Variance In Cognitive Performance Research Articles

Effects of stochastic vestibular stimulation on cognitive performance in children with ADHD

Previous work has shown that exposure to auditory white noise (WN) can improve cognitive performance in children with ADHD, but it is unknown whether this improvement generalizes to other sensory modalities. To address this knowledge gap, we tested the effect of Stochastic Vestibular Stimulation (SVS) on cognitive performance and reaction time (RT) variability in two groups: children with ADHD and typically developing children (TDC). Children with ADHD (N=42) and TDC (N=28) performed three cognitive tasks (Spanboard, Word Recall and N-back tasks) at two different occasions, with and without exposure to SVS, in a double blinded design. The results showed no main effects of SVS on neither performance nor RT variability for children in any of the groups, and no interactions between SVS and group. Based on these results we conclude that, using our stimulation protocol, the positive effects of WN exposure on cognition in children with ADHD do not generalize to Stochastic Vestibular Stimulation.

Validating virtual administration of neuropsychological testing in Parkinson disease: a pilot study

COVID-19 has highlighted the need for remote cognitive testing, but the reliability and validity of virtual cognitive testing in Parkinson disease (PD) is unknown. Therefore, we assessed PD participants enrolled in an observational, cognition-focused study with an extensive cognitive battery completed both in-person and via video conference close in time. Data for 35 PD participants with normal cognition to mild dementia were analyzed. Only one test (semantic verbal fluency) demonstrated a difference in score by administration type, with a significantly better score virtually. Only three tests demonstrated good reliability for in-person versus virtual testing, but reliability values for visit 1 versus visit 2 were similarly low overall. Trail Making Test B was successfully administered virtually to only 18 participants due to technical issues. Virtual and in-person cognitive testing generate similar scores at the group level, but with poor to moderate reliability for most tests. Mode of test administration, learning effects, and technical difficulties explained little of the low test–retest reliability, indicating possible significant short-term variability in cognitive performance in PD in general, which has implications for clinical care and research. In-person cognitive testing with a neuropsychologist remains the gold standard, and it remains to be determined if virtual cognitive testing is feasible in PD.

Unexpected cognitive similarities between older adults and young people: Scores variability and cognitive performances

BackgroundIncreased interindividual variability in cognitive performance during aging has been proposed as an indicator of cognitive reserve. ObjectiveTo determine if interindividual variability performance in episodic memory (PAL), working memory (SWM), reaction time (RTI), and sustained attention (RVP) could differentiate clusters of differential cognitive performance in healthy young and older adults and search for cognitive tests that most contribute to these differential performances. MethodsWe employed hierarchical cluster and canonical discriminant function analyses of cognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) to identify cognitive variability in older and young adults using the coefficient of variability of cognitive performances between and within groups. We also analyzed potential influences of age, education, and physical activity. ResultsCluster analysis distinguished groups with differential cognitive performance and correlation analysis revealed coefficient of variability and cognitive performance associations. The greater the coefficient of variability the poorer was cognitive performance in RTI but not in PAL and SWM. Older adults showed diverse trajectories of cognitive decline, and better education or higher percentage of physically active individuals exhibited better cognitive performance in both older and young adults. ConclusionPAL and SWM are the most sensitive tests to investigate the wide age range encompassing older and young adults. In older adults’ intragroup analysis PAL showed greater discriminatory capacity, indicating its potential for clinical applications late in life. Our data underscore the importance of studying variability as a tool for early detection of subtle cognitive declines and for interpreting results that deviate from normality.

Strength and multiple types of physical activity predict cognitive function independent of low muscle mass in NHANES 1999–2002

AbstractIntroductionMultiple domains of cognitive function decline with age, resulting in a significant burden on quality of life and the healthcare system. Recent studies increasingly point to links between muscle mass, particularly low muscle mass, and risk of cognitive decline. However, complex relationships exist between muscle mass, muscle function, physical activity, and overall health.MethodsData from 1,424 adults 60+ years old in the 1999‐2000 and 2001‐2002 editions of the National Health and Nutrition Examination Survey (NHANES) were used to investigate the relationship between low muscle mass and cognitive function after accounting for strength, physical activity, and nutritional and metabolic risk factors for cognitive decline.ResultsMuscle strength and physical activity independently predicted performance in the digit symbol substitution test, with muscle mass and muscle strength explaining 0.5% and 5% of the variance in cognitive function, respectively. In graphical network analyses, the association between low muscle mass and cognitive function appeared to be primarily mediated by neuromuscular function. Physical activity was associated with strength but, surprisingly, not muscle mass, which was instead more closely related to total mass.ConclusionsLow muscle mass is a relatively poor predictor of cognitive function after accounting for physical activity and strength in older individuals from a representative population dataset in the US. Future studies should account for the way in which muscle mass is accrued, which is likely to confound any association between muscle mass and health outcomes.

Bidirectional genetic overlap between autism spectrum disorder and cognitive traits

Autism spectrum disorder (ASD) is a highly heritable condition with a large variation in cognitive function. Here we investigated the shared genetic architecture between cognitive traits (intelligence (INT) and educational attainment (EDU)), and risk loci jointly associated with ASD and the cognitive traits. We analyzed data from genome-wide association studies (GWAS) of INT (n = 269,867), EDU (n = 766,345) and ASD (cases n = 18,381, controls n = 27,969). We used the bivariate causal mixture model (MiXeR) to estimate the total number of shared genetic variants, local analysis of co-variant annotation (LAVA) to estimate local genetic correlations, conditional false discovery rate (cond/conjFDR) to identify specific overlapping loci. The MiXeR analyses showed that 12.7k genetic variants are associated with ASD, of which 12.0k variants are shared with EDU, and 11.1k are shared with INT with both positive and negative relationships within overlapping variants. The majority (59–68%) of estimated shared loci have concordant effect directions, with a positive, albeit modest, genetic correlation between ASD and EDU (rg = 0.21, p = 2e−13) and INT (rg = 0.22, p = 4e−12). We discovered 43 loci jointly associated with ASD and cognitive traits (conjFDR<0.05), of which 27 were novel for ASD. Functional analysis revealed significant differential expression of candidate genes in the cerebellum and frontal cortex. To conclude, we quantified the genetic architecture shared between ASD and cognitive traits, demonstrated mixed effect directions, and identified the associated genetic loci and molecular pathways. The findings suggest that common genetic risk factors for ASD can underlie both better and worse cognitive functioning across the ASD spectrum, with different underlying biology.

Impact of sleep deprivation on neurocognition and inflammation in rhesus macaques

Sleep deprivation in humans is associated with both cognitive impairment and immune dysregulation. An animal model of neuropathogenesis may provide insight to understand the effects of sleep deprivation on the brain. Human neurocognition is more closely mirrored by nonhuman primates (NHP) than other animals. As such, we developed an NHP model to assess the impact of sleep deprivation on neurocognition and markers of systemic immune activation. Six male rhesus macaques underwent three rounds of sleep deprivation (48 h without sleep) at days 0, 14, and 28. We performed domain specific cognitive assessments using the Cambridge Neuropsychological Test Automated Battery (CANTAB) via a touch screen before and after 24 and 48 h of sleep deprivation. Immune activation markers were measured in the blood by multiplex assay and flow cytometry. Although we observed variability in cognitive performance between the three rounds of sleep deprivation, cognitive impairments were identified in all six animals. We noted more cognitive impairments after 48 h than after 24 h of sleep deprivation. Following 48 h of sleep deprivation, elevations in markers of immune activation in the blood were observed in most animals. The observed impairments largely normalized after sleep. The co-occurrence of systemic immune alterations and cognitive impairment establishes this model as useful for studying the impact of sleep deprivation on neurobehavior and immune perturbations in rhesus macaques.

Multivariate prediction of cognitive performance from the sleep electroencephalogram

Human cognitive performance is a key function whose biological foundations have been partially revealed by genetic and brain imaging studies. The sleep electroencephalogram (EEG) is tightly linked to structural and functional features of the central nervous system and serves as another promising biomarker. We used data from MrOS, a large cohort of older men and cross-validated regularized regression to link sleep EEG features to cognitive performance in cross-sectional analyses. In independent validation samples 2.5–10% of variance in cognitive performance can be accounted for by sleep EEG features, depending on the covariates used. Demographic characteristics account for more covariance between sleep EEG and cognition than health variables, and consequently reduce this association by a greater degree, but even with the strictest covariate sets a statistically significant association is present. Sigma power in NREM and beta power in REM sleep were associated with better cognitive performance, while theta power in REM sleep was associated with worse performance, with no substantial effect of coherence and other sleep EEG metrics. Our findings show that cognitive performance is associated with the sleep EEG (r = 0.283), with the strongest effect ascribed to spindle-frequency activity. This association becomes weaker after adjusting for demographic (r = 0.186) and health variables (r = 0.155), but its resilience to covariate inclusion suggest that it also partially reflects trait-like differences in cognitive ability.

Cognitive performance is linked to fitness in a wild primate.

Cognitive performance varies widely across animal species, but the processes underlying cognitive evolution remain poorly known. For cognitive abilities to evolve, performance must be linked to individual fitness benefits, but these links have been rarely studied in primates even though they exceed most other mammals in these traits. We subjected 198 wild gray mouse lemurs to four cognitive and two personality tests and subsequently monitored their survival in a mark-recapture study. Our study revealed that survival was predicted by individual variation in cognitive performance as well as body mass and exploration. Because cognitive performance covaried negatively with exploration, individuals gathering more accurate information enjoyed better cognitive performance and lived longer, but so did heavier and more explorative individuals. These effects may reflect a speed-accuracy trade-off, with alternative strategies yielding similar overall fitness. The observed intraspecific variation in selective benefits of cognitive performance, if heritable, can provide the basis for the evolution of cognitive abilities in members of our lineage.

Intra-individual variability adaptively increases following inhibition training during middle childhood

There is ongoing debate on the relationship between intra-individual variability (IIV) of cognitive processes and task performance. While psychological research has traditionally assumed that lower intra-individual variability (IIV) aids consistent task performance, some studies suggest that greater IIV can also be adaptive, especially when flexible responding is required. Here we selectively manipulate inhibitory control (Stopping) and response speed (Going) by means of a training paradigm to 1) assess how this manipulation impacts Stopping IIV and its relationship to task performance, and 2) replicate previous findings showing that reductions in Going IIV are adaptive. A group of 208 6–13-year-old children were randomly allocated to an 8-week training targeting Stopping (experimental group) or Going (control group). The stop signal task was administered before and after training. Training Stopping led to adaptive increases in Stopping IIV, where greater flexibility in cognitive processing may be required to meet higher task demands. In line with previous studies, training Going led to adaptive reductions in Going IIV, which allows more consistent and efficient Going performance. These findings provide systematic and causal evidence of the process-dependent relationship of IIV and task performance in the context of Stopping and Going, suggesting a more nuanced perspective on IIV with implications for developmental, ageing and intervention studies.

The impact of early adversity and education on genetic and brain morphological predictors of cognitive ability.

Cognitive ability is a strong predictor of occupational achievement, quality of life and physical health. While variation in cognition is strongly heritable and has been robustly associated with early environment and brain morphology, little is known about how these factors combine and interact to explain this variation in cognition. To address this, we modelled the relationship between common genetic variation, grey matter volume, early life adversity and education and cognitive ability in a UK Biobank sample of N = 5237 individuals using structural equation modelling. We tested the hypotheses that total grey matter volume would mediate the association between genetic variation and cognitive ability, and that early life adversity and educational attainment would moderate this relationship. Common genetic variation, grey matter volume and early life adversity were each significant predictors in the model, explaining ~15% of variation in cognitive ability. Contrary to our hypothesis, grey matter volume did not mediate the relation between genetic variation and cognition performance. Neither did early life adversity or educational attainment moderate this relation, although educational attainment was observed to moderate the relationship between grey matter volume and cognitive performance. We interpret these findings in terms of the modest explanatory value of currently estimated polygenic scores accounting for variation in cognitive performance (~5%), making potential mediating and moderating variables difficult to confirm.

The role of cognitive factors in second language writing and writing to learn a second language

AbstractThis article revisits the role of cognitive individual differences in creating synergies between second language (L2) writing and second language acquisition research that were proposed by Kormos (2012). It takes stock of the advances in research findings, in the past decade, on the role of working memory and language learning aptitude in L2 writing processes and performance. The article offers an overview of how cognitive factors can mediate learning gains when L2 users engage in writing. Using theoretical accounts of cognitive individual differences, the article discusses how the characteristics of writing tasks can interact with individual variation in cognitive functioning. The article concludes by proposing a Task-Mediated Cognitive Model of L2 Writing and Writing to Learn that describes the role of cognitive factors in L2 writing processes and in learning through writing, and an outline of a research agenda for future studies.

Cortical thickness moderates intraindividual variability in prefrontal cortex activation patterns of older adults during walking.

Increased intraindividual variability (IIV) in behavioral and cognitive performance is a risk factor for adverse outcomes but research concerning hemodynamic signal IIV is limited. Cortical thinning occurs during aging and is associated with cognitive decline. Dual-task walking (DTW) performance in older adults has been related to cognition and neural integrity. We examined the hypothesis that reduced cortical thickness would be associated with greater increases in IIV in prefrontal cortex oxygenated hemoglobin (HbO2) from single tasks to DTW in healthy older adults while adjusting for behavioral performance. Participants were 55 healthy community-dwelling older adults (mean age = 74.84, standard deviation (SD) = 4.97). Structural MRI was used to quantify cortical thickness. Functional near-infrared spectroscopy (fNIRS) was used to assess changes in prefrontal cortex HbO2 during walking. HbO2 IIV was operationalized as the SD of HbO2 observations assessed during the first 30 seconds of each task. Linear mixed models were used to examine the moderation effect of cortical thickness throughout the cortex on HbO2 IIV across task conditions. Analyses revealed that thinner cortex in several regions was associated with greater increases in HbO2 IIV from the single tasks to DTW (ps < .02). Consistent with neural inefficiency, reduced cortical thickness in the PFC and throughout the cerebral cortex was associated with increases in HbO2 IIV from the single tasks to DTW without behavioral benefit. Reduced cortical thickness and greater IIV of prefrontal cortex HbO2 during DTW may be further investigated as risk factors for developing mobility impairments in aging.

Predictors of within-individual variability in cognitive performance in schizophrenia in a South African case-control study.

Cognitive dysfunction in schizophrenia may be assessed by measuring within-individual variability (WIV) in performance across a range of cognitive tests. Previous studies have found increased WIV in people with schizophrenia, but no studies have been conducted in low- to middle-income countries where the different sociocultural context may affect WIV. We sought to address this gap by exploring the relationship between WIV and a range of clinical and demographic variables in a large study of people with schizophrenia and matched controls in South Africa. 544 people with schizophrenia and 861 matched controls completed an adapted version of The University of Pennsylvania Computerized Neurocognitive Battery (PennCNB). Demographic and clinical information was collected using the Structured Clinical Interview for DSM-IV Diagnoses. Across-task WIV for performance speed and accuracy on the PennCNB was calculated. Multivariate linear regression was used to assess the relationship between WIV and a diagnosis of schizophrenia in the whole sample, and WIV and selected demographic and clinical variables in people with schizophrenia. Increased WIV of performance speed across cognitive tests was significantly associated with a diagnosis of schizophrenia. In people with schizophrenia, increased speed WIV was associated with older age, a lower level of education and a lower score on the Global Assessment of Functioning scale. Increased accuracy WIV was significantly associated with a younger age in people with schizophrenia. Measurements of WIV of performance speed can add to the knowledge gained from studies of cognitive dysfunction in schizophrenia in resource-limited settings.

Within-Individual Variation in Cognitive Performance Is Not Noise: Why and How Cognitive Assessments Should Examine Within-Person Performance.

Despite evidence that it exists, short-term within-individual variability in cognitive performance has largely been ignored as a meaningful component of human cognitive ability. In this article, we build a case for why this within-individual variability should not be viewed as mere measurement error and why it should be construed as a meaningful component of an individual's cognitive abilities. We argue that in a demanding and rapidly changing modern world, between-individual analysis of single-occasion cognitive test scores does not account for the full range of within-individual cognitive performance variation that is implicated in successful typical cognitive performance. We propose that short-term repeated-measures paradigms (e.g., the experience sampling method (ESM)) be used to develop a process account of why individuals with similar cognitive ability scores differ in their actual performance in typical environments. Finally, we outline considerations for researchers when adapting this paradigm for cognitive assessment and present some initial findings from two studies in our lab that piloted the use of ESM to assess within-individual cognitive performance variation.

Impacts of cerebral small vessel disease on global and domain‐specific cognition

AbstractBackgroundThe 2021 Alzheimer’s Association International Conference press release forecasted global dementia cases to triple by 2050, due to the major contribution of increases in vascular risk factors. The Global Vascular Risk Score (GVRS) was developed to predict vascular events using a point‐based index for risk factor variables, though has demonstrated to be a significant predictor of global and domain‐specific cognitive performance in a multi‐ethnic cohort (Rundek, T. et al. Global Vascular Risk Score and CAIDE Dementia Risk Score Predict Cognitive Function in the Northern Manhattan Study. J Alzheimers Dis 73, 1221‐1231 (2020)). However, more than half of the variance in global and domain‐specific cognitive performance is still unexplained by GVRS variables. We sought to explain additional variance in cognitive performance by addition of MRI biomarkers of cerebral small vessel disease to the GVRS model.MethodWe included 1290 subjects from the multiethnic Northern Manhattan Study population (age 64+/‐8 years, 40% women, 66% Hispanic, 17% non‐Hispanic Black, 15% non‐Hispanic White, education 10+/‐5 years). Multivariate linear regression models were employed to assess the added value of the cerebral small vessel disease MRI measures (white matter hyperintensity volume, silent brain infarcts, cerebral microbleeds, and perivascular spaces) beyond GVRS variables in explaining more variance in global and domain‐specific (episodic memory, executive function, semantic memory, and processing speed) cognitive performance. The explained variance (R2) of the GVRS model was compared to the proposed model with added imaging markers to determine their predictive performance. Statistical significance was determined using F‐statistic difference test between the models.ResultThe explained variance (R2) and F‐statistic for models of global and domain‐specific cognition are in the table. Addition of MRI measures significantly improved the model for global cognition (F(4, 1108) = 2.68, p &lt; 0.05) and domain‐specific cognitive performance models of episodic memory (F(4, 1096) = 3.34, p &lt; 0.01) and processing speed (F(4, 1096) = 2.40, p &lt; 0.05).ConclusionMRI measures of cerebral small vessel disease explain more variance in global cognition, episodic memory, and processing speed than GVRS factors alone. However, most of the variance in cognitive performance remains unexplained.

Sleep quality and psychological well-being of university students

The duration and time of sleep affect the general health and well-being of individuals. It has been recommended that adults, aged 18 –64 years, should sleep for 7 to 9 hours per night, however, many people struggle with sleep problems of various kinds and hardly meet these recommendations. Sleep is necessary for cognition, alertness, vigilance, and sustenance of attention as well as control of emotions. The effects of sleep deprivation on cognitive performance and other psychological variables have been widely studied. Sleepiness, the short-term effect of inadequate sleep, may lead to irritability, reduced alertness, poor motor skills, and attention problems. Among the long-term effects are obesity, type 2 diabetes, hypertension, and mental health disorders. Sleep deprivation in adults of all ages is defined as getting less than 7 hours of sleep per night.

White Matter Degeneration Pathways Associated With Tau Deposition in Alzheimer Disease.

The dynamics of white matter (WM) changes are understudied in Alzheimer disease (AD). Our goal was to study the association between flortaucipir PET and WM health using neurite orientation dispersion and density imaging (NODDI) and evaluate its association with cognitive performance. Specifically, we focused on NODDI's Neurite Density Index (NDI), which aids in capturing axonal degeneration in WM and has greater specificity than single-shell diffusion MRI methods. We estimated regional flortaucipir PET standard uptake value ratios (SUVRs) from 3 regions corresponding to Braak stage I, III/IV, and V/VI to capture the spatial distribution pattern of the 3R/4R tau in AD. Then, we evaluated the associations between these measurements and NDIs in 29 candidate WM tracts using Pearson correlation and multiple regression models. Based on 223 participants who were amyloid positive (mean age of 78 years and 57.0% male, 119 cognitively unimpaired, 56 mild cognitive impairment, and 48 dementia), the results showed that WM tracts NDI decreased with increasing regional Braak tau SUVRs. Of all the significant WM tracts, the uncinate fasciculus (r = -0.274 for Braak I, -0.311 for Braak III/IV, and -0.292 for Braak V/VI, p < 0.05) and cingulum adjoining hippocampus (r = -0.274, -0.288, -0.233, p < 0.05), both tracts anatomically connected to areas of early tau deposition, were consistently found to be within the top 5 distinguishing WM tracts associated with flortaucipir SUVRs. The increase in tau deposition measurable outside the medial temporal lobes in Braak III-VI was associated with a decrease in NDI in the middle and inferior temporal WM tracts. For cognitive performance, WM NDI had similar coefficients of determination (r 2 = 31%) as regional Braak flortaucipir SUVRs (29%), and together WM NDI and regional Braak flortaucipir SUVRs explained 46% of the variance in cognitive performance. We found spatially dependent WM degeneration associated with regional flortaucipir SUVRs in Braak stages, suggesting a spatial pattern in WM damage. NDI, a specific marker of axonal density, provides complementary information about disease staging and progression in addition to tau deposition. Measurements of WM changes are important for the mechanistic understanding of multifactorial pathways through which AD causes cognitive dysfunction.

Cognitive reserve and dementia risk management in people with an intellectual disability.

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Assessing Flexibility of Solution Strategy: Strategy Shifting as a Measure of Cognitive Reserve.

This series of experiments explores whether flexibility in strategy shifting might function as an expression of cognitive reserve (CR). A reasoning task was designed using matrix reasoning stimuli that each required 1 of 2 specific solution strategies: logicoanalytic and visuospatial. It was formatted as a task-switching paradigm, assessing the ability to switch between solution strategies as measured by switch costs. Study 1 was done on Amazon Mechanical Turk and included an assessment of CR proxies. Study 2 used participants who had been studied extensively with neuropsychological assessments and structural neuroimaging. Study 1 found that switch costs increased with aging. In addition, a relationship between switch costs and CR proxies was noted, suggesting a relationship between the flexibility of strategy shifting and CR. The results of Study 2 again indicated that age negatively affected strategy-shifting flexibility, but that individuals with higher CR as measured with standard proxies performed better. The flexibility measure accounted for additional variance in cognitive performance over that explained by cortical thickness, suggesting that it may contribute to CR. Overall, the results are consistent with the idea that flexibility in strategy shifting might be 1 cognitive process that underlies cognitive reserve.

Assessment of executive functions through a virtual reality task in euthymic patients with bipolar disorder and influence in psychosocial functioning

Introduction Previous research has shown that neurocognitive deficits, especially deficits in executive functions, may persist during euthymia in in patients with bipolar disorder (BD) and that those are associated with an impairment of psychosocial functioning. The assessment of executive functions (EFs) is normally carried out using laboratory tests. Novel methodologies such as virtual reality (VR) allow the creation of immersive environments, to evaluate executive performance with greater potential for ecological validity than evaluations with standard tasks. Objectives The objectives of this project are to evaluate executive performance in euthymic patients with BD with a novel virtual reality task compared to standard computerized tasks, and to find predictors of functioning associated with cognitive performance. Methods This is a cross sectional study in which 46 euthymic patients with BD treated at La Fe University and Polytechnic Hospital were assessed with a battery of standard computerized tasks (ST) (TMT/Stroop,/Go-No-Go/TOL/DOT) and with the Cooking Task virtual reality task. The Cooking Task presents 4 tasks of increasing difficulty in which you must cook food in a specific time. It records total time to complete the task, whether food is cooled or burned, the simultaneous use of two fires, the proper use of seasonings and the time to set the table. Functioning was assessed with the Functioning Assessment Short Test (FAST) that evaluates the overall functioning of patients with a mental illness in 6 subscales. Correlation analyses between cognitive performance variables and clinical variables were done. Multiple linear regression was performed with the FAST score as a dependent variable and cognitive performance variables and relevant clinical variables to executive functioning (months of euthymia, age, and number of total episodes) were included as independent variables. Results A worse psychosocial functioning was significantly associated with a worse performance in standard tasks (TMTA, TMTB, STROOP, and TOL) and cooking task (total time spent on task 2, burning time and total time spent on task 3, and total time spent on task 4). In the regression analysis, the correct simultaneous use of the two fires was the best predictor of a better psychosocial functioning in BD patient. This implies the preserved ability of planning and performing dual tasks. Conclusions Our findings suggest that euthymic patients with BD present deficits in executive functions related with a worse psychosocial functioning. Among the tasks, the cooking task may have a greater sensitivity than standards task to predict real functioning. This in an opportunity to design virtual applications for diagnostic and therapeutic purposes. Disclosure of Interest None Declared