, male gender), this percentage exceeded 35%. The APOE4 allele independently contributed another 6%. Cognitive changes had a modest but still significant negative association with MTL volume loss. Our data support a multifactorial model including amyloid deposition, older age, male gender, APOE4 allele, and slight decline of cognitive abilities as independent predictors of MTL volume loss in brain aging.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
APOE, Amyloid load, Cognitive changes, Mesial temporal lobe, Normal aging, Structural MRI
National Category
Geriatrics Neurosciences
Identifiers
urn:nbn:se:uu:diva-404491 (URN)10.1016/j.neurobiolaging.2019.12.002 (DOI)000518217600013 ()32057528 (PubMedID)
Available from: 2020-02-20 Created: 2020-02-20 Last updated: 2020-04-03Bibliographically approved
Giannakopoulos, P., Rodriguez, C., Montandon, M.-L., Garibotto, V., Haller, S. & Herrmann, F. R. (2020). Less agreeable, better preserved?: A PET amyloid and MRI study in a community-based cohort. Neurobiology of Aging, 89, 24-31
Open this publication in new window or tab >>Less agreeable, better preserved?: A PET amyloid and MRI study in a community-based cohort
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2020 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 89, p. 24-31Article in journal (Refereed) Published
Abstract [en]

The relationship between personality profiles and brain integrity in old age is still a matter of debate. We examined the association between Big Five factor and facet scores and MRI brain volume changes on a 54-month follow-up in 65 elderly controls with 3 neurocognitive assessments (baseline, 18 months, and 54 months), structural brain MRI (baseline and 54 months), brain amyloid PET during follow-up, and APOE genotyping. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE epsilon 4 allele, and cognitive evolution. Lower agreeableness factor scores (and 4 of its facets) were associated with lower volume loss in the hippocampus, entorhinal cortex, amygdala, mesial temporal lobe, and precuneus bilaterally. Higher openness factor scores (and 2 of its facets) were also associated with lower volume loss in the left hippocampus. Our findings persisted when adjusting for confounders in multivariable models. These data suggest that the combination of low agreeableness and high openness is an independent predictor of better preservation of brain volume in areas vulnerable to neurodegeneration. (C) 2020 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Amyloid load, Cognitive aging, Cohort studies, Personality, Structural MRI
National Category
Geriatrics
Identifiers
urn:nbn:se:uu:diva-409848 (URN)10.1016/j.neurobiolaging.2020.02.004 (DOI)000522552900003 ()32169357 (PubMedID)
Available from: 2020-05-28 Created: 2020-05-28 Last updated: 2020-05-28Bibliographically approved
Georgiopoulos, C., Witt, S. T., Haller, S., Dizdar, N., Zachrisson, H., Engström, M. & Larsson, E.-M. (2019). A study of neural activity and functional connectivity within the olfactory brain network in Parkinson's disease. NeuroImage: Clinical, 23, Article ID 101946.
Open this publication in new window or tab >>A study of neural activity and functional connectivity within the olfactory brain network in Parkinson's disease
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2019 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 23, article id 101946Article in journal (Refereed) Published
Abstract [en]

Olfactory dysfunction is an early manifestation of Parkinson's disease (PD). The present study aimed to illustrate potential differences between PD patients and healthy controls in terms of neural activity and functional connectivity within the olfactory brain network. Twenty PD patients and twenty healthy controls were examined with olfactory fMRI and resting-state fMRI. Data analysis of olfactory fMRI included data-driven tensorial independent component (ICA) and task-driven general linear model (GLM) analyses. Data analysis of resting-state fMRI included probabilistic ICA based on temporal concatenation and functional connectivity analysis within the olfactory network. ICA of olfactory fMRI identified an olfactory network consisting of the posterior piriform cortex, insula, right orbitofrontal cortex and thalamus. Recruitment of this network was less significant for PD patients. GLM analysis revealed significantly lower activity in the insula bilaterally and the right orbitofrontal cortex in PD compared to healthy controls but no significant differences in the olfactory cortex itself. Analysis of resting-state fMRI did not reveal any differences in the functional connectivity within the olfactory, default mode, salience or central executive networks between the two groups. In conclusion, olfactory dysfunction in PD is associated with less significant recruitment of the olfactory brain network. ICA could demonstrate differences in both the olfactory cortex and its main projections, compared to GLM that revealed differences only on the latter. Resting-state fMRI did not reveal any significant differences in functional connectivity within the olfactory, default mode, salience and central executive networks in this cohort.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Functional connectivity, Olfaction, Parkinson, fMRI
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-392823 (URN)10.1016/j.nicl.2019.101946 (DOI)000485804400125 ()31491835 (PubMedID)
Available from: 2019-09-10 Created: 2019-09-10 Last updated: 2019-10-25Bibliographically approved
Haller, S., Montandon, M.-L., Rodriguez, C., Garibotto, V., Lilja, J., Herrmann, F. R. & Giannakopoulos, P. (2019). Amyloid Load, Hippocampal Volume Loss, and Diffusion Tensor Imaging Changes in Early Phases of Brain Aging. Frontiers in Neuroscience, 13, Article ID 1228.
Open this publication in new window or tab >>Amyloid Load, Hippocampal Volume Loss, and Diffusion Tensor Imaging Changes in Early Phases of Brain Aging
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2019 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 13, article id 1228Article in journal (Refereed) Published
Abstract [en]

Background and Purpose Amyloid imaging, gray matter (GM) morphometry and diffusion tensor imaging (DTI) have all been used as predictive biomarkers in dementia. Our objective was to define the imaging profile of healthy elderly controls as a function of their cognitive trajectories and explore whether amyloid burden and white matter (WM) microstructure changes are associated with subtle decrement of neuropsychological performances in old age. Materials and Methods We performed a 4.5-year longitudinal study in 133 elderly individuals who underwent cognitive testing at inclusion and follow-up, amyloid PET, MRI including DTI sequences at inclusion, and APOE epsilon 4 genotyping. All cases were assessed using a continuous cognitive score (CCS) taking into account the global evolution of neuropsychological performances. Data processing included region of interest analysis of amyloid PET analysis, GM densities and tract-based spatial statistics (TBSS)-DTI. Regression models were built to explore the association between the CCS and imaging parameters controlling for significant demographic and clinical covariates. Results Amyloid uptake was not related to the cognitive outcome. In contrast, GM densities in bilateral hippocampus were associated with worst CCS at follow-up. In addition, radial and axial diffusivities in left hippocampus were negatively associated with CCS. Amyloid load was associated with decreased VBM and increased radial and axial diffusivity in the same area. These associations persisted when adjusting for gender and APOE4 genotype. Importantly, they were absent in amygdala and neocortical areas studied. Conclusion The progressive decrement of neuropsychological performances in normal aging is associated with volume loss and WM microstructure changes in hippocampus long before the emergence of clinically overt symptoms. Higher amyloid load in hippocampus is compatible with cognitive preservation in cases with better preservation of GM densities and WM microstructure in this area.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2019
Keywords
amyloid deposition, APOE genotyping, magnetic resonance imaging, normal aging, positron emission tomography
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:uu:diva-400019 (URN)10.3389/fnins.2019.01228 (DOI)000499822900001 ()31803008 (PubMedID)
Available from: 2019-12-19 Created: 2019-12-19 Last updated: 2019-12-19Bibliographically approved
Vernooij, M. W., Pizzini, F. B., Schmidt, R., Smits, M., Yousry, T. A., Bargallo, N., . . . Barkhof, F. (2019). Dementia imaging in clinical practice: a European-wide survey of 193 centres and conclusions by the ESNR working group. Neuroradiology, 61(6), 633-642
Open this publication in new window or tab >>Dementia imaging in clinical practice: a European-wide survey of 193 centres and conclusions by the ESNR working group
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2019 (English)In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 61, no 6, p. 633-642Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Through a European-wide survey, we assessed the current clinical practice of imaging in the primary evaluation of dementia, with respect to standardised imaging, evaluation and reporting.

METHODS: An online questionnaire was emailed to all European Society of Neuroradiology (ESNR) members (n = 1662) and non-members who had expressed their interest in ESNR activities in the past (n = 6400). The questionnaire featured 42 individual items, divided into multiple choice, single best choice and free text answers. Information was gathered on the context of the practices, available and preferred imaging modalities, applied imaging protocols and standards for interpretation, reporting and communication.

RESULTS: A total of 193 unique (non-duplicate) entries from the European academic and non-academic institutions were received from a total of 28 countries. Of these, 75% were neuroradiologists, 12% general radiologists and 11% (neuro) radiologists in training. Of responding centres, 38% performed more than five scans/week for suspected dementia. MRI was primarily used in 72% of centres. Over 90% of centres acquired a combination of T2w, FLAIR, T1w, DWI and T2*w sequences. Visual rating scales were used in 75% of centres, most often the Fazekas and medial temporal atrophy scale; 32% of respondents lacked full confidence in their use. Only 23% of centres performed volumetric analysis. A minority of centres (28%) used structured reports.

CONCLUSIONS: Current practice in dementia imaging is fairly homogeneous across Europe, in terms of image acquisition and image interpretation. Hurdles identified include training on the use of visual rating scales, implementation of volumetric assessment and structured reporting.

Keywords
Dementia, Imaging, MRI, Survey
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-382952 (URN)10.1007/s00234-019-02188-y (DOI)000467659100002 ()30852630 (PubMedID)
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-19Bibliographically approved
Herrmann, F. R., Rodriguez, C., Haller, S., Garibotto, V., Montandon, M.-L. & Giannakopoulos, P. (2019). Gray Matter Densities in Limbic Areas and APOE4 Independently Predict Cognitive Decline in Normal Brain Aging. Frontiers in Aging Neuroscience, 11, Article ID 157.
Open this publication in new window or tab >>Gray Matter Densities in Limbic Areas and APOE4 Independently Predict Cognitive Decline in Normal Brain Aging
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2019 (English)In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 11, article id 157Article in journal (Refereed) Published
Abstract [en]

Cross-sectional magnetic resonance imaging (MRI) studies reported significant associations between gray matter (GM) density changes in various limbic and neocortical areas and worst cognitive performances in elderly controls. Longitudinal studies in this field remain scarce and led to conflicting data. We report a clinico-radiological investigation of 380 cognitively preserved individuals who undergo neuropsychological assessment at baseline and after 18 months. All cases were assessed using a continuous cognitive score taking into account the global evolution of neuropsychological performances. The vast majority of Mini Mental State Examination (MMSE) 29 and 30 cases showed equal or worst performance at follow-up due to a ceiling effect. GM densities, white matter hyperintensities and arterial spin labeling (ASL) values were assessed in the hippocampus, amygdala, mesial temporal and parietal cortex at inclusion using 3 Tesla MRI Scans. Florbetapir positron emission tomography (PET) amyloid was available in a representative subsample of 64 cases. Regional amyloid uptake ratios (SUVr), mean cortical SUVr values (mcSUVr) and corresponding z-scores were calculated. Linear regression models were built to explore the association between the continuous cognitive score and imaging variables. The presence of an APOE-epsilon 4 allele was negatively related to the continuous cognitive score. Among the areas studied, significant associations were found between GM densities in the hippocampus and amygdala but not mesial temporal and parietal areas and continuous cognitive score. Neither ASL values, Fazekas score nor mean and regional PET amyloid load was related to the cognitive score. In multivariate models, the presence of APOE-epsilon 4 allele and GM densities in the hippocampus and amygdala were independently associated with worst cognitive evolution at follow-up. Our data support the idea that early GM damage in the hippocampus and amygdala occur long before the emergence of the very first signs of cognitive failure in brain aging.

Keywords
amygdala, arterial spin labeling, cognition, gray matter density, hippocampus, longitudinal study, magnetic resonance imaging, white matter hyperintensity
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-390963 (URN)10.3389/fnagi.2019.00157 (DOI)000473279800001 ()31316372 (PubMedID)
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2019-08-16Bibliographically approved
Garibotto, V., Corpataux, T., Dupuis-Lozeron, E., Haller, S., Fontolliet, T. & Picard, F. (2019). Higher nicotinic receptor availability in the cingulo-insular network is associated with lower cardiac parasympathetic tone. Journal of Comparative Neurology, 527(18), 3014-3022
Open this publication in new window or tab >>Higher nicotinic receptor availability in the cingulo-insular network is associated with lower cardiac parasympathetic tone
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2019 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 527, no 18, p. 3014-3022Article in journal (Refereed) Published
Abstract [en]

The dorsal anterior cingulate cortex (dACC) and the anterior insula (AI) constitute the salience network and form as well the major cortical components of the central autonomic nervous system. These two cortical regions have the highest density in α4β2 nicotinic acetylcholine receptors (nAChRs) within the whole cortex.The aim of the study was to test the association between nAChRs density/availability in the salience network and the heart rate variability in humans. We selected subjects from a previous positron emission tomography (PET) imaging study in epilepsy with 18F-FA-85380, a specific marker for α4β2 nAChRs, including 10 healthy controls, 10 patients with nonlesional focal epilepsy and 8 patients with idiopathic generalized epilepsy. Participants underwent a 10 min-resting electrocardiogram as they were lying still in a semi-supine position while watching an emotionally neutral video. We tested the association between parasympathetic tone and the regional brain nAChR availability, as measured by 18F-F-A-85380 binding potential (BP), using linear regression. We observed an association between higher nAChRs availability in the bilateral dACC and the right dorsal AI/frontal operculum and a lower parasympathetic tone, without significant effect of the clinical group on this relation. Our study is the first one to show a neurochemical correlate to the parasympathetic role of the anterior cingulate cortex and the AI. The nicotinic system, which plays a major role in the peripheral autonomic nervous system intervening both in the parasympathetic and sympathetic chains, seems also to play a role in the central autonomic nervous system.

Keywords
PET, RRID:SCR_001622, RRID:SCR_001905, RRID:SCR_002823, RRID:SCR_007037, anterior cingulate cortex, heart rate variability, insula, nicotinic receptors
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-390962 (URN)10.1002/cne.24726 (DOI)000492277200005 ()31168797 (PubMedID)
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2020-01-16Bibliographically approved
Zhang, H., Giannakopoulos, P., Haller, S., Lee, S.-W., Qiu, S. & Shen, D. (2019). Inter-Network High-Order Functional Connectivity (IN-HOFC) and its Alteration in Patients with Mild Cognitive Impairment. Neuroinformatics, 17(4), 547-561
Open this publication in new window or tab >>Inter-Network High-Order Functional Connectivity (IN-HOFC) and its Alteration in Patients with Mild Cognitive Impairment
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2019 (English)In: Neuroinformatics, ISSN 1539-2791, E-ISSN 1559-0089, Vol. 17, no 4, p. 547-561Article in journal (Refereed) Published
Abstract [en]

Little is known about the high-order interactions among brain regions measured by the similarity of higher-order features (other than the raw blood-oxygen-level-dependent signals) which can characterize higher-level brain functional connectivity (FC). Previously, we proposed FC topographical profile-based high-order FC (HOFC) and found that this metric could provide supplementary information to traditional FC for early Alzheimer's disease (AD) detection. However, whether such findings apply to network-level brain functional integration is unknown. In this paper, we propose an extended HOFC method, termed inter-network high-order FC (IN-HOFC), as a useful complement to the traditional inter-network FC methods, for characterizing more complex organizations among the large-scale brain networks. In the IN-HOFC, both network definition and inter-network FC are defined in a high-order manner. To test whether IN-HOFC is more sensitive to cognition decline due to brain diseases than traditional inter-network FC, 77 mild cognitive impairments (MCIs) and 89 controls are compared among the conventional methods and our IN-HOFC. The result shows that IN-HOFCs among three temporal lobe-related high-order networks are dampened in MCIs. The impairment of IN-HOFC is especially found between the anterior and posterior medial temporal lobe and could be a potential MCI biomarker at the network level. The competing network-level low-order FC methods, however, either revealing less or failing to detect any group difference. This work demonstrates the biological meaning and potential diagnostic value of the IN-HOFC in clinical neuroscience studies.

Keywords
Alzheimer’s disease (AD), Brain network, Functional connectivity, Functional magnetic resonance imaging (fMRI), High-order, Mild cognitive impairment (MCI)
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-382955 (URN)10.1007/s12021-018-9413-x (DOI)000495242400006 ()30739281 (PubMedID)
Funder
NIH (National Institute of Health), EB006733 EB008374 EB009634 MH100217 AG041721 AG049371 AG042599
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-12-04Bibliographically approved
Haller, S., Scheffler, M., Salomir, R., Herrmann, F. R., Gold, G., Montandon, M.-L. & Kövari, E. (2019). MRI detection of cerebral microbleeds: size matters. Neuroradiology, 61(10), 1209-1213
Open this publication in new window or tab >>MRI detection of cerebral microbleeds: size matters
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2019 (English)In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 61, no 10, p. 1209-1213Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Cerebral microbleeds (CMB) play an important role as an imaging biomarker notably in vascular and neurodegenerative diseases. Current clinical brain MRI underestimates the number of CMB with respect to histopathology. It is expected that small CMBs are more likely to be false-negatives, yet this has not been demonstrated and the average size of false-negative and true-positive CMBs have not been established.

METHODS: The radiologic-histopathologic correlation study was approved by the local review board and included 42 consecutive cases (mean age at death, 80.7 ± 10.0 years; 23 females and 19 men) between 12 January 2012 and 10 December 2012 having undergone brain autopsy. Postmortem SWI (susceptibility-weighted imaging) images were acquired on a clinical 3T system using parameters similar to clinical routine. The detection of CMB on postmortem MRI was compared with corresponding histopathological slices.

RESULTS: Postmortem MRI detected 23 true-positive CMB. Histopathology additionally detected 68 CMBs (false-negative MRI CMBs). The average size true-positive MRI CMBs had on histopathology was 3.6 ± 7.1 mm3. The average size false-negative MRI CMBs was significantly smaller (p < 0.05), measuring 0.3 ± 1.2 mm3 on histopathology.

CONCLUSION: Size matters. As expected, the average size of true-positive MRI CMB was around 10 times larger as compared with false-negative MRI CMB. Evidently, in addition to size, other factors will influence the detectability of CMB, including iron content, ratio of Fe2+/Fe3+, spatial configuration, and location, yet this remains to be elucidated in future studies.

Keywords
Dementia, MRI, Microbleeds, Pathology
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-390964 (URN)10.1007/s00234-019-02267-0 (DOI)000487139100013 ()31396662 (PubMedID)
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2019-10-31Bibliographically approved
Garibotto, V., Wissmeyer, M., Giavri, Z., Goldstein, R., Seimbille, Y., Seeck, M., . . . Picard, F. (2019). Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy. European Journal of Nuclear Medicine and Molecular Imaging, 46(2), 385-395
Open this publication in new window or tab >>Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy
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2019 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 46, no 2, p. 385-395Article in journal (Refereed) Published
Abstract [en]

Purpose: Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4β2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy.

Methods: We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis.

Results: In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy.

Conclusions: We observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4β2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.

Keywords
F-A-85380, Focal epilepsy, Idiopathic generalized epilepsy, Nicotinic receptors, PET
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-362194 (URN)10.1007/s00259-018-4175-0 (DOI)000455817600014 ()30269157 (PubMedID)
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2019-02-05Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-7433-0203

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