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Related Experiment Video

Updated: Feb 14, 2026

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How distributed processing produces false negatives in voxel-based lesion-deficit analyses.

Andrea Gajardo-Vidal1, Diego L Lorca-Puls2, Jennifer T Crinion3

  • 1Wellcome Centre for Human Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom; Department of Speech, Language and Hearing Sciences, Faculty of Health Sciences, Universidad del Desarrollo, Concepcion 4070001, Chile.

Neuropsychologia
|February 26, 2018
PubMed
Summary

Voxel-based analyses may miss crucial brain lesion sites when damage to different areas causes the same deficit. An iterative approach revealed the left putamen as a previously undetected critical region for word retrieval.

Keywords:
AnomiaVoxel-based lesion-deficit mappingVoxel-based lesion-symptom mapping, strokeVoxel-based morphometryWord-finding difficulties

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Area of Science:

  • Neuroscience
  • Cognitive Neurology
  • Neuroimaging

Background:

  • Distributed neural systems can lead to similar functional deficits despite damage to different brain regions.
  • Traditional voxel-based analyses may fail to identify critical lesion sites when multiple areas contribute to a deficit.

Purpose of the Study:

  • To investigate how voxel-based analyses can miss critical lesion sites in distributed neural systems.
  • To identify brain regions associated with word retrieval deficits in stroke survivors.
  • To explore an iterative approach to uncover previously undetected lesion-deficit relationships.

Main Methods:

  • Voxel-based multiple regression analyses were performed on 359 right-handed stroke survivors.
  • Analyses focused on picture naming abilities, controlling for object recognition, semantics, and speech articulation.
  • An iterative approach excluded patients with lesions in initially identified regions to reveal new associations.

Main Results:

  • Initial analyses identified significant lesion-deficit relationships in left temporal and frontal/premotor regions for word retrieval.
  • Damage to these initial sites explained the deficit in less than half of affected patients.
  • An iterative analysis revealed the anterior left putamen as a critical region, previously undetected due to compensatory damage in other areas.

Conclusions:

  • Distributed lesion-deficit relationships can lead to false negatives in standard voxel-based analyses.
  • An iterative exclusion method can uncover missed lesion sites in distributed systems.
  • Univariate voxel-based lesion-deficit mapping alone is insufficient for predicting patient outcomes.