Poster B66, Thursday, August 16, 3:05 – 4:50 pm, Room 2000AB
How distributed processing produces false negatives in voxel-based lesion-deficit analyses
Andrea Gajardo-Vidal1, Diego Lorca-Puls1, Jennifer Crinion1, Jitrachote White1, Mohamed Seghier1,2, Alex Leff1, Thomas Hope1, Philipp Ludersdorfer1, David Green1, Howard Bowman3,4, Cathy Price1;1University College London, 2Emirates College for Advanced Education, 3University of Kent, 4University of Birmingham
Introduction: In this study, we hypothesized that if the same deficit can be caused by damage to one or another part of a distributed neural system, then voxel-based analyses might miss critical lesion sites because preservation of each site will not be consistently associated with preserved function. Methods: Patients were selected from the Predicting Language Outcome and Recovery After Stroke (PLORAS) database (Seghier et al., 2016) according to the following criteria: (i) left-hemisphere stroke attested by a clinical neurologist and defined by an automated lesion identification algorithm (Seghier et al., 2008); (ii) patients with lesions larger than 1 cm3; (iii) native speakers of English; (iv) right-handed prior to their stroke; and, (v) more than 3 months since stroke. These criteria were met by 359 left-hemisphere stroke patients, aged between 21 and 90 (mean age 59.4). The first part of our investigation used voxel-based multiple regression analyses of data from 359 right-handed stroke survivors to identify brain regions where lesion load is associated with picture naming abilities after factoring out variance related to object recognition, semantics and speech articulation so as to focus on deficits arising at the word retrieval level. Results: A highly significant lesion-deficit relationship was identified in left temporal and frontal/premotor regions. Post-hoc analyses showed that damage to either of these sites caused the deficit of interest in less than half the affected patients (76/162 = 47%). After excluding all patients with damage to one or both of the identified regions, our second analysis revealed a new region, in the anterior part of the left putamen, which had not been previously detected because many patients had the deficit of interest after temporal or frontal damage that preserved the left putamen. Conclusions: Our results illustrate how: (i) false negative results arise when the same deficit can be caused by different lesion sites; (ii) some of the missed effects can be unveiled by adopting an iterative approach that systematically excludes patients with lesions to the areas identified in previous analyses; (iii) statistically significant voxel-based lesion-deficit mappings can be driven by a subset of patients; (iv) focal lesions to the identified regions are needed to determine whether the deficit of interest is the consequence of focal damage or much more extensive damage that includes the identified region; and, finally; (v) univariate voxel-based lesion-deficit mappings cannot, in isolation, be used to predict outcome in other patients.
Topic Area: Methods