Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

Abstract

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’.

Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale

“…Other studies have identified regions of infarct associated with higher NIHSS scores although they have shown a stronger association between LH regions than RH regions. 8 , 34 One study compared several methods of lesion–symptom mapping, including multi-perturbation shapley value analysis, 35 voxel-symptom lesion mapping, 36 and volume of interest lesion–symptom correlation, and multi-area pattern prediction 37 for identifying regions associated with NIHSS score. 34 All of these approaches found the strongest association with left caudate and also left insula (2 areas where we also identified percent damage to be strongly associated with the NIHSS score in LH stroke).…”

Game theoretical mapping of causal interactions underlying visuo‐spatial attention in the human brain based on stroke lesions

“…MSA is a rigorous multivariate game-theorybased method to infer causal regional contributions from behavioral performance, treating brain regions as interacting players in a coalition game. The approach has already found a wide range of applications in neuroscience [Keinan et al, 2004b;Kaufman et al, 2009;Zavaglia et al, 2015, Zavaglia & Hilgetag, 2016a as well as biochemistry and genetics [Kaufman et al, 2005]. It can also compute redundancy in the functional interactions of the brain as well as synergistic interactions between different brain regions.…”

Revisiting ‘brain modes’ in a new computational era: approaches for the characterization of brain-behavioural associations

“…MSA also reveals redundant interactions (between areas with functional overlap) and synergistic interactions (between areas presenting complementary functions). Recently published studies concerning the use of MSA in post-stroke lesion data have revealed plausible evidence in favour of a causal implication of different grey and white matter structures to specific cognition domains, illustrating the potential of this approach in clinical datasets (Zavaglia et al, 2015(Zavaglia et al, , 2019Toba et al, 2017). BA = Brodmann area; IPS = intraparietal sulcus; FEF = frontal eye field; IOG = inferior occipital gyrus; IFG = inferior frontal gyrus; TPJ = temporo-parietal junction.…”