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Halai, A. D.

Publications and source records attributed to Halai, A. D..

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Multidimensional semantic representations emerge from multi-frequency representational similarity learning

Current theories of semantic representation are agnostic about how fine-grained neurophysiological activity corresponds to representation of multidimensional semantic information. By applying an innovative multivariate technique (representational similarity learning; RSL), we adjudicated three hypotheses: (1) that multidimensional semantic structure is represented within a single frequency range (e.g., gamma/high gamma); (2) that each semantic dimension is independently represented within a different frequency range; and (3) that multidimensional semantic information is "transfrequency" (at least some information emerges only when multiple frequencies are considered together). RSL was applied to time-frequency power and phase data extracted from electrocorticography (ECoG) grid electrodes on the surface of human ventral anterior temporal lobe (vATL). We found significant decoding of graded, multidimensional semantic information from a wide range of frequencies (4 - 200 Hz), but not from individual frequency bands, providing clear evidence that multidimensional semantic information is coded in a transfrequency fashion.

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Adjudicating competing theories of semantic representation with 7T-fMRI and multivariate decoding

The anterior temporal lobes (ATLs) are known to support semantic cognition, but theories about their precise representational coding vary. We collected 7T-fMRI data with a novel acquisition sequence designed to improve signal quality in the ATLs, then employed a pioneering analytical approach (comparative multivariate decoding) to adjudicate between theories. Specifically, we applied multiple decoding methods, each making different assumptions about the content, nature or location of representations within the ATLs, then used the pattern of results across methods to adjudicate competing hypotheses. The results suggest that the ATLs represent domain-general semantic information via a multidimensional inchoate vector-space code that is anatomically clustered within and across individuals, and that posterior temporal and occipitotemporal regions utilise a similar domain-general, inchoate vector-space code. More generally, the comparative multivariate analytical framework utilised here has the potential to reveal how the brain represents, not just semantic knowledge, but any kind of information.

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All spectral frequencies of neural activity reveal semantic representation in the human anterior ventral temporal cortex

Intracranial electrophysiology offers a unique insight into the nature of information representation in the brain - it can be used to disentangle information encoded in local neuronal activity (gamma and high gamma frequencies) from information encoded via long-range interactions (lower frequencies). We used regularised logistic regression to decode animacy from time-frequency power and phase extracted from electrocorticography (ECoG) grid electrode data recorded on the surface of human vATL. Power in gamma (30 - 60 Hz) and high gamma (60 - 200 Hz) produced reliable decoding, indicating that semantic information is indeed expressed by local populations in vATL. However, power from a wide range of frequencies (4 - 200 Hz) produced significantly higher decoding accuracy and also exhibited the same rapidly-changing dynamic code previously observed when decoding voltage. These findings support the theory that semantic information is encoded by a local vATL "hub" that interacts with distributed cortical "spokes".

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Optimising 7T-fMRI for imaging regions of magnetic susceptibility

The temporal signal-to-noise ratio (tSNR) of functional magnetic resonance imaging (fMRI) is particularly poor in ventral anterior temporal and orbitofrontal regions because of B0 and B1+ magnetic field inhomogeneity, a problem that is exacerbated at higher field strengths. In this 7T-fMRI study we compared three methods of improving sensitivity in these areas: parallel transmit, which uses multiple transmit elements, controlled independently, to homogenise the flip angle experienced by the tissue; multi-echo, which entails collection of multiple volumes at different echo times following a single radiofrequency pulse; and multiband, in which multiple slices are acquired simultaneously. We found that parallel transmit and multi-echo increased the magnitude of the BOLD signal change, but only multi-echo increased BOLD magnitude in areas prone to susceptibility artefacts. Multiband and denoising of multi-echo data with independent components analysis (ICA) both improved precision of GLM fit. Exploratory results suggested that multi-echo and ICA denoising can both benefit multivariate analyses. In conclusion, a multi-echo, multiband sequence improved fMRI quality in areas prone to susceptibility artefacts while maintaining sensitivity across the whole brain. We recommend this approach for studies investigating the functional roles of ventral temporal and orbitofrontal regions with 7T fMRI.

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The multidimensional neurocognitive geometry in Alzheimer's disease and posterior cortical atrophy

Background and ObjectivesAlzheimers disease spans heterogeneous typical and atypical phenotypes. Posterior cortical atrophy is one striking example, characterised by prominent impairment in visual and other posterior functions in contrast to typical, amnestic Alzheimers disease. The primary study objective was to establish how the similarities and differences of cognition and brain volumes within Alzheimers disease and posterior cortical atrophy (and by extension other Alzheimers disease variants), can be conceptualised as systematic variations across a transdiagnostic, graded multidimensional space. MethodsThis was a cross-sectional, single-center, observational, cohort study performed at the National Hospital for Neurology & Neurosurgery, London, UK. Data were collected from a cohort of PCA and AD patients, matched for age, disease duration and MMSE scores. There were two sets of outcome measures: (1) scores on a neuropsychological battery containing 22 tests spanning visuoperceptual and visuospatial processing, episodic memory, language, executive functions, calculation, and visuospatial processing; and (2) measures extracted from high-resolution T1-weighted volumetric MRI scans. Principal component analysis was used to extract the transdiagnostic dimensions of phenotypical variation from the detailed neuropsychological data. Voxel-based morphometry was used to examine associations between the PCA-derived clinical phenotypes and the structural measures. ResultsWe enrolled 93 PCA participants (mean: age = 59.9 yrs, MMSE = 21.2; 59/93 female) and 58 AD participants (mean: age = 57.1 yrs, MMSE = 19.7; 22/58 female). The principal component analysis for posterior cortical atrophy (sample adequacy confirmed: Kaiser-Meyer-Olkin = 0.865) extracted three dimensions accounting for 61.0% of variance in patients performance, reflecting general cognitive impairment, visuoperceptual deficits and visuospatial impairments. Plotting Alzheimers disease cases into the posterior cortical atrophy-derived multidimensional space, and vice versa, revealed graded, overlapping variations between cases along these dimensions, with no evidence for categorical-like patient clustering. Likewise, the relationship between brain volumes and scores on the extracted dimensions was overlapping for posterior cortical atrophy and Alzheimers disease cases. DiscussionThese results provide evidence supporting a reconceptualization of clinical and radiological variation in these heterogenous Alzheimers disease phenotypes as being along shared phenotypic continua spanning posterior cortical atrophy and Alzheimers disease, arising from systematic graded variations within a transdiagnostic, multidimensional neurocognitive geometry.

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The angular gyrus is engaged by autobiographical recall not object-semantics, or event-semantics: Evidence from contrastive propositional speech production

The angular gyrus (AG) has been implicated in a myriad of cognitive functions. Using the previously under-studied naturalistic task of propositional speech production, we investigated the engagement of the left posterior AG (pAG) by three forms of memory: 1) episodic/autobiographical memory, 2) object semantic-memory, and 3) event-semantic knowledge. We conducted an ALE meta-analysis, followed by an fMRI study. The meta-analysis showed that pAG is only engaged as part of the propositional speech network when the task carries an autobiographical component. This finding was supported by the fMRI results, which also showed that: 1) pAG was positively engaged during autobiographical memory retrieval; 2) pAG was strongly deactivated for definitions of object semantics and non-propositional speech; 3) pAG activation increased with the degree to which the event descriptions relied on autobiographical information; 4) critically, the pAG showed a different pattern to known semantic representation regions (e.g., ventral anterior temporal lobe (vATL)) thereby providing clear evidence that the pAG is not acting as a semantic hub. Instead, the pAG activation profile directly mirrored that found in the wider autobiographical retrieval network. We propose that information stored elsewhere in the episodic system is temporally buffered online in the pAG during autobiographical retrieval/memory construction.

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Direct neural evidence for the contrastive roles of the complementary learning systems in adult acquisition of native vocabulary.

The Complementary Learning Systems (CLS) theory provides a powerful framework for considering the acquisition, consolidation and generalisation of new knowledge. We tested this proposed neural division of labour in adults through an investigation of the consolidation and long-term retention of newly-learned native vocabulary with post-learning functional neuroimaging. Newly-learned items were compared to two conditions: (i) previously known items to highlight the similarities and differences with established vocabulary; and (ii) unknown/untrained items to provide a control for non-specific perceptual and motor-speech output. Consistent with the CLS, retrieval of newly-learned items was supported by a combination of regions associated with episodic memory (including left hippocampus) and the language-semantic areas that support established vocabulary (left inferior frontal gyrus and left anterior temporal lobe). Furthermore, there was a shifting division of labour across these two networks in line with the items consolidation status; faster naming was associated with more activation of language-semantic areas and lesser activation of episodic memory regions. Hippocampal activity during naming predicted more than half the variation in naming retention six months later.

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Graded, multi dimensional intragroup and intergroup variations in primary progressive aphasia and post stroke aphasia.

Language impairments caused by stroke (post-stroke aphasia) and neurodegeneration (primary progressive aphasia) have overlapping symptomatology, nomenclature and are classically divided into categorical subtypes. Surprisingly, primary progressive aphasia (PPA) and post-stroke aphasia (PSA) have rarely been directly compared in detail. Rather previous studies have compared certain subtypes (e.g., semantic variants) or have focussed on a specific cognitive/linguistic task (e.g., reading). This study assessed a large range of linguistic and cognitive tasks across the full spectra of PSA and PPA. We applied varimax-rotated principal component analysis to explore the underlying structure of the variance in the assessment scores. Similar phonological, semantic and fluency-related components were found for PSA and PPA. A combined principal component analysis across the two aetiologies revealed graded intragroup and intergroup variations on all four extracted components. Classification analysis was employed to test, formally, whether there were any categorical boundaries for any subtypes of PPA or PSA. Semantic dementia proved to form a true diagnostic category (i.e., within group homogeneity and distinct between group differences), whereas there was considerable overlap and graded variations within and between other subtypes of PPA and PSA. These results suggest that (a) a multi-dimensional rather than categorical classification system may be a better conceptualisation of aphasia from both causes, and (b) despite the very different types of pathology, these broad classes of aphasia have considerable features in common.

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Evaluating the granularity and statistical structure of lesions and behaviour in post-stroke aphasia

The pursuit of relating the location of neural damage to the pattern of acquired language and general cognitive deficits post-stroke stems back to 19th century behavioural neurology. Whilst spatial specificity has improved dramatically over time, from the large areas of damage specified by post-mortem investigation to the millimetre precision of modern MRI, there is an underlying issue that is rarely addressed, which relates to the fact that damage to a given area of the brain is not random but constrained by the brains vasculature. Accordingly, the aim of this study was to uncover the statistical structure underlying the lesion profile in chronic aphasia post-stroke. By applying varimax-rotated principal component analysis to the lesions of 70 patients with chronic post-stroke aphasia, we identified 17 interpretable clusters, largely reflecting the vascular supply of middle cerebral artery sub-branches and other sources of individual variation in vascular supply as shown in classical angiography studies. This vascular parcellation produced smaller displacement error in simulated lesion-symptom analysis compared with individual voxels and Brodmann regions. A second principal component analysis of the patients detailed neuropsychological data revealed a four factor solution reflecting phonological, semantic, executive-demand and speech fluency abilities. As a preliminary exploration, stepwise regression was used to relate behavioural factor scores to the lesion principal components. Phonological ability was related to two components, which covered the posterior temporal region including the posterior segment of the arcuate fasciculus, and the inferior frontal gyrus. Three components were linked to semantic ability and were located in the white matter underlying the anterior temporal lobe, the supramarginal gyrus and angular gyrus. Executive-demand related to two components covering the dorsal edge of the middle cerebral artery territory, while speech fluency was linked to two components that were located in the middle frontal gyrus, precentral gyrus, and subcortical regions (putamen and thalamus). Future studies can explore in formal terms the utility of these PCA-derived lesion components for relating post-stroke lesions and symptoms.

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