[Show abstract][Hide abstract] ABSTRACT: Naming abilities are typically preserved in amnestic Mild Cognitive Impairment (aMCI), a condition associated with increased risk of progression to Alzheimer's disease (AD). We compared the functional correlates of covert picture naming and word reading between a group of aMCI subjects and matched controls. Unimpaired picture naming performance was associated with more extensive activations, in particular involving the parietal lobes, in the aMCI group. In addition, in the condition associated with higher processing demands (blocks of categorically homogeneous items, living items), increased activity was observed in the aMCI group, in particular in the left fusiform gyrus. Graph analysis provided further evidence of increased modularity and reduced integration for the homogenous sets in the aMCI group. The functional modifications associated with preserved performance may reflect, in the case of more demanding tasks, compensatory mechanisms for the subclinical involvement of semantic processing areas by AD pathology.
[Show abstract][Hide abstract] ABSTRACT: We investigated the contribution of cortical lesions to cognitive impairment in 41 paediatric MS patients. Thirteen (32%) paediatric MS patients were considered as cognitively impaired. T2-hyperintense and T1-hypointense white matter lesion volumes did not differ between cognitively impaired and cognitively preserved MS patients. Cortical lesions number, cortical lesions volume and grey matter volume did not differ between cognitively impaired and cognitively preserved patients, whereas white matter volume was significantly lower in cognitively impaired versus cognitively preserved MS patients (p=0.01). Contrary to adult MS, cortical lesions do not seem to contribute to cognitive impairment in paediatric MS patients, which is likely driven by white matter damage.
[Show abstract][Hide abstract] ABSTRACT: Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase-3β (GSK-3β). The less active GSK-3β promoter gene variants have been associated with less detrimental clinical features of BD. GSK-3β gene variants and lithium can influence brain gray and white matter structure in psychiatric conditions, so we studied their combined effect in BD.
[Show abstract][Hide abstract] ABSTRACT: Aim of this study was to explore the topological organization of functional brain network connectivity in a large cohort of multiple sclerosis (MS) patients and to assess whether its disruption contributes to disease clinical manifestations. Graph theoretical analysis was applied to resting state fMRI data from 246 MS patients and 55 matched healthy controls (HC). Functional connectivity between 116 cortical and subcortical brain regions was estimated using a bivariate correlation analysis. Global network properties (network degree, global efficiency, hierarchy, path length and assortativity) were abnormal in MS patients vs HC, and contributed to distinguish cognitively impaired MS patients (34 %) from HC, but not the main MS clinical phenotypes. Compared to HC, MS patients also showed: (1) a loss of hubs in the superior frontal gyrus, precuneus and anterior cingulum in the left hemisphere; (2) a different lateralization of basal ganglia hubs (mostly located in the left hemisphere in HC, and in the right hemisphere in MS patients); and (3) a formation of hubs, not seen in HC, in the left temporal pole and cerebellum. MS patients also experienced a decreased nodal degree in the bilateral caudate nucleus and right cerebellum. Such a modification of regional network properties contributed to cognitive impairment and phenotypic variability of MS. An impairment of global integration (likely to reflect a reduced competence in information exchange between distant brain areas) occurs in MS and is associated with cognitive deficits. A regional redistribution of network properties contributes to cognitive status and phenotypic variability of these patients.
Brain Structure and Function 09/2014; · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Posterior cortical atrophy (PCA) is characterized by basic visual and high order visual-spatial dysfunctions. In this study, we investigated long-distance deafferentation processes within the frontal-parietal-occipital network in ten PCA patients using a MRI-PET combined approach. Objective voxel-based [18F]FDG-PET imaging measured metabolic changes in single patients. Comprehensive investigation of diffusion tensor imaging (DTI) metrics and grey-matter density with voxel-based morphometry were obtained in a subgroup of 6 patients. Fractional anisotropy in the superior longitudinal fasciculus correlated with the PET metabolic changes within the inferior parietal and frontal eye field regions. [18F]FDG-PET analysis showed in each PCA case the typical bilateral hypometabolic pattern, involving posterior temporal, parietal, and occipital cortex, with additional hypometabolic foci in the frontal eye fields. Voxel-based morphometry showed right-sided atrophy in the parieto-occipital cortex, as well as a limited temporal involvement. DTI revealed extensive degeneration of the major anterior-posterior connecting fiber bundles and of commissural frontal lobe tracts. Microstructural measures in the superior longitudinal fasciculus were correlated with the PET metabolic changes within the inferior parietal and frontal eye field regions. Our results confirmed the predominant occipital-temporal and occipital-parietal degeneration in PCA patients. [18F]FDG-PET and DTI-MRI combined approaches revealed neurodegeneration effects well beyond the classical posterior cortical involvement, most likely as a consequence of deafferentation processes within the occipital-parietal-frontal network that could be at the basis of visuo-perceptual, visuo-spatial integration and attention deficits in PCA.
Journal of Alzheimer's disease: JAD 08/2014; · 3.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This guideline provides recommendations for diagnostic and therapeutic procedures for patients with malignant gliomas. We differentiate evidence-based standards from reasonable options or non-evidence-based measures that should no longer be considered. The recommendations herein should provide a framework and assurance for the choice of diagnostic procedures and therapeutic measures and aim to reduce complications from unnecessary treatment and cost. The guideline contributes to a critical appreciation of concurrent drugs with a focus on the controlled use of anticonvulsants and steroids. It should serve as a guideline for all professionals involved in the diagnostics and care of glioma patients and also as a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in Europe. Implementation of the recommendations summarised here will need interdisciplinary structures of care for patients with brain tumours and structured processes of diagnostic and therapeutic procedures.
The Lancet Oncology 08/2014; 15(9):e395–e403. · 24.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
The DCDC2 gene is involved in neuronal migration. Heterotopias have been found within the white matter of DCDC2-knockdown rats. A deletion in DCDC2/intron 2 (DCDC2d), which encompasses a regulatory region named ‘regulatory element associated with dyslexia 1’ (READ1), increases the risk for dyslexia. We hypothesized that DCDC2d can be associated to alterations of the white matter structure in general and in dyslexic brains.
Based on a full factorial ANCOVA model, we investigated Voxel Based-Diffusion Tensor Imaging data of 4 groups of subjects: dyslexia with/without DCDC2d, and normal readers with/without DCDC2d. We also tested DCDC2d effects upon correlation patterns between fractional anisotropy (FA) and reading scores.
We found that FA was reduced in the left arcuate fasciculus and splenium of the corpus callosum in subjects with versus without DCDC2d, irrespective of dyslexia. Subjects with dyslexia and DCDC2d showed reduced FA, mainly in the left hemisphere and in the corpus callosum; their counterpart without DCDC2d showed similar FA alterations. Noteworthy, a conjunction analysis in impaired readers revealed common regions with lower FA mainly in the left hemisphere. When we compared subjects with dyslexia with versus without DCDC2d, we found lower FA in the inferior longitudinal fasciculus and genu of the corpus callosum, bilaterally. Normal readers with versus without DCDC2d had FA increases and decreases in both the right and left hemisphere.
The major contribution of our study was to provide evidence relating genes, brain and behaviour. Overall, our findings support the hypothesis that DCDC2d is associated with altered FA. In normal readers, DCDC2-related anatomical patterns may mark some developmental cognitive vulnerability to learning disabilities. In subjects with dyslexia, DCDC2d accounted for both common – mainly located in the left hemisphere – and unique – a more severe and extended pattern – alterations of white matter fibre tracts.
[Show abstract][Hide abstract] ABSTRACT: Using resting-state functional magnetic resonance imaging and graph analysis, the topological organization of the functional brain network connectivity was explored in patients with left-sided onset semantic variant (SV) of primary progressive aphasia relative to healthy controls. Functional brain networks in SV patients were characterized by a significantly lower mean network degree, clustering coefficient, and global efficiency, longer characteristic path length and higher assortativity compared with controls. SV patients showed also a strongly left-lateralized loss of hubs, and reduced nodal degree in the inferior and ventral temporal regions and occipital cortices. In SV, the decreased nodal degree extended into the medial and ventral frontal cortex bilaterally, left amygdala and/or hippocampus, and left caudate nucleus. These findings provide evidence that the focal structural degeneration of the inferior temporal, and perysilvian language regions in SV patients ultimately results in a distributed pattern of functional connectivity abnormalities. The local network analysis shows that SV is associated with a functional degradation in the "pan-modal" inferior and/or ventral temporal regions, and the "modality-specific" visual cortical origin of the ventral processing pathway.
Neurobiology of Aging 05/2014; · 4.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: To study the specificity of cellular MRI based on superparamagnetic iron oxide particles (SPIOs), especially within the CNS. Materials & methods: A microglial cell line was engineered for the expression of a suicide gene, the receptor of diphtheria toxin (DT), and two reporter genes, green fluorescent protein and luciferase, in order to induce, in a controlled manner, cell death and test it through bioluminescence. SPIO-labeled DT-sensitive and control DT-insensitive cells were transplanted into the brains of mice, which underwent serial MRI and bioluminescence studies before and up to 90 days after DT-induced cell death. Results: No variations in SPIO signal voids were detected along longitudinal monitoring in brain hemispheres transplanted with DT-sensitive cells. Ex vivo analyses showed persistence of iron nanoparticle deposits at transplantation sites. Conclusion: Due to the long-term persistence of signal after transplanted cell death, caution is advised when SPIOs are employed for cell tracking. Original submitted 27 January 2014; Revised submitted 18 April 2014.
[Show abstract][Hide abstract] ABSTRACT: Using diffusion tensor magnetic resonance imaging (DT MRI), we analyzed the architectural integrity of the brain white matter (WM) from a large cohort of MS patients to identify the structural substrates of the concomitant presence of depression and fatigue.
Brain dual-echo, 3D T1-weighted and DT MRI scans were acquired from 147 MS patients and 90 gender- and age-matched healthy controls (HCs). Patients were stratified by the presence of depression (92 depressed (D), 55 not depressed (nD)) and fatigue (81 fatigued (F), 66 not fatigued (nF)). Sixty-five patients had co-occurrence of depression and fatigue (DF). Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). Tract-specific analyses were run in brain WM tracts using standard-space templates.
Whole-brain voxel-wise analysis yielded no significant differences between patient subgroups. At tract-specific analysis, DF patients had reduced fractional anisotropy (FA) of the forceps minor. Reduced FA of the right anterior thalamic radiation and right uncinate fasciculus was found in F-MS vs not F-MS patients after correcting for depression. No significant differences were found between D vs not D-MS patients, after correcting for fatigue.
This study provides evidence for partially overlapping damage to frontal and fronto-temporal pathways underlying depression and fatigue in MS.
[Show abstract][Hide abstract] ABSTRACT: Amyotrophic Lateral Sclerosis (ALS) is associated in about half of the cases with behavioral and cognitive disorders, including impairments in socio-emotional processing, considered as key-features for the diagnosis of the behavioral variant of frontotemporal dementia (bv-FTD). The neurostructural bases of emotional deficits in ALS, however, still remain largely unexplored. Here we aim to assess emotion recognition in non-demented sporadic ALS patients compared with healthy controls, and to explore for the first time its microstructural white-matter correlates. Twenty-two subjects with either probable or definite diagnosis of ALS and 55 age-, gender-, and education-matched healthy controls were recruited in the study. All participants performed the Ekman 60-Faces Test, assessing the recognition of six basic emotions (i.e., anger, disgust, fear, sadness, surprise and happiness). A subgroup of subjects, comprising 19 patients and 20 healthy controls, also underwent a Diffusion Tensor Imaging scanning. Behavioral analysis highlighted a significant decline of emotion recognition skills in patients compared to controls, particularly affecting the identification of negative emotions. Moreover, the Diffusion Tensor Imaging analyses revealed a correlation between this impairment and the alteration of white-matter integrity along the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus. Our findings indicate the presence of an early emotion recognition deficit in non-demented sporadic ALS patients, associated with microstructural changes in ventral associative bundles connecting occipital, temporo-limbic and orbitofrontal regions in the right hemisphere. These changes may represent a frontotemporal-limbic microstructural marker of socio-emotional impairment in ALS.
[Show abstract][Hide abstract] ABSTRACT: Bipolar disorder (BD) is associated with adverse childhood experiences (ACE), which worsen the lifetime course of illness, and with signs of widespread disruption of white matter (WM) integrity in adult life. ACE are associated with changes in WM microstructure in healthy humans.
Psychological Medicine 03/2014; · 5.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We combined structural and functional MRI to better understand the mechanisms responsible for cognitive impairment in pediatric patients with multiple sclerosis (MS).
Brain dual-echo, diffusion tensor, 3D T1-weighted, and resting-state (RS) fMRI scans were acquired from 35 consecutive pediatric patients with MS and 16 sex- and age-matched healthy controls. Patients with abnormalities in ≥2 neuropsychological tests were classified as cognitively impaired. The regional distribution of white matter (WM) and gray matter (GM) damage was assessed using voxel-wise analyses. Default mode network (DMN) RS functional connectivity (FC) was also measured.
Sixteen patients (45%) were classified as cognitively impaired. Compared to cognitively preserved (CP) patients, cognitively impaired patients with MS had higher occurrence of T2 lesions as well as more severe damage to the WM and GM, as measured by atrophy and diffusivity abnormalities, in the posterior regions of the parietal lobes close to the midline (precuneus, posterior cingulum, and corpus callosum). Compared to the other study groups, they also showed reduced RS FC of the precuneus, whereas CP patients experienced an increased RS FC of the anterior cingulate cortex. A multivariable model identified diffusivity abnormalities of the cingulum and corpus callosum and RS FC of the precuneus as the covariates more strongly associated with cognitive impairment (C-index = 0.99).
In pediatric patients with MS, cognitive dysfunction is associated with structural and functional abnormalities of the posterior core regions of the DMN. WM structural abnormalities co-occurring at this level are likely to be the substrate of such modifications.
[Show abstract][Hide abstract] ABSTRACT: To compare extraocular muscles (EOMs) T2, post-contrast T1 (T1Gad) signal intensity ratios (SIRs) and normalized-apparent diffusion coefficient (n-ADC) values in patients with thyroid-associated orbitopathy (TAO) at different phases of activity and severity and correlate MRI modifications to clinical evolution during follow-up.
A total of 74 TAO patients were classified as active or inactive on the basis of the clinical activity score (CAS). Severity of EOM impairment was evaluated by assigning a functional score to each rectus. T2, T1Gad SIRs and n-ADC of EOMs were compared in patients with active inflammation, those with inactive disease and 26 healthy controls, and correlated with clinical scores. MRI parameter variation was correlated with clinical modifications during follow-up.
All MRI parameters in TAO EOMs were significantly higher than in healthy subjects and correlated with muscle dysfunction and CAS. EOMs of active patients showed higher T2 and T1Gad SIRs than those with inactive disease. The T2 SIR and n-ADC of normally functioning TAO EOMs were higher than those of healthy controls. SIRs decreased in clinically improved and clinically stable EOMs after therapy.
T2 SIR, T1Gad SIR and n-ADC are objective measures of activity and severity of EOMs in TAO patients. MRI shows clinically silent muscle involvement and modifications.
• MRI and DWI measures are objective, quantitative parameters of TAO activity and severity • MRI and DWI measures significantly correlate with clinical scores in TAO patients • MRI and DWI can identify clinically silent inflammation of deep orbital structures • MRI and DWI can depict subclinical modifications during follow-up • MRI and DWI may aid clinicians in choosing the most appropriate treatment.
[Show abstract][Hide abstract] ABSTRACT: Background
Resection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation modalities, which efficiency is based on the ability to recognize essential sites with the highest possible resolution in most clinical conditions. Two stimulation paradigms evolved for intraoperative guidance of motor tumors removal: the 60 Hz-technique [low frequency (LF)] and the pulse-technique [high frequency-(HF)], delivered by bipolar or monopolar probe respectively. Most surgical teams rely on to either of the 2 techniques. The key point is the integration of the choice of the stimulation modality with the clinical context.Methods
In 591 tumors involving the corticospinal tract, the use of HF and LF was tailored to the clinical context defined by patient clinical history and tumor features (by imaging). The effect was evaluated on the feasibility of mapping, the impact on immediate and permanent morbidity, the extent of resection, and the number of patients treated.ResultsBy integrating the choice of the probe and the stimulation protocol with patient clinical history and tumor characteristics, the best probe-frequency match was identified for the different sets of clinical conditions. This integrative approach allows increasing the extent of resection and patient functional integrity, and greatly expands the number of patients who could benefit from surgery.Conclusions
The integration of stimulation modalities with clinical context enhances the extent and safety of resection and expands the population of patients who could benefit from surgical treatment.
[Show abstract][Hide abstract] ABSTRACT: Objective
Loss of empathy is a symptom of the behavioral variant of frontotemporal dementia (bvFTD), constituting a clue for early diagnosis. In this study, we directly compared two empathy components (intention attribution [IA] and emotion attribution [EA]), correlating them with possible specific patterns of gray-matter density reduction within the mentalizing network.
We evaluated IA and EA in 18 mild bvFTD patients compared with 36 healthy controls (HCs) using a single nonverbal test. A subgroup entered a voxel-based morphometry study.
Compared with HC, bvFTD patients showed IA and EA impairments. EA performance correlated with gray-matter reduction in the right amygdala, left insula, and posterior-superior temporal sulcus extending into the temporoparietal junction.
We proved an empathic impairment, with the ability to infer emotional states showing the most severe deficit. These results provide further evidence of selective disease-specific vulnerability of the limbic and frontoinsular network in bvFTD and highlight the usefulness of empathy assessment in early patients.
Alzheimer's & dementia: the journal of the Alzheimer's Association 02/2014; · 14.48 Impact Factor