Valeria Contarino

Diagnostic differentiation of mild cognitive impairment due to Alzheimer's disease using a hippocampus-dependent test of spatial memory.

The hippocampus is one of the earliest brain regions affected in Alzheimers disease (AD) and tests of hippocampal function have the potential to detect AD in its earliest stages. Given that the hippocampus is critically involved in allocentric spatial memory, this study applied a short test of spatial memory, the 4 Mountains Test (4MT), to determine whether test performance can differentiate mild cognitive impairment (MCI) patients with and without CSF biomarker evidence of underlying AD and whether the test can distinguish patients with MCI and mild AD dementia when applied in different cultural settings. Healthy controls (HC), patients with MCI, and mild AD dementia were recruited from study sites in UK and Italy. Study numbers were: HC (UK 20, Italy 10), MCI (UK 21, Italy 14), and AD (UK 11, Italy 9). Nineteen UK MCI patients were grouped into CSF biomarker‐positive (MCI+, n = 10) and biomarker‐negative (MCI–, n = 9) subgroups. Behavioral data were correlated with hippocampal volume and cortical thickness of the precuneus and posterior cingulate gyrus. Spatial memory was impaired in both UK and Italy MCI and AD patients. Test performance additionally differentiated between MCI+ and MCI– subgroups (P = 0.001). A 4MT score of ≤8/15 was associated with 100% sensitivity and 90% specificity for detection of early AD (MCI+ and mild AD dementia) in the UK population, and with 100% sensitivity and 50% specificity for detection of MCI and AD in the Italy sample. 4MT performance correlated with hippocampal volume in the UK population and cortical thickness of the precuneus in both study populations. In conclusion, performance on a hippocampus‐sensitive test of spatial memory differentiates MCI due to AD with high diagnostic sensitivity and specificity. The observation that similar diagnostic sensitivity was obtained in two separate study populations, allied to the scalability and usability of the test in community memory clinics, supports future application of the 4MT in the diagnosis of pre‐dementia due to AD.

Neuroimaging findings in 41 low-functioning children with autism spectrum disorder: A single-center experience

The data on the rate of brain imaging abnormalities in autistic spectrum disorders are still inconsistent. A recent study on patients with high-functioning autism found that approximately 90% of children had normal magnetic resonance imaging (MRI) scans whereas an unexpected high rate of MRI abnormalities was reported in 77 nonsyndromic autistic children with or without intellectual disability. The aim of this study was to evaluate the prevalence of neuroradiologic findings in low-functioning autistic children compared to controls matched for age. Minor brain abnormalities were found in 44% of patients and 22% of controls. Our main result is the high rate of mega cisterna magna in autistic patients. High rate of minor neuroradiologic abnormalities in low-functioning autistic patients could contribute to the research about the various endophenotypes and complete the clinical assessment of children with autistic spectrum disorder and intellectual disability.

Disentangling subgroups of participants recruiting shared as well as different brain regions for the execution of the verb generation task: A data-driven fMRI study

The spatial pattern of task-related brain activity in fMRI studies might be expected to change according to several variables such as handedness and age. However this spatial heterogeneity might also be due to other unmodeled sources of inter-subject variability. Since group-level results reflect patterns of task-evoked brain activity common to most of the subjects in the sample, they could conceal the presence of subgroups recruiting other brain regions beyond the common pattern. To deal with these issues, data-driven methods can be used to detect the presence of sources of inter-subject variability that might be hard to identify and therefore model a priori. Here we assess the potential of Independent Component Analysis (ICA) to detect the presence of unexpected subgroups of participants. To this end, we acquired task-evoked fMRI data on 45 healthy adults using the verb generation (VGEN) task, in which participants are visually presented with the noun of an object of everyday use, and asked to covertly generate a verb describing the corresponding action. As expected, the task elicited activity in a temporo-parieto-frontal network typically found in previous VGEN experiments. We then quantified the contribution of every subject to nine task-related spatio-temporal processes identified by ICA. A cluster analysis of this quantity yielded three subgroups of participants. Differences between the three identified subgroups were distributed in left and right prefrontal, posterior parietal and extrastriate occipital regions. These results could not be explained by differences in sex, age or handedness across the participants. Furthermore, some regions where a significant difference was found between subgroups were not present in the group-level pattern of task-related activity. We discuss the potential application of this approach for characterizing brain activity in different subgroups of patients with neuropsychiatric or neurological conditions.

Low-Functioning Autism and Nonsyndromic Intellectual Disability Magnetic Resonance Imaging (MRI) Findings

Previous neuroradiologic studies reported a high incidence of abnormalities in low-functioning autistic children. In this population, it is difficult to know which abnormality depends on autism itself and which is related to intellectual disability associated with autism. The aim of this study was to evaluate the frequency of neuroradiologic abnormalities in low-functioning autistic children compared to Intellectual Quotient and age-matched nonsyndromic children, using the same set of magnetic resonance imaging (MRI) sequences. MRI was rated as abnormal in 44% of autistic and 54% of children with intellectual disability. The main results were mega cisterna magna in autism and hypoplastic corpus callosum in intellectual disability. These abnormalities are morphologically visible signs of altered brain development. These findings, more frequent than expected, are not specific to the 2 conditions. Although MRI cannot be considered mandatory, it allows an in-depth clinical assessment in nonsyndromic intellectual-disabled and autistic children.

Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series

BACKGROUND Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. OBJECTIVES The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimers disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. METHOD PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohens kappa. RESULTS Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0-0.25 for PCA to 0.29-0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. CONCLUSION The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practice.

Erratum to: Substantia nigra in Parkinson's disease: A multimodal MRI comparison between early and advanced stages of the disease (Neurological Sciences DOI: 10.1007/s10072-013-1595-2)

Unfortunately the following co-author name was incorrectly published as Antonio Elia in the original publication. The name of the author should read as Antonio Emanuele Elia. Inadvertently, one of the co-author name (Luigi Romito) and affiliation were omitted in the author group of published article. The rearranged author group is given below. Domenico Aquino, Valeria Contarino, Alberto Albanese, Ludovico Minati, Laura Farina, Marina Grisoli, Luigi Romito, Antonio Emanuele Elia, Maria Grazia Bruzzone, Luisa Chiapparini.

Constrained spherical deconvolution-based tractography to depict and characterize a case of “hyperplastic fornix dorsalis”

The authors report the relevance of Constrained Spherical Deconvolution (CSD)-based tractography in demonstrating and quantitatively assessing a complex midline structure malformation in a 9-year-old girl with moderate intellectual disability and thickening of corpus callosum (CC) body discovered through conventional MRI (cMRI). Color-encoded fractional anisotropy (FA) maps clearly demonstrated what the cMRI showed as a thicknening of CC: a green, longitudinal bundle running dorsally to the body of CC. A more complex midline maldevelopmental disorder was suspected. CSD-based tractography was performed to virtually dissect the anomalous supracallosal longitudinal bundle (SLB), CC, fornix, anterior commissure (AC) and cingula. In addition, DTI-derived metrics were calculated for each virtually dissected fiber tract. The tractography study evidenced projections of the anomalous SLB in left forceps minor and to parietal regions, and projections of the fornix in right forceps minor. CC virtual dissection showed no gross abnormality, and cingula appeared slightly less extended than normal. The considerable thinning of AC hampered its virtual dissection. DTI-derived metrics suggested alterations in fornix microstructure, attributable to higher fiber density. In investigating white matter, cMRI may not be sufficient in addressing and assessing possible anomalies, while advanced CSD-based tractography and DTI-derived metrics may prove helpful in depicting and characterizing white matter anomalies in developmental disorders.