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

Abstract

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 brain’s 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 principal component analysis derived lesion components for relating post-stroke lesions and symptoms.

Structural brain disconnectivity mapping of post-stroke fatigue

“…right hemispheric strokes were more densely sampled than left hemispheric strokes, and prefrontal cortex was marginally affected. This lack of full or random sampling of the brain represents a common caveat in stroke research, because stroke lesions are not randomly or evenly dispersed throughout the brain, but are dependent on vascular organization and architecture and tend to occur in proximity to major arteries ( Rorden et al, 2007 , Zhao et al, 2020 ). In line with this, degree of voxel-wise lesion overlap between patients in the current sample was low, and although a sample size of 84 is comparable with common practice in MRI studies targeting stroke ( Nickel and Thomalla, 2017 , Nott et al, 2019 , Sihvonen et al, 2017 ), further studies with even larger samples are needed.…”

Brain disconnectivity mapping of post-stroke fatigue

“…right hemispheric strokes were more densely sampled than left hemispheric strokes, and prefrontal cortex was marginally affected. This lack of full or random sampling of the brain represents a common caveat in stroke research, because stroke lesions are not randomly or evenly dispersed throughout the brain, but are dependent on vascular organization and architecture and tend to occur in proximity to major arteries (Rorden, Karnath, & Bonilha, 2007; Zhao, Halai, & Lambon Ralph, 2020). In line with this, degree of voxel-wise lesion overlap between patients in the current sample was low, and although a sample size of 84 is comparable with common practice in MRI studies targeting stroke (Nickel & Thomalla, 2017; Nott et al, 2019; Sihvonen, Ripollés, Rodríguez-Fornells, Soinila, & Särkämö, 2017), further studies with even larger samples are needed.…”

The use of principal component and factor analysis to measure fundamental cognitive processes in neuropsychological data

“…Statistical dependence of neuropsychological deficits will be the norm rather than the exception. Brain lesions after stroke follow the vascular architecture of the brain and, thereby, are highly systematic (Zhao, Halai & Lambon Ralph, 2020). Whenever a lesion induces a cognitive deficit by damage to a specific brain region, the probability of damage to other regions will not be independent anymore.…”