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Cosottini M.,IMAGO7 Foundation | Frosini D.,University of Pisa | Pesaresi I.,Neuroradiology Unit | Costagli M.,IMAGO7 Foundation | And 4 more authors.
Radiology | Year: 2014

Purpose: To evaluate the anatomy of the substantia nigra (SN) in healthy subjects by performing 7-T magnetic resonance (MR) imaging of the SN, and to prospectively define the accuracy of 7-T MR imaging in distinguishing Parkinson disease (PD) patients from healthy subjects on an individual basis. Materials and Methods: The 7-T MR imaging protocol was approved by the Italian Ministry of Health and by the local competent ethics committee. SN anatomy was described ex vivo on a gross brain specimen by using highly resolved proton-density (spin-echo proton density) and gradient-recalled-echo (GRE) images, and in vivo in eight healthy subjects (mean age, 40.1 years) by using GRE three-dimensional multiecho susceptibility-weighted images. After training on appearance of SN in eight healthy subjects, the SN anatomy was evaluated twice by two blinded observers in 13 healthy subjects (mean age, 54.7 years) and in 17 PD patients (mean age, 56.9 years). Deviations from normal SN appearance were described and indicated as abnormal, and both diagnostic accuracy and intra-and interobserver agreement for diagnosis of PD with 7-T MR imaging were calculated. Results: Three-dimensional multiecho susceptibility-weighted 7-T MR imaging reveals a three-layered organization of the SN allowing readers to distinguish pars compacta ventralis and dorsalis from pars reticulata. The abnormal architecture of the SN allowed a discrimination between PD patients and healthy subjects with sensitivity and specificity of 100% and 96.2% (range, 92.3%-100%), respectively. Intraobserver agreement (k = 1) and interobserver agreement (k = 0.932) were excellent. Conclusion: MR imaging at 7-T allows a precise characterization of the SN and visualization of its inner organization. Threedimensional multiecho susceptibility-weighted images can be used to accurately differentiate healthy subjects from PD patients, which provides a novel diagnostic opportunity. © 2014 RSNA.


Tinelli F.,University of Florence | Tinelli F.,Stella Maris Scientific Institute | Cicchini G.M.,Stella Maris Scientific Institute | Cicchini G.M.,CNR Institute of Neuroscience | And 7 more authors.
Cortex | Year: 2013

It has been shown that unconscious visual function can survive lesions to optical radiations and/or primary visual cortex (V1), a phenomenon termed "blindsight". Studies on animal models (cat and monkey) show that the age when the lesion occurs determines the extent of residual visual capacities. Much less is known about the functional and underlying neuronal repercussions of early cortical damage in humans. We measured sensitivity to several visual tasks in four children with congenital unilateral brain lesions that severely affected optic radiations, and in another group of three children with similar lesions, acquired in childhood. In two of the congenital patients, we measured blood oxygenation level dependent (BOLD) activity in response to stimulation of each visual field quadrants. Results show clear evidence of residual unconscious processing of position, orientation and motion of visual stimuli displayed in the scotoma of congenitally lesioned children, but not in the children with acquired lesions. The calcarine cortical BOLD responses were abnormally elicited by stimulation of the ipsilateral visual field and in the scotoma region, demonstrating a profound neuronal reorganization. In conclusion, our data suggest that congenital lesions can trigger massive reorganization of the visual system to alleviate functional effects of early brain insults. © 2012 Elsevier Ltd.


Fiori S.,Stella Maris Scientific Institute | Guzzetta A.,Stella Maris Scientific Institute | Guzzetta A.,University of Pisa
Seminars in Perinatology | Year: 2015

Over the last decade, the application of novel advanced neuroimaging techniques to study congenital brain damage has provided invaluable insights into the mechanisms underlying early neuroplasticity. The concept that is clearly emerging, both from human and nun-human studies, is that functional reorganization in the immature brain is substantially different from that of the more mature, developed brain. This applies to the reorganization of language, the sensorimotor system, and the visual system. The rapid implementation and development of higher order imaging methods will offer increased, currently unavailable knowledge about the specific mechanisms of cerebral plasticity in infancy, which is essential to support the development of early therapeutic interventions aimed at supporting and enhancing functional reorganization during a time of greatest potential brain plasticity. © 2015.


Basu A.,Northumbria University | Graziadio S.,Northumbria University | Smith M.,Oswestry and Birmingham Childrens Hospital | Clowry G.J.,Northumbria University | And 3 more authors.
Annals of Neurology | Year: 2010

We report motor cortical function in the left occipital cortex of a subject who suffered a left middle cerebral artery stroke early in development. Transcranial magnetic stimulation of the left occipital cortex evoked contraction of right hand muscles. Electroencephalogram recorded over the left occipital cortex showed: 1) coherence with electromyogram from a right hand muscle; 2) a typical sensorimotor Mu rhythm at rest that was suppressed during contraction of right hand muscles. This is the first evidence that cortical plasticity extends beyond reshaping of primary sensory cortical fields to respecification of the cortical origin of subcortically projecting pathways. © 2010 American Neurological Association.


Pooresmaeili A.,Stella Maris Scientific Institute
Journal of vision | Year: 2012

Recently, M. Boi, H. Ogmen, J. Krummenacher, T. U. Otto, & M. H. Herzog (2009) reported a fascinating visual effect, where the direction of apparent motion was disambiguated by cues along the path of apparent motion, the Ternus-Pikler group motion, even though no actual movement occurs in this stimulus. They referred to their study as a "litmus test" to distinguish "non-retinotopic" (motion-based) from "retinotopic" (retina-based) image processing. We adapted the test to one with simple grating stimuli that could be more readily modeled and replicated their psychophysical results quantitatively with this stimulus. We then modeled our experiments in 3D (x, y, t) Fourier space and demonstrated that the observed perceptual effects are readily accounted for by integration of information within a detector that is oriented in space and time, in a similar way to previous explanations of other motion illusions. This demonstration brings the study of Boi et al. into the more general context of perception of moving objects.


Campatelli G.,Stella Maris Scientific Institute | Federico R.R.,University of Pisa | Apicella F.,Stella Maris Scientific Institute | Sicca F.,Stella Maris Scientific Institute | Muratori F.,Stella Maris Scientific Institute
Research in Autism Spectrum Disorders | Year: 2013

Face processing has been studied and discussed in depth during previous decades in several branches of science, and evidence from research supports the view that this process is a highly specialized brain function. Several authors argue that difficulties in the use and comprehension of the information conveyed by human faces could represent a core deficit in autism. Neuroimaging and ERP studies show that the brains of individuals with autism spectrum disorders (ASD) fail to activate and coordinate the activation of the cortical regions that are specialized in face processing. However, the mechanisms for the occurrence of this impairment remain poorly understood. ERP studies that investigate brain activity in ASD individuals during face processing have yielded mixed results. This review reports several debates in the literature regarding the interpretation of recorded neural components, their correlation with ASD, the possible organization of neural networks, the strategies of encoding structural and emotional stimuli, and the future goals of research. © 2012 Elsevier Ltd.


Morgan C.,The University of Notre Dame Australia | Novak I.,The University of Notre Dame Australia | Dale R.C.,University of Sydney | Guzzetta A.,Stella Maris Scientific Institute | Badawi N.,University of Sydney
BMC Neurology | Year: 2014

Background: Cerebral palsy is the most common physical disability of childhood and early detection is possible using evidence based assessments. Systematic reviews indicate early intervention trials rarely demonstrate efficacy for improving motor outcomes but environmental enrichment interventions appear promising. This study is built on a previous pilot study and has been designed to assess the effectiveness of a goal - oriented motor training and enrichment intervention programme, " GAME" , on the motor outcomes of infants at very high risk of cerebral palsy (CP) compared with standard community based care.Methods/design: A two group, single blind randomised controlled trial (n = 30) will be conducted. Eligible infants are those diagnosed with CP or designated " at high risk of CP" on the basis of the General Movements Assessment and/or abnormal neuroimaging. A physiotherapist and occupational therapist will deliver home-based GAME intervention at least fortnightly until the infant's first birthday. The intervention aims to optimize motor function and engage parents in developmental activities aimed at enriching the home learning environment. Primary endpoint measures will be taken 16 weeks after intervention commences with the secondary endpoint at 12 months and 24 months corrected age. The primary outcome measure will be the Peabody Developmental Motor Scale second edition. Secondary outcomes measures include the Gross Motor Function Measure, Bayley Scales of Infant and Toddler Development, Affordances in the Home Environment for Motor Development - Infant Scale, and the Canadian Occupational Performance Measure. Parent well-being will be monitored using the Depression Anxiety and Stress Scale.Discussion: This paper presents the background, design and intervention protocol of a randomised trial of a goal driven, motor learning approach with customised environmental interventions and parental education for young infants at high risk of cerebral palsy.Trial registration: This trial is registered on the Australian New Zealand Clinical Trial register: ACTRN12611000572965. © 2014 Morgan et al.; licensee BioMed Central Ltd.


Guzzetta A.,Stella Maris Scientific Institute | Fiori S.,University of Pisa | Scelfo D.,Stella Maris Scientific Institute | Conti E.,Stella Maris Scientific Institute | And 2 more authors.
Developmental Medicine and Child Neurology | Year: 2013

Visual functions are often impaired in preterm infants with periventricular haemorrhagic infarction, because of the involvement of the region where the optic radiations are located. In some cases an unexpected sparing of the visual fields has been described, and related to the plasticity of thalamo-cortical afferents that are supposedly able to bypass the lesion when it occurs in the early third trimester of gestation. We systematically reviewed the literature in the field to determine the limits and potentials of this type of reorganization. We found four studies meeting our criteria, from which we extracted case reports on 19 individuals with intraventricular haemorrhagic infarction. Eleven of the 19 did not have visual field defects, five had a bilateral visual field defect, and the remaining three had a unilateral visual field defect. The involvement of the optic radiations was often associated with normal visual fields as only one of the four individuals with damaged optic radiations showed visual field defects. Conversely, the presence of basal ganglia/thalamus involvement apparently prevented such reorganization, as the only two individuals with unilateral field restriction and available magnetic resonance imaging data both showed abnormalities in those structures. Consistent with this, we report on a further individual in which visual field restriction was associated with abnormal tractography on brain magnetic resonance imaging. Overall, this review supports the existence of effective mechanisms of plastic reorganization that allow a rewiring of geniculo-calcarine connections with restoration of full field vision but which are hindered by the involvement of the basal ganglia and thalamus. © 2013 Mac Keith Press.


Brizzolara D.,Stella Maris Scientific Institute | Brizzolara D.,University of Pisa | Gasperini F.,Stella Maris Scientific Institute | Pfanner L.,Stella Maris Scientific Institute | And 3 more authors.
Cortex | Year: 2011

Specific language impairment (SLI) diagnosed in the pre-school years is frequently associated with reading and writing difficulties at school age. The nature of this relationship is unclear, despite the availability of a large number of studies, mostly on English speaking children. Phonological processing deficits have been considered the prominent cause of both difficulties. However recent findings in both children with SLI and in children with reading difficulties are not easily accommodated within a single dimensional model explaining the relationship between oral and written language deficits.Our study focuses on the long-term reading and spelling outcome in relation to preschool oral language skills in a group of Italian adolescents with a documented history of SLI.Sixteen Italian adolescents diagnosed as SLI at our Hospital in the pre-school years and 32 normal controls were submitted to an extensive assessment of oral and written language skills. At a group level SLI adolescents had weak oral and written language skills in almost all tests.Results show that reading difficulties have some features in common with those of Italian developmental dyslexics but also have distinct characteristics, since reading accuracy and written comprehension, usually relatively spared in Italian developmental dyslexics, were impaired in adolescents with SLI.Longitudinal analyses showed that expressive morpho-syntactic and lexical abilities at pre-school age were the oral language skills that best predicted reading and spelling outcomes in adolescents with SLI.However, also children with severe phonological impairment in the absence of other oral language deficits showed later literacy difficulties, although less severe and mainly limited to reading accuracy.Our study supports the notion that there is a complex relationship between oral and written language difficulties which may change at different developmental time points, not captured by a single deficit model, but best conceptualized considering multiple interactions between language skills and literacy abilities. © 2011 Elsevier Srl.


Steeb H.,University of Cambridge | Ramsey J.M.,University of Cambridge | Guest P.C.,University of Cambridge | Stocki P.,University of Cambridge | And 8 more authors.
Molecular Autism | Year: 2014

Background: The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Methods. Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MS§ssup§E§esup§). The main objective was to identify sex-specific serum protein changes associated with AS. Results: Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MS§ssup§E§esup§ profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls. Conclusion: Taken together, the serum multiplex immunoassay and shotgun LC- MS§ssup§E§esup§ profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches. © 2014 Steeb et al.; licensee BioMed Central Ltd.

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