Publications by authors named "Giovanni Giulietti"

39 Publications

Motor and non-motor outcomes of subthalamic deep brain stimulation in a case of juvenile PARK-PINK1.

Brain Stimul 2021 Apr 5. Epub 2021 Apr 5.

Department of Neuroscience 'Rita Levi Montalcini', University of Torino; Neurology 2 Unit, A.O.U. Città Della Salute e Della Scienza di Torino, Corso Bramante 88, 10124, Torino, Italy.

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http://dx.doi.org/10.1016/j.brs.2021.04.002DOI Listing
April 2021

Lesion distribution and substrate of white matter damage in myotonic dystrophy type 1: Comparison with multiple sclerosis.

Neuroimage Clin 2021 14;29:102562. Epub 2021 Jan 14.

Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, United Kingdom; UOC Neurologia e Neurofisiopatologia, AO San Camillo Forlanini, Rome, Italy. Electronic address:

Myotonic Dystrophy type 1 (DM1) is an autosomal dominant condition caused by expansion of the CTG triplet repeats within the myotonic dystrophy protein of the kinase (DMPK) gene. The central nervous system is involved in the disease, with multiple symptoms including cognitive impairment. A typical feature of DM1 is the presence of widespread white matter (WM) lesions, whose total volume is associated with CTG triplet expansion. The aim of this study was to characterize the distribution and pathological substrate of these lesions as well as the normal appearing WM (NAWM) using quantitative magnetization transfer (qMT) MRI, and comparing data from DM1 patients with those from patients with multiple sclerosis (MS). Twenty-eight patients with DM1, 29 patients with relapsing-remitting MS, and 15 healthy controls had an MRI scan, including conventional and qMT imaging. The average pool size ratio (F), a proxy of myelination, was computed within lesions and NAWM for every participant. The lesion masks were warped into MNI space and lesion probability maps were obtained for each patient group. The lesion distribution, total lesion load and the tissue-specific mean F were compared between groups. The supratentorial distribution of lesions was similar in the 2 patient groups, although mean lesion volume was higher in MS than DM1. DM1 presented higher prevalence of anterior temporal lobe lesions, but none in the cerebellum and brainstem. Significantly reduced F values were found within DM1 lesions, suggesting a loss of myelin density. While F was reduced in the NAWM of MS patients, it did not differ between DM1 and controls. Our results provide further evidence for a need to compare histology and imaging using new MRI techniques in DM1 patients, in order to further our understanding of the underlying disease process contributing to WM disease.
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http://dx.doi.org/10.1016/j.nicl.2021.102562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848627PMC
January 2021

Evidence for interhemispheric imbalance in stroke patients as revealed by combining transcranial magnetic stimulation and electroencephalography.

Hum Brain Mapp 2021 Apr 13;42(5):1343-1358. Epub 2021 Jan 13.

Non-Invasive Brain Stimulation Unit/Department of Behavioral and Clinical Neurology, Santa Lucia Foundation, Rome, Italy.

Interhemispheric interactions in stroke patients are frequently characterized by abnormalities, in terms of balance and inhibition. Previous results showed an impressive variability, mostly given to the instability of motor-evoked potentials when evoked from the affected hemisphere. We aim to find reliable interhemispheric measures in stroke patients with a not-evocable motor-evoked potential from the affected hemisphere, by combining transcranial magnetic stimulation (TMS) and electroencephalography. Ninteen stroke patients (seven females; 61.26 ± 9.8 years) were studied for 6 months after a first-ever stroke in the middle cerebral artery territory. Patients underwent four evaluations: clinical, cortical, corticospinal, and structural. To test the reliability of our measures, the evaluations were repeated after 3 weeks. To test the sensitivity, 14 age-matched healthy controls were compared to stroke patients. In stroke patients, stimulation of the affected hemisphere did not result in any inhibition onto the unaffected. The stimulation of the unaffected hemisphere revealed a preservation of the inhibition mechanism onto the affected. This resulted in a remarkable interhemispheric imbalance, whereas this mechanism was steadily symmetric in healthy controls. This result was stable when cortical evaluation was repeated after 3 weeks. Importantly, patients with a better recovery of the affected hand strength were the ones with a more stable interhemispheric balance. Finally, we found an association between microstructural integrity of callosal fibers, suppression of interhemispheric TMS-evoked activity and interhemispheric connectivity. We provide direct and sensitive cortical measures of interhemispheric imbalance in stroke patients. These measures offer a reliable means of distinguishing healthy and pathological interhemispheric dynamics.
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http://dx.doi.org/10.1002/hbm.25297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927297PMC
April 2021

Automatic multispectral MRI segmentation of human hippocampal subfields: an evaluation of multicentric test-retest reproducibility.

Brain Struct Funct 2021 Jan 24;226(1):137-150. Epub 2020 Nov 24.

Center for Mind/Brain Sciences (CIMeC), University of Trento, Rovereto, Italy.

Accurate and reproducible automated segmentation of human hippocampal subfields is of interest to study their roles in cognitive functions and disease processes. Multispectral structural MRI methods have been proposed to improve automated hippocampal subfield segmentation accuracy, but the reproducibility in a multicentric setting is, to date, not well characterized. Here, we assessed test-retest reproducibility of FreeSurfer 6.0 hippocampal subfield segmentations using multispectral MRI analysis pipelines (22 healthy subjects scanned twice, a week apart, at four 3T MRI sites). The harmonized MRI protocol included two 3D-T1, a 3D-FLAIR, and a high-resolution 2D-T2. After within-session T1 averaging, subfield volumes were segmented using three pipelines with different multispectral data: two longitudinal ("long_T1s" and "long_T1s_FLAIR") and one cross-sectional ("long_T1s_FLAIR_crossT2"). Volume reproducibility was quantified in magnitude (reproducibility error-RE) and space (DICE coefficient). RE was lower in all hippocampal subfields, except for hippocampal fissure, using the longitudinal pipelines compared to long_T1s_FLAIR_crossT2 (average RE reduction of 0.4-3.6%). Similarly, the longitudinal pipelines showed a higher spatial reproducibility (1.1-7.8% of DICE improvement) in all hippocampal structures compared to long_T1s_FLAIR_crossT2. Moreover, long_T1s_FLAIR provided a small but significant RE improvement in comparison to long_T1s (p = 0.015), whereas no significant DICE differences were found. In addition, structures with volumes larger than 200 mm had better RE (1-2%) and DICE (0.7-0.95) than smaller structures. In summary, our study suggests that the most reproducible hippocampal subfield FreeSurfer segmentations are derived from a longitudinal pipeline using 3D-T1s and 3D-FLAIR. Adapting a longitudinal pipeline to include high-resolution 2D-T2 may lead to further improvements.
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http://dx.doi.org/10.1007/s00429-020-02172-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817563PMC
January 2021

Abnormal Cortical Thickness Is Associated With Deficits in Social Cognition in Patients With Myotonic Dystrophy Type 1.

Front Neurol 2020 28;11:113. Epub 2020 Feb 28.

Neuroimaging Laboratory, IRCCS Fondazione Santa Lucia, Rome, Italy.

To investigate the cortical thickness in myotonic dystrophy type 1 (DM1) and its potential association with patients' genetic triplet expansion and social cognition deficits. Thirty patients with DM1 underwent the Social Cognition Battery Test and magnetic resonance imaging (MRI) scanning at 3 T. Twenty-five healthy subjects (HSs) were enrolled in the study to serve as a control group for structural MRI data. To assess changes in cortical thickness in DM1 patients, they were compared to HSs using a -test model. Correlations were used to assess potential associations between genetic and clinical characteristics and social cognition performances in the patient group. Additionally, multiple regression models were used to explore associations between cortical thickness, CTG triplet expansion size, and scores obtained by DM1 patients on the Social Cognition Battery. DM1 patients showed low performances in several subtests of the Social Cognition Battery. Specifically, they obtained pathological scores at Emotion Attribution Test (i.e., Sadness, Embarrassment, Happiness, and Anger) and at the Social Situations Test (i.e., recognition of normal situation, recognition of aberrant behavior). Significant negative correlations were found between CTG triplet expansion size and Embarrassment, and Severity of Aberrant Behavior. Similarly, a negative correlation was found between patients' MIRS scores and Sadness. DM1 patients compared to HSs showed reduced thickness in the right premotor cortex, angular gyrus, precuneus, and inferior parietal lobule. Significant associations were found between patients' CTG triplet expansion size and thickness in left postcentral gyrus and in the left primary somatosensory cortex, in the posterior cingulate cortex bilaterally, and in the right lingual gyrus. Finally, significant associations were found between cortical thickness and sadness in the superior temporal gyrus, the right precentral gyrus, the right angular gyrus, and the left medial frontal gyrus bilaterally. DM1 patients showed a negative correlation between cortical thickness in the bilateral precuneus and in the left lateral occipital cortex and performance at the Social Situations Test. Finally, DM1 patients showed a negative correlation between cortical thickness in the left precuneus and in the superior frontal gyrus and scores at the Moral Distinction Test. The present study shows both cortical thickness changes in DM1 patients compared to controls and significant associations between cortical thickness and patients' social cognition performances. These data confirm the presence of widespread brain damages associated with cognitive impairment in DM1 patients.
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http://dx.doi.org/10.3389/fneur.2020.00113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059122PMC
February 2020

Right fronto-parietal white matter disruption contributes to speech impairments in amyotrophic lateral sclerosis.

Brain Res Bull 2020 05 28;158:77-83. Epub 2020 Feb 28.

Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom. Electronic address:

Introduction: Non-linguistic properties of speech are widely heterogeneous and require complex neurological integration. The association between white matter integrity and the severity of dysarthria was investigated in a group of patients diagnosed with amyotrophic lateral sclerosis (ALS).

Methods: Thirty-six patients diagnosed with amyotrophic lateral sclerosis completed a magnetic resonance imaging protocol inclusive of diffusion-weighted images. A clinical assessment of pneumo-phono-articulatory abilities was conducted for each patient, and a composite score of residual speech capacity was calculated. Tract-Based Spatial Statistics was carried out to model the potential association between residual speech capacity and microstructural properties of white matter (fractional anisotropy, mean and radial diffusivity).

Results: A significant negative association was found between residual speech capacity and mean diffusivity in a large white matter cluster located in frontal, parietal and right temporal regions. These subcortical areas were characterised by pathological microstructural disruption, as revealed by post hoc analyses.

Conclusions: Non-linguistic aspects of speech are associated with microstructural integrity of frontal, parietal and right temporal white matter in amyotrophic lateral sclerosis. Such mapping is consistent with the centres responsible of volitional control of speech and sensory feedback during non-linguistic speech production.
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http://dx.doi.org/10.1016/j.brainresbull.2020.02.016DOI Listing
May 2020

Disruption of neurite morphology parallels MS progression.

Neurol Neuroimmunol Neuroinflamm 2018 Nov 26;5(6):e502. Epub 2018 Sep 26.

Neuroimaging Laboratory (B.S., G.G., M.B., M.C.), Santa Lucia Foundation, IRCCS; Department of Clinical and Behavioural Neurology (V.P., U.N., C.C.), Santa Lucia Foundation, IRCCS; Neurovascular Diagnosis Unit (M.M.), Department of Medical and Surgical Sciences and Biotechnology, Section of Neurology, Sapienza, University of Rome; Department of Neurology and Psychiatry (M.M., A.F.), Multiple Sclerosis Center, Sapienza, University of Rome, Italy; High Field Magnetic Resonance (E.T.), Max Planck Institute for Biological Cybernetics, Tuebingen, Germany; Department of System Medicine (U.N., C.C.), University of Rome "Tor Vergata," Italy; and Department of Neuroscience (M.B., M.C.), Brighton & Sussex Medical School, Falmer, United Kingdom.

Objectives: To apply advanced diffusion MRI methods to the study of normal-appearing brain tissue in MS and examine their correlation with measures of clinical disability.

Methods: A multi-compartment model of diffusion MRI called neurite orientation dispersion and density imaging (NODDI) was used to study 20 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 20 healthy controls. Maps of NODDI were analyzed voxel-wise to assess the presence of abnormalities within the normal-appearing brain tissue and the association with disease severity. Standard diffusion tensor imaging (DTI) parameters were also computed for comparing the 2 techniques.

Results: Patients with MS showed reduced neurite density index (NDI) and increased orientation dispersion index (ODI) compared with controls in several brain areas ( < 0.05), with patients with SPMS having more widespread abnormalities. DTI indices were also sensitive to some changes. In addition, patients with SPMS showed reduced ODI in the thalamus and caudate nucleus. These abnormalities were associated with scores of disease severity ( < 0.05). The association with the MS functional composite score was higher in patients with SPMS compared with patients with RRMS.

Conclusions: NODDI and DTI findings are largely overlapping. Nevertheless, NODDI helps interpret previous findings of increased anisotropy in the thalamus of patients with MS and are consistent with the degeneration of selective axon populations.
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http://dx.doi.org/10.1212/NXI.0000000000000502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192688PMC
November 2018

Amyloid PET as a marker of normal-appearing white matter early damage in multiple sclerosis: correlation with CSF β-amyloid levels and brain volumes.

Eur J Nucl Med Mol Imaging 2019 02 21;46(2):280-287. Epub 2018 Oct 21.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy.

Purpose: The disease course of multiple sclerosis (MS) is unpredictable, and reliable prognostic biomarkers are needed. Positron emission tomography (PET) with β-amyloid tracers is a promising tool for evaluating white matter (WM) damage and repair. Our aim was to investigate amyloid uptake in damaged (DWM) and normal-appearing WM (NAWM) of MS patients, and to evaluate possible correlations between cerebrospinal fluid (CSF) β-amyloid (Aβ) levels, amyloid tracer uptake, and brain volumes.

Methods: Twelve MS patients were recruited and divided according to their disease activity into active and non-active groups. All participants underwent neurological examination, neuropsychological testing, lumbar puncture, brain magnetic resonance (MRI) imaging, and F-florbetapir PET. Aβ levels were determined in CSF samples from all patients. MRI and PET images were co-registered, and mean standardized uptake values (SUV) were calculated for each patient in the NAWM and in the DWM. To calculate brain volumes, brain segmentation was performed using statistical parametric mapping software. Nonparametric statistical analyses for between-group comparisons and regression analyses were conducted.

Results: We found a lower SUV in DWM compared to NAWM (p < 0.001) in all patients. Decreased NAWM-SUV was observed in the active compared to non-active group (p < 0.05). Considering only active patients, NAWM volume correlated with NAWM-SUV (p = 0.01). Interestingly, CSF Aβ concentration was a predictor of both NAWM-SUV (r = 0.79; p = 0.01) and NAWM volume (r = 0.81, p = 0.01).

Conclusions: The correlation between CSF Aβ levels and NAWM-SUV suggests that the predictive role of β-amyloid may be linked to early myelin damage and may reflect disease activity and clinical progression.
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http://dx.doi.org/10.1007/s00259-018-4182-1DOI Listing
February 2019

CSF β-amyloid predicts prognosis in patients with multiple sclerosis.

Mult Scler 2019 08 7;25(9):1223-1231. Epub 2018 Aug 7.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy/University of Milan, Dino Ferrari Center, Milan, Italy.

Background: The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognized, and hence reliable biomarkers are needed.

Objectives: To investigate the prognostic role of cerebrospinal fluid (CSF) amyloid beta (Aβ) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white matter (WM) and grey matter (GM) damage at early disease stages.

Methods: Sixty patients were recruited and followed up for 3-5 years. Patients underwent clinical assessment, brain magnetic resonance imaging (MRI; at baseline and after 1 year), and CSF analysis to determine Aβ levels. T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads.

Results: Lower CSF Aβ levels were observed in patients with a worse follow-up Expanded Disability Status Scale (EDSS;  = -0.65,  < 0.001). The multiple regression analysis confirmed CSF Aβ concentration as a predictor of patients' EDSS increase ( = -0.59,  < 0.0001). Generating a receiver operating characteristic curve, a cut-off value of 813 pg/mL was determined as the threshold able to identify patients with worse prognosis (95% confidence interval (CI): 0.690-0.933,  = 0.0001). No differences in CSF tau and neurofilament light chain (NfL) levels were observed ( > 0.05).

Conclusion: Low CSF Aβ levels may represent a predictive biomarker of disease progression in MS.
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http://dx.doi.org/10.1177/1352458518791709DOI Listing
August 2019

Whole brain white matter histogram analysis of diffusion tensor imaging data detects microstructural damage in mild cognitive impairment and alzheimer's disease patients.

J Magn Reson Imaging 2018 Jan 21. Epub 2018 Jan 21.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

Background: Amnestic mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD). However, the clinical conversion from MCI to AD is unpredictable. Hence, identification of noninvasive biomarkers able to detect early changes induced by dementia is a pressing need.

Purpose: To explore the added value of histogram analysis applied to measures derived from diffusion tensor imaging (DTI) for detecting brain tissue differences between AD, MCI, and healthy subjects (HS).

Study Type: Prospective.

Population/subjects: A local cohort (57 AD, 28 MCI, 23 HS), and an Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (41 AD, 58 MCI, 41 HS).

Field Strength: 3T. Dual-echo turbo spin echo (TSE); fluid-attenuated inversion recovery (FLAIR); modified-driven-equilibrium-Fourier-transform (MDEFT); inversion-recovery spoiled gradient recalled (IR-SPGR); diffusion tensor imaging (DTI).

Assessment: Normal-appearing white matter (NAWM) masks were obtained using the T -weighted volumes for tissue segmentation and T -weighted images for removal of hyperintensities/lesions. From DTI images, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AXD), and radial diffusivity (RD) were obtained. NAWM histograms of FA, MD, AXD, and RD were derived and characterized estimating: peak height, peak location, mean value (MV), and quartiles (C25, C50, C75), which were compared between groups. Receiver operating characteristic (ROC) and area under ROC curves (AUC) were calculated. To confirm our results, the same analysis was repeated on the ADNI dataset.

Statistical Tests: One-way analysis of variance (ANOVA), post-hoc Student's t-test, multiclass ROC analysis.

Results: For the local cohort, C25 of AXD had the maximum capability of group discrimination with AUC of 0.80 for "HS vs. patients" comparison and 0.74 for "AD vs. others" comparison. For the ADNI cohort, MV of AXD revealed the maximum group discrimination capability with AUC of 0.75 for "HS vs. patients" comparison and 0.75 for "AD vs. others" comparison.

Data Conclusion: AXD of NAWM might be an early marker of microstructural brain tissue changes occurring during the AD course and might be useful for assessing disease progression.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.
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http://dx.doi.org/10.1002/jmri.25947DOI Listing
January 2018

CSF β-amyloid and white matter damage: a new perspective on Alzheimer's disease.

J Neurol Neurosurg Psychiatry 2018 04 20;89(4):352-357. Epub 2017 Oct 20.

Department of Pathophysiology and Transplantation, Neurodegenerative Disease Unit, University of Milan, Centro Dino Ferrari, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.

Objective: To assess the connection between amyloid pathology and white matter (WM) macrostructural and microstructural damage in demented patients compared with controls.

Methods: Eighty-five participants were recruited: 65 with newly diagnosed Alzheimer's disease (AD), non-AD dementia or mild cognitive impairment and 20 age-matched and sex-matched healthy controls. β-amyloid (Aβ) levels were determined in cerebrospinal fluid (CSF) samples from all patients and five controls. Among patients, 42 had pathological CSF Aβ levels (Aβ(+)), while 23 had normal CSF Aβ levels (Aβ(-)). All participants underwent neurological examination, neuropsychological testing and brain MRI. We used T2-weighted scans to quantify WM lesion loads (LLs) and diffusion-weighted images to assess their microstructural substrate. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses.

Results: We found an increased WM-LL in Aβ(+) compared with both, healthy controls (p=0.003) and Aβ(-) patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor of patients' WM-LL (r=-0.30, p<0.05) when using age as a covariate. Lesion apparent diffusion coefficient value was higher in all patients than in controls (p=0.0001) and correlated with WM-LL (r=0.41, p=0.001). In Aβ(+), WM-LL correlated with WM microstructural damage in the left peritrigonal WM (p<0.0001).

Conclusions: WM damage is crucial in AD pathogenesis. The correlation between CSF Aβ levels and WM-LL suggests a direct link between amyloid pathology and WM macrostructural and microstructural damage.
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http://dx.doi.org/10.1136/jnnp-2017-316603DOI Listing
April 2018

Damage to the Frontal Aslant Tract Accounts for Visuo-Constructive Deficits in Alzheimer's Disease.

J Alzheimers Dis 2017 ;60(3):1015-1024

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

The frontal aslant tract (FAT) has been described as a bundle connecting the Broca's area to the supplementary motor area (SMA) and the pre-SMA in both hemispheres. The functional properties of this tract and its role in degenerative dementia, such as Alzheimer's disease (AD), still need to be fully clarified. The aim of this study was to explore the microstructural integrity of the FAT in patients with AD and its potential relationship with cognitive functioning. Twenty-three patients with AD and 25 healthy subjects (HS) were enrolled. All subjects underwent cognitive and MRI examination. MRI, including diffusion sequences, was used for probabilistic tractography analysis. We reconstructed individual FATs bilaterally and assessed their microstructural integrity using fractional anisotropy (FA), computed as both mean tract value and voxel-wise using SPM-8. Mean FA values were then used to test for correlations with cognitive measures. Mean tract FA and voxel-wise analyses revealed that patients with AD, compared to HS, had decreased FA in the FAT bilaterally. In addition, positive associations were found between FA in the FATs and patients' performance at tests for constructional praxis and visuospatial logical reasoning. The present results reveal a bilateral damage of FAT in AD patients. The association between FATs' microscopic abnormalities and constructive abilities fits well with the knowledge of a functional involvement of SMA and pre-SMA in movement sequences when executing constructive praxis tasks. The FAT is an associative bundle critically involved in the network sub-serving constructional praxis in patients with AD.
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http://dx.doi.org/10.3233/JAD-170638DOI Listing
May 2018

Introducing axonal myelination in connectomics: A preliminary analysis of g-ratio distribution in healthy subjects.

Neuroimage 2018 11 14;182:351-359. Epub 2017 Sep 14.

Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy; Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.

Microstructural imaging and connectomics are two research areas that hold great potential for investigating brain structure and function. Combining these two approaches can lead to a better and more complete characterization of the brain as a network. The aim of this work is characterizing the connectome from a novel perspective using the myelination measure given by the g-ratio. The g-ratio is the ratio of the inner to the outer diameters of a myelinated axon, whose aggregated value can now be estimated in vivo using MRI. In two different datasets of healthy subjects, we reconstructed the structural connectome and then used the g-ratio estimated from diffusion and magnetization transfer data to characterize the network structure. Significant characteristics of g-ratio weighted graphs emerged. First, the g-ratio distribution across the edges of the graph did not show the power-law distribution observed using the number of streamlines as a weight. Second, connections involving regions related to motor and sensory functions were the highest in myelin content. We also observed significant differences in terms of the hub structure and the rich-club organization suggesting that connections involving hub regions present higher myelination than peripheral connections. Taken together, these findings offer a characterization of g-ratio distribution across the connectome in healthy subjects and lay the foundations for further investigating plasticity and pathology using a similar approach.
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http://dx.doi.org/10.1016/j.neuroimage.2017.09.018DOI Listing
November 2018

A Pilot Study on Brain Plasticity of Functional Connectivity Modulated by Cognitive Training in Mild Alzheimer's Disease and Mild Cognitive Impairment.

Brain Sci 2017 Apr 29;7(5). Epub 2017 Apr 29.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome 00179, Italy.

Alzheimer's disease (AD) alters the functional connectivity of the default mode network (DMN) but also the topological properties of the functional connectome. Cognitive training (CT) is a tool to slow down AD progression and is likely to impact on functional connectivity. In this pilot study, we aimed at investigating brain functional changes after a period of CT and active control (AC) in a group of 26 subjects with mild AD (mAD), 26 with amnestic mild cognitive impairment (aMCI), and a control group of 29 healthy elderly (HE) people. They all underwent a CT and AC in a counterbalanced order following a crossover design. Resting-state functional MRI and neuropsychological testing were acquired before and after each period. We tested post-CT and post-AC changes of cognitive abilities, of the functional connectivity of the DMN, and of topological network properties derived from graph theory and network-based statistics. Only CT produced functional changes, increasing the functional connectivity of the posterior DMN in all three groups. mAD also showed functional changes in the medial temporal lobe and topological changes in the anterior cingulum, whereas aMCI showed more widespread topological changes involving the frontal lobes, the cerebellum and the thalamus. Our results suggest specific functional connectivity changes after CT for aMCI and mAD.
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http://dx.doi.org/10.3390/brainsci7050050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447932PMC
April 2017

Estimating multimodal brain connectivity in multiple sclerosis: an exploratory factor analysis.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:1131-1134

Graph-theoretical approaches have become a popular way to model brain data collected using magnetic resonance imaging (MRI), both from the structural and the functional perspectives. In structural networks, tract-based mapping allows to model different aspects of brain structures by means of the specific characteristics of the different MRI modalities. However, there has been little effort to join the information carried by each modality and to understand what level of common variance is shown in these data. In this paper, we proposed a combined approach based on graph theory and factor analysis to model magnetization transfer and microstructural properties in 18 relapsing remitting multiple sclerosis (RRMS) patients and 17 healthy controls. After defining the common factors and outlining their relationships with MRI data, we evaluated between-group differences using global and local graph measures. The results showed that one common factor describes brain structures in terms of myelin and global integrity, and such factor is able to highlight specific between-group differences.
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http://dx.doi.org/10.1109/EMBC.2016.7590903DOI Listing
August 2016

Characterizing axonal myelination within the healthy population: a tract-by-tract mapping of effects of age and gender on the fiber g-ratio.

Neurobiol Aging 2017 01 30;49:109-118. Epub 2016 Sep 30.

Neuroimaging Laboratory, Santa Lucia Foundation, Rome, Italy.

The g-ratio, equal to the ratio of the inner-to-outer diameter of a myelinated axon, is associated with the speed of conduction, and thus reflects axonal function and integrity. It is now possible to estimate an "aggregate" g-ratio in vivo using MRI. The aim of this study was to assess the variation of the MRI-derived fiber g-ratio in the brain of healthy individuals, and to characterize its variation across the lifespan. Thirty-eight healthy participants, aged between 20 and 76, were recruited. Whole-brain g-ratio maps were computed and analyzed voxel-wise. Median tract g-ratio values were also extracted. No significant effect of gender was found, whereas age was found to be significantly associated with the g-ratio within the white matter. The tract-specific analysis showed this relationship to follow a nearly-linear increase, although the slope appears to slow down slightly after the 6th decade of life. The most likely interpretation is a subtle but consistent reduction in myelin throughout adulthood, with the density of axons beginning to decrease between the 4th and 5th decade.
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http://dx.doi.org/10.1016/j.neurobiolaging.2016.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5156474PMC
January 2017

Network-Based Substrate of Cognitive Reserve in Alzheimer's Disease.

J Alzheimers Dis 2017 ;55(1):421-430

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

Cognitive reserve (CR) is known to modulate the clinical features of Alzheimer's disease (AD). This concept may be critical for the development of non-pharmacological interventions able to slow down patients' cognitive decline in the absence of disease-modifying treatments. We aimed at identifying the neurobiological substrates of CR (i.e., neural reserve) over the transition between normal aging and AD, by assessing the underlying brain networks and their topological properties. A cohort of 154 participants (n = 68 with AD, n = 61 with amnestic mild cognitive impairment (aMCI), and 25 healthy subjects) underwent resting-state functional MRI and neuropsychological testing. Within each group, participants were classified as having high or low CR, and functional connectivity measures were compared, within group, between high and low CR individuals. Network-based statistics and topological network properties derived from graph theory were explored. Connectivity differences between high and low CR were evident only for aMCI patients, with participants with high CR showing a significant increase of connectivity in a network involving mainly fronto-parietal nodes. Conversely, they showed significantly decreased connectivity in a network involving fronto-temporo-cerebellar nodes. Consistently, changes to topological measures were observed in either direction, and were associated with measures of global cognitive function. These findings support the hypothesis that CR impacts on neurodegenerative process in the early phase of AD only. In addition, they fit with the existence of a "neural reserve", characterized by specific neural networks and their efficiency. It remains to be demonstrated whether interventions later in life can modulate this "neural reserve".
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http://dx.doi.org/10.3233/JAD-160735DOI Listing
February 2018

Longitudinal Changes in Functional Brain Connectivity Predicts Conversion to Alzheimer's Disease.

J Alzheimers Dis 2016 ;51(2):377-89

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

This longitudinal study investigates the modifications in structure and function occurring to typical Alzheimer's disease (AD) brains over a 2-year follow-up, from pre-dementia stages of disease, with the aim of identifying biomarkers of prognostic value. Thirty-one patients with amnestic mild cognitive impairment were recruited and followed-up with clinical, neuropsychological, and MRI assessments. Patients were retrospectively classified as AD Converters or Non-Converters, and the data compared between groups. Cross-sectional MRI data at baseline, assessing volume and functional connectivity abnormalities, confirmed previous findings, showing a more severe pattern of regional grey matter atrophy and default-mode network disconnection in Converters than in Non-Converters. Longitudinally, Converters showed more grey matter atrophy in the frontotemporal areas, accompanied by increased connectivity in the precuneus. Discriminant analysis revealed that functional connectivity of the precuneus within the default mode network at baseline is the parameter able to correctly classify patients in Converters and Non-Converters with high sensitivity, specificity, and accuracy.
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http://dx.doi.org/10.3233/JAD-150961DOI Listing
December 2016

Different Patterns of Correlation between Grey and White Matter Integrity Account for Behavioral and Psychological Symptoms in Alzheimer's Disease.

J Alzheimers Dis 2016 ;50(2):591-604

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.

Behavioral disorders and psychological symptoms (BPSD) in Alzheimer's disease (AD) are known to correlate with grey matter (GM) atrophy and, as shown recently, also with white matter (WM) damage. WM damage and its relationship with GM atrophy are reported in AD, reinforcing the interpretation of the AD pathology in light of a disconnection syndrome. It remains uncertain whether this disconnection might account also for different BPSD observable in AD. Here, we tested the hypothesis of different patterns of association between WM damage of the corpus callosum (CC) and GM atrophy in AD patients exhibiting one of the following BPSD clusters: Mood (i.e., anxiety and depression; ADmood), Frontal (i.e., dishinibition and elation; ADfrontal), and Psychotic (delusions and hallucinations; ADpsychotic) related symptoms, as well as AD patients without BPSD. Overall, this study brings to light the strict relationship between WM alterations in different parts of the CC and GM atrophy in AD patients exhibiting BPSD, supporting the hypothesis that such symptoms are likely to be caused by characteristic patterns of neurodegeneration of WM and GM, rather than being a reactive response to accumulation of cognitive disabilities, and should therefore be regarded as potential markers of diagnostic and prognostic value in AD.
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http://dx.doi.org/10.3233/JAD-150612DOI Listing
November 2016

How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1.

Funct Neurol 2015 Jan-Mar;30(1):21-31

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder dominated by muscular impairment and brain dysfunctions. Although brain damage has previously been demonstrated in DM1, its associations with the genetics and clinical/neuropsychological features of the disease are controversial. This study assessed the differential role of gray matter (GM) and white matter (WM) damage in determining higher-level dysfunctions in DM1. Ten patients with genetically confirmed DM1 and 16 healthy How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1 matched controls entered the study. The patients underwent a neuropsychological assessment and quantification of CTG triplet expansion. All the subjects underwent MR scanning at 3T, with studies including T1-weighted volumes and diffusion-weighted images. Voxel-based morphometry and tractbased spatial statistics were used for unbiased quantification of regional GM atrophy and WM integrity. The DM1 patients showed widespread involvement of both tissues. The extent of the damage correlated with CTG triplet expansion and cognition. This study supports the idea that genetic abnormalities in DM1mainly target the WM, but GM involvement is also crucial in determining the clinical characteristics of DM1.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520669PMC
April 2016

Strategic lesions in the anterior thalamic radiation and apathy in early Alzheimer's disease.

PLoS One 2015 1;10(5):e0124998. Epub 2015 May 1.

Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.

Background: Behavioural disorders and psychological symptoms of Dementia (BPSD) are commonly observed in Alzheimer's disease (AD), and strongly contribute to increasing patients' disability. Using voxel-lesion-symptom mapping (VLSM), we investigated the impact of white matter lesions (WMLs) on the severity of BPSD in patients with amnestic mild cognitive impairment (a-MCI).

Methods: Thirty-one a-MCI patients (with a conversion rate to AD of 32% at 2 year follow-up) and 26 healthy controls underwent magnetic resonance imaging (MRI) examination at 3T, including T2-weighted and fluid-attenuated-inversion-recovery images, and T1-weighted volumes. In the patient group, BPSD was assessed using the Neuropsychiatric Inventory-12. After quantitative definition of WMLs, their distribution was investigated, without an a priori anatomical hypothesis, against patients' behavioural symptoms. Unbiased regional grey matter volumetrics was also used to assess the contribution of grey matter atrophy to BPSD.

Results: Apathy, irritability, depression/dysphoria, anxiety and agitation were shown to be the most common symptoms in the patient sample. Despite a more widespread anatomical distribution, a-MCI patients did not differ from controls in WML volumes. VLSM revealed a strict association between the presence of lesions in the anterior thalamic radiations (ATRs) and the severity of apathy. Regional grey matter atrophy did not account for any BPSD.

Conclusions: This study indicates that damage to the ATRs is strategic for the occurrence of apathy in patients with a-MCI. Disconnection between the prefrontal cortex and the mediodorsal and anterior thalamic nuclei might represent the pathophysiological substrate for apathy, which is one of the most common psychopathological symptoms observed in dementia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124998PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416903PMC
January 2016

Cognitive reserve and the risk for Alzheimer's disease: a longitudinal study.

Neurobiol Aging 2015 Feb 16;36(2):592-600. Epub 2014 Oct 16.

Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy. Electronic address:

This study investigates how cognitive reserve (CR) interacts with neurodegeneration (quantified by medial temporal atrophy, MTA) and macroscopic white matter lesions (WMLs) in delaying the conversion from amnestic mild cognitive impairment to Alzheimer's disease (AD). Forty-two amnestic mild cognitive impairment patients were consecutively recruited. They underwent magnetic resonance imaging and a comprehensive questionnaire to classify them as individuals with low or high CR. Patients were then clinically followed-up for 2 years. The patients' risk for conversion to AD because of CR was estimated by controlling for cognitive efficiency, MTA, and WMLs at baseline. Global cognition was the best predictor of conversion to AD in low CR patients. Conversely, in high CR patients only, WMLs (but not MTA) highly contributed in increasing the risk for conversion to AD. In conclusion, CR interacts with both patients' cognitive features and WMLs in modulating the impact of AD pathology. This seems relevant for clinical prognosis and therapeutic strategies.
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http://dx.doi.org/10.1016/j.neurobiolaging.2014.10.010DOI Listing
February 2015

Network based statistical analysis detects changes induced by continuous theta-burst stimulation on brain activity at rest.

Front Psychiatry 2014 5;5:97. Epub 2014 Aug 5.

Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia , Rome , Italy ; Department of Neuroscience, University of Rome Tor Vergata , Rome , Italy.

We combined continuous theta-burst stimulation (cTBS) and resting state (RS)-fMRI approaches to investigate changes in functional connectivity (FC) induced by right dorsolateral prefrontal cortex (DLPFC)-cTBS at rest in a group of healthy subjects. Seed-based fMRI analysis revealed a specific pattern of correlation between the right prefrontal cortex and several brain regions: based on these results, we defined a 29-node network to assess changes in each network connection before and after, respectively, DLPFC-cTBS and sham sessions. A decrease of correlation between the right prefrontal cortex and right parietal cortex (Brodmann areas 46 and 40, respectively) was detected after cTBS, while no significant result was found when analyzing sham-session data. To our knowledge, this is the first study that demonstrates within-subject changes in FC induced by cTBS applied on prefrontal area. The possibility to induce selective changes in a specific region without interfering with functionally correlated area could have several implications for the study of functional properties of the brain, and for the emerging therapeutic strategies based on transcranial stimulation.
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http://dx.doi.org/10.3389/fpsyt.2014.00097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122173PMC
August 2014

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct.

PLoS One 2014 3;8(6):e64578. Epub 2013 Jun 3.

Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0064578PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670907PMC
January 2015

Microstructural damage of the posterior corpus callosum contributes to the clinical severity of neglect.

PLoS One 2012 24;7(10):e48079. Epub 2012 Oct 24.

Neuroimaging Laboratory, Santa Lucia Foundation Istituto Di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

One theory to account for neglect symptoms in patients with right focal damage invokes a release of inhibition of the right parietal cortex over the left parieto-frontal circuits, by disconnection mechanism. This theory is supported by transcranial magnetic stimulation studies showing the existence of asymmetric inhibitory interactions between the left and right posterior parietal cortex, with a right hemispheric advantage. These inhibitory mechanisms are mediated by direct transcallosal projections located in the posterior portions of the corpus callosum. The current study, using diffusion imaging and tract-based spatial statistics (TBSS), aims at assessing, in a data-driven fashion, the contribution of structural disconnection between hemispheres in determining the presence and severity of neglect. Eleven patients with right acute stroke and 11 healthy matched controls underwent MRI at 3T, including diffusion imaging, and T1-weighted volumes. TBSS was modified to account for the presence of the lesion and used to assess the presence and extension of changes in diffusion indices of microscopic white matter integrity in the left hemisphere of patients compared to controls, and to investigate, by correlation analysis, whether this damage might account for the presence and severity of patients' neglect, as assessed by the Behavioural Inattention Test (BIT). None of the patients had any macroscopic abnormality in the left hemisphere; however, 3 cases were discarded due to image artefacts in the MRI data. Conversely, TBSS analysis revealed widespread changes in diffusion indices in most of their left hemisphere tracts, with a predominant involvement of the corpus callosum and its projections on the parietal white matter. A region of association between patients' scores at BIT and brain FA values was found in the posterior part of the corpus callosum. This study strongly supports the hypothesis of a major role of structural disconnection between the right and left parietal cortex in determining 'neglect'.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0048079PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480503PMC
April 2013

Mild cognitive impairment: same identity for different entities.

J Alzheimers Dis 2013 ;33(4):1157-65

Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.

This study investigates whether different patterns of grey matter (GM) loss may account for the different neuropsychological profiles observed in patients with amnestic (a-) and non-amnestic (na-) mild cognitive impairment (MCI), and may predict patients' clinical evolution. Fifty-five consecutive individuals complaining of cognitive dysfunction (referred to specialist dementia clinics) were screened and included in the study if they met the diagnostic criteria for MCI on a neurodegenerative basis. After an extensive neuropsychological assessment, patients were classified as suffering from a-MCI or na-MCI. Twenty-eight healthy individuals were also recruited and served as controls. All participants underwent magnetic resonance imaging at 3T, including conventional images and volumetric scans. Volumetric data were processed using voxel-based morphometry to assess between-group differences in regional GM volumes and correlations with neuropsychological performances. When compared to controls, a-MCI patients showed prominent GM volume reductions in the medial temporal lobes, while those with na-MCI showed reduced GM volumes in the orbito-frontal cortex and basal ganglia. In a-MCI patients, significant associations were found between verbal long-term memory performance and GM volumes in the hippocampus. Conversely, in na-MCI patients, associations were found between scores at tests exploring executive functions and GM volumes in the orbito-frontal cortex. At one-year follow-up, conversions were recorded exclusively toward Alzheimer's disease (AD) in the a-MCI group, and toward non-AD dementia in the na-MCI group. This study confirms that MCI is a heterogeneous clinical identity including different neurodegenerative entities; specific patterns of regional GM loss appear to account for specific neuropsychological features and are likely to predict patients' clinical evolution.
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http://dx.doi.org/10.3233/JAD-2012-121663DOI Listing
October 2013

Structural brain signature of FTLD driven by Granulin mutation.

J Alzheimers Dis 2013 ;33(2):483-94

Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, Rome, Italy.

Several causative gene mutations have been identified in frontotemporal lobar degeneration (FTLD), including mutations within Granulin (GRN) genes. It was recently shown that FTLD patients carriers of GRN Thr272fs mutation [FTLD-GRN(m+)] exhibit more severe abnormalities, as assessed by magnetic resonance imaging (MRI), than those with sporadic FTLD [FTLD-GRN(m-)]. The aim of this study was to investigate the relationship between grey (GM) and white matter (WM) microstructural damage in FTLD patients, carriers and non-carriers of the mutation. Twenty-three FTLD patients [6 GRN(m+) and 17 GRN(m-)] and 12 healthy subjects received an MRI scan including volumetric and diffusion imaging. GM was assessed using voxel-based morphometry, while the corpus callosum was reconstructed using diffusion tractography. Mean diffusivity and fractional anisotropy of the corpus callosum were compared between groups. FTLD patients showed widespread GM atrophy and altered diffusion indices in the corpus callosum when compared to healthy subjects. When contrasting GRN(m+) against GRN(m-) patients, the former group had more atrophy in the left frontal GM, and reduced fractional anisotropy and increased mean diffusivity in the left anterior part of the corpus callosum. Significant correlations between the GM and WM damage were found in GRN(m+) patients. This pattern of damage was able to predict some of the additional neuropsychological deficits observed in GRN(m+) as compared to GRN(m-) patients. A more prominent involvement of WM in GRN(m+) patients is consistent with the knowledge that GRN genes are expressed in the microglia. This involvement might be responsible for the accrual of additional GM atrophy via disconnection mechanisms.
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http://dx.doi.org/10.3233/JAD-2012-121273DOI Listing
May 2013

Brain tissue modifications induced by cholinergic therapy in Alzheimer's disease.

Hum Brain Mapp 2013 Dec 19;34(12):3158-67. Epub 2012 Jun 19.

Neuorimaging Laboratory, Santa Lucia Foundation, Rome, Italy.

A previous preliminary investigation based on a novel MRI approach to map anatomical connectivity revealed areas of increased connectivity in Alzheimer's disease (AD) but not in mild cognitive impairment patients. This prompted the hypothesis tested here, that these areas might reflect phenomena of brain plasticity driven by acetylcholinesterase inhibitors (AChEIs). Thirty-eight patients with probable AD (19 under medication with AChEIs and 19 drug-naïve) were recruited together with 11 healthy controls. All subjects had MRI scanning at 3T, including volumetric and diffusion-weighted scans. Probabilistic tractography was used to initiate streamlines from all parenchymal voxels, and anatomical connectivity maps (ACMs) were obtained by counting, among the total number of streamlines initiated, the fraction passing through each brain voxel. After normalization into standard space, ACMs were used to test for between-group comparisons, and for interactions between the exposure to AChEIs and global level of cognition. Patients with AD had reduced ACM values in the fornix, cingulum, and supramarginal gyri. The ACM value was strongly associated with the AChEI dosage-x-duration product in the anterior limb (non-motor pathway) of the internal capsule. Tractography from this region identified the anterior thalamic radiation as the main white matter (WM) tract passing through it. The reduced connectivity in WM bundles connecting the hippocampi with the rest of the brain (fornix/cingulum) suggests a possible mechanism for the spread of AD pathology. An intriguing explanation for the interaction between AChEIs and ACM is related to the mechanisms of brain plasticity, partially driven by neurotrophic properties of acetylcholine replacement.
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http://dx.doi.org/10.1002/hbm.22130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870488PMC
December 2013

Semiautomated segmentation of the human spine based on echoplanar images.

Magn Reson Imaging 2011 Dec;29(10):1429-36

MARBILab, Museo storico della fisica e Centro di studi e ricerche Enrico Fermi, c/o Fondazione Santa Lucia, 00179 Rome, Italy.

The number of functional magnetic resonance imaging (fMRI) studies performed on the human spinal cord (SC) has considerably increased in recent years. The lack of a validated processing pipeline is, however, a significant obstacle to the spread of SC fMRI. One component likely to be involved in any such pipeline is the process of SC masking, analogous to brain extraction in cerebral fMRI. In general, SC masking has been performed manually, with the incumbent costs of being very time consuming and operator dependent. To overcome these drawbacks, we have developed a tailored semiautomatic method for segmenting echoplanar images (EPI) of human spine that is able to identify the spinal canal and the SC. The method exploits both temporal and spatial features of the EPI series and was tested and optimized on EPI images of cervical spine acquired at 3 T. The dependence of algorithm performance on the degree of EPI image distortion was assessed by computing the displacement warping field that best matched the EPI to the corresponding high-resolution T(2) images. Segmentation accuracy was above 80%, a significant improvement over values obtained with similar approaches, but not exploiting temporal information. Geometric distortion was found to explain about 50% of the variance of algorithm classification efficiency.
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http://dx.doi.org/10.1016/j.mri.2011.08.006DOI Listing
December 2011

Quantitative magnetization transfer provides information complementary to grey matter atrophy in Alzheimer's disease brains.

Neuroimage 2012 Jan 1;59(2):1114-22. Epub 2011 Oct 1.

Neuroimaging Laboratory, Santa Lucia Foundation IRCCS, via Ardeatina 306, 00179 Rome, Italy.

Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimer's disease (AD). The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach. We recruited 19AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0T including a T(1)-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T(1) and B(1) maps. The T(1)-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM(0)(B), showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM(0)(B) differences between AD and HS groups, adjusting for local GM atrophy. Widespread areas of reduced RM(0)(B) were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex. These results indicate that, among qMT parameters, RM(0)(B) is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid β deposition. RM(0)(B) might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM(0)(B) and intracellular pH, an intriguing speculation is that our findings might reflect metabolic changes related to mitochondrial dysfunction, which has been proposed as a contributor to neurodegeneration in AD.
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http://dx.doi.org/10.1016/j.neuroimage.2011.09.043DOI Listing
January 2012