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Primary progressive aphasia (PPA) is an overarching term for a heterogeneous group of neurodegenerative diseases which affect language processing. Impaired picture naming has been linked to atrophy of the anterior temporal lobe in the semantic variant of PPA. Although atrophy of the anterior temporal lobe proposedly impairs picture naming by undermining access to semantic knowledge, picture naming also entails object recognition and lexical retrieval. Using multivariate analysis, we investigated whether cortical atrophy relates to different types of naming errors generated during picture naming in 43 PPA patients (13 semantic, 9 logopenic, 11 nonfluent, and 10 mixed variant). Omissions were associated with atrophy of the anterior temporal lobes. Semantic errors, for example, mistaking a rhinoceros for a hippopotamus, were associated with atrophy of the left mid and posterior fusiform cortex and the posterior middle and inferior temporal gyrus. Semantic errors and atrophy in these regions occurred in each PPA subtype, without major between-subtype differences. We propose that pathological changes to neural mechanisms associated with semantic errors occur across the PPA spectrum. ispartof: NEUROBIOLOGY OF AGING vol:88 pages:71-82 ispartof: location:United States status: published

Objective: In some patients with apraxia of speech (AOS), we observed impaired perceptual timing abilities, which lead us to propose a shared mechanism of impaired perceptual timing underlying impaired rhythm discrimination (perceptual processing) and AOS (motor speech output). Given that considerable white matter damage is often observed in these patients, we here investigate whether white matter changes are related to impaired rhythm processing as one possible mechanism underlying AOS. Methods: We applied deformation-based morphometry (DBM) and diffusion tensor imaging (DTI) in 12 patients with the nonfluent variant (NFV) of Primary Progressive Aphasia (PPA) with AOS, as well as 11 patients with the semantic variant and 24 controls. Results: Seventy-five percent of the patients with NFV displayed impaired rhythm processing and the severity of their impairment correlated with their degree of AOS. Moreover, left frontal white matter volume loss adjacent to the supplementary motor area (SMA) correlated with impaired rhythm processing. In addition, we obtained tract-based metrics of the left Aslant tract, which is typically damaged in NFV. The structural integrity of the left Aslant tract also correlated with rhythmic discrimination abilities in NFV. Conclusions: Our data suggest that a shared white matter substrate adjacent to the SMA contributes to impaired rhythm perception and motor speech impairments. This indicates that impaired perceptual timing may be one of the neurocomputational mechanisms underlying AOS. Our observation that regional variations in left frontal lobe atrophy are linked to the phenotypical heterogeneity in NFV may lead the way for earlier diagnosis.

Background: Word finding symptoms are frequent early in the course of Alzheimer’s disease. The posterior superior temporal sulcus (STS) is the earliest language area affected in amnestic MCI and in early-stage probable AD (Vandenbulcke et al., 2007; Nelissen et al., 2007). We examined how amyloid load affects the network for language and associative-semantic processing in cognitively intact older adults. Methods: Fifty-seven community-recruited right-handed adults (mean age1⁄465, SD1⁄45.5, range 52-74) underwent 18 F-flutemetamol PET, volumetric and functional MRI, and neurolinguistic evaluation. The fMRI design contained two factors: task (associative-semantic versus visuoperceptual judgment) and input modality (written words versus pictures). Standardized uptake value ratios (SUVR) were calculated on normalized PET images with cerebellar grey matter as reference region. As primary outcome analysis, we conducted a whole-brain linear regression analysis between SUVR calculated in a composite cortical VOI (SUVRcomp) and activity levels obtained from the contrast of the associative-semantic minus the visuoperceptual control condition for words and pictures (cluster-level P 0.7). Stepwise multiple linear regression analysis showed that mean fMRI response in the posterior left STS and mTG during associative-semantic contitions minus visuoperceptual conditions was best predicted by SUVRcomp (r1⁄40.62, P

We investigated the critical contribution of right ventral occipitotemporal cortex to knowledge of visual and functional-associative attributes of biological and non-biological entities and how this relates to category-specificity during confrontation naming. In a consecutive series of 7 patients with lesions confined to right ventral occipitotemporal cortex, we conducted an extensive assessment of oral generation of visual-sensory and functional-associative features in response to the names of biological and nonbiological entities. Subjects also performed a confrontation naming task for these categories. Our main novel finding related to a unique case with a small lesion confined to right medial fusiform gyrus who showed disproportionate naming impairment for nonbiological versus biological entities, specifically for tools. Generation of visual and functional-associative features was preserved for biological and non-biological entities. In two other cases, who had a relatively small posterior lesion restricted to primary visual and posterior fusiform cortex, retrieval of visual attributes was disproportionately impaired compared to functional-associative attributes, in particular for biological entities. However, these cases did not show a category-specific naming deficit. Two final cases with the largest lesions showed a classical dissociation between biological versus nonbiological entities during naming, with normal feature generation performance. This is the first lesion-based evidence of a critical contribution of the right medial fusiform cortex to tool naming. Second, dissociations along the dimension of attribute type during feature generation do not co-occur with category-specificity during naming in the current patient sample. publisher: Elsevier articletitle: Noun and knowledge retrieval for biological and non-biological entities following right occipitotemporal lesions journaltitle: Neuropsychologia articlelink: http://dx.doi.org/10.1016/j.neuropsychologia.2014.07.021 content_type: article copyright: Copyright © 2014 Elsevier Ltd. All rights reserved. ispartof: Neuropsychologia vol:62 issue:1 pages:163-74 ispartof: location:England status: published

Background: Previous work has shown clinical and neuroimaging-based measures that display differences between MCI individuals who will later show progressive decline from those who will remain stable. The goal of this project was to identify changes in normal subjects which are associated with subsequent cognitive decline and conversion to MCI or AD.Methods: Utilizing the ADNI database, we identified 41 individuals who remained stable for 48-months (NC) and 16 who converted to MCI (CNV). Of these 57 subjects, all had available baseline clinical andMRI data, but only 16 NC and 11 CNV had available FDG-PET data. Wilcoxon Rank Sum tests assessed baseline demographic and clinical imbalances between CNV and NC. The effect of conversion status on neuroimaging measures at baseline was tested using linear regression modeling. Finally, linear discriminant analysis (LDA) models were created using features from an a-priori subset of clinical metrics, MRI measures, and FDG-PET measures obtained at baseline to predict which individuals would later convert to MCI and which would remain stable. We used a leave-one-out cross validation strategy and permutation analysis to confirm significance. Results: Significant differences between CNV and NC were found in ADAS-cog (P 1⁄4 0.006), FAQ (P 1⁄4 0.009), and AVLT (P 1⁄4 0.047) with no accompanying differences in age, gender, or education level. There was a marginal difference between groups in APOE status, but it did not reach significance (likely due to sample size). Conversion status was found to have a significant effect on several apriori selected neuroimaging measures including hippocampal (P 1⁄4 0.014) and entorhinal (P1⁄4 0.017) cortical volumes, entorhinal cortical thickness (P 1⁄4 0.021), and regional FDG-PET average of posterior cingulate (P 1⁄4 0.003). LDA models created using a combination of baseline MRI and FDG-PET measures were able to predict MCI conversion with up to 81% accuracy (P 1⁄4 0.005). Conclusions: The present study indicates that individuals destined for future cognitive decline may begin to express subtle but informative, and even predictive, differences in clinical assessments as well as brain structure and metabolism up to 4 years prior to displaying overt neuropsychological symptoms of decline.

There was an error in the name of the 13th author. The correct name is Florence Nguyen-Khac.

The mean expression value: a new method for accurate and reliable normalization of microRNA expression data from RT-qPCR experiments., Gene expression analysis of microRNA molecules is becoming increasingly important. In this study we assess the use of the mean expression value of all expressed microRNAs in a given sample as a normalization factor for microRNA real-time quantitative PCR data and compare its performance to the currently adopted approach. We demonstrate that the mean expression value outperforms the current normalization strategy in terms of better reduction of technical variation and more accurate appreciation of biological changes.

Graph analysis is a promising tool to quantify brain connectivity. However, an essential requirement is that the graph measures are reproducible and robust. We have studied the reproducibility and robustness of various graph measures in group based and in individual binary and weighted networks derived from a task fMRI experiment during explicit associative-semantic processing of words and pictures. The nodes of the network were defined using an independent study and the connectivity was based on the partial correlation of the time series between any pair of nodes. The results showed that in case of binary networks, global graph measures exhibit a good reproducibility and robustness for networks which are not too sparse and these figures of merit depend on the graph measure and on the density of the network. Furthermore, group based binary networks should be derived from groups of sufficient size and the lower the density the more subjects are required to obtain robust values. Local graph measures are very variable in terms of reproducibility and should be interpreted with care. For weighted networks, we found good reproducibility (average test-retest variability 0.4) when using subject specific networks and this will allow us to relate network properties to individual subject information. ispartof: PLoS One vol:9 issue:12 ispartof: location:United States status: published