1,721,069 research outputs found

    Beyond and below the cortex: The contribution of striatal dysfunction to cognition and behaviour in neurodegeneration

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    Investigations of cognitive and behavioural changes in neurodegeneration have been mostly focussed on how cortical changes can explain these symptoms. In the proposed review, we will argue that the striatum has been overlooked as a critical nexus in understanding the generation of such symptoms. Although the striatum is historically more associated with motor dysfunction, there is increasing evidence from functional neuroimaging studies in the healthy that striatal regions modulate behaviour and cognition. This should not be surprising, as the striatum has strong anatomical connections to many cortical regions including the frontal, temporal and insula lobes, as well as some subcortical regions (amygdala, hippocampus). To date, however, it is largely unclear to what extent striatal regions are affected in many neurodegenerative conditions - and if so, how striatal dysfunction can potentially influence cognition and behaviour. The proposed review will examine the existing evidence of striatal changes across selected neurodegenerative conditions (Parkinson's disease, progressive supranuclear palsy, Huntington's disease, motor neuron disease, frontotemporal dementia and Alzheimer's disease), and will document their link with the cognitive and behavioural impairments observed. Thus, by reviewing the varying degrees of cortical and striatal changes in these conditions, we can start outlining the contributions of the striatal nexus to cognitive and behavioural symptoms. In turn, this knowledge will inform future studies investigating corticostriatal networks and also diagnostic strategies, disease management and future therapeutics of neurodegenerative conditions

    In two minds: executive functioning versus theory of mind in behavioural variant frontotemporal dementia

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    Background: The relationship of executive function (EF) and theory of mind (ToM) deficits in neurodegeneration is still debated. There is contradicting evidence as to whether these cognitive processes are overlapping or distinct, which has clear clinical relevance for the evaluation of their associated clinical symptoms. Aim: To investigate the relationship of EF and ToM deficits via a data-driven approach in a large sample of patients with behavioural variant frontotemporal dementia (bvFTD). Methods: Data of 46 patients with bvFTD were employed in a hierarchical cluster analysis to determine the similarity of variance between different EF measures (verbal abstraction, verbal initiation, motor programming, sensitivity to interference, inhibitory control, visual abstraction, flexibility, working memory/attention) and ToM (faux pas). Results: Overall results showed that EF measures were clustered separately from the ToM measure. A post hoc analysis revealed a more complex picture where selected ToM subcomponents (empathy; intention) showed a relationship to specific EF measures (verbal abstraction; working memory/attention), whereas the remaining EF and ToM subcomponents were separate. Conclusions: Taken together, these findings suggest that EF and ToM are distinct components; however, ToM empathy and intention subcomponents might share some functions with specific EF processes. This has important implications for guiding diagnostic assessment of these deficits in clinical conditions

    Sensitivity and specificity of ventromedial prefrontal cortex tests in behavioral variant frontotemporal dementia

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    Background: Behavioral variant frontotemporal dementia (bvFTD) is characterized by early and substantial ventromedial prefrontal cortex (VMPFC) dysfunction. To date, however, there is no consensus regarding which tests are most sensitive and specific to assess VMPFC dysfunction in this condition.   Methods: In this study we compared the sensitivity and specificity of four common VMPFC specific tests (Mini-SEA, Go/No-Go Subtest of the Frontal Assessment Battery, Reversal-Learning Test, and Iowa Gambling Task) at first clinic presentation in two neurodegenerative cohorts (bvFTD, Alzheimer's disease) and age-matched, healthy controls.   Results: We found that the Mini-SEA, evaluating theory of mind and emotion processes, emerged as the most sensitive and specific of the VMPFC tests employed. The Mini-SEA alone successfully distinguished bvFTD and Alzheimer's disease (AD) in >82% of subjects at first presentation. Similarly, the FAB Go/No-Go and Reversal-Learning Tests also showed very good discrimination power, but to a lesser degree. The Iowa Gambling Task, one of the most common measures of VMPFC function, was the least specific of these tests.   Conclusion: Sensitivity to detect VMPFC dysfunction was high across all test employed, but specificity varied considerably. The Mini-SEA emerged as the most promising of the VMPFC-specific diagnostic tests. Clinicians should take into account the variable specificity of currently available VMPFC tests, which can complement current carer-based questionnaires and clinical evaluation to improve the diagnosis of behavioral dysfunctions due to VMPFC dysfunction

    Fronto-striatal atrophy in behavioral variant frontotemporal dementia and Alzheimer's disease

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    Behavioral variant frontotemporal dementia (bvFTD) has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD). Considering the critical role the striatum has in cognition and behavior, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white-matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. In contrast, AD showed few fronto-striatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal–ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms

    GREY AND WHITE MATTER BRAIN NETWORK CHANGES IN FRONTOTEMPORAL DEMENTIA SUBTYPES

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    Background: Frontotemporal dementia (FTD) comprises of three clinical syndromes, behavioural-variant frontotemporal dementia (bvFTD), semantic dementia (SV-PPA), and progressive nonfluent aphasia (NFV-PPA) with unique underlying neuroanatomical deficits. To date, however, grey matter structural differences and their connecting white matter tracts in this network have been mostly characterised in comparison to controls, whereas within FTD subtype comparisons in the same patients have not been explored. Methodology: In 94 participants, including bvFTD (n = 16), SV-PPA (n = 16) and NFV-PPA (n = 16), as well as an age-matched control group (n = 46), we employed voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to examine grey and white matter key signatures in each of the three FTD subtypes. Results: Our results showed that bvFTD had specific ventromedial prefrontal cortex and striatum grey matter atrophy along with their connecting white matter tracts compared to other FTD subtypes. By contrast, SV-PPA showed additional temporal pole grey matter damage to bvFTD and grey and white matter temporal, amygdala and insula changes compared to NFV-PPA. Finally, NFV-PPA showed mild insula grey and white matter changes compared to bvFTD but differed from SV-PPA only on anterior corpus callosum white matter changes. Conclusions: Our findings clearly indicate that not only grey matter regions of the FTD network but also their white matter connecting tracts have specific signatures for each FTD subtype. These promising findings highlight how neural network approaches can shed new light on neurodegenerative conditions and FTD in particular, which will inform future diagnostic and disease management. © Versita Sp. z o.o

    Money for nothing - Atrophy correlates of gambling decision making in behavioural variant frontotemporal dementia and Alzheimer's disease

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    Neurodegenerative patients show often severe everyday decision making problems. Currently it is however not clear which brain atrophy regions are implicated in such decision making problems. We investigated the atrophy correlates of gambling decision making in a sample of 63 participants, including two neurodegenerative conditions (behavioural variant frontotemporal dementia - bvFTD; Alzheimer's disease - AD) as well as healthy age-matched controls. All participants were tested on the Iowa Gambling Task (IGT) and the behavioural IGT results were covaried against the T1 MRI scans of all participants to identify brain atrophy regions implicated in gambling decision making deficits. Our results showed a large variability in IGT performance for all groups with both patient groups performing especially poor on the task. Importantly, bvFTD and AD groups did not differ significantly on the behavioural performance of the IGT. However, by contrast, the atrophy gambling decision making correlates differed between bvFTD and AD, with bvFTD showing more frontal atrophy and AD showing more parietal and temporal atrophy being implicated in decision making deficits, indicating that both patient groups fail the task on different levels. Frontal (frontopolar, anterior cingulate) and parietal (retrosplenial) cortex atrophy covaried with poor performance on the IGT. Taken together, the atrophy correlates of gambling decision making show that such deficits can occur due to a failure of different neural structures, which will inform future diagnostics and treatment options to alleviate these severe everyday problems in neurodegenerative patients

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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