151 results on '"Elisa Canu"'
Search Results
2. Awareness impairment in Alzheimer’s disease and frontotemporal dementia: a systematic MRI review
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Michela Leocadi, Elisa Canu, Angela Paldino, Federica Agosta, and Massimo Filippi
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Neurology ,Neurology (clinical) - Published
- 2022
3. Brain structural abnormalities and cognitive changes in a patient with 17q21.31 microduplication and early onset dementia: a case report
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Michela Leocadi, Elisa Canu, Camilla Cividini, Tommaso Russo, Giordano Cecchetti, Claudia Celico, Rosalinda Cardamone, Valeria Barcella, Giuseppe Magnani, Federica Agosta, and Massimo Filippi
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Neurology ,Neurology (clinical) - Abstract
We describe brain structural damage and cognitive profile evolution of an adult patient with 17q21.31 microduplication, a rare condition associated with psychomotor delay, behavioural disturbances and poor social interaction.A.B., 57 years old, male, displayed obsessive and repetitive behaviours, irritability, scarce hygiene and memory loss at disease onset. He had strong familiarity for adult-onset behavioural alterations (his father and sister) and neuropsychiatric conditions (his son). Blood and cerebrospinal fluid (CSF) samples revealed 17q21.31 microduplication, shared also by his son and sister, and raised CSF tau, respectively. He was hospitalized 1 year after disease onset and underwent an MRI scan and a neuropsychological assessment, the latter being repeated 7 months later. To quantitatively investigate patient's grey matter (GM) volume, 16 age- and education-matched male controls were selected and voxel-based morphometry analysis was performed.During hospitalization, his behavioural profile was characterized by anosognosia, impulsivity, apathy and aggressiveness. Cognitive testing revealed main attentive-executive disturbances and difficulties in understanding non-literal language. Compared to controls, A.B. had greater GM atrophy mainly in the right hemisphere, involving amygdala, hippocampus, inferior/superior temporal gyri and temporal pole. He received a diagnosis of early onset dementia. After 7 months, he developed empathy loss, perseverative behaviour, changes in eating habits and worsening in executive-attentive abilities.In A.B., 17q21.31 microduplication caused a neurodegenerative condition with prevalent right temporal damage, raised CSF tau level, behavioural disturbances, memory impairment, attentive-executive and abstract language dysfunctions and fast disease progression, thus reflecting the complex interaction between such genetic substrate and clinical phenotypes.
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- 2022
4. Structural and functional connectome alterations across King’s stages in amyotrophic lateral sclerosis (S33.006)
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Edoardo Spinelli, Alma Ghirelli, Silvia Basaia, Camilla Cividini, Nilo Riva, Tommaso Russo, Elisa Canu, Veronica Castelnovo, Massimo Filippi, and Federica Agosta
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- 2023
5. EEG correlates in the three variants of Primary Progressive Aphasia (P13-6.002)
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Giordano Cecchetti, Federica Agosta, Silvia Basaia, Edoardo Spinelli, Camilla Cividini, Marco Cursi, Elisa Canu, Michela Leocadi, Roberto Santangelo, Francesca Caso, Giovanna Fanelli, Fabio Minicucci, Giuseppe Magnani, and Massimo Filippi
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- 2023
6. Age - related vulnerability of the human brain connectome (P11-6.008)
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Federica Agosta, Camilla Cividini, Silvia Basaia, Edoardo Spinelli, Veronica Castelnovo, Michela Leocadi, Elisa Canu, and Massimo Filippi
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- 2023
7. Characterization of FTLD spectrum through advanced diffusion-weighted MRI metrics: a connectome approach (P11-6.003)
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Federica Agosta, Silvia Basaia, Federica Facente, Camilla Cividini, Edoardo Spinelli, Elisa Canu, Veronica Castelnovo, Giuseppe Magnani, Francesca Caso, Paola Caroppo, Sara Prioni, Cristina Villa, Lucio Tremolizzo, Ildebrando Appollonio, Vincenzo Silani, and Massimo Filippi
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- 2023
8. Stepwise functional brain architecture from disease epicenter correlates with atrophy in progressive supranuclear palsy (P11-6.001)
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Edoardo Spinelli, Alma Ghirelli, Ilaria Bottale, Silvia Basaia, Camilla Cividini, M. Antonietta Volonte, Sebastiano Galantucci, Giuseppe Magnani, Francesca Caso, Elisa Canu, Veronica Castelnovo, Paola Caroppo, Sara Prioni, Cristina Villa, Keith Josephs, Jennifer Whitwell, Federica Agosta, and Massimo Filippi
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- 2023
9. Basal ganglia alterations in amyotrophic lateral sclerosis
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Veronica Castelnovo, Elisa Canu, Filippo De Mattei, Massimo Filippi, and Federica Agosta
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General Neuroscience - Abstract
Amyotrophic lateral sclerosis (ALS) has traditionally been associated with brain damage involving the primary motor cortices and corticospinal tracts. In the recent decades, most of the research studies in ALS have focused on extra-motor and subcortical brain regions. The aim of these studies was to detect additional biomarkers able to support the diagnosis and to predict disease progression. The involvement of the frontal cortices, mainly in ALS cases who develop cognitive and/or behavioral impairment, is amply recognized in the field. A potential involvement of fronto-temporal and fronto-striatal connectivity changes in the disease evolution has also been reported. On this latter regard, there is still a shortage of studies which investigated basal ganglia (BG) alterations and their role in ALS clinical manifestation and progression. The present review aims to provide an overview on the magnetic resonance imaging studies reporting structural and/or functional BG alterations in patients with ALS, to clarify the role of BG damage in the disease clinical evolution and to propose potential future developments in this field.
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- 2023
10. Correction: Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I‑UDSNB 1.0): development and normative data
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Francesca Conca, Valentina Esposito, Francesco Rundo, Davide Quaranta, Cristina Muscio, Rosa Manenti, Giulia Caruso, Ugo Lucca, Alessia Antonella Galbussera, Sonia Di Tella, Francesca Baglio, Federica L’Abbate, Elisa Canu, Valentina Catania, Massimo Filippi, Giulia Mattavelli, Barbara Poletti, Vincenzo Silani, Raffaele Lodi, Maddalena De Matteis, Michelangelo Stanzani Maserati, Andrea Arighi, Emanuela Rotondo, Antonio Tanzilli, Andrea Pace, Federica Garramone, Carlo Cavaliere, Matteo Pardini, Cristiano Rizzetto, Sandro Sorbi, Roberta Perri, Pietro Tiraboschi, Nicola Canessa, Maria Cotelli, Raffaele Ferri, Sandra Weintraub, Camillo Marra, Fabrizio Tagliavini, Eleonora Catricalà, and Stefano Francesco Cappa
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Neurology ,Cognitive Neuroscience ,Neurology (clinical) - Published
- 2023
11. Italian reference values and brain correlates of verbal fluency index - vs standard verbal fluency test - to assess executive dysfunction in ALS
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Elisa Canu, Veronica Castelnovo, Paola MV Rancoita, Michela Leocadi, Alessandra Lamanuzzi, Edoardo Gioele Spinelli, Silvia Basaia, Nilo Riva, Barbara Poletti, Federica Solca, Federico Verde, Nicola Ticozzi, Vincenzo Silani, Sharon Abrahams, Massimo Filippi, and Federica Agosta
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amyotrophic lateral sclerosis ,Neurology ,cognitive classification ,motor neuron disease ,verbal fluency index ,Neurology (clinical) ,normative data - Abstract
Objectives: In amyotrophic lateral sclerosis (ALS), verbal fluency index (Vfi) is used to investigate fluency accounting for motor impairment. This study has three aims: (1) to provide Vfi reference values from a cohort of Italian healthy subjects; (2) to assess the ability of Vfi reference values (vs standard verbal fluency test [VFT]) in distinguishing ALS patients with and without executive dysfunction; and (3) to investigate the association between Vfi and brain structural features of ALS patients. Methods: We included 180 healthy subjects and 157 ALS patients who underwent neuropsychological assessment, including VFT and Vfi, and brain MRI. Healthy subjects were split into four subgroups according to sex and education. For each subgroup, we defined the 95th percentile of Vfi as the cutoff. In ALS, the distributions of "abnormal" cases based on Vfi and standard VFT cutoffs were compared using Fisher's exact test. Using quantile regressions in patients, we assessed the association between Vfi and VFT scores, separately, with gray matter volumes and white matter (WM) tract integrity. Results: Applying Vfi and VFT cutoffs, 9 and 13% of ALS cases, respectively, had abnormal scores (p
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- 2023
12. Functional Connectivity From Disease Epicenters in Frontotemporal Dementia
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Federica Agosta, Edoardo Gioele Spinelli, Silvia Basaia, Camilla Cividini, Francesco Falbo, Costanza Pavone, Nilo Riva, Elisa Canu, Veronica Castelnovo, Giuseppe Magnani, Francesca Caso, Paola Caroppo, Sara Prioni, Cristina Villa, Lucio Tremolizzo, Ildebrando Appollonio, Vincenzo Silani, Keith A. Josephs, Jennifer Whitwell, Massimo Filippi, Agosta, F, Spinelli, E, Basaia, S, Cividini, C, Falbo, F, Pavone, C, Riva, N, Canu, E, Castelnovo, V, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Villa, C, Tremolizzo, L, Appollonio, I, Silani, V, Josephs, K, Whitwell, J, and Filippi, M
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frontotemporal ,connectivity ,network ,FTD ,Neurology (clinical) ,MRI - Abstract
Background and ObjectivesMRI connectomics is an ideal tool to test a network-based model of pathologic propagation from a disease epicenter in neurodegenerative disorders. In this study, we used a novel graph theory-based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), and semantic variant of primary progressive aphasia (svPPA).MethodsIn this observational cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of frontotemporal lobar degeneration pathology (Mayo Clinic). These were used as seed regions for stepwise functional connectivity (SFC) analyses in an independent (Milan) set of patients with FTD to assess connectivity in regions directly and indirectly connected to the epicenters. Correlations between SFC architecture in healthy conditions and atrophy patterns in patients with FTD were also tested.ResultsAs defined by comparing the 42 Mayo Clinic patients with 15 controls, disease epicenters were the left anterior insula for bvFTD, left supplementary motor area for nfvPPA, and left inferior temporal gyrus (ITG) for svPPA. Compared with 94 age-matched controls, patients with bvFTD (n = 64) and nfvPPA (n = 34) of the Milan cohort showed widespread decreased SFC in bilateral cortical regions with direct/indirect connections with epicenters and increased SFC either in directly connected regions, physically close to the respective seed region, or in more distant cortical/cerebellar areas with indirect connections. Across all link steps, svPPA (n = 36) showed SFC decrease mostly within the temporal lobes, with co-occurrent SFC increase in cerebellar regions at indirect link steps. The average stepwise topological distance from the left ITG in a reference group of 50 young healthy controls correlated with regional gray matter volume in svPPA, consistent with network-based degeneration.DiscussionOur findings demonstrate that each FTD syndrome is associated with a characteristic interplay of decreased and increased functional connectivity with the disease epicenter, affecting both direct and indirect connections. SFC revealed novel insights regarding the topology of functional disconnection across FTD syndromes, holding the promise to be used to model disease progression in future longitudinal studies.
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- 2023
13. Cognitive, EEG, and MRI features of COVID-19 survivors: a 10-month study
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Giordano Cecchetti, Federica Agosta, Elisa Canu, Silvia Basaia, Alessandra Barbieri, Rosalinda Cardamone, Maria Paola Bernasconi, Veronica Castelnovo, Camilla Cividini, Marco Cursi, Marco Vabanesi, Matteo Impellizzeri, Serena Marita Lazzarin, Giovanna Franca Fanelli, Fabio Minicucci, Giacomo Giacalone, Andrea Falini, Monica Falautano, Patrizia Rovere-Querini, Luisa Roveri, Massimo Filippi, Cecchetti, G., Agosta, F., Canu, E., Basaia, S., Barbieri, A., Cardamone, R., Bernasconi, M. P., Castelnovo, V., Cividini, C., Cursi, M., Vabanesi, M., Impellizzeri, M., Lazzarin, S. M., Fanelli, G. F., Minicucci, F., Giacalone, G., Falini, A., Falautano, M., Rovere-Querini, P., Roveri, L., and Filippi, M.
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Adult ,Long COVID ,Anosmia ,COVID-19 ,Electroencephalography ,Neuropsychological Tests ,Dysgeusia ,Magnetic Resonance Imaging ,Cognition ,Neurology ,Humans ,Cognitive Dysfunction ,EEG ,Survivors ,Neurology (clinical) ,Cognitive disturbances ,MRI - Abstract
Background and objectives: To explore cognitive, EEG, and MRI features in COVID-19 survivors up to 10months after hospital discharge. Methods: Adult patients with a recent diagnosis of COVID-19 and reporting subsequent cognitive complaints underwent neuropsychological assessment and 19-channel-EEG within 2months (baseline, N = 49) and 10months (follow-up, N = 33) after hospital discharge. A brain MRI was obtained for 36 patients at baseline. Matched healthy controls were included. Using eLORETA, EEG regional current densities and linear lagged connectivity values were estimated. Total brain and white matter hyperintensities (WMH) volumes were measured. Clinical and instrumental data were evaluated between patients and controls at baseline, and within patient whole group and with/without dysgeusia/hyposmia subgroups over time. Correlations among findings at each timepoint were computed. Results: At baseline, 53% and 28% of patients showed cognitive and psychopathological disturbances, respectively, with executive dysfunctions correlating with acute-phase respiratory distress. Compared to healthy controls, patients also showed higher regional current density and connectivity at delta band, correlating with executive performances, and greater WMH load, correlating with verbal memory deficits. A reduction of cognitive impairment and delta band EEG connectivity were observed over time, while psychopathological symptoms persisted. Patients with acute dysgeusia/hyposmia showed lower improvement at memory tests than those without. Lower EEG delta band at baseline predicted worse cognitive functioning at follow-up. Discussion: COVID-19 patients showed interrelated cognitive, EEG, and MRI abnormalities 2months after hospital discharge. Cognitive and EEG findings improved at 10months. Dysgeusia and hyposmia during acute COVID-19 were related with increased vulnerability in memory functions over time.
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- 2022
14. Measuring social cognition in frontotemporal lobar degeneration: a clinical approach
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Elisa Canu, Massimo Filippi, Federica Agosta, Maria Antonietta Magno, Magno, M. A., Canu, E., Agosta, F., and Filippi, M.
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Social Cognition ,medicine.medical_specialty ,Neurology ,Social perception ,media_common.quotation_subject ,Theory of Mind ,Empathy ,Social stimuli ,050105 experimental psychology ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Social cognition ,Theory of mind ,Perception ,medicine ,Humans ,0501 psychology and cognitive sciences ,Social behavior ,Frontotemporal degeneration ,media_common ,05 social sciences ,Frontotemporal lobar degeneration ,medicine.disease ,Frontotemporal Dementia ,Neurology (clinical) ,Frontotemporal Lobar Degeneration ,Psychology ,030217 neurology & neurosurgery ,Cognitive psychology - Abstract
Alterations in social cognition, a broad term indicating our ability to understand others and adapt our behavior accordingly, have been the focus of growing attention in the past years. Some neurological conditions, such as those belonging to the frontotemporal lobar degeneration (FTLD) spectrum, are associated to varying degrees with social cognition deficits, encompassing problems with theory of mind (ToM), empathy, perception of social stimuli, and social behavior. In this review, we outline a clinical framework for the evaluation of social cognition and discuss its role in the assessment of patients affected by a range of FTLD conditions.
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- 2021
15. Functional MRI connectivity of the primary motor cortex in functional dystonia patients
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Nataša Dragašević Mišković, Aleksandra Tomić, Noemi Piramide, Federica Agosta, Elisa Canu, Silvia Basaia, Elisabetta Sarasso, Massimo Filippi, Marina Svetel, Igor Petrović, Vladimir S. Kostic, Piramide, N., Sarasso, E., Tomic, A., Canu, E., Petrovic, I. N., Svetel, M., Basaia, S., Dragasevic Miskovic, N., Kostic, V. S., Filippi, M., and Agosta, F.
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Precuneus ,Pathophysiology ,03 medical and health sciences ,0302 clinical medicine ,Cortex (anatomy) ,medicine ,Humans ,Anterior cingulate cortex ,030304 developmental biology ,Brain Mapping ,0303 health sciences ,Resting state fMRI ,Supplementary motor area ,business.industry ,Motor Cortex ,Brain ,Magnetic Resonance Imaging ,Psychogenic movement disorders (PMD) ,Functional magnetic resonance imaging (fMRI) ,Dystonia ,medicine.anatomical_structure ,Visual cortex ,Neurology ,Dystonic Disorders ,Posterior cingulate ,Neurology (clinical) ,Primary motor cortex ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Background: Functional movement disorders include a wide spectrum of clinically documented movement disorders without an apparent organic substrate. Objective: To explore the functional connectivity (FC) of the primary motor (M1) cortex in functional dystonia (FD) patients relative to healthy controls, with a focus on different clinical phenotypes. Methods: Forty FD patients (12 fixed [FixFD]; 28 mobile [MobFD]) and 43 healthy controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]) underwent resting state fMRI. A seed-based FC analysis was performed using bilateral M1 as regions of interest. Results: Compared to controls, FD patients showed reduced FC between left M1 and left dorsal anterior cingulate cortex, and between right M1 and left M1, premotor/supplementary motor area (SMA), dorsal posterior cingulate cortex (PCC), and bilateral precuneus. Relative to yHC, FixFD patients showed reduced FC between M1 and precuneus bilaterally. Compared to oHC, MobFD patients revealed reduced FC between right M1 and left M1, premotor/SMA, dorsal-PCC, bilateral primary sensory cortices and parieto-occipital areas, and increased FC of right M1 with right associative visual cortex and bilateral ventral-PCC. FixFD patients, relative to MobFD, showed lower FC between the right M1 and right associative visual area, and bilateral precuneus and ventral-PCC. Conclusions: This study suggests an altered brain FC of the motor circuit with areas involved in emotional processes and sense of agency in FD. FixFD patients showed FC abnormalities mainly in areas related to sense of agency, while MobFD in regions involved in sensorimotor functions (reduced FC) and emotional processing (increased FC).
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- 2021
16. A multiparametric MRI study of structural brain damage in dementia with lewy bodies: A comparison with Alzheimer's disease
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Giuseppe Magnani, Federica Agosta, Massimo Filippi, Maria Antonietta Volontè, Elisa Canu, Pietro Giuseppe Scamarcia, Silvia Basaia, Francesca Caso, Caso, F., Agosta, F., Scamarcia, P. G., Basaia, S., Canu, E., Magnani, G., Volonte, M. A., and Filippi, M.
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Lewy Body Disease ,Male ,Pathology ,medicine.medical_specialty ,Dementia with Lewy bodies ,Brain damage ,computer.software_genre ,behavioral disciplines and activities ,White matter ,α-synuclein ,Atrophy ,Alzheimer Disease ,Voxel ,mental disorders ,medicine ,Humans ,Dementia ,Neuropsychological assessment ,Gray Matter ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Brain ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,Hyperintensity ,nervous system diseases ,Normal-appearing white matter ,White-matter hyperintensities ,medicine.anatomical_structure ,Diffusion-tensor magnetic resonance imaging ,nervous system ,Neurology ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,medicine.symptom ,business ,computer - Abstract
Introduction Differential diagnosis between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is crucial for an adequate patients' management but might be challenging. We investigated with advanced MRI techniques gray (GM) and white matter (WM) damage in DLB patients compared to those with AD. Methods 24 DLB patients, 26 age- and disease severity-matched AD patients, and 20 age and sex-matched controls performed clinical and neuropsychological assessment, and brain structural and diffusion-tensor MRI. We measured GM atrophy using voxel-based morphometry, WM hyperintensities (WMH) using a local thresholding segmentation technique, and normal-appearing WM (NAWM) damage using tract-based spatial statistic. Results DLB and AD patients exhibited mild-to-moderate-stage dementia. Compared to controls, GM damage was diffuse in AD, while limited to bilateral thalamus and temporal regions in DLB. Compared to DLB, AD patients exhibited GM atrophy in bilateral fronto-temporal and occipital regions. DLB and AD patients showed higher WMH load than controls, with no differences among each other. WMH in DLB were diffuse with relative prevalence in posterior parietal-occipital regions. Compared to controls, both DLB and AD patients showed reduced microstructural integrity of the main supratentorial and infratentorial NAWM tracts. AD patients exhibited greater posterior NAWM damage than DLB. Conclusions DLB showed prominent WM degeneration compared to the limited GM atrophy, while in AD both tissue compartments were severely involved. In DLB, NAWM microstructural degeneration was independent of WMH, thus revealing two possible underlying processes. Different pathophysiological mechanisms are likely to drive GM and WM damage distribution in DLB and AD.
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- 2021
17. Brain-Based Classification of Youth with Anxiety Disorders: an ENIGMA-ANXIETY Transdiagnostic Examination using Machine Learning
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Willem B. Bruin, Paul Zhutovsky, Guido van Wingen, Janna Marie Bas-Hoogendam, Nynke A. Groenewold, Kevin Hilbert, Anderson M. Winkler, André Zugman, Federica Agosta, Fredrik Åhs, Carmen Andreescu, Chase Antonacci, Takeshi Asami, Michal Assaf, Jacques Barber, Jochen Bauer, Shreya Bavdekar, Katja Beesdo-Baum, Francesco Benedetti, Rachel Bernstein, Johannes Björkstrand, Robert Blair, Karina S. Blair, Laura Blanco-Hinojo, Joscha Böhnlein, Paolo Brambilla, Rodrigo Bressan, Fabian Breuer, Marta Cano, Elisa Canu, Elise M Cardinale, Narcís Cardoner, Camilla Cividini, Henk Cremers, Udo Dannlowski, Gretchen J. Diefenbach, Katharina Domschke, Alexander Doruyter, Thomas Dresler, Angelika Erhardt, Massimo Filippi, Gregory Fonzo, Gabrielle Felice Freitag, Tomas Furmark, Tian Ge, Andrew J. Gerber, Savannah Gosnell, Hans J. Grabe, Dominik Grotegerd, Ruben C. Gur, Raquel E. Gur, Alfons O. Hamm, Laura K. M. Han, Jennifer Harper, Anita Harrewijn, Alexandre Heeren, David Hoffman, Andrea P. Jackowski, Neda Jahanshad, Laura Jett, Antonia N. Kaczkurkin, Parmis Khosravi, Ellen Kingsley, Tilo Kircher, Milutin Kostić, Bart Larsen, Sang-Hyuk Lee, Elisabeth Leehr, Ellen Leibenluft, Christine Lochner, Su Lui, Eleonora Maggioni, Gisele Gus Manfro, Kristoffer Månsson, Claire Marino, Frances Meeten, Barbara Milrod, Ana Munjiza, Benson Irungu, Michael Myers, Susanne Neufang, Jared Nielsen, Patricia Ohrmann, Cristina Ottaviani, Martin P Paulus, Michael T. Perino, K Luan Phan, Sara Poletti, Daniel Porta-Casteràs, Jesus Pujol, Andrea Reinecke, Grace Ringlein, Pavel Rjabtsenkov, Karin Roelofs, Ramiro Salas, Giovanni Salum, Theodore D. Satterthwaite, Elisabeth Schrammen, Lisa Sindermann, Jordan Smoller, Jair Soares, Rudolf Stark, Frederike Stein, thomas straube, Benjamin Straube, Jeffrey Strawn, Benjamin Suarez-Jimenez, Chad M. Sylvester, Ardesheer Talati, Sophia I Thomopoulos, Raşit Tükel, Helena van Nieuwenhuizen, Katy E. Werwath, Katharina Wittfeld, Barry Wright, Mon-Ju Wu, Yunbo Yang, Anna Zilverstand, Peter Zwanzger, Jennifer Blackford, Suzanne Avery, Jacqueline Clauss, Ulrike Lueken, Paul Thompson, Daniel Pine, Dan J. Stein, Nic van der Wee, Dick Veltman, and Moji Aghajani
- Abstract
Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Here, we built and validated neurostructural machine learning (ML) models for individual-level inferences based on the largest-ever multi-site neuroimaging sample of youth with anxiety disorders (age: 10-25 years, N=3,343 individuals from 32 global sites), as compiled by three ENIGMA Anxiety Working Groups: Panic Disorder (PD), Generalized Anxiety Disorder (GAD), and Social Anxiety Disorder (SAD). ML classifiers were trained on MRI-derived regional measures of cortical thickness, surface area, and subcortical volumes to classify patients and healthy controls (HC) for each anxiety disorder separately and across disorders (transdiagnostic classification). Modest, yet robust, classification performance was achieved for PD vs. HC (AUC=0.62), but other disorder-specific and transdiagnostic classifications were not significantly different from chance. However, above chance-level transdiagnostic classifications were obtained in exploratory subgroup analyses of male patients vs. male HC, unmedicated patients vs. HC, and patients with low anxiety severity vs. HC (AUC 0.59-0.63). The above chance-level classifications were based on plausible and specific neuroanatomical features in fronto-striato-limbic and temporo-parietal regions. This study provides a realistic estimate of classification performance in a large, ecologically valid, multi-site sample of youth with anxiety disorders, and may as such serve as a benchmark.
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- 2022
18. Semantic and right temporal variant of FTD: Next generation sequencing genetic analysis on a single-center cohort
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Giacomina Rossi, Erika Salvi, Elkadia Mehmeti, Martina Ricci, Cristina Villa, Sara Prioni, Fabio Moda, Giuseppe Di Fede, Pietro Tiraboschi, Veronica Redaelli, Cinzia Coppola, Giacomo Koch, Elisa Canu, Massimo Filippi, Federica Agosta, Giorgio Giaccone, Paola Caroppo, Rossi, Giacomina, Salvi, Erika, Mehmeti, Elkadia, Ricci, Martina, Villa, Cristina, Prioni, Sara, Moda, Fabio, Di Fede, Giuseppe, Tiraboschi, Pietro, Redaelli, Veronica, Coppola, Cinzia, Koch, Giacomo, Canu, Elisa, Filippi, Massimo, Agosta, Federica, Giaccone, Giorgio, and Caroppo, Paola
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genetic variant ,next generation sequencing ,Aging ,Cognitive Neuroscience ,semantic variant ,pathogenic ,mutation ,frontotemporal dementia ,right temporal variant - Abstract
Semantic and right temporal variant of frontotemporal dementia (svFTD and rtvFTD) are rare clinical phenotypes in which, in most cases, the underlying pathology is TDP-43 proteinopathy. They are usually sporadic disorders, but recent evidences suggest a higher frequency of genetic mutations for the right temporal versus the semantic variant. However, the genetic basis of these forms is not clear. In this study we performed a genetic screening of a single-center cohort of svFTD and rtvFTD patients, aiming at identifying the associated genetic variants. A panel of 73 dementia candidate genes has been analyzed by NGS target sequencing including both causal and risk/modifier genes in 23 patients (15 svFTD and 8 rtvFTD) and 73 healthy age-matched controls. We first performed a single variant analysis considering rare variants and then a gene-based aggregation analysis to evaluate the cumulative effects of multiple rare variants in a single gene. We found 12 variants in nearly 40% of patients (9/23), described as pathogenic or classified as VUS/likely pathogenic. The overall rate was higher in svFTD than in rtvFTD. Three mutations were located in MAPT gene and single mutations in the following genes: SQSTM1, VCP, PSEN1, TBK1, OPTN, CHCHD10, PRKN, DCTN1. Our study revealed the presence of variants in genes involved in pathways relevant for the pathology, especially autophagy and inflammation. We suggest that molecular analysis should be performed in all svFTD and rtvFTD patients, to better understand the genotype–phenotype correlation and the pathogenetic mechanisms that could drive the clinical phenotypes in FTD.
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- 2022
19. Tms-evoked potentials in physiological ageing and Alzheimer’s disease
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Giacomo Bertazzoli, Chiara Bagattini, Claudia Fracassi, Martina Bulgari, Giacomo Guidali, Giulia Quattrini, Moira Marizzoni, Davide Calderaro, Elisa Canu, Federica Agosta, Massimo Filippi, and Marta Bortoletto
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General Neuroscience ,Biophysics ,Neurology (clinical) - Published
- 2023
20. Cerebellar alterations in Parkinson's disease with postural instability and gait disorders
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Andrea, Gardoni, Federica, Agosta, Elisabetta, Sarasso, Silvia, Basaia, Elisa, Canu, Michela, Leocadi, Veronica, Castelnovo, Andrea, Tettamanti, Maria Antonietta, Volontè, and Massimo, Filippi
- Abstract
Few studies interrogated the involvement of cerebellum in modulating gait in Parkinson's disease (PD) patients with postural instability and gait disorders (PD-PIGD). This study aimed at assessing cerebellar atrophy and activity alterations during functional MRI (fMRI) gait-simulating motor- and dual-tasks in PD-PIGD.Twenty-one PD-PIGD and 23 healthy controls underwent clinical assessment, structural MRI, and fMRI including a motor-task (foot anti-phase movements) and a dual-task (foot anti-phase movements while counting backwards by threes). Grey matter cerebellar volumes were assessed using SUIT atlas. FMRI activations were extracted from each cerebellar lobule, and we correlated cerebellar and basal ganglia activity.PD-PIGD patients had reduced volumes of cerebellar motor and non-motor areas relative to controls. During fMRI motor-task, patients showed greater activation of cognitive cerebellar areas (VI and Crus I-II) vs controls. During fMRI dual-task, PD-PIGD patients showed increased activity of cognitive areas (Crus II) and reduced activity of motor areas (I-IV). Cerebellar structural alterations correlated with increased fMRI activity of cerebellar cognitive areas and with lower executive-attentive performance. The increased activity of Crus I during the motor-task correlated with a better motor performance in PD-PIGD. Moreover, the increased activity of cerebellum correlated with a reduced activity of putamen.In PD-PIGD, the increased activity of non-motor cerebellar areas during gait-simulating tasks may be a consequence of grey matter atrophy or an attempt to compensate the functional failure of cerebellar motor areas and basal ganglia. Cerebellar MRI metrics are useful to characterize brain correlates of motor and dual-task abilities in PD-PIGD patients.
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- 2022
21. Awareness impairment in Alzheimer's disease and frontotemporal dementia: a systematic MRI review
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Michela, Leocadi, Elisa, Canu, Angela, Paldino, Federica, Agosta, and Massimo, Filippi
- Abstract
This review aims to define awareness impairment and related disturbances in neurodegenerative diseases, including Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) spectrum of disorders. An update of the available scientific literature on the use of magnetic resonance imaging (MRI) in the study of awareness in these disorders is also offered. MRI plays an important role in the characterization of neurodegenerative signatures and can increase our knowledge on brain structural and functional correlates of awareness. In the reviewing process, we established a-priori criteria and we searched the scientific literature for relevant articles on this topic. In summary, we selected 36 articles out of 1340 publications retrieved from PubMed. Based on this selection, this review discusses the multiple terms used to define different or overlapping aspects of awareness impairment, and specifically summarizes recent application of MRI for investigating anosognosia, social cognition, including theory of mind and emotional processing, free will, and autonoetic awareness alterations in different neurodegenerative disorders, with most of these studies focused on AD and FTLD. This systematic review highlights the importance of awareness impairment and related domains in neurodegenerative disorders, especially in AD and FTLD, and it outlines MRI structural and functional correlates in these populations.
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- 2022
22. Italian adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB 1.0): development and normative data
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Francesca Conca, Valentina Esposito, Francesco Rundo, Davide Quaranta, Cristina Muscio, Rosa Manenti, Giulia Caruso, Ugo Lucca, Alessia Antonella Galbussera, Sonia Di Tella, Francesca Baglio, Federica L’Abbate, Elisa Canu, Valentina Catania, Massimo Filippi, Giulia Mattavelli, Barbara Poletti, Vincenzo Silani, Raffaele Lodi, Maddalena De Matteis, Michelangelo Stanzani Maserati, Andrea Arighi, Emanuela Rotondo, Antonio Tanzilli, Andrea Pace, Federica Garramone, Carlo Cavaliere, Matteo Pardini, Cristiano Rizzetto, Sandro Sorbi, Roberta Perri, Pietro Tiraboschi, Nicola Canessa, Maria Cotelli, Raffaele Ferri, Sandra Weintraub, Camillo Marra, Fabrizio Tagliavini, Eleonora Catricalà, Stefano Francesco Cappa, Conca, Francesca, Esposito, Valentina, Rundo, Francesco, Quaranta, Davide, Muscio, Cristina, Manenti, Rosa, Caruso, Giulia, Lucca, Ugo, Galbussera, Alessia Antonella, Di Tella, Sonia, Baglio, Francesca, L'Abbate, Federica, Canu, Elisa, Catania, Valentina, Filippi, Massimo, Mattavelli, Giulia, Poletti, Barbara, Silani, Vincenzo, Lodi, Raffaele, De Matteis, Maddalena, Stanzani Maserati, Michelangelo, Arighi, Andrea, Rotondo, Emanuela, Tanzilli, Antonio, Pace, Andrea, Garramone, Federica, Cavaliere, Carlo, Pardini, Matteo, Rizzetto, Cristiano, Sorbi, Sandro, Perri, Roberta, Tiraboschi, Pietro, Canessa, Nicola, Cotelli, Maria, Ferri, Raffaele, Weintraub, Sandra, Marra, Camillo, Tagliavini, Fabrizio, Catricalà, Eleonora, and Cappa, Stefano Francesco
- Subjects
Settore M-PSI/02 - PSICOBIOLOGIA E PSICOLOGIA FISIOLOGICA ,Cognitive Neuroscience ,Settore MED/37 - Neuroradiologia ,Neuropsychological Tests ,Cognition ,Neurology ,Italy ,Alzheimer Disease ,Settore M-PSI/08 - Psicologia Clinica ,Neuropsychological tests ,Humans ,Settore MED/26 - Neurologia ,Neurology (clinical) ,Alzheimer’s disease ,UDS - Abstract
Background Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer’s disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue. Methods Following the initiative of the University of Washington’s National Alzheimer’s Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms. Results Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward. Conclusions The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings.
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- 2022
23. Profiling morphologic MRI features of motor neuron disease caused by
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Edoardo Gioele, Spinelli, Alma, Ghirelli, Nilo, Riva, Elisa, Canu, Veronica, Castelnovo, Teuta, Domi, Laura, Pozzi, Paola, Carrera, Vincenzo, Silani, Adriano, Chiò, Massimo, Filippi, and Federica, Agosta
- Abstract
Mutations in theEleven MND patients carrying aMND with
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- 2022
24. Progression of cognitive and behavioral disturbances in motor neuron diseases assessed using standard and computer-based batteries
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Veronica Castelnovo, Barbara Poletti, Federica Agosta, Andrea Fontana, Massimo Filippi, Elisa Canu, Camilla Cividini, Vincenzo Silani, Nilo Riva, Federica Solca, Castelnovo, V., Canu, E., Riva, N., Poletti, B., Cividini, C., Fontana, A., Solca, F., Silani, V., Filippi, M., and Agosta, F.
- Subjects
amyotrophic lateral sclerosis ,medicine.medical_specialty ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Physical medicine and rehabilitation ,Rating scale ,Humans ,Medicine ,Motor neuron disease ,Motor Neuron Disease ,Cognitive decline ,Amyotrophic lateral sclerosis ,Retrospective Studies ,Primary Lateral Sclerosis ,Mini–Mental State Examination ,medicine.diagnostic_test ,Computers ,business.industry ,Amyotrophic Lateral Sclerosis ,Neuropsychology ,Progressive muscular atrophy ,cognitive decline ,medicine.disease ,Neurology ,test of attentional performance ,Neurology (clinical) ,business ,computer-based neuropsychological evaluation ,030217 neurology & neurosurgery - Abstract
Objective: Detecting and monitoring cognitive and behavioral deficits in motor neuron diseases (MND) is critical due to their considerable clinical impact. In this scenario, computer-based batteries may play an important role. In this study, we investigated the progression of cognitive and behavioral deficits in MND patients using both standard and computer-based neuropsychological batteries. Methods: This is a retrospective study on 74 MND patients (52 amyotrophic lateral sclerosis [ALS], 12 primary lateral sclerosis [PLS], and 10 progressive muscular atrophy [PMA]) who were followed up for 12 months and underwent up to three cognitive/behavioral assessments, 6 months apart, including standard and/or computerized based (the Test of Attentional Performance [TAP]) batteries. Behavioral/cognitive changes were investigated over time using generalized linear model for longitudinal data accounting for time and revised-ALS Functional Rating Scale. Results: Over 12 months, ALS patients showed a global cognitive decline (Mini Mental State Examination) at the standard battery and reduced performance in the alertness, sustained and divided attention, go/nogo, cross-modal and incompatibility TAP tasks. Most of these findings remained significant when ALSFRS-R changes over time were included as covariate in the analyses. ALS patients did not show significant behavioral abnormalities over time. No cognitive and behavioral changes were found in PLS and PMA cases. Conclusions: Computer-based neuropsychological evaluations are able to identify subtle cognitive changes in ALS, unique to this condition. This study highlights the need of specific, accurate and well-tolerated tools for the monitoring of cognitive deficits in MND.
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- 2021
25. Principles of Behavioral and Cognitive Neurology
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Federica Agosta, Elisa Canu, Michela Leocadi, Veronica Castelnovo, Maria Antonietta Magno, Davide Calderaro, and Massimo Filippi
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- 2022
26. Longitudinal White Matter Damage Evolution in Parkinson's Disease
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Federica Agosta, Tanja Stojkovic, Elisa Canu, Igor Petrović, Iva Stankovic, Vladana Markovic, Massimo Filippi, Silvia Basaia, Elisabetta Sarasso, Vladimir S. Kostic, Elisabetta Pagani, Edoardo G. Spinelli, Pietro Giuseppe Scamarcia, Elka Stefanova, Scamarcia, P. G., Agosta, F., Spinelli, E. G., Basaia, S., Stojkovic, T., Stankovic, I., Sarasso, E., Canu, E., Markovic, V., Petrovic, I., Stefanova, E., Pagani, E., Kostic, V. S., and Filippi, M.
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medicine.medical_specialty ,Longitudinal study ,Parkinson's disease ,White matter ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Cognitive Dysfunction ,normal-appearing white matter ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,Proportional hazards model ,white matter hyperintensity ,longitudinal study ,Parkinson Disease ,Magnetic resonance imaging ,Executive functions ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,Hyperintensity ,3. Good health ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Neurology ,Cardiology ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Diffusion MRI ,MRI - Abstract
Background White matter hyperintensities (WMHs) have a role in cognitive impairment in normal brain aging, while the effect on Parkinson's disease (PD) progression is still controversial. Objective To investigate the longitudinal evolution of micro- and macrostructural damage of cerebral white matter (WM) and its relationship with the clinical picture in PD. Methods A total of 154 PD patients underwent clinical, cognitive, and magnetic resonance imaging (MRI) assessment once a year for up to 4 years. Sixty healthy controls underwent the same protocol at baseline. WMHs were identified and total WMH volume was measured. WMHs were also used as exclusion masks to define normal-appearing white matter (NAWM). Using tract-based spatial statistics, diffusion tensor (DT) MRI metrics of whole-brain WM and NAWM were obtained. Linear mixed-effects models defined the longitudinal evolution and association between variables. WM alterations were tested as risk factors of disease progression using linear regression and Cox proportional hazards models. Results At baseline, PD patients showed alterations of all DT MRI measures compared to controls. Longitudinally, DT MRI measures did not vary significantly and no association with clinical variables was found. WMH volume changed over time and was associated with impairment in global cognition, executive functions, and language. Baseline WMH volume was a moderate risk factor for progression to mild cognitive impairment. Conclusions Our study suggests an association between WMHs and cognitive deterioration in PD, whereas WM microstructural damage is a negligible contributor to clinical deterioration. WMHs assessed by MRI can provide an important tool for monitoring the development of cognitive impairment in PD patients. © 2021 International Parkinson and Movement Disorder Society.
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- 2022
27. Profiling morphologic MRI features of motor neuron disease caused by TARDBP mutations
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Edoardo Gioele Spinelli, Alma Ghirelli, Nilo Riva, Elisa Canu, Veronica Castelnovo, Teuta Domi, Laura Pozzi, Paola Carrera, Vincenzo Silani, Adriano Chiò, Massimo Filippi, Federica Agosta, Spinelli, Edoardo Gioele, Ghirelli, Alma, Riva, Nilo, Canu, Elisa, Castelnovo, Veronica, Domi, Teuta, Pozzi, Laura, Carrera, Paola, Silani, Vincenzo, Chiò, Adriano, Filippi, Massimo, and Agosta, Federica
- Subjects
motor neuron disease (MND) ,amyotrophic lateral sclerosis (ALS) ,magnetic resonance imaging (MRI) ,voxel-based morphometry (VBM) ,Neurology ,Settore MED/37 - Neuroradiologia ,Settore MED/26 - Neurologia ,Neurology (clinical) ,Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica ,transactive response (TAR) DNA binding protein 43 (TARDBP) - Abstract
ObjectiveMutations in the TARDBP gene are a rare cause of genetic motor neuron disease (MND). Morphologic MRI characteristics of MND patients carrying this mutation have been poorly described. Our objective was to investigate distinctive clinical and MRI features of a relatively large sample of MND patients carrying TARDBP mutations.MethodsEleven MND patients carrying a TARDBP mutation were enrolled. Eleven patients with sporadic MND (sMND) and no genetic mutations were also selected and individually matched by age, sex, clinical presentation and disease severity, along with 22 healthy controls. Patients underwent clinical and cognitive evaluations, as well as 3D T1-weighted and diffusion tensor (DT) MRI on a 3 Tesla scanner. Gray matter (GM) atrophy was first investigated at a whole-brain level using voxel-based morphometry (VBM). GM volumes and DT MRI metrics of the main white matter (WM) tracts were also obtained. Clinical, cognitive and MRI features were compared between groups.ResultsMND with TARDBP mutations was associated with all possible clinical phenotypes, including isolated upper/lower motor neuron involvement, with no predilection for bulbar or limb involvement at presentation. Greater impairment at naming tasks was found in TARDBP mutation carriers compared with sMND. VBM analysis showed significant atrophy of the right lateral parietal cortex in TARDBP patients, compared with controls. A distinctive reduction of GM volumes was found in the left precuneus and right angular gyrus of TARDBP patients compared to controls. WM microstructural damage of the corticospinal tract (CST) and inferior longitudinal fasciculi (ILF) was found in both sMND and TARDBP patients, compared with controls, although decreased fractional anisotropy of the right CST and increased axial diffusivity of the left ILF (p = 0.017) was detected only in TARDBP mutation carriers.ConclusionsTARDBP patients showed a distinctive parietal pattern of cortical atrophy and greater damage of motor and extra-motor WM tracts compared with controls, which sMND patients matched for disease severity and clinical presentation were lacking. Our findings suggest that TDP-43 pathology due to TARDBP mutations may cause deeper morphologic alterations in both GM and WM.
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- 2022
28. Resting state functional brain networks associated with emotion processing in frontotemporal lobar degeneration
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Elisa Canu, Davide Calderaro, Veronica Castelnovo, Silvia Basaia, Maria Antonietta Magno, Nilo Riva, Giuseppe Magnani, Francesca Caso, Paola Caroppo, Sara Prioni, Cristina Villa, Debora Pain, Gabriele Mora, Lucio Tremolizzo, Ildebrando Appollonio, Barbara Poletti, Vincenzo Silani, Massimo Filippi, Federica Agosta, Canu, E, Calderaro, D, Castelnovo, V, Basaia, S, Magno, M, Riva, N, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Villa, C, Pain, D, Mora, G, Tremolizzo, L, Appollonio, I, Poletti, B, Silani, V, Filippi, M, Agosta, F, Canu, Elisa, Calderaro, Davide, Castelnovo, Veronica, Basaia, Silvia, Magno, Maria Antonietta, Riva, Nilo, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Villa, Cristina, Pain, Debora, Mora, Gabriele, Tremolizzo, Lucio, Appollonio, Ildebrando, Poletti, Barbara, Silani, Vincenzo, Filippi, Massimo, and Agosta, Federica
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MED/26 - NEUROLOGIA ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,MED/37 - NEURORADIOLOGIA ,Resting state, fMRI, FTLD, frontotemporal lobar degeneration, frontotemporal dementia, FTD ,Molecular Biology - Abstract
This study investigated the relationship between emotion processing and resting-state functional connectivity (rs-FC) of the brain networks in frontotemporal lobar degeneration (FTLD). Eighty FTLD patients (including cases with behavioral variant of frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy syndrome, motor neuron disease) and 65 healthy controls underwent rs-functional MRI. Emotion processing was tested using the Comprehensive Affect Testing System (CATS). In patients and controls, correlations were investigated between each emotion construct and rs-FC changes within critical networks. Mean rs-FC of the clusters significantly associated with CATS scoring were compared among FTLD groups. FTLD patients had pathological CATS scores compared with controls. In controls, increased rs-FC of the cerebellar and visuo-associative networks correlated with better scores in emotion-matching and discrimination tasks, respectively; while decreased rs-FC of the visuo-spatial network was related with better performance in the affect-matching and naming. In FTLD, the associations between rs-FC and CATS scores involved more brain regions, such as orbitofrontal and middle frontal gyri within anterior networks (i.e., salience and default-mode), parietal and somatosensory regions within visuo-spatial and sensorimotor networks, caudate and thalamus within basal-ganglia network. Rs-FC changes associated with CATS were similar among all FTLD groups. In FTLD compared to controls, the pattern of rs-FC associated with emotional processing involves a larger number of brain regions, likely due to functional specificity loss and compensatory attempts. These associations were similar across all FTLD groups, suggesting a common physiopathological mechanism of emotion processing breakdown, regardless the clinical presentation and pattern of atrophy.
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- 2022
29. Social cognition in the FTLD spectrum: evidence from MRI
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Elisa Canu, Massimo Filippi, Federica Agosta, Maria Antonietta Magno, Magno, M. A., Canu, E., Filippi, M., and Agosta, F.
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Social Cognition ,media_common.quotation_subject ,Theory of Mind ,Empathy ,050105 experimental psychology ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Magnetic resonance imaging ,Social cognition ,Theory of mind ,Humans ,0501 psychology and cognitive sciences ,Social Behavior ,10. No inequality ,Frontotemporal degeneration ,media_common ,Social perception ,05 social sciences ,fMRI ,Magnetic Resonance Imaging ,Social Perception ,Neurology ,Neurology (clinical) ,Frontotemporal Lobar Degeneration ,Psychology ,030217 neurology & neurosurgery ,Social cognitive theory ,Cognitive psychology - Abstract
Over the past few years, there has been great interest in social cognition, a wide term referring to the human ability of understanding others' emotions, thoughts, and intentions, to empathize with them and to behave accordingly. While there is no agreement on the classification of social cognitive processes, they can broadly be categorized as consisting of theory of mind, empathy, social perception, and social behavior. The study of social cognition and its relative deficits is increasingly assuming clinical relevance. However, the clinical and neuroanatomical correlates of social cognitive alterations in neurodegenerative conditions, such as those belonging to the frontotemporal lobar (FTLD) spectrum, are not fully established. In this review, we describe the current understanding of social cognition impairments in different FTLD conditions with respect to MRI.
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- 2022
30. MAPT Q336H mutation: intra-familial phenotypic heterogeneity in a new Italian family
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Cristina Villa, Giacomina Rossi, Ilaria Bizzozero, Sara Prioni, Chiara Boiocchi, Federica Agosta, Elisa Canu, Massimo Filippi, Giorgio Giaccone, Paola Caroppo, Villa, Cristina, Rossi, Giacomina, Bizzozero, Ilaria, Prioni, Sara, Boiocchi, Chiara, Agosta, Federica, Canu, Elisa, Filippi, Massimo, Giaccone, Giorgio, and Caroppo, Paola
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Male ,semantic variant ,tau Proteins ,FTD ,svPPA ,Phenotype ,Neurology ,Alzheimer Disease ,Frontotemporal Dementia ,Positron-Emission Tomography ,Mutation ,MAPT ,Humans ,Neurology (clinical) ,Frontotemporal dementia - Abstract
Background: Q336H is a rare MAPT mutation, previously found in a single patient with behavioral variant of FTD and tau pathology (Pick bodies). Here, we describe the clinical characteristics of two members of a new family, carrying the Q336H MAPT mutation. Methods: Clinical, genetic and neuroradiological assessment and follow-up of the proband. Results: At age 37, the proband developed naming and objects recognition impairment, due to a lack of knowledge. After 3 years, he developed behavioral disorders. MRI and FDG-PET showed the involvement of the left temporal pole. A diagnosis of semantic variant of primary progressive aphasia (svPPA) was made. At follow-up after 6 and 12 months, a rapid worsening of cognitive deficits occurred. His parent presented, at age 65, slowly progressive memory deficits without behavioral impairment, and, on MRI, evidence of mesial temporal atrophy, consistent with a clinical diagnosis of Alzheimer's disease (AD). Discussion: and conclusion This is the second family carrying the MAPT Q336H mutation reported so far. We showed that svPPA and AD-like phenotype can be associated with this mutation. A wide clinical variability exists at intra-familial level for Q336H MAPT mutation, pointing to genetic and/or environmental influencing factors on disease expression. We also confirmed that svPPA can be associated with MAPT mutations, suggesting that this gene should be analyzed also in patients with svPPA, especially with early onset. In addition, an AD-like phenotype may be associated with this mutation, suggesting its different effects on protein misfolding and aggregation. Background and purpose: Q336H is a rare MAPT mutation, previously found in a single patient with behavioral variant frontotemporal dementia and tau pathology (Pick bodies). Here, we describe the clinical characteristics of two members of a new family carrying the Q336H MAPT mutation. Methods: Clinical, genetic, and neuroradiological assessment and follow-up of the proband were made. Results: At age 37 years, the proband developed naming and object recognition impairment, due to a lack of knowledge. After 3 years, he developed behavioral disorders. Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography showed the involvement of the left temporal pole. A diagnosis of semantic variant primary progressive aphasia (svPPA) was made. At follow-up after 6 and 12 months, a rapid worsening of cognitive deficits occurred. His parent presented, at age 65 years, slowly progressive memory deficits without behavioral impairment, and, on MRI, evidence of mesial temporal atrophy, consistent with a clinical diagnosis of Alzheimer disease (AD). Conclusions: This is the second family carrying the MAPT Q336H mutation reported so far. We showed that svPPA and AD-like phenotype can be associated with this mutation. A wide clinical variability exists at the intrafamilial level for Q336H MAPT mutation, pointing to genetic and/or environmental influencing factors on disease expression. We also confirmed that svPPA can be associated with MAPT mutations, suggesting that this gene should be analyzed also in patients with svPPA, especially with early onset. In addition, an AD-like phenotype may be associated with this mutation, suggesting its different effects on protein misfolding and aggregation.
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- 2022
31. Breakdown of the affective‐cognitive network in functional dystonia
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Elisa Canu, Alberto Inuggi, Nataša Dragašević Mišković, Igor Petrović, Noemi Piramide, Federica Agosta, Aleksandra Tomić, Elisabetta Sarasso, Vladimir S. Kostic, Massimo Filippi, Marina Svetel, Canu, E., Agosta, F., Tomic, A., Sarasso, E., Petrovic, I., Piramide, N., Svetel, M., Inuggi, A., D. Miskovic, N., Kostic, V. S., and Filippi, M.
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Adult ,Male ,Cerebellum ,brain functional connectivity ,resting state fMRI ,Posterior parietal cortex ,Biology ,Amygdala ,050105 experimental psychology ,Young Adult ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Connectome ,medicine ,Humans ,Medial dorsal nucleus ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,Somatoform Disorders ,Research Articles ,Anterior cingulate cortex ,Cerebral Cortex ,Dystonia ,affective‐cognitive network ,Radiological and Ultrasound Technology ,Resting state fMRI ,affective-cognitive network ,fMRI ,05 social sciences ,Brain ,functional dystonia ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Affect ,Cross-Sectional Studies ,medicine.anatomical_structure ,Neurology ,Dystonic Disorders ,Female ,Neurology (clinical) ,Anatomy ,Neuroscience ,030217 neurology & neurosurgery ,Research Article - Abstract
Previous studies suggested that brain regions subtending affective‐cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective‐cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS‐fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD‐age‐matched [yHC]; 29 old MobFD‐age‐matched [oHC]). FC of brain regions of interest, known to be involved in affective‐cognitive processes, and independent component analysis of RS‐fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective‐cognitive seeds of interest and the fronto‐subcortical and limbic circuits; enhanced FC between the right affective‐cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective‐cognitive seeds of interest and the sensorimotor and high‐order function (“cognitive”) areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective‐cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.
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- 2020
32. Impaired recognition of disgust is related to subcortical volume loss in amyotrophic lateral sclerosis
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Elisa Canu, Michela Leocadi, Veronica Castelnovo, Maria Antonietta Magno, Nilo Riva, Barbara Poletti, Vincenzo Silani, Massimo Filippi, and Federica Agosta
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2021
33. Physiotherapy with dual task improves cognition in Parkinson’s disease with postural instability and gait disorders
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Michela Leocadi, Elisa Canu, Elisabetta Sarasso, Andrea Gardoni, Veronica Castelnovo, Noemi Piramide, Maria Antonietta Volonté, Massimo Filippi, and Federica Agosta
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2021
34. Longitudinal clinical, cognitive and neuroanatomical changes over five years in GBA‐positive Parkinson’s disease patients
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Michela Leocadi, Federica Agosta, Elisa Canu, Giulia Donzuso, Silvia Basaia, Noemi Piramide, Tanja Stojkovic, Iva Stankovic, Aleksandra Tomic, Vladana Markovic, Igor Petrovic, Elka Stefanova, Vladimir S. Kostic, and Massimo Filippi
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2021
35. Task‐free functional networks related to emotion processing in frontotemporal lobar degeneration
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Elisa Canu, Davide Calderaro, Veronica Castelnovo, Michela Leocadi, Silvia Basaia, Massimo Filippi, and Federica Agosta
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2021
36. Brain architecture changes across the FTLD spectrum
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Camilla Cividini, Federica Agosta, Silvia Basaia, Edoardo Gioele Spinelli, Veronica Castelnovo, Elisa Canu, Nilo Riva, Giuseppe Magnani, Francesca Caso, and Massimo Filippi
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2021
37. Cortical and subcortical brain structure in generalized anxiety disorder
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Paolo Brambilla, Tali M. Ball, Dan J. Stein, Courtney A. Filippi, Kathryn E. Werwath, Pedro Mario Pan, Heidi K. Schroeder, Hannah Zwiebel, Andrea Parolin Jackowski, Jared A. Nielsen, Savannah N. Gosnell, Hans J. Grabe, Christian Grillon, Paul M. Thompson, Gabrielle F. Freitag, Murray B. Stein, Karina S. Blair, Narcís Cardoner, Neda Jahanshad, Ana Munjiza Jovanovic, Cristina Ottaviani, Massimo Filippi, André Zugman, Katharina Wittfeld, Antonia N. Kaczkurkin, Camilla Cividini, Hugo D. Critchley, Nynke A. Groenewold, Elise M. Cardinale, Moji Aghajani, Bianca A.V. Alberton, Michael T. Perino, Anderson M. Winkler, Ellen Leibenluft, Sophia I. Thomopoulos, Mohammed R. Milad, Kevin Hilbert, Matteo Mancini, Randy L. Buckner, Henry Völzke, Robin Bülow, Carmen Andreescu, Milutin Kostić, Raquel E. Gur, Benson Mwangi, Daniel Porta-Casteràs, Michael J. Myers, Federica Agosta, Thomas Straube, Giovana Zunta-Soares, Gretchen J. Diefenbach, Martin P. Paulus, Erica Tamburo, Brenda E. Benson, Elena Makovac, Grace V. Ringlein, Andrea L. Gold, David Hofmann, Mon-Ju Wu, Jeffrey R. Strawn, Janna Marie Bas-Hoogendam, Dick J. Veltman, Eleonora Maggioni, Sandra Van der Auwera, Gregory A. Fonzo, Ramiro Salas, Giovanni Abrahão Salum, Daniel S. Pine, Gisele Gus Manfro, Bart Larsen, Monique Ernst, Nic J.A. van der Wee, Helena van Nieuwenhuizen, Mira Z. Hammoud, Ruben C. Gur, Katie L. Burkhouse, Chad M. Sylvester, Rachel Berta, Elisa Canu, Jair C. Soares, Theodore D. Satterthwaite, Qiongru Yu, Frances Meeten, Ulrike Lueken, Jordan W. Smoller, Michal Assaf, Lilianne R. Mujica-Parodi, K. Luan Phan, Jennifer Harper, Nicholas L. Balderston, James R. Blair, Anita Harrewijn, Rebecca B. Price, Katja Beesdo-Baum, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Harrewijn, A., Cardinale, E. M., Groenewold, N. A., Bas-Hoogendam, J. M., Aghajani, M., Hilbert, K., Cardoner, N., Porta-Casteras, D., Gosnell, S., Salas, R., Jackowski, A. P., Pan, P. M., Salum, G. A., Blair, K. S., Blair, J. R., Hammoud, M. Z., Milad, M. R., Burkhouse, K. L., Phan, K. L., Schroeder, H. K., Strawn, J. R., Beesdo-Baum, K., Jahanshad, N., Thomopoulos, S. I., Buckner, R., Nielsen, J. A., Smoller, J. W., Soares, J. C., Mwangi, B., Wu, M. -J., Zunta-Soares, G. B., Assaf, M., Diefenbach, G. J., Brambilla, P., Maggioni, E., Hofmann, D., Straube, T., Andreescu, C., Berta, R., Tamburo, E., Price, R. B., Manfro, G. G., Agosta, F., Canu, E., Cividini, C., Filippi, M., Kostic, M., Munjiza Jovanovic, A., Alberton, B. A. V., Benson, B., Freitag, G. F., Filippi, C. A., Gold, A. L., Leibenluft, E., Ringlein, G. V., Werwath, K. E., Zwiebel, H., Zugman, A., Grabe, H. J., Van der Auwera, S., Wittfeld, K., Volzke, H., Bulow, R., Balderston, N. L., Ernst, M., Grillon, C., Mujica-Parodi, L. R., van Nieuwenhuizen, H., Critchley, H. D., Makovac, E., Mancini, M., Meeten, F., Ottaviani, C., Ball, T. M., Fonzo, G. A., Paulus, M. P., Stein, M. B., Gur, R. E., Gur, R. C., Kaczkurkin, A. N., Larsen, B., Satterthwaite, T. D., Harper, J., Myers, M., Perino, M. T., Sylvester, C. M., Yu, Q., Lueken, U., Veltman, D. J., Thompson, P. M., Stein, D. J., Van der Wee, N. J. A., Winkler, A. M., and Pine, D. S.
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Adult ,Male ,medicine.medical_specialty ,endocrine system ,Generalized anxiety disorder ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Anxiety ,Audiology ,Article ,Structural magnetic resonance imaging ,Cellular and Molecular Neuroscience ,Secondary analysis ,medicine ,Psychology ,Humans ,ddc:610 ,Cortical surface ,generalized anxiety disorder ,structural brain imaging ,cortical thickness ,Child ,diagnostic imaging [Brain] ,Biological Psychiatry ,Medication use ,diagnostic imaging [Anxiety Disorders] ,medicine.diagnostic_test ,business.industry ,Brain ,Small sample ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Anxiety Disorders ,Psychiatry and Mental health ,multicentric network ,Female ,medicine.symptom ,business ,RC321-571 ,Neuroscience - Abstract
The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.
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- 2021
38. Action Observation and Motor Imagery Improve Dual Task in Parkinson's Disease: A Clinical/fMRI Study
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Elisabetta Sarasso, Andrea Tettamanti, Veronica Castelnovo, Maria Antonietta Volontè, Noemi Piramide, Silvia Basaia, Elisa Canu, Federica Agosta, Michela Leocadi, Massimo Filippi, Andrea Gardoni, Sarasso, E., Agosta, F., Piramide, N., Gardoni, A., Canu, E., Leocadi, M., Castelnovo, V., Basaia, S., Tettamanti, A., Volonte, M. A., and Filippi, M.
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medicine.medical_specialty ,Parkinson's disease ,action observation ,motor imagery ,Gait (human) ,Motor imagery ,Physical medicine and rehabilitation ,medicine ,Humans ,dual task ,Gait ,Postural Balance ,Gait Disorders, Neurologic ,Balance (ability) ,Supplementary motor area ,business.industry ,fMRI ,Motor control ,Parkinson Disease ,Executive functions ,medicine.disease ,Magnetic Resonance Imaging ,Exercise Therapy ,medicine.anatomical_structure ,Neurology ,Neurology (clinical) ,Motor learning ,business - Abstract
Background Action observation training and motor imagery may improve motor learning in Parkinson's disease (PD). Objectives The objectives of this study were to assess mobility and balance (performing motor and dual tasks) and brain functional reorganization following 6 weeks of action observation training and motor imagery associated with dual-task gait/balance exercises in PD patients with postural instability and gait disorders relative to dual-task training alone. Methods Twenty-five PD-postural instability and gait disorder patients were randomized into 2 groups: the DUAL-TASK+AOT-MI group performed a 6-week gait/balance training consisting of action observation training-motor imagery combined with practicing the observed-imagined exercises; the DUAL-TASK group performed the same exercises combined with watching landscape videos. Exercises were increasingly difficult to include the dual task. At baseline and at 6 weeks, patients underwent: mobility, gait, and balance evaluations (also repeated 2 months after training), cognitive assessment, and functional MRI, including motor and dual tasks. Results Dual-task gait/balance training enhanced mobility, during both single- and dual-task conditions, and executive functions in PD-postural instability and gait disorders, with a long-lasting effect at 14 weeks. When exercises were preceded by action observation training-motor imagery, PD-postural instability and gait disorders showed greater improvement of balance and gait velocity both with and without the dual task, particularly during the turning phase. After training, the DUAL-TASK+AOT-MI group showed reduced recruitment of frontal areas and increased activity of cerebellum during functional-MRI motor and dual task, correlating with balance/turning velocity and executive improvements, respectively. The DUAL-TASK group showed reduced activity of supplementary motor area and increased recruitment of temporo-parietal areas during the dual task and decreased cerebellar activity during the motor task correlating with faster turning velocity. Functional MRI results were not corrected for multiple comparisons and should be interpreted carefully. Conclusions Adding action observation training-motor imagery to dual-task gait/balance training promotes specific functional reorganization of brain areas involved in motor control and executive-attentive abilities and more long-lasting effects on dual-task mobility and balance in PD-postural instability and gait disorders. © 2021 International Parkinson and Movement Disorder Society.
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- 2021
39. Amyotrophic Lateral Sclerosis-Frontotemporal Dementia: Shared and Divergent Neural Correlates Across the Clinical Spectrum
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Camilla Cividini, Giuseppe Magnani, Nilo Riva, Elisa Canu, Veronica Castelnovo, Federica Agosta, Silvia Basaia, Giordano Cecchetti, Francesca Caso, Massimo Filippi, Edoardo G. Spinelli, Andrea Falini, Cividini, Camilla, Basaia, Silvia, Spinelli, Edoardo G, Canu, Elisa, Castelnovo, Veronica, Riva, Nilo, Cecchetti, Giordano, Caso, Francesca, Magnani, Giuseppe, Falini, Andrea, Filippi, Massimo, and Agosta, Federica
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Neural correlates of consciousness ,business.industry ,Functional connectivity ,Cognition ,Disease ,medicine.disease ,Phenotype ,medicine ,Neurology (clinical) ,Amyotrophic lateral sclerosis ,business ,Neuroscience ,Pathological ,Frontotemporal dementia ,Research Article - Abstract
Background and ObjectivesA significant overlap between amyotrophic lateral sclerosis (ALS) and behavioral variant of frontotemporal dementia (bvFTD) has been observed at clinical, genetic, and pathologic levels. Within this continuum of presentations, the presence of mild cognitive or behavioral symptoms in patients with ALS has been consistently reported, although it is unclear whether this is to be considered a distinct phenotype or rather a natural evolution of ALS. Here, we used mathematical modeling of MRI connectomic data to decipher common and divergent neural correlates across the ALS–frontotemporal dementia (FTD) spectrum.MethodsWe included 83 patients with ALS, 35 patients with bvFTD, and 61 healthy controls, who underwent clinical, cognitive, and MRI assessments. Patients with ALS were classified according to the revised Strong criteria into 54 ALS with only motor deficits (ALS-cn), 21 ALS with cognitive or behavioral involvement (ALS-ci/bi), and 8 ALS with bvFTD (ALS-FTD). First, we assessed the functional and structural connectivity patterns across the ALS-FTD spectrum. Second, we investigated whether and where MRI connectivity alterations of patients with ALS with any degree of cognitive impairment (i.e., ALS-ci/bi and ALS-FTD) resembled more the pattern of damage of one (ALS-cn) or the other end (bvFTD) of the spectrum, moving from group-level to single-subject analysis.ResultsAs compared with controls, extensive structural and functional disruption of the frontotemporal and parietal networks characterized bvFTD (bvFTD-like pattern), while a more focal structural damage within the sensorimotor-basal ganglia areas characterized ALS-cn (ALS-cn-like pattern). ALS-ci/bi patients demonstrated an ALS-cn-like pattern of structural damage, diverging from ALS-cn with similar motor impairment for the presence of enhanced functional connectivity within sensorimotor areas and decreased functional connectivity within the bvFTD-like pattern. On the other hand, patients with ALS-FTD resembled both structurally and functionally the bvFTD-like pattern of damage with, in addition, the structural ALS-cn-like damage in the motor areas.DiscussionOur findings suggest a maladaptive role of functional rearrangements in ALS-ci/bi concomitantly with similar structural alterations compared to ALS-cn, supporting the hypothesis that ALS-ci/bi might be considered as a phenotypic variant of ALS, rather than a consequence of disease worsening.
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- 2021
40. Longitudinal clinical, cognitive, and neuroanatomical changes over 5 years in GBA-positive Parkinson's disease patients
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Giulia Donzuso, Federica Agosta, Nikola Kresojević, Aleksandra Tomić, Tanja Stojkovic, Elisa Canu, Igor Petrović, Iva Stankovic, Noemi Piramide, Michela Leocadi, Vladana Markovic, Massimo Filippi, Silvia Basaia, Elisabetta Sarasso, Vladimir S. Kostic, Elka Stefanova, Leocadi, M., Canu, E., Donzuso, G., Stojkovic, T., Basaia, S., Kresojevic, N., Stankovic, I., Sarasso, E., Piramide, N., Tomic, A., Markovic, V., Petrovic, I., Stefanova, E., Kostic, V. S., Filippi, M., and Agosta, F.
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medicine.medical_specialty ,Neurology ,Parkinson's disease ,Amygdala ,Cortical thickness ,03 medical and health sciences ,0302 clinical medicine ,Magnetic resonance imaging ,Cognition ,Glucocerebrosidase gene ,Internal medicine ,medicine ,Humans ,Cognitive Dysfunction ,Cognitive decline ,Gray Matter ,030304 developmental biology ,Neuroradiology ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,Neuropsychology ,Parkinson Disease ,medicine.disease ,medicine.anatomical_structure ,Mutation ,Cardiology ,Parkinson’s disease ,Glucosylceramidase ,GBA ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Objective: To study the longitudinal disease course of Parkinson’s disease (PD) patients with glucocerebrosidase (GBA) mutation (GBA-positive) compared to PD non-carriers (GBA-negative) along a 5-year follow-up, evaluating changes in clinical and cognitive outcomes, cortical thickness, and gray-matter (GM) volumes. Methods: Ten GBA-positive and 20 GBA-negative PD patients underwent clinical, neuropsychological, and MRI assessments (cortical thickness and subcortical, hippocampal, and amygdala volumes) at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared with 22 age-matched healthy controls. Clinical, cognitive, and MRI features were compared between groups at baseline and over time. Results: At baseline, GBA-positive and GBA-negative PD patients had similar clinical and cognitive profiles. Compared to GBA-negative and controls, GBA-positive patients showed cortical thinning of left temporal, parietal, and occipital gyri. Over time, compared to GBA-negative, GBA-positive PD patients progressed significantly in motor and cognitive symptoms, and showed a greater pattern of cortical thinning of posterior regions, and frontal and orbito-frontal cortices. After 5 years, compared to controls, GBA-negative PD patients showed a pattern of cortical thinning similar to that showed by GBA-positive cases at baseline. The two groups of patients showed similar patterns of subcortical, hippocampal, and amygdala volume loss over time. Conclusions: Compared to GBA-negative PD, GBA-positive patients experienced a more rapid motor and cognitive decline together with a greater, earlier and faster cortical thinning. Cortical thickness measures may be a useful tool for monitoring and predicting PD progression in accordance with the genetic background.
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- 2021
41. Dual-task clinical and functional MRI correlates in Parkinson's disease with postural instability and gait disorders
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Andrea Tettamanti, Federica Agosta, Noemi Piramide, Massimo Filippi, Maria Antonietta Volontè, Elisabetta Sarasso, Andrea Gardoni, Elisa Canu, Sarasso, E., Gardoni, A., Piramide, N., Volonte, M. A., Canu, E., Tettamanti, A., Filippi, M., and Agosta, F.
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Male ,medicine.medical_specialty ,Brain activity and meditation ,fMRI (MeSH term) ,Inferior frontal gyrus ,Neuropsychological Tests ,behavioral disciplines and activities ,Executive Function ,Gait (human) ,Physical medicine and rehabilitation ,Gait analysis (MeSH term) ,Task Performance and Analysis ,medicine ,Humans ,Attention ,Cognitive Dysfunction ,Gait ,Postural Balance ,Gait Disorders, Neurologic ,Balance (ability) ,Aged ,Aged, 80 and over ,Supplementary motor area ,business.industry ,Neuropsychology ,Brain ,Parkinson Disease ,Middle Aged ,Magnetic Resonance Imaging ,Gait disorders (MeSH term) ,Dual-task ,medicine.anatomical_structure ,Neurology ,Gait analysis ,Case-Control Studies ,Parkinson disease (MeSH term) ,Postural balance (MeSH term) ,Sensation Disorders ,Female ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Gait Analysis ,psychological phenomena and processes ,Executive dysfunction - Abstract
Background Dual-task is a challenge for Parkinson’s disease patients with postural instability and gait disorders (PD-PIGD). Objective This study investigated clinical, cognitive and functional brain correlates of dual-task deficits in PD-PIGD patients using quantitative gait analysis, neuropsychological evaluations and functional MRI (fMRI). Methods Twenty-three PD-PIGD patients performed a clinical assessment of gait/balance abilities. Single and dual-task Timed-Up-and-Go tests were monitored using an optoelectronic system to study turning velocity. Patients underwent executive-attentive function evaluation and two fMRI tasks: motor-task (foot anti-phase movements), and dual-task (foot anti-phase movements while counting backwards by threes starting from 100). Twenty-three healthy subjects underwent neuropsychological and fMRI assessments. Results Dual-task in PD-PIGD patients resulted in worse gait performance, particularly during turning. Performing the dual-task relative to the motor-fMRI task, healthy subjects showed widespread increased recruitment of sensorimotor, cognitive and cerebellar areas and reduced activity of inferior frontal and supramarginal gyri, while PD-PIGD patients showed increased recruitment of inferior frontal gyrus and supplementary motor area and reduced activity of primary motor, supramarginal and caudate areas. Dual-task gait alterations in patients correlated with balance and executive deficits and with altered dual-task fMRI brain activity of frontal areas. Conclusions This study suggested the correlation between dual-task gait difficulties, postural instability and executive dysfunction in PD-PIGD patients. FMRI results suggest that an optimized recruitment of motor and cognitive networks is associated with a better dual-task performance in PD-PIGD. Future studies should evaluate the effect of specific gait/balance and dual-task trainings to improve gait parameters and optimize brain functional activity during dual-tasks.
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- 2021
42. Brain activity of the emotional circuit in Parkinson’s disease patients with freezing of gait
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Elisabetta Sarasso, Federica Agosta, Elisa Canu, Massimo Filippi, Noemi Piramide, Maria Antonietta Volontè, Sarasso, E., Agosta, F., Piramide, N., Canu, E., Volonte, M. A., and Filippi, M.
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medicine.medical_specialty ,Parkinson's disease ,genetic structures ,Brain activity and meditation ,Emotional circuit ,Cognitive Neuroscience ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Hippocampus ,Walking ,Audiology ,behavioral disciplines and activities ,050105 experimental psychology ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,medicine ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,RC346-429 ,Prefrontal cortex ,Gait ,Mirror neuron ,Gait Disorders, Neurologic ,Freezing of gait ,business.industry ,05 social sciences ,fMRI ,Neuropsychology ,Brain ,Regular Article ,Parkinson Disease ,medicine.disease ,Executive functions ,Neurology ,nervous system ,Parkinson’s disease ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,business ,psychological phenomena and processes ,030217 neurology & neurosurgery - Abstract
Highlights • Limbic/cognitive circuits play an important role in the mechanisms underlying FoG. • PD-FoG patients show increased activity of self-related emotions brain areas. • Worse FoG and executive functions correlate with altered fronto-parietal activity., Objective Emotional processes might influence freezing of gait (FoG) in Parkinson’s disease (PD) patients. We assessed brain functional MRI (fMRI) activity during a “FoG-observation-task” in PD-FoG patients relative to healthy controls. Methods Twenty-four PD-FoG patients and 18 age- and sex-matched healthy controls performed clinical and neuropsychological evaluations, and fMRI experiments including: i) “FoG-observation-task” consisting of watching a patient experiencing FoG during a walking task (usually evoking FoG); ii) “gait-observation-task” consisting of watching a healthy subject performing similar walking tasks without experiencing FoG. Results During both tasks, PD-FoG patients showed reduced activity of the fronto-parietal mirror neuron system (MNS) relative to controls. In the “FoG-observation-task” relative to the “gait-observation-task”, PD-FoG patients revealed an increased recruitment of the anterior medial prefrontal cortex and a reduced recruitment of the dorsomedial prefrontal cortex and hippocampus relative to controls. Healthy controls in the “FoG-observation-task” relative to the “gait-observation-task” showed increased recruitment of cognitive empathy areas and decreased activity of the fronto-parietal MNS. Conclusion Our results suggest that when PD-FoG patients observe a subject experiencing FoG, there is an increased activity of brain areas involved in self-reflection emotional processes and a reduced activity of areas related to motor programming, executive functions and cognitive empathy. These findings support previous evidence on the critical role of the emotional circuit in the mechanisms underlying FoG.
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- 2021
43. Impaired recognition of disgust in amyotrophic lateral sclerosis is related to basal ganglia involvement
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Veronica Castelnovo, Maria Antonietta Magno, Barbara Poletti, Silvia Basaia, Federica Agosta, Massimo Filippi, Nilo Riva, Elisa Canu, Vincenzo Silani, Castelnovo, V., Canu, E., Magno, M. A., Basaia, S., Riva, N., Poletti, B., Silani, V., Filippi, M., and Agosta, F.
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medicine.medical_specialty ,Cognitive Neuroscience ,Computer applications to medicine. Medical informatics ,Emotions ,R858-859.7 ,Hippocampus ,Neuropsychological Tests ,Audiology ,Amygdala ,Basal ganglia ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Neuropsychological assessment ,Amyotrophic lateral sclerosis ,Cognitive decline ,RC346-429 ,medicine.diagnostic_test ,business.industry ,Brain ,Recognition, Psychology ,Regular Article ,Cognition ,medicine.disease ,humanities ,Disgust ,medicine.anatomical_structure ,Neurology ,Neurology (clinical) ,Neurology. Diseases of the nervous system ,business ,MRI - Abstract
Highlights • Altered ability to correctly recognize disgust in pure motor ALS patients. • Potential role of the left pallidum in the altered processing of disgust. • Disgust as one of the first emotion that ALS patients fail to recognize., In the present study we investigated emotion recognition in pure motor amyotrophic lateral sclerosis (ALS) patients and its relationship with the integrity of basal ganglia, hippocampus and amygdala. Twenty ALS patients without either cognitive or behavioural impairment, and 52 matched healthy controls performed a neuropsychological assessment including the Comprehensive Affect Testing System (CATS) investigating emotion recognition. All participants underwent also a 3T brain MRI. Volumes of basal ganglia, hippocampus and amygdala bilaterally were measured using FIRST in FSL. Sociodemographic, cognitive and MRI data were compared between groups. In ALS patients, correlations between CATS significant findings, brain volumes, cognition, mood and behaviour were explored. ALS patients showed altered performances at the CATS total score and, among the investigated emotions, patients were significantly less able to recognize disgust compared with controls. No brain volumetric differences were observed between groups. In ALS patients, a lower performance in disgust recognition was related with a reduced volume of the left pallidum and a lower performance on the Edinburgh Cognitive and Behavioural ALS Screen. Cognitively/behaviourally unimpaired ALS patients showed impaired disgust recognition, which was associated with pallidum volume. The association with cognitive alterations may suggest impaired disgust recognition as an early marker of cognitive decline.
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- 2021
44. Structural MRI Signatures in Genetic Presentations of the Frontotemporal Dementia-Motor Neuron Disease Spectrum
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Federica Agosta, Lucio Tremolizzo, Giuseppe Magnani, Francesca Caso, Veronica Castelnovo, Sara Prioni, Massimo Filippi, Edoardo G. Spinelli, Camilla Cividini, Alma Ghirelli, Teuta Domi, Nilo Riva, Paola Carrera, Paola Caroppo, Giacomina Rossi, Ildebrando Appollonio, Elisa Canu, Vincenzo Silani, Silvia Basaia, Spinelli, E, Ghirelli, A, Basaia, S, Cividini, C, Riva, N, Canu, E, Castelnovo, V, Domi, T, Magnani, G, Caso, F, Caroppo, P, Prioni, S, Rossi, G, Tremolizzo, L, Appollonio, I, Silani, V, Carrera, P, Filippi, M, Agosta, F, Spinelli, Edoardo Gioele, Ghirelli, Alma, Basaia, Silvia, Cividini, Camilla, Riva, Nilo, Canu, Elisa, Castelnovo, Veronica, Domi, Teuta, Magnani, Giuseppe, Caso, Francesca, Caroppo, Paola, Prioni, Sara, Rossi, Giacomina, Tremolizzo, Lucio, Appollonio, Ildebrando, Silani, Vincenzo, Carrera, Paola, Filippi, Massimo, and Agosta, Federica
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Cerebellum ,Neuroimaging ,computer.software_genre ,TARDBP ,Atrophy ,C9orf72 ,Voxel ,mental disorders ,Image Interpretation, Computer-Assisted ,Humans ,Medicine ,Motor Neuron Disease ,Aged ,MRI, frontotemporal dementia ,business.industry ,Brain ,Frontotemporal lobar degeneration ,Middle Aged ,Motor neuron ,medicine.disease ,Magnetic Resonance Imaging ,nervous system diseases ,medicine.anatomical_structure ,Case-Control Studies ,Female ,Neurology (clinical) ,Frontotemporal Lobar Degeneration ,business ,computer ,Research Article ,Frontotemporal dementia - Abstract
Background and ObjectivesTo assess cortical, subcortical, and cerebellar gray matter (GM) atrophy using MRI in patients with disorders of the frontotemporal lobar degeneration (FTLD) spectrum with known genetic mutations.MethodsSixty-six patients carrying FTLD-related mutations were enrolled, including 44 with pure motor neuron disease (MND) and 22 with frontotemporal dementia (FTD). Sixty-one patients with sporadic FTLD (sFTLD) matched for age, sex, and disease severity with genetic FTLD (gFTLD) were also included, as well as 52 healthy controls. A whole-brain voxel-based morphometry (VBM) analysis was performed. GM volumes of subcortical and cerebellar structures were obtained.ResultsCompared with controls, GM atrophy on VBM was greater and more diffuse in genetic FTD, followed by sporadic FTD and genetic MND cases, whereas patients with sporadic MND (sMND) showed focal motor cortical atrophy. Patients carrying C9orf72 and GRN mutations showed the most widespread cortical volume loss, in contrast with GM sparing in SOD1 and TARDBP. Globally, patients with gFTLD showed greater atrophy of parietal cortices and thalami compared with sFTLD. In volumetric analysis, patients with gFTLD showed volume loss compared with sFTLD in the caudate nuclei and thalami, in particular comparing C9-MND with sMND cases. In the cerebellum, patients with gFTLD showed greater atrophy of the right lobule VIIb than sFTLD. Thalamic volumes of patients with gFTLD with a C9orf72 mutation showed an inverse correlation with Frontal Behavioral Inventory scores.DiscussionMeasures of deep GM and cerebellar structural involvement may be useful markers of gFTLD, particularly C9orf72-related disorders, regardless of the clinical presentation within the FTLD spectrum.
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- 2021
45. Brain Structural Changes in Focal Dystonia—What About Task Specificity? A Multimodal MRI Study
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Elisa Canu, Vladimir S. Kostic, Aleksandra Tomić, Nikola Kresojević, Federica Agosta, Massimo Filippi, Elisabetta Sarasso, Igor Petrović, Marina Svetel, Andrea Fontana, Tomic, A., Agosta, F., Sarasso, E., Svetel, M., Kresojevic, N., Fontana, A., Canu, E., Petrovic, I., Kostic, V. S., and Filippi, M.
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0301 basic medicine ,Blepharospasm ,Thalamus ,White matter ,03 medical and health sciences ,focal dystonia ,0302 clinical medicine ,Basal ganglia ,Humans ,Medicine ,magnetic resonance imaging ,Cervical dystonia ,Gray Matter ,Dystonia ,Brain Mapping ,business.industry ,Brain ,gray matter ,Focal dystonia ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,Botulinum toxin ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Dystonic Disorders ,Neurology (clinical) ,task specificity ,medicine.symptom ,business ,Neuroscience ,white matter ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background The neural basis of task specificity in dystonia is still poorly understood. This study investigated gray and white matter (WM) brain alterations in patients with task-specific dystonia (TSD) and non-task-specific dystonia (NTSD). Methods Thirty-six patients with TSD (spasmodic dysphonia, writer's cramp), 61 patients with NTSD (blepharospasm, cervical dystonia), and 83 healthy controls underwent 3D T1-weighted and diffusion tensor magnetic resonance imaging (MRI). Whole brain cortical thickness and voxel-based morphometry; volumes of basal ganglia, thalamus, nucleus accumbens, amygdala, and hippocampus; and WM damage were assessed. Analysis of variance models were used to compare MRI measures between groups, adjusting for age and botulinum toxin (BoNT) treatment. Results The comparison between focal dystonia patients showed cortical thickness and gray matter (GM) volume differences (ie, decreased in NTSD, increased in TSD) in frontal, parietal, temporal, and occipital cortical regions; basal ganglia; thalamus; hippocampus; and amygdala. Cerebellar atrophy was found in NTSD patients relative to controls. WM damage was more severe and widespread in task-specific relative to NTSD patients. TSD patients receiving BoNT, relative to nontreated patients, had cortical thickening and increased GM volume in frontoparietal, temporal, and occipital regions. NTSD patients experiencing pain showed cortical thickening of areas involved in pain-inhibitory mechanisms. Conclusions TSD and NTSD are characterized by opposite alterations of the main cortical and subcortical sensorimotor and cognitive-controlling brain structures, suggesting the possible presence of different pathophysiological and/or compensatory mechanisms underlying the complexity of the two clinical phenotypes of focal dystonia. © 2020 International Parkinson and Movement Disorder Society.
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- 2021
46. Tracking Cortical Changes Throughout Cognitive Decline in Parkinson's Disease
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Aleksandra Tomić, Elisa Canu, Igor Petrović, Elka Stefanova, Iva Stankovic, Giulia Donzuso, Federica Agosta, Vladimir S. Kostic, Tanja Stojkovic, Vladana Markovic, Massimo Filippi, Silvia Basaia, Filippi, Massimo, Canu, Elisa, Donzuso, Giulia, Stojkovic, Tanja, Basaia, Silvia, Stankovic, Iva, Tomic, Aleksandra, Markovic, Vladana, Petrovic, Igor, Stefanova, Elka, Kostic, Vladimir S, and Agosta, Federica
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0301 basic medicine ,Longitudinal study ,medicine.medical_specialty ,Parkinson's disease ,Thalamus ,Precuneus ,Disease ,Neuropsychological Tests ,03 medical and health sciences ,0302 clinical medicine ,mild cognitive impairment ,Internal medicine ,Medicine ,Dementia ,Humans ,Cognitive Dysfunction ,Cognitive decline ,Gray Matter ,business.industry ,longitudinal study ,Cognition ,Parkinson Disease ,cortical thickness ,medicine.disease ,cognitive decline ,Magnetic Resonance Imaging ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Cardiology ,Neurology (clinical) ,Atrophy ,business ,030217 neurology & neurosurgery - Abstract
Background The objectives of this study were to investigate progressive cortical thinning and volume loss in Parkinson's disease (PD) patients with different longitudinal patterns of cognitive decline: with stable normal cognition, with stable mild cognitive impairment, with conversion to mild cognitive impairment, and with conversion to dementia. Methods We recruited 112 patients (37 Parkinson's disease with stable normal cognition, 20 Parkinson's disease with stable mild cognitive impairment, 36 Parkinson's disease with conversion to mild cognitive impairment, 19 Parkinson's disease with conversion to dementia) and 38 healthy controls. All patients underwent at least 2 visits within 4 years including clinical/cognitive assessments and structural MRI (total visits, 393). Baseline cortical thickness and gray matter volumetry were compared between groups. In PD, gray matter changes over time were investigated and compared between groups. Results At baseline, compared with Parkinson's disease with stable normal cognition cases, Parkinson's disease with conversion to mild cognitive impairment patients showed cortical atrophy of the parietal and occipital lobes, similar to Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia patients. The latter groups (ie, patients with cognitive impairment from the study entry) showed additional involvement of the frontotemporal cortices. No baseline volumetric differences among groups were detected. The longitudinal analysis (group-by-time interaction) showed that, versus the other patient groups, Parkinson's disease with stable mild cognitive impairment and Parkinson's disease with conversion to dementia cases accumulated the least cortical damage, with Parkinson's disease with conversion to dementia showing unique progression of right thalamic and hippocampal volume loss; Parkinson's disease with conversion to mild cognitive impairment patients showing specific cortical thinning accumulation in the medial and superior frontal gyri, inferior temporal, precuneus, posterior cingulum, and supramarginal gyri bilaterally; and Parkinson's disease with stable normal cognition patients showing cortical thinning progression, mainly in the occipital and parietal regions bilaterally. Conclusions Cortical thinning progression is more prominent in the initial stages of PD cognitive decline. The involvement of frontotemporoparietal regions, the hippocampus, and the thalamus is associated with conversion to a more severe stage of cognitive impairment. In PD, gray matter alterations of critical brain regions may be an MRI signature for the identification of patients at risk of developing dementia. © 2020 International Parkinson and Movement Disorder Society.
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- 2020
47. Speech production differences in English and Italian speakers with nonfluent variant PPA
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Federica Agosta, Ariane E. Welch, Stefano F. Cappa, Giovanni Battistella, Andrea Moro, H. Isabel Hubbard, Giuseppe Magnani, Elisa Canu, Maria Luisa Gorno-Tempini, Maria Luisa Mandelli, Massimo Filippi, Jessica Deleon, Bruce L. Miller, Edoardo G. Spinelli, Canu, Elisa, Agosta, Federica, Battistella, Giovanni, Spinelli, Edoardo G, Deleon, Jessica, Welch, Ariane E, Mandelli, Maria Luisa, Hubbard, H Isabel, Moro, Andrea, Magnani, Giuseppe, Cappa, Stefano F, Miller, Bruce L, Filippi, Massimo, and Gorno-Tempini, Maria Luisa
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Male ,Speech production ,Aging ,Audiology ,Neurodegenerative ,Severity of Illness Index ,Primary progressive aphasia ,0302 clinical medicine ,2.1 Biological and endogenous factors ,Aetiology ,Psycholinguistics ,Language Tests ,medicine.diagnostic_test ,05 social sciences ,Rehabilitation ,Neuropsychological test ,Middle Aged ,Magnetic Resonance Imaging ,Italy ,Female ,Cognitive Sciences ,medicine.symptom ,Grammatical Impairment ,medicine.medical_specialty ,Primary Progressive ,Clinical Sciences ,Article ,050105 experimental psychology ,03 medical and health sciences ,Rare Diseases ,Progressive nonfluent aphasia ,Clinical Research ,Aphasia ,Behavioral and Social Science ,medicine ,Acquired Cognitive Impairment ,Humans ,0501 psychology and cognitive sciences ,Connected speech ,Aged ,Mini–Mental State Examination ,Neurology & Neurosurgery ,business.industry ,Neurosciences ,medicine.disease ,United States ,Brain Disorders ,Aphasia, Primary Progressive ,Cross-Sectional Studies ,Dementia ,Neurology (clinical) ,Atrophy ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveTo understand whether the clinical phenotype of nonfluent/agrammatic primary progressive aphasia (nfvPPA) could present differences depending on the patient’s native language.MethodsIn this cross-sectional study, we analyzed connected speech samples in monolingual English (nfvPPA-E) and Italian speakers (nfvPPA-I) who were diagnosed with nfvPPA and matched for age, sex, and Mini-Mental State Examination scores. Patients also received a comprehensive neuropsychological battery. All patients and 2 groups of age-matched healthy controls underwent an MRI scan with 3D T1-weighted sequences. Connected speech measures and the other cognitive features were compared between patient groups. MRI variables, in terms of gray matter volume, were compared between each patient group and the corresponding controls.ResultsCompared to nfvPPA-E, nfvPPA-I had fewer years of education and shorter reported disease duration. The 2 groups showed similar regional atrophy compatible with clinical diagnosis. Patients did not differ in nonlanguage domains, comprising executive scores. Connected speech sample analysis showed that nfvPPA-E had significantly more distortions than nfvPPA-I, while nfvPPA-I showed reduced scores in some measures of syntactic complexity. On language measures, Italian speakers performed more poorly on syntactic comprehension.ConclusionsnfvPPA-E showed greater motor speech impairment than nfvPPA-I despite higher level of education and comparable disease severity and atrophy changes. The data also suggest greater grammatical impairment in nfvPPA-I. This study illustrates the need to take into account the possible effect of the individual's spoken language on the phenotype and clinical presentation of primary progressive aphasia variants.
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- 2020
48. Structural and functional brain connectome in motor neuron diseases: A multicenter MRI study
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Yuri Matteo Falzone, Camilla Cividini, Silvia Basaia, Maria Rosaria Monsurrò, Francesca Trojsi, Andrea Falini, Gioacchino Tedeschi, Elisa Canu, Cristina Moglia, Nilo Riva, Edoardo G. Spinelli, Adriano Chiò, Veronica Castelnovo, Massimo Filippi, Cinzia Femiano, Federica Agosta, Basaia, Silvia, Agosta, Federica, Cividini, Camilla, Trojsi, Francesca, Riva, Nilo, Spinelli, Edoardo G, Moglia, Cristina, Femiano, Cinzia, Castelnovo, Veronica, Canu, Elisa, Falzone, Yuri, Monsurrò, Maria Rosaria, Falini, Andrea, Chiò, Adriano, Tedeschi, Gioacchino, Filippi, Massimo, Basaia, S., Agosta, F., Cividini, C., Trojsi, F., Riva, N., Spinelli, E. G., Moglia, C., Femiano, C., Castelnovo, V., Canu, E., Falzone, Y., Monsurro, M. R., Falini, A., Chio, A., Tedeschi, G., and Filippi, M.
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Adult ,Male ,Connectomics ,Neuropsychological Tests ,Article ,030218 nuclear medicine & medical imaging ,Muscular Atrophy, Spinal ,03 medical and health sciences ,0302 clinical medicine ,Basal ganglia ,medicine ,Connectome ,Humans ,Cognitive Dysfunction ,Prospective Studies ,Amyotrophic lateral sclerosis ,Motor Neuron Disease ,Primary Lateral Sclerosis ,Aged ,Aged, 80 and over ,business.industry ,Amyotrophic Lateral Sclerosis ,Neuropsychology ,Brain ,Motor neuron ,Progressive muscular atrophy ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Case-Control Studies ,Female ,Neurology (clinical) ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
ObjectiveTo investigate structural and functional neural organization in amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and progressive muscular atrophy (PMA).MethodsA total of 173 patients with sporadic ALS, 38 patients with PLS, 28 patients with PMA, and 79 healthy controls were recruited from 3 Italian centers. Participants underwent clinical, neuropsychological, and brain MRI evaluations. Using graph analysis and connectomics, global and lobar topologic network properties and regional structural and functional brain connectivity were assessed. The association between structural and functional network organization and clinical and cognitive data was investigated.ResultsCompared with healthy controls, patients with ALS and patients with PLS showed altered structural global network properties, as well as local topologic alterations and decreased structural connectivity in sensorimotor, basal ganglia, frontal, and parietal areas. Patients with PMA showed preserved global structure. Patient groups did not show significant alterations of functional network topologic properties relative to controls. Increased local functional connectivity was observed in patients with ALS in the precentral, middle, and superior frontal areas, and in patients with PLS in the sensorimotor, basal ganglia, and temporal networks. In patients with ALS and patients with PLS, structural connectivity alterations correlated with motor impairment, whereas functional connectivity disruption was closely related to executive dysfunction and behavioral disturbances.ConclusionsThis multicenter study showed widespread motor and extramotor network degeneration in ALS and PLS, suggesting that graph analysis and connectomics might represent a powerful approach to detect upper motor neuron degeneration, extramotor brain changes, and network reorganization associated with the disease. Network-based advanced MRI provides an objective in vivo assessment of motor neuron diseases, delivering potential prognostic markers.
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- 2020
49. An update on magnetic resonance imaging markers in AD
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Elisa Canu, Davide Calderaro, Federica Agosta, Michela Leocadi, Davide Corbetta, Massimo Filippi, Leocadi, M., Canu, E., Calderaro, D., Corbetta, D., Filippi, M., and Agosta, F.
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Advances in Neuroimaging ,Brain Structure and Function ,Review ,Cerebral pathology ,Scientific literature ,Disease ,050105 experimental psychology ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,mild cognitive impairment ,Neuroimaging ,medicine ,0501 psychology and cognitive sciences ,lcsh:Neurology. Diseases of the nervous system ,Pharmacology ,neuroimaging ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Disease progression ,biomarkers ,Magnetic resonance imaging ,Clinical trial ,Neurology ,Neurology (clinical) ,business ,Neuroscience ,Alzheimer’s disease ,030217 neurology & neurosurgery ,MRI - Abstract
The purpose of the present review is to provide an update of the available recent scientific literature on the use of magnetic resonance imaging (MRI) in Alzheimer’s disease (AD). MRI is playing an increasingly important role in the characterization of the AD signatures, which can be useful in both the diagnostic process and monitoring of disease progression. Furthermore, this technique is unique in assessing brain structure and function and provides a deep understanding of in vivo evolution of cerebral pathology. In the reviewing process, we established a priori criteria and we thoroughly searched the very recent scientific literature (January 2018–March 2020) for relevant articles on this topic. In summary, we selected 73 articles out of 1654 publications retrieved from PubMed. Based on this selection, this review summarizes the recent application of MRI in clinical trials, defining the predementia stages of AD, the clinical utility of MRI, proposal of novel biomarkers and brain regions of interest, and assessing the relationship between MRI and cognitive features, risk and protective factors of AD. Finally, the value of a multiparametric approach in clinical and preclinical stages of AD is discussed.
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- 2020
50. Virtual reality and real-time neurofeedback functional MRI: a breakthrough in foreseeing Alzheimer's disease?
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Federica Agosta, Elisa Canu, Massimo Filippi, Agosta, F., Canu, E., and Filippi, M.
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Amyloid ,Hippocampus ,Down-Regulation ,Disease ,Virtual reality ,p-tau ,CA1 ,03 medical and health sciences ,0302 clinical medicine ,rt-fMRI ,Alzheimer Disease ,medicine ,Humans ,030304 developmental biology ,0303 health sciences ,ECM ,medicine.diagnostic_test ,business.industry ,Virtual Reality ,Magnetic resonance imaging ,Original Articles ,Neurofeedback ,medicine.disease ,Magnetic Resonance Imaging ,Neurology (clinical) ,Alzheimer's disease ,amyloid-β42 ,business ,Functional magnetic resonance imaging ,Neuroscience ,030217 neurology & neurosurgery - Abstract
See Agosta et al. (doi:10.1093/brain/awaa038) for a scientific commentary on this article. Hippocampal hyperactivity is a promising neuromarker for Alzheimer’s disease. Using neurofeedback and virtual reality to train participants at risk of Alzheimer’s disease to downregulate CA1 activity, Skouras et al. explore how elevated amyloid and tau affect functional networks involved in hippocampal self-regulation., Research into hippocampal self-regulation abilities may help determine the clinical significance of hippocampal hyperactivity throughout the pathophysiological continuum of Alzheimer’s disease. In this study, we aimed to identify the effects of amyloid-β peptide 42 (amyloid-β42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-β peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based ‘Alzheimer’s and Families’ study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. We developed a closed-loop, real-time functional MRI neurofeedback task with virtual reality and tailored it for training downregulation of hippocampal subfield cornu ammonis 1 (CA1). Neurofeedback performance score, cognitive reserve score, hippocampal volume, number of apolipoprotein ε4 alleles and sex were controlled for as confounds in all cross-sectional analyses. First, using voxel-wise multiple regression analysis and controlling for CSF biomarkers, we identified the effect of healthy ageing on eigenvector centrality, a measure of each voxel’s overall influence based on iterative whole-brain connectomics, during hippocampal CA1 downregulation. Then, controlling for age, we identified the effects of abnormal CSF amyloid-β42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. Across subjects, our main findings during hippocampal downregulation were: (i) in the absence of abnormal biomarkers, age correlated with eigenvector centrality negatively in the insula and midcingulate cortex, and positively in the inferior temporal gyrus; (ii) abnormal CSF amyloid-β42 (19.2) correlated with eigenvector centrality positively in the ventral striatum, anterior cingulate and somatosensory cortex, and negatively in the precuneus and orbitofrontal cortex. During resting state functional MRI, similar eigenvector centrality patterns in the cingulate had previously been associated to CSF biomarkers in mild cognitive impairment and dementia patients. Using the developed closed-loop paradigm, we observed such patterns, which are characteristic of advanced disease stages, during a much earlier presymptomatic phase. In the absence of CSF biomarkers, our non-invasive, interactive, adaptive and gamified neuroimaging procedure may provide important information for clinical prognosis and monitoring of therapeutic efficacy. We have released the developed paradigm and analysis pipeline as open-source software to facilitate replication studies.
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- 2020
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