Article
How distributed processing produces false negatives in voxel-based lesion deficit analyses
Date
2018-06Registration in:
Neuropsychologia, 2018, 115, pp.124-133
0028-3932
Author
Gajardo-Vidal, Andrea
Lorca-Puls, Diego L.
Crinion, Jennifer
White, Jitrachote
Seghier, Mohamed L.
Leff, Alex P.
Hope, Thomas M.H.
Ludersdorfer, Philipp
Green, David W.
Bowman, Howard
Price, Cathy J.
Institutions
Abstract
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. The first part of our investigation used voxelbased
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. 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. The 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 lesiondeficit
mappings cannot, in isolation, be used to predict outcome in other patients.