Biology subjects

Irish, M.

Publications and source records attributed to Irish, M..

3 recordsLinked to original sources

bioRxiv2019

Establishing two principal dimensions of cognitive variation in Logopenic Progressive Aphasia

Logopenic Progressive Aphasia (LPA) is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal atrophy. Clinical descriptions of LPA largely concentrate on profiling language deficits, however, accumulating evidence points to the presence of cognitive deficits, even on tasks with minimal language demands. Although non-linguistic cognitive deficits in LPA are thought to scale with disease severity, patients at discrete stages of language dysfunction display overlapping cognitive profiles, suggesting individual-level variation in cognitive performance, independent of primary language dysfunction. To address this issue, we used principal component analysis to decompose individual-level variation in cognitive performance in 43 well-characterised LPA patients who underwent multi-domain neuropsychological assessments and structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected speech production and verbal memory deficits which typify LPA. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable Factor 1 scores, regardless of their severity, diverge considerably on visuo-executive test performance, underscoring the inter-individual variability in cognitive profiles in comparably logopenic patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralised temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, LPA patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralised temporoparietal and frontal atrophy. Our findings demonstrate the inherent variation in cognitive performance at an individual- and group-level in LPA, suggesting the presence of a genuine co-occurring cognitive impairment that is independent of language function and disease severity.

neuroscience↗

bioRxiv2018

Default mode and primary visual network coupling is associated with increased mind-wandering frequency in Parkinson’s disease with visual hallucinations

A mismatch between top-down expectations and incoming sensory information is thought to be associated with hallucinations across a range of neuropsychiatric disorders. In Parkinsons disease with visual hallucinations, abnormal activity within the default network, and its pattern of connectivity with early visual regions, has been identified as a potential pathological source of the internally generated expectations that override incoming sensory input. In the context of attention deficits and visual dysfunction, mental imagery and perceptual expectancies generated across the default network are suggested to exert excessive influence over earlier visual regions, leading to aberrant perceptual experiences. Whilst converging neuroimaging evidence has identified unconstrained default network activity in Parkinsons disease with hallucinations, to date there has been a lack of behavioural evidence to confirm the consequences of an over-engaged default mode network - therefore the contributions it might make to hallucination phenomenology remain speculative. To address this, we administered a validated thought-sampling task to 38 Parkinsons disease patients (18 with hallucinations; 20 without) and 40 controls, to test the hypothesis that individuals with hallucinations experience an increased frequency of mind-wandering - a form of spontaneous cognition strongly associated with mental imagery and default network activity. The neural correlates of mind-wandering frequency were examined in relation to resting-state functional connectivity. Our results showed that patients with hallucinations exhibited significantly higher mind-wandering frequencies compared to non-hallucinators, who in turn had reduced levels of mind-wandering relative to controls. Inter-network connectivity and seed-to-voxel analyses confirmed that increased mind-wandering in the hallucinating vs. non-hallucinating group was associated with greater coupling between the primary visual cortex and dorsal default network. Taken together, both elevated mind-wandering and increased default-visual network coupling emerged as a distinguishing feature of the hallucinatory phenotype. We propose that the finding of increased mind-wandering reflects unconstrained spontaneous thought and mental imagery, which in turn furnish the content of visual hallucinations. Our findings suggest that primary visual cortex to dorsal default network coupling may provide a neural substrate by which regions of the default network exert disproportionate influence over ongoing visual perception. These findings refine current models of visual hallucinations by identifying a specific cognitive phenomenon and neural substrate consistent with the top-down influences over perception that have been implicated in visual hallucinations.

neuroscience↗

bioRxiv2017

Hippocampal atrophy and intrinsic brain network alterations relate to impaired capacity for mind wandering in neurodegeneration

Mind wandering represents the human capacity for internally focussed thought, and relies upon the brains default network and its interactions with attentional networks. Studies have characterised mind wandering in healthy people, yet there is limited understanding of how this capacity is affected in clinical populations. This study used a validated thought-sampling task to probe mind wandering capacity in two neurodegenerative disorders: behavioural variant frontotemporal dementia (bvFTD; n=35) and Alzheimers disease (AD; n=24), compared to older controls (n=37). These patient groups were selected due to canonical structural and functional changes across sites of the default and frontoparietal networks, and well-defined impairments in cognitive processes that support mind wandering. Relative to controls, bvFTD patients displayed significantly reduced mind wandering capacity, offset by a significant increase in stimulus-bound thought. In contrast, AD patients demonstrated comparable levels of mind wandering to controls, in the context of a relatively subtle shift towards stimulus-/task-related forms of thought. In the patient groups, mind wandering was associated with grey matter integrity in the hippocampus/parahippocampus, striatum, insula and orbitofrontal cortex. Resting state functional connectivity revealed associations between mind wandering capacity and connectivity within and between regions of the frontoparietal and default networks, with distinct patterns evident in patients vs. controls. These findings support a relationship between altered mind wandering capacity in neurodegenerative disorders, and structural and functional integrity of the default and frontoparietal networks. This study highlights a dimension of cognitive dysfunction not well documented in neurodegenerative disorders, and validates current models of mind wandering in a clinical population.\n\nSignificance statementHumans spend much of their waking life engaged in mind wandering. Underlying brain systems supporting this complex ability have been established in healthy individuals, yet it remains unclear how mind wandering is altered in neuropsychiatric populations. We reveal changes in the thought profiles elicited during periods of low cognitive demand in dementia, resulting in reduced mind wandering and an increased propensity towards stimulus-bound thought. These altered thought profiles were associated with structural and functional brain changes in the hippocampus, default and frontoparietal networks; key regions implicated in internal mentation in healthy individuals. Our findings provide a unique clinical validation of current theoretical models of mind wandering, and reveal a dimension of cognitive dysfunction that has received scant attention in dementia.

neuroscience↗