Biology subjects

Hillis, A. E.

Publications and source records attributed to Hillis, A. E..

4 recordsLinked to original sources

bioRxiv2023

Gesture profiles distinguish primary progressive aphasia variants

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by progressive language deficits. There are three main variants of PPA - semantic (svPPA), logopenic (lvPPA), and nonfluent (nfvPPA) - that can be challenging to distinguish. Limb praxis may also be affected in PPA, but it is unclear whether different variants of PPA are associated with differences in gesture production. Prior research with neurotypical individuals indicates that the left temporal lobe is a critical locus of manipulable object and hand posture representations. Moreover, when imitating gestures, individuals whose strokes include the left temporal lobe show reduced benefit of gesture meaning and disproportionate impairment in hand posture as compared to arm kinematics. We tested the hypothesis that svPPA - who typically exhibit primarily temporal lobe atrophy - would differentially show these expected patterns of gesture imitation performance. Nineteen participants with PPA completed meaningful and meaningless gesture imitation tasks, and performance was scored for hand posture and arm kinematics accuracy. Generalized logistic mixed-effect regression models controlling for dementia severity showed overall benefits from gesture meaning, and greater impairments in hand posture than arm kinematics. We also found that svPPA participants were the most impaired in gesture imitation overall. Critically, there was also a significant three-way interaction of group, meaning, and gesture component: only svPPA participants showed relative impairments of hand posture for meaningful gestures as well as meaningless gestures. Thus, unlike lvPPA and nfvPPA, the hand postures of svPPA failed to benefit from gesture meaning. This research extends prior findings on the role of the temporal lobe in hand posture representations associated with manipulable objects, and is the first to indicate that there may be distinct gesture imitation patterns as a function of PPA variant. Characterizing componential gesture deficits in PPA may help to inform differential diagnosis, compensatory communication strategies, and cognitive praxis models of PPA.

neuroscience↗

bioRxiv2021

The Wernicke conundrum revisited: evidence from connectome-based lesion-symptom mapping in post-stroke aphasia

Wernickes area has been assumed since the 1800s to be the primary region supporting word and sentence comprehension. However, Mesulam et al. (2015; 2019) raised what they termed the Wernicke conundrum, noting widespread variability in the anatomical definition of this area and presenting data from primary progressive aphasia that challenged this classical assumption. To resolve the conundrum, they posited a double disconnection hypothesis: that word and sentence comprehension deficits in stroke-based aphasia result from disconnection of anterior temporal and inferior frontal regions from other parts of the brain due to white matter damage, rather than dysfunction of Wernickes area itself. To test this hypothesis, we performed lesiondeficit correlations, including connectome-based lesion-symptom mapping, in four large, partially overlapping groups of English-speaking chronic left hemisphere stroke survivors. After removing variance due to object recognition and associative semantic processing, the same middle and posterior temporal lobe regions were implicated in both word comprehension deficits and complex noncanonical sentence comprehension deficits. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and noncanonical sentence comprehension, including the temporal pole. We found an additional significant temporal-parietal disconnection for noncanonical sentence comprehension deficits, which may indicate a role for phonological working memory in processing complex syntax, but no significant frontal disconnections. Moreover, damage to these middle-posterior temporal lobe regions was associated with both word and noncanonical sentence comprehension deficits even when accounting for variance due to the strongest anterior temporal and inferior frontal white matter disconnections, respectively. Our results largely agree with the classical notion that Wernickes area, defined here as middle superior temporal gyrus and middle-posterior superior temporal sulcus, supports both word and sentence comprehension, suggest a supporting role for temporal pole in both word and sentence comprehension, and speak against the hypothesis that comprehension deficits in Wernickes aphasia result from double disconnection.

neuroscience↗

bioRxiv2021

Digital 3D Brain MRI Arterial Territories Atlas

The locus and extent of brain damage in the event of vascular insult can be quantitatively established quickly and easily with vascular atlases. Although highly anticipated by clinicians and clinical researchers, no digital MRI arterial atlas is readily available for automated data analyses. We created a digital arterial territory atlas based on lesion distributions in 1,298 patients with acute stroke. The lesions were manually traced in the diffusion-weighted MRIs, binary stroke masks were mapped to a common space, probability maps of lesions were generated and the boundaries for each arterial territory was defined based on the ratio between probabilistic maps. The atlas contains the definition of four major supra- and infra-tentorial arterial territories: Anterior, Middle, Posterior Cerebral Arteries and Vertebro-Basilar, and sub-territories (thalamoperforating, lenticulostriate, basilar and cerebellar arterial territories), in two hierarchical levels. This study provides the first publicly-available, digital, 3D deformable atlas of arterial brain territories, which may serve as a valuable resource for large-scale, reproducible processing and analysis of brain MRIs of patients with stroke and other conditions.

neuroscience↗

bioRxiv2020

Automatic subtyping of individuals with Primary Progressive Aphasia

BackgroundThe classification of patients with Primary Progressive Aphasia (PPA) into variants is time-consuming, costly, and requires combined expertise by clinical neurologists, neuropsychologists, speech pathologists, and radiologists. ObjectiveThe aim of the present study is to determine whether acoustic and linguistic variables provide accurate classification of PPA patients into one of three variants: nonfluent PPA, semantic PPA, and logopenic PPA. MethodsIn this paper, we present a machine learning model based on Deep Neural Networks (DNN) for the subtyping of patients with PPA into three main variants, using combined acoustic and linguistic information elicited automatically via acoustic and linguistic analysis. The performance of the DNN was compared to the classification accuracy of Random Forests, Support Vector Machines, and Decision Trees, as well as expert clinicians classifications. ResultsThe DNN model outperformed the other machine learning models with 80% classification accuracy, providing reliable subtyping of patients with PPA into variants and it even outperformed auditory classification of patients into variants by clinicians. ConclusionsWe show that the combined speech and language markers from connected speech productions provide information about symptoms and variant subtyping in PPA. The end-to-end automated machine learning approach we present can enable clinicians and researchers to provide an easy, quick and inexpensive classification of patients with PPA.

neuroscience↗