Andrea Falini

San Raffaele Scientific Institute, Milano, Lombardy, Italy

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Publications (379)1780.51 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: Amnestic mild cognitive impairment (aMCI) is a clinical condition characterized by memory impairment in the absence of any other cognitive impairment and is commonly associated with high conversion to Alzheimer's disease. Recent evidence shows that executive functions and selective attention mechanisms could also be impaired in aMCI. In this study, we investigated performance differences (i.e., reaction times [RTs] and accuracy) between a group of aMCI participants and a group of age-matched healthy individuals on the attentional network task (ANT) focusing on situations with increased interference. In particular, we assessed the relationship between interference and conflict effects and grey matter volumes (GMVs) of the anterior cingulate cortex (ACC)/pre-supplementary motor area in the entire sample because of its crucial role in conflict monitoring. When compared with controls, aMCI participants were less accurate on the ANT, showing increased interference and conflict effects, but no differences in RTs. In addition, aMCI participants exhibited lower GMV in the ACC than controls. While better accuracy for interference and conflict effects was associated with an increase of GMV in the ACC for both groups, RTs from the interference effect were negatively correlated with GMV of the ACC only in aMCI participants. In other words, lower GMV values of the ACC were paralleled with significantly impaired performance in terms of interference resolution. In conclusion, our study suggests the presence of a selective impairment in interference and conflict monitoring in aMCI, which in turn is associated with decreased GMVs in the ACC.
    Full-text · Article · May 2016 · Journal of Neuropsychology
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: Neurite orientation dispersion and density imaging (NODDI) has recently been developed to overcome diffusion technique limitations in modeling biological systems. This manuscript reports a preliminary investigation into the use of a single color-coded map to represent NODDI-derived information. Materials and methods: An optimized diffusion-weighted imaging protocol was acquired in several clinical neurological contexts including demyelinating disease, neoplastic process, stroke, and toxic/metabolic disease. The NODDI model was fitted to the diffusion datasets. NODDI is based on a three-compartment diffusion model and provides maps that quantify the contributions to the total diffusion signal in each voxel. The NODDI compartment maps were combined into a single 4-dimensional volume visualized as RGB image (red for anisotropic Gaussian diffusion, green for non-Gaussian anisotropic diffusion, and blue for isotropic Gaussian diffusion), in which the relative contributions of the different microstructural compartments can be easily appreciated. Results: The NODDI color maps better describe the heterogeneity of neoplastic as well inflammatory lesions by identifying different tissue components within areas apparently homogeneous on conventional imaging. Moreover, NODDI color maps seem to be useful for identifying vasogenic edema differently from tumor-infiltrated edema. In multiple sclerosis, the NODDI color maps enable a visual assessment of the underlying microstructural changes, possibly highlighting an increased inflammatory component, within lesions and potentially in normal-appearing white matter. Conclusion: The NODDI color maps could make this technique valuable in a clinical setting, providing comprehensive and accessible information in normal and pathological brain tissues in different neurological pathologies.
    No preview · Article · May 2016 · Journal of neuroimaging: official journal of the American Society of Neuroimaging
  • [Show abstract] [Hide abstract] ABSTRACT: Adrenomyeloneuropathy is the late-onset form of X-linked adrenoleukodystrophy, and is considered the most frequent metabolic hereditary spastic paraplegia. In adrenomyeloneuropathy the spinal cord is the main site of pathology. Differently from quantitative magnetic resonance imaging of the brain, little is known about the feasibility and utility of advanced neuroimaging in quantifying the spinal cord abnormalities in hereditary diseases. Moreover, little is known about the subtle pathological changes that can characterize the brain of adrenomyeloneuropathy subjects in the early stages of the disease. We performed a cross-sectional study on 13 patients with adrenomyeloneuropathy and 12 age-matched healthy control subjects who underwent quantitative magnetic resonance imaging to assess the structural changes of the upper spinal cord and brain. Total cord areas from C2-3 to T2-3 level were measured, and diffusion tensor imaging metrics, i.e. fractional anisotropy, mean, axial and radial diffusivity values were calculated in both grey and white matter of spinal cord. In the brain, grey matter regions were parcellated with Freesurfer and average volume and thickness, and mean diffusivity and fractional anisotropy from co-registered diffusion maps were calculated in each region. Brain white matter diffusion tensor imaging metrics were assessed using whole-brain tract-based spatial statistics, and tractography-based analysis on corticospinal tracts. Correlations among clinical, structural and diffusion tensor imaging measures were calculated. In patients total cord area was reduced by 26.3% to 40.2% at all tested levels (P < 0.0001). A mean 16% reduction of spinal cord white matter fractional anisotropy (P ≤ 0.0003) with a concomitant 9.7% axial diffusivity reduction (P < 0.009) and 34.5% radial diffusivity increase (P < 0.009) was observed, suggesting co-presence of axonal degeneration and demyelination. Brain tract-based spatial statistics showed a marked reduction of fractional anisotropy, increase of radial diffusivity (P < 0.001) and no axial diffusivity changes in several white matter tracts, including corticospinal tracts and optic radiations, indicating predominant demyelination. Tractography-based analysis confirmed the results within corticospinal tracts. No significant cortical volume and thickness reduction or grey matter diffusion tensor imaging values alterations were observed in patients. A correlation between radial diffusivity and disease duration along the corticospinal tracts (r = 0.806,P < 0.01) was found. In conclusion, in adrenomyeloneuropathy patients quantitative magnetic resonance imaging-derived measures identify and quantify structural changes in the upper spinal cord and brain which agree with the expected histopathology, and suggest that the disease could be primarily caused by a demyelination rather than a primitive axonal damage. The results of this study may also encourage the employment of quantitative magnetic resonance imaging in other hereditary diseases with spinal cord involvement.
    No preview · Article · Apr 2016 · Brain
  • [Show abstract] [Hide abstract] ABSTRACT: Action observation and execution activate regions that are part of the motor and mirror neuron systems (MNS). Using functional magnetic resonance (fMRI), we defined the presence and extent of MNS activation during three different motor tasks with the dominant, right-upper limb in healthy individuals. The influence of the modality of task administration (execution, observation, observation and execution) was also investigated. fMRI scans during the execution (E) of a motor task, the observation (O) of a video showing the same task performed by another person and the simultaneous observation and execution (OE) of the task were obtained from three groups of healthy subjects (15 subjects per group) randomized to perform: a simple motor (SM) task, a complex motor (CM) task and a finalistic motor (FM) task. Manual dexterity was assessed using the 9-hole peg test and maximum finger tapping frequency. MNS activation was higher during FM than SM or CM tasks, independently from the modality of administration (E, O, or OE). Inferior frontal gyrus recruitment was more significant during SM than CM tasks in the E and O conditions. Compared to SM and FM, CM task resulted in increased recruitment of brain regions involved in complex motor task performance. Compared to O and E, OE resulted in the recruitment of additional, specific, brain areas in the cerebellum, temporal and parietal lobes. The modality of administration and the type of task modulated MNS recruitment during motor acts. This might have practical implications for the set-up of individualized motor rehabilitation strategies.
    No preview · Article · Mar 2016 · Brain Imaging and Behavior
  • No preview · Article · Mar 2016 · American Journal of Neuroradiology
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose To investigate the patterns of cortical thinning and white matter tract damage in patients with lower motor neuron (LMN)-predominant disease compared with healthy control subjects and those with classic amyotrophic lateral sclerosis (ALS) and to evaluate the relationship between brain structural changes and clinical and cognitive features in these patients. Materials and Methods This study was approved by the local ethical committee, and written informed consent was obtained from all subjects before enrollment. Twenty-eight patients with LMN-predominant disease were compared with 55 patients with ALS and 56 healthy control subjects. Patients underwent a clinical and neuropsychological assessment and T1-weighted and diffusion-tensor magnetic resonance (MR) imaging. Surface-based morphometry was used to assess cortical thickness. Tract-based spatial statistics and tractography were used to study white matter tract damage. Results Patients with LMN-predominant disease did not show differences compared with healthy control subjects in cortical thickness and diffusion-tensor MR imaging metrics. Patients with ALS showed cortical thinning of the motor-related cortices and a distributed involvement of the prefrontal, temporal, and parietal gyri (P < .05, false discovery rate corrected). Patients with ALS also showed white matter damage along motor and extramotor tracts compared with control subjects and patients with LMN-predominant disease (tract-based spatial statistics: P < .05, family-wise error corrected; tractography: P values < .001 to .05, false discovery rate corrected). In patients with LMN-predominant disease, cognitive deficits correlated with alterations in diffusivity in the left cingulum (r = -0.66, P = .01) and superior longitudinal fasciculus (r = -0.65, P = .05). Conclusion Motor and extramotor cortical thinning and diffusion-tensor MR imaging alterations were specific for motor neuron disease phenotypes, with clinically overt upper motor neuron involvement. However, the lack of significant differences in cortical thickness between subjects with LMN-predominant disease and those with ALS and cognitive deficits associated with alterations in diffusivity in patients with LMN-predominant disease suggest that investigating brain structural and microstructural MR imaging features may provide markers of central nervous system damage in patients with rare motor neuron disease. (©) RSNA, 2016 Online supplemental material is available for this article.
    No preview · Article · Mar 2016 · Radiology
  • [Show abstract] [Hide abstract] ABSTRACT: Background Functional Magnetic Resonance Imaging (fMRI) is often used in preoperative assessment before epilepsy surgery, tumor or cavernous malformation resection, or cochlear implantation. As it requires complete immobility, sedation is needed for uncooperative patients. Objective The aim of this study was to compare the fMRI cortical activation pattern after auditory stimuli in propofol-sedated 5- to 8-year-old children with that of similarly aged nonsedated children. Methods When possible, children underwent MRI without sedation, otherwise it was induced with i.v. propofol 2 mgkg(-1) and maintained with i.v. propofol 4-5 mgkg(-1)h(-1). Following diagnostic MRI, fMRi was carried out, randomly alternating two passive listening tasks (a fairy-tale and nonsense syllables). ResultsWe studied 14 awake and 15 sedated children. During the fairy-tale task, the nonsedated children's blood-oxygen-level-dependent (BOLD) signal was bilaterally present in the posterior superior temporal gyrus (STG), Wernicke's area, and Broca's area. Sedated children showed similar activation, with lesser extension to Wernicke's area, and no activation in Broca's area. During the syllable task, the nonsedated children's BOLD signal was bilaterally observed in the STG and Wernicke's area, in Broca's area with leftward asymmetry, and in the premotor area. In sedated children, cortical activation was present in the STG, but not in the frontal lobes. BOLD signal change areas in sedated children were less extended than in nonsedated children during both the fairy-tale and syllable tasks. Modeling the temporal derivative during both the fairy-tale and syllable tasks, nonsedated children showed no response while sedated children did. Conclusions After auditory stimuli, propofol-sedated 5- to 8-year-old children exhibit an fMRI cortical activation pattern which is different from that in similarly aged nonsedated children.
    No preview · Article · Mar 2016 · Pediatric Anesthesia
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives: Impaired cognitive functioning is a core feature of schizophrenia. Cognitive impairment in schizophrenia has been associated with white-matter (WM) abnormalities and degenerative changes of cortical myelin in the cerebral cortex. Furthermore, findings suggested a role of the COMT gene in affecting both WM and neuropsychological performances.We thus hypothesized that the COMT ValMet genotype would affect the association between cognitive functions and WM microstructure in a sample of schizophrenic patients. Materials and methods: Seventy-eight schizophrenic patients performed the brief assessment of cognition in schizophrenia for assessment of cognitive performances. Sixty-nine patients provided a venous blood sample for genotypic analysis. WM integrity was evaluated using tract-based spatial statistics with threshold-free cluster enhancement (P<0.05). Results: Analysis indicated an association between cognitive functions and WM microstructure in the Val/Val group, but not in the Met carriers group. WM tracts include the corpus callosum, thalamic radiations, corona radiata, forceps major and minor, superior and inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and cingulum. Conclusion: Results suggested a moderating effect of the COMT ValMet polymorphism on the association between cognitive functioning and WM microstructure. Our findings support the importance of myelination in cognition, identifying measures of WM microstructure as important neurobiological features of cognitive performances.
    No preview · Article · Mar 2016 · Psychiatric Genetics
  • [Show abstract] [Hide abstract] ABSTRACT: Introduction: Dynamic susceptibility contrast (DSC)-MRI is a perfusion technique with high diagnostic accuracy for glioma grading, despite limitations due to inherent susceptibility effects. Dynamic contrast-enhanced (DCE)-MRI has been proposed as an alternative technique able to overcome the DSC-MRI shortcomings. This pilot study aimed at comparing the diagnostic accuracy of DSC and DCE-MRI for glioma grading by evaluating two estimates of blood volume, the DCE-derived plasma volume (Vp) and the DSC-derived relative cerebral blood volume (rCBV), and a measure of vessel permeability, the DCE-derived volume transfer constant Ktrans. Methods: Twenty-six newly diagnosed glioma patients underwent 3T-MR DCE and DSC imaging. Parametric maps of CBV, Vp and Ktrans were calculated and the region of highest value (hotspot) was measured on each map. Histograms of rCBV, Vp and Ktrans values were calculated for the tumor volume. Statistical differences according to WHO grade were assessed. The diagnostic accuracy for tumor grading of the two techniques was determined by ROC analysis. Results: rCBV, Vp and Ktrans measures differed significantly between high and low-grade gliomas. Hotspot analysis showed the highest correlation with grading. Ktrans hotspots co-localized with Vp hotspots only in 56% of enhancing gliomas. For differentiating high from low-grade gliomas the AUC was 0.987 for rCBVmax, and 1.000 for Vpmax and Ktransmax. Combination of DCE-derived Vp and Ktrans parameters improved the diagnostic performance of the histogram method. Conclusion: This initial experience of DCE-derived Vp evaluation shows that this parameter is as accurate as the well-established DSC-derived rCBV for glioma grading. DCE-derived Ktrans is equally useful for grading, providing different informations with respect to Vp.
    No preview · Article · Mar 2016
  • No preview · Article · Feb 2016 · Journal of Neurology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To assess the structural correlates of cognitive and behavioral impairment in motor neuron diseases (MND) using multimodal MRI. Methods: One hundred one patients with sporadic MND (56 classic amyotrophic lateral sclerosis, 31 upper motor neuron phenotype, and 14 lower motor neuron phenotype) and 51 controls were enrolled. Patients were classified into MND with a pure motor syndrome (MND-motor) and with cognitive/behavioral symptoms (MND-plus). Cortical thickness measures and diffusion tensor (DT) metrics of white matter (WM) tracts were assessed. A random forest approach was used to explore the independent role of cortical and WM abnormalities in explaining major cognitive and behavioral symptoms. Results: There were 48 MND-motor and 53 MND-plus patients. Relative to controls, both patient groups showed a distributed cortical thinning of the bilateral precentral gyrus, insular and cingulate cortices, and frontotemporal regions. In all regions, there was a trend toward a more severe involvement in MND-plus cases, particularly in the temporal lobes. Both patient groups showed damage to the motor callosal fibers, which was more severe in MND-plus. MND-plus patients also showed a more severe involvement of the extra-motor WM tracts. The best predictors of executive and non-executive deficits and behavioral symptoms in MND were diffusivity abnormalities of the corpus callosum and frontotemporal tracts, including the uncinate, cingulum, and superior longitudinal fasciculi. Conclusions: Cortical thinning and WM degeneration are highly associated with neuropsychological and behavioral symptoms in patients with MND. DT MRI metrics seem to be the most sensitive markers of extra-motor deficits within the MND spectrum. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
    No preview · Article · Feb 2016 · Human Brain Mapping
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose: To investigate the role of orbital color Doppler ultrasound (OCDUS) in the diagnosis of carotid-cavernous fistula (CCF) with anterior drainage and particularly whether a negative OCDUS could avoid an invasive diagnostic cerebral angiography (DSA). Materials and methods: Twenty-two consecutive patients with ophthalmic signs suspecting CCF were submitted to ophthalmologic examination, OCDUS and DSA. CCF diagnosis with OCDUS was based on the finding of a reversed, arterialized and low-resistive-index (RI <0.5) blood flow in the superior ophthalmic vein (SOV). Sensibility, specificity, PPV, NPV, and accuracy of OCDUS were calculated considering both patients and eyes, using DSA as gold standard. Results: DSA demonstrated 20 CCFs in 18 patients. Considering the patients, in 18/22 CCF diagnosis was positive at OCDUS and DSA while 4/22 were negative at both. Considering the eyes, in 24/43 CCF diagnosis was positive at both DSA and OCDUS (total eyes = 43, due to one case of SOV thrombosis). In 19/43 eyes diagnosis was negative at both OCDUS and DSA. So sensitivity, specificity, PPV, NPV, and accuracy of OCDUS in the patients and eyes analysis were all 100 %. Conclusions: OCDUS is a reliable, noninvasive tool in the diagnosis of CCF; a negative OCDUS could avoid an invasive DSA in patients suspected for anterior-draining CCF.
    No preview · Article · Dec 2015 · La radiologia medica
  • [Show abstract] [Hide abstract] ABSTRACT: Purpose To assess brachial plexus magnetic resonance (MR) imaging features and limb-girdle muscle abnormalities as signs of muscle denervation in patients with amyotrophic lateral sclerosis (ALS). Materials and Methods This study was approved by the local ethical committees on human studies, and written informed consent was obtained from all subjects before enrollment. By using an optimized protocol of brachial plexus MR imaging, brachial plexus and limb-girdle muscle abnormalities were evaluated in 23 patients with ALS and clinical and neurophysiologically active involvement of the upper limbs and were compared with MR images in 12 age-matched healthy individuals. Nerve root and limb-girdle muscle abnormalities were visually evaluated by two experienced observers. A region of interest-based analysis was performed to measure nerve root volume and T2 signal intensity. Measures obtained at visual inspection were analyzed by using the Wald χ(2) test. Mean T2 signal intensity and volume values of the regions of interest were compared between groups by using a hierarchical linear model, accounting for the repeated measurement design. Results The level of interrater agreement was very strong (κ = 0.77-1). T2 hyperintensity and volume alterations of C5, C6, and C7 nerve roots were observed in patients with ALS (P < .001 to .03). Increased T2 signal intensity of nerve roots was associated with faster disease progression (upper-limb Medical Research Council scale progression rate, r = 0.40; 95% confidence interval: 0.001, 0.73). Limb-girdle muscle alterations (ie, T2 signal intensity alteration, edema, atrophy) and fat infiltration also were found, in particular, in the supraspinatus muscle, showing more frequent T2 signal intensity alterations and edema (P = .01) relative to the subscapularis and infraspinatus muscles. Conclusion Increased T2 signal intensity and volume of brachial nerve roots do not exclude a diagnosis of ALS and suggest involvement of the peripheral nervous system in the ALS pathogenetic cascade. MR imaging of the peripheral nervous system and the limb-girdle muscle may be useful for monitoring the evolution of ALS and distinguishing patients with ALS from those with inflammatory neuropathy, respectively. (©) RSNA, 2015.
    No preview · Article · Nov 2015 · Radiology
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    [Show abstract] [Hide abstract] ABSTRACT: When stroke occurs in adulthood, mirror movements (MMs: involuntary movements occurring in one hand when performing unilateral movements with the contralateral hand) in the paretic hand rarely occur. We present a case of an apparently healthy 54-year-old male presenting MMs in his left (non-dominant) hand. Further evaluation revealed diminished strength and dexterity in left hand, increased spinal excitability, decreased corticospinal excitability, occurrence of ipsilateral motor responses, enlarged cortical motor representation and imaging findings consistent with a previously undiagnosed right-subcortical stroke. MMs and ipsilateral motor responses may reflect the increased spinal motor neurons' excitability sustained by the spared non-primary ipsilesional motor areas.
    Full-text · Article · Oct 2015 · PM&R
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives: Using functional magnetic resonance imaging (fMRI) during a motor task, we investigated the functional correlates of central fatigue in multiple sclerosis (MS), and adaptation of motor network recruitment during a prolonged effort. Methods: Motor fMRI was obtained from 79 MS patients (50 fatigued (F), 29 non-fatigued (nF)) and 26 matched healthy controls (HC). Cognitive and physical fatigue were rated using the Modified Fatigue Impact Scale (MFIS). Results: Compared to HC and nF patients, F-MS patients experienced reduced activations of the left middle temporal gyrus, left supplementary motor area (SMA), bilateral superior frontal gyrus, left postcentral gyrus and basal ganglia regions. They also showed increased activation of the right middle frontal gyrus (MFG). Time-modulation analysis showed a reduced activity of the SMA and right precentral gyrus, and increased activity of the basal ganglia in HC. Such a trend was impaired in F-MS patients. In MS patients, increased MFG activity was related to MFIS scores. Physical MFIS score was related to a reduced recruitment of the right thalamus and SMA. Conclusions: Abnormalities and impaired timing of activation between different areas of the motor and executive networks occur in F-MS patients. The dysfunction of critical cortical areas contributes to the occurrence of central fatigue.
    No preview · Article · Oct 2015 · Multiple Sclerosis
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    Full-text · Dataset · Oct 2015
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    [Show abstract] [Hide abstract] ABSTRACT: Background: Longitudinal MRI studies in Alzheimer's disease (AD) are one of the most reliable way to track brain changes along the course of the disease. Objective: To investigate the evolution of grey matter (GM) atrophy and white matter (WM) damage in AD patients, and to assess the relationships of MRI changes with baseline clinical and cognitive variables and their evolution over time. Methods: Clinical, neuropsychological, and MRI assessments (T1-weighted and diffusion tensor [DT]-MRI) were obtained from 14 patients with AD at baseline and after a 16 ± 3 month period. Lumbar puncture was obtained at study entry. At baseline, AD patients were compared to 37 controls. GM atrophy progression was assessed with tensor-based morphometry and GM volumes of interest, and WM damage progression using tract-based spatial statistics and tractography. Results: At baseline, patients showed cortical atrophy in the medial temporal and parietal regions and a widespread pattern of WM damage involving the corpus callosum, cingulum, and temporo-occipital, parietal, and frontal WM tracts. During follow up, AD patients showed total GM atrophy, while total WM volume did not change. GM tissue loss was found in frontal, temporal, and parietal regions. In addition, AD patients showed a progression of WM microstructural damage to the corpus callosum, cingulum, fronto-parietal and temporo-occipital connections bilaterally. Patients with higher baseline cerebrospinal fluid total tau showed greater WM integrity loss at follow up. GM and WM changes over time did not correlate with each other nor with cognitive evolution. Conclusion: In AD, GM atrophy and WM tract damage are likely to progress, at least partially, independently. This study suggests that a multimodal imaging approach, which includes both T1-weighted and DT MR imaging, may provide additional markers to monitor disease progression.
    Full-text · Article · Sep 2015 · Journal of Alzheimer's disease: JAD
  • [Show abstract] [Hide abstract] ABSTRACT: The hippocampus is part of the default-mode network (DMN) and is functionally hit early in multiple sclerosis (MS). Hippocampal and DMN dysfunctions have been associated with depression, both in patients with MS and in major depressive disorders. We hypothesized that white matter lesions may contribute, through a disconnection mechanism, to hippocampal dysfunction. To test this, we assessed the relationship between hippocampal resting-state (RS) functional connectivity (FC) abnormalities with brain T2 lesion volumes and the presence and severity of depression. Structural and RS fMRI images were acquired from 69 patients with cognitively intact MS and 42 matched healthy controls (HC). Depression was quantified using the Montgomery-Asberg Depression Rating Scale. Seed-voxel hippocampal RS FC was assessed. SPM8 was used for between-group comparisons and correlation analysis between RS FC abnormalities with clinical and structural MRI variables. Compared to HC, patients with MS showed a significant atrophy of the whole brain and left hippocampus (P < 0.001), and a distributed pattern of decreased RS FC between the hippocampi and several cortical-subcortical regions, which were mostly located within the DMN. Reduced hippocampal RS FC with regions of the DMN was strongly correlated with higher T2 lesion volume, longer disease duration, and the severity of depression and disability. In patients with cognitively preserved MS, brain focal WM lesions are related to the functional integration of the hippocampus to other brain regions of the DMN, suggesting a disconnection syndrome. Such a disruption of hippocampal RS FC is likely to contribute to the occurrence of depression and to clinical disability. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Sep 2015 · Human Brain Mapping
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To use a multimodal approach to assess brain structural pathways and resting state (RS) functional connectivity abnormalities in patients with Parkinson's disease and freezing of gait (PD-FoG). Methods: T1-weighted, diffusion tensor (DT) MRI and RS functional MRI (fMRI) were obtained from 22 PD-FoG patients and 35 controls on a 3.0 T MR scanner. Patients underwent clinical, motor, and neuropsychological evaluations. Gray matter (GM) volumes and white matter (WM) damage were assessed using voxel based morphometry and tract-based spatial statistics, respectively. The pedunculopontine tract (PPT) was studied using tractography. RS fMRI data were analyzed using a model free approach investigating the main sensorimotor and cognitive brain networks. Multiple regression models were performed to assess the relationships between structural, functional, and clinical/cognitive variables. Analysis of GM and WM structural abnormalities was replicated in an independent sample including 28 PD-FoG patients, 25 PD patients without FoG, and 30 healthy controls who performed MRI scans on a 1.5 T scanner. Results: Compared with controls, no GM atrophy was found in PD-FoG cases. PD-FoG patients showed WM damage of the PPT, corpus callosum, corticospinal tract, cingulum, superior longitudinal fasciculus, and WM underneath the primary motor, premotor, prefrontal, orbitofrontal, and inferior parietal cortices, bilaterally. In PD-FoG, right PTT damage was associated with a greater disease severity. Analysis on the independent PD sample showed similar findings in PD-FoG patients relative to controls as well as WM damage of the genu and body of the corpus callosum and right parietal WM in PD-FoG relative to PD no-FoG patients. RS fMRI analysis showed that PD-FoG is associated with a decreased functional connectivity of the primary motor cortex and supplementary motor area bilaterally in the sensorimotor network, frontoparietal regions in the default mode network, and occipital cortex in the visual associative network. Conclusions: This study suggests that FoG in PD can be the result of a poor structural and functional integration between motor and extramotor (cognitive) neural systems. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Sep 2015 · Human Brain Mapping
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    [Show abstract] [Hide abstract] ABSTRACT: The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI). We evaluated the supportive role of CSF Aβ42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression. Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aβ42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease. In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.
    Full-text · Article · Sep 2015 · European Journal of Nuclear Medicine

Publication Stats

7k Citations
1,780.51 Total Impact Points


  • 2001-2014
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 2005-2012
    • University of Milan
      Milano, Lombardy, Italy
  • 2011
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      Giovanni Rotondo, Apulia, Italy
  • 2010
    • Università degli Studi di Torino
      Torino, Piedmont, Italy
  • 2008
    • Università Telematica San Raffaele
      Milano, Lombardy, Italy
  • 2006
    • Università Vita-Salute San Raffaele
      Milano, Lombardy, Italy
    • Università degli Studi di Genova
      Genova, Liguria, Italy
  • 2003
    • University of Florence
      Florens, Tuscany, Italy