Silvia Primativo

Consensus classification of posterior cortical atrophy

A classification framework for posterior cortical atrophy (PCA) is proposed to improve the uniformity of definition of the syndrome in a variety of research settings.

Impaired oculo-motor behaviour affects both reading and scene perception in neglect patients.

Unilateral spatial neglect (USN) is a common neuropsychological disorder following a right-sided brain lesion. Although USN is mostly characterized by symptoms involving the left hemispace, other symptoms are not left lateralized. Recently, it was shown that patients with neglect dyslexia, a reading disturbance that affects about 40% of USN patients, manifest a non-lateralized impairment of eye movement behaviour in association with their reading deficit when they read aloud and perform non-verbal saccadic tasks (Primativo et al., 2013). In the present paper, we aimed to demonstrate that the eye movement impairment shown by some USN patients reflects a more general oculo-motor disorder that is not confined to orthographic material, the horizontal axis or constrained saccadic tasks. We conjectured that inaccurate oculo-motor behaviour in USN patients indicates the presence of a reading deficit. With this aim we evaluated 20 patients, i.e., 10 right-sided brain-damaged patients without neglect and 10 patients affected by USN. On the basis of the patients eye movement patterns during a scene exploration task, we found that 4 out of the 10 USN patients presented an abnormal oculo-motor pattern. These same four patients (but not the others) also failed in performing 5 different saccadic tasks and produced neglect dyslexia reading errors in both single words and texts. First, we show that a large proportion of USN patients have inaccurate eye movement behaviour in non-reading tasks. Second, we demonstrate that this exploratory deficit is predictive of the reading impairment. Thus, we conclude that the eye movement deficit prevents reading and impairs the performance on many other perceptual tests, including scene exploration. The large percentage of patients with impaired eye-movement pattern suggests that particular attention should be paid to eye movement behaviour during the diagnostic phase in order to program the best rehabilitation strategy for each patient.

The oral spelling profile of posterior cortical atrophy and the nature of the graphemic representation

ABSTRACT Spelling is a complex cognitive task where central and peripheral components are involved in engaging resources from many different cognitive processes. The present paper aims to both characterize the oral spelling deficit in a population of patients affected by a neurodegenerative condition and to clarify the nature of the graphemic representation within the currently available spelling models. Indeed, the nature of graphemic representation as a linear or multi‐componential structure is still debated. Different hypotheses have been raised about its nature in the orthographic lexicon, with one positing that graphemes are complex objects whereby quantity and identity are separately represented in orthographic representations and can thus be selectively impaired. Posterior cortical atrophy (PCA) is a neurodegenerative condition that mainly affects visuoperceptual and visuospatial functions. Spelling impairments are considered part of the disease. Nonetheless the spelling deficit has received little attention so far and often it has been interpreted in relation to peripheral impairments such as writing difficulties associated with visuoperceptual and visuospatial deficits. In the present study we provide a detailed characterization of the oral spelling profile in PCA. The data suggest that multiple deficits underpin oral spelling problems in PCA, with elements of surface and phonological dysgraphia but also suggesting the involvement of the graphemic buffer. A large phenotypic individual variability is reported. Moreover, the larger proportion and the specific nature of errors involving geminate (i.e., double) as compared to non‐geminate (i.e., non‐double) letters suggest that a further central impairment might be associated with the abstract graphemic representation of letter numerosity. The present study contributes to the clinical characterization of PCA and to the current debate in the cognitive literature on spelling models; findings, despite not definitive, support the hypothesis that graphemic representations are multidimensional mental objects that separately encode information about grapheme identity and quantity. HighlightsA spelling deficit is evident in a large proportion of individuals with PCA.Elements of both surface and phonological dysgraphia are highlighted.Features suggesting a graphemic buffer deficit are also reported.A larger proportion of errors involving geminate (double) letters is described.Results support the hypothesis of graphemes as multidimensional mental objects.

Eyetracking Metrics in Young Onset Alzheimer’s Disease: A Window into Cognitive Visual Functions

Young onset Alzheimer’s disease (YOAD) is defined as symptom onset before the age of 65u2009years and is particularly associated with phenotypic heterogeneity. Atypical presentations, such as the clinic-radiological visual syndrome posterior cortical atrophy (PCA), often lead to delays in accurate diagnosis. Eyetracking has been used to demonstrate basic oculomotor impairments in individuals with dementia. In the present study, we aim to explore the relationship between eyetracking metrics and standard tests of visual cognition in individuals with YOAD. Fifty-seven participants were included: 36 individuals with YOAD (nu2009=u200926 typical AD; nu2009=u200910 PCA) and 21 age-matched healthy controls. Participants completed three eyetracking experiments: fixation, pro-saccade, and smooth pursuit tasks. Summary metrics were used as outcome measures and their predictive value explored looking at correlations with visuoperceptual and visuospatial metrics. Significant correlations between eyetracking metrics and standard visual cognitive estimates are reported. A machine-learning approach using a classification method based on the smooth pursuit raw eyetracking data discriminates with approximately 95% accuracy patients and controls in cross-validation tests. Results suggest that the eyetracking paradigms of a relatively simple and specific nature provide measures not only reflecting basic oculomotor characteristics but also predicting higher order visuospatial and visuoperceptual impairments. Eyetracking measures can represent extremely useful markers during the diagnostic phase and may be exploited as potential outcome measures for clinical trials.

Abstract Conceptual Feature Ratings Predict Gaze Within Written Word Arrays: Evidence From a Visual Wor(l)d Paradigm

The Abstract Conceptual Feature (ACF) framework predicts that word meaning is represented within a high-dimensional semantic space bounded by weighted contributions of perceptual, affective, and encyclopedic information. The ACF, like latent semantic analysis, is amenable to distance metrics between any two words. We applied predictions of the ACF framework to abstract words using eyetracking via an adaptation of the classical visual word paradigm (VWP). Healthy adults (nxa0=xa020) selected the lexical item most related to a probe word in a 4-item written word array comprising the target and three distractors. The relation between the probe and each of the four words was determined using the semantic distance metrics derived from ACF ratings. Eye movement data indicated that the word that was most semantically related to the probe received more and longer fixations relative to distractors. Importantly, in sets where participants did not provide an overt behavioral response, the fixation rates were nonetheless significantly higher for targets than distractors, closely resembling trials where an expected response was given. Furthermore, ACF ratings which are based on individual words predicted eye fixation metrics of probe-target similarity at least as well as latent semantic analysis ratings which are based on word co-occurrence. The results provide further validation of Euclidean distance metrics derived from ACF ratings as a measure of one facet of the semantic relatedness of abstract words and suggest that they represent a reasonable approximation of the organization of abstract conceptual space. The data are also compatible with the broad notion that multiple sources of information (not restricted to sensorimotor and emotion information) shape the organization of abstract concepts. While the adapted VWP is potentially a more metacognitive task than the classical visual world paradigm, we argue that it offers potential utility for studying abstract word comprehension.

Stress in Context: Morpho-Syntactic Properties Affect Lexical Stress Assignment in Reading Aloud

Recent findings from English and Russian have shown that grammatical category plays a key role in stress assignment. In these languages, some grammatical categories have a typical stress pattern and this information is used by readers. However, whether readers are sensitive to smaller distributional differences and other morpho-syntactic properties (e.g., gender, number, person) remains unclear. We addressed this issue in word and non-word reading in Italian, a language in which: (1) nouns and verbs differ in the proportion of words with a dominant stress pattern; (2) information specified by words sharing morpho-syntactic properties may contrast with other sources of information, such as stress neighborhood. Both aspects were addressed in two experiments in which context words were used to induce the desired morpho-syntactic properties. Experiment 1 showed that the relatively different proportions of stress patterns between grammatical categories do not affect stress processing in word reading. In contrast, Experiment 2 showed that information specified by words sharing morpho-syntactic properties outweighs stress neighborhood in non-word reading. Thus, while general information specified by grammatical categories may not be used by Italian readers, stress neighbors with morpho-syntactic properties congruent with those of the target stimulus have a primary role in stress assignment. These results underscore the importance of expanding investigations of stress assignment beyond single words, as current models of single-word reading seem unable to account for our results.

Non-Parametric Mixture Modelling and its Application to Disease Progression Modelling

Dementia is characterised by its progressive degeneration of cognitive abilities. In research cohorts, detailed neuropsychological test batteries are often administered to better understand how cognition changes over time. Understanding cognitive changes in dementia is of great importance, particularly in determining how structural changes in the brain may affect cognition and in facilitating earlier detection of symptomatic changes. Disease progression models are often applied to these data to understand how a disease changes over time from cross-sectional data or to disease trajectories from large numbers of individuals. Previous disease progression models used to build longitudinal models from cross-sectional data have focused on brain imaging data; however, these models are not directly applicable to cognitive data. Here we use the novel, non-parametric, Kernel Density Estimation Mixture Modelling (KDEMM) approach and demonstrate accurate modelling of the progression of cognitive test data. We found that using KDEMM resulted in more accurate models of disease progression in simulated data compared to Gaussian Mixture Models (GMMs) for the majority of parameters used to simulate the data. When comparing KDEMM and GMM to cognitive data collected in different Alzheimers Disease subtypes, we found the KDEMM resulted in a model much more in line with clinical phenotype. We anticipate that the KDEMM will be used to integrate cognitive test data, and other non-normally distributed datasets into complex disease progression models.

CAN EYETRACKING METRICS PROVIDE INSIGHT INTO THE DIAGNOSIS OF DIFFERENT DEMENTIA TYPES? A SPATIAL ANTICIPATION TASK

BDNF polymorphisms on the net change in Memory (Tab 1). In particular, subjects with Tallele of SOD2 and subjects with A allele of BDNF showed a lower decrease of visuospatial and memory domains respectively. SNPs and development of dementia and cognitive impairment: Bivariate analysis showed that among the 176 subjects APOE4 carriers, 14 (8%) developed dementia, and among the 789 non-carriers 35 (4,4%) developed dementia ( p1⁄40.055). Similarly, among the 576 subjects in the BDNF-GG group, 36 (6.3%) developed dementia, and among the 389 subject with BDNF-A allele, 13 (3.3%) developed dementia (p1⁄40.044). Logistic regression showed an increased likelihood of AD for APOE4, whereas the allele A of BDNF decreased the probability of overall dementia and non-aMCI. Conclusions: We found two SNPs (SOD2RS4880-T and BDNF-A) known to be less favorable to gene expression associated with less decline on specific cognitive domains. It has been postulated an age-modulated effect that can reverse the meaning of val/met polymorphism of BDNF (Erickson et al. 2008). APOE4 confirmed its role in development of AD.More epidemiological and experimental studies are needed to better understand the real meaning of these polymorphisms.

Eyetracking metrics reveal impaired spatial anticipation in behavioural variant frontotemporal dementia

Abstract Eyetracking technology has had limited application in the dementia field to date, with most studies attempting to discriminate syndrome subgroups on the basis of basic oculomotor functions rather than higher‐order cognitive abilities. Eyetracking‐based tasks may also offer opportunities to reduce or ameliorate problems associated with standard paper‐and‐pencil cognitive tests such as the complexity and linguistic demands of verbal test instructions, and the problems of tiredness and attention associated with lengthy tasks that generate few data points at a slow rate. In the present paper we adapted the Brixton spatial anticipation test to a computerized instruction‐less version where oculomotor metrics, rather than overt verbal responses, were taken into account as indicators of high level cognitive functions. Twelve bvFTD (in whom spatial anticipation deficits were expected), six SD patients (in whom deficits were predicted to be less frequent) and 38 healthy controls were presented with a 10 × 7 matrix of white circles. During each trial (N = 24) a black dot moved across seven positions on the screen, following 12 different patterns. Participants’ eye movements were recorded. Frequentist statistical analysis of standard eye movement metrics were complemented by a Bayesian machine learning (ML) approach in which raw eyetracking time series datasets were examined to explore the ability to discriminate diagnostic group performance not only on the overall performance but also on individual trials. The original pen and paper Brixton test identified a spatial anticipation deficit in 7/12 (58%) of bvFTD and in 2/6 (33%) of SD patients. The eyetracking frequentist approach reported the deficit in 11/12 (92%) of bvFTD and in none (0%) of the SD patients. The machine learning approach had the main advantage of identifying significant differences from controls in 24/24 individual trials for bvFTD patients and in only 12/24 for SD patients. Results indicate that the fine grained rich datasets obtained from eyetracking metrics can inform us about high level cognitive functions in dementia, such as spatial anticipation. The ML approach can help identify conditions where subtle deficits are present and, potentially, contribute to test optimisation and the reduction of testing times. The absence of instructions also favoured a better distinction between different clinical groups of patients and can help provide valuable disease‐specific markers. HighlightsWe developed an eyetracking instruction‐less test for measuring spatial anticipation.Frequentist and bayesian machine learning (ML) approaches were used.bvFTD patients produced less correct and more incorrect anticipatory saccades.The novel assessment and analysis can provide valuable disease‐specific markers.

CAN EYETRACKING METRICS RELATE TO PERFORMANCE ON VISUAL COGNITIVE TESTS OF INDIVIDUALS WITH YOUNG-ONSET ALZHEIMER’S DISEASE?

compare AD patients with and without confabulations. Methods: 37 healthy control (HC) and 35 individuals with mild to moderate AD were recruited at the Piti e-Salpêtri ere University Hospital. All participants were evaluated on Dalla Barba’s Confabulation Battery to determine their tendency to produce provoked confabulations. Thus, among AD patients, we distinguish between those who produced episodic confabulations, and those who didn’t. Accordingly 27 AD patients were considered free of confabulations (ADC-), and 8 as confabulators (ADC+) (none HC met the criteria). Then, all participants were assessed on a comprehensive neuropsychological battery which evaluate notably episodic memory, language, executive functioning and working memory. Participants also went through a structural MRI to determine whether ADCand ADC+ are similar. Results:Statistical analyses showed a significant difference between HC participants and the two groups of AD patients, in almost all cognitive domains assessed in our battery. However when comparing the two AD groups, they didn’t demonstrate distinct profiles. Regarding the neuroimaging data, and particularly hippocampal subfields volumes, the results showed the same pattern. Conclusions: In demonstrating that there is no cognitive differences between patients with and without confabulations, our results put in doubt some confabulation models supposing a unique and sufficient cognitive (e.g. executive) process underlying the onset of confabulations.