Voxel-based lesion-symptom mapping (VLSM) is an important method for basic and translational human neuroscience research. VLSM leverages modern neuroimaging analysis techniques to build on the classic approach of examining the relationship between location of brain damage and cognitive deficits. Testing an association between deficit severity and lesion status in each voxel involves very many individual tests and requires statistical correction for multiple comparisons. Several strategies have been adapted from analysis of functional neuroimaging data, though VLSM faces a more difficult trade-off between avoiding false positives and statistical power (missing true effects). Non-parametric, permutation-based methods are generally preferable because they do not make assumptions that are likely to be violated by skewed distributions of behavioral deficit (symptom) scores and by the necessary spatial contiguity of stroke lesions. We used simulated and real deficit scores from a sample of approximately 100 individuals with left hemisphere stroke to evaluate two such permutation-based approaches. Using permutation to set a minimum cluster size identified a region that systematically extended well beyond the true region, even under the most conservative settings tested here, making it ill-suited to identifying brainbehavior relationships. In contrast, generalizing the standard permutation-based family-wise error correction approach provided a principled way to balance false positives and false negatives. An implementation of this continuous permutation-based FWER correction method is available at 1 Address correspondence to Daniel Mirman, dan@danmirman.org. Portions of this work were previously described in arXiv:1606.00475 [stat.AP].

Producing a word requires selecting among a set of similar alternatives. When many semantically related items become activated, the difficulty of the selection process is increased. Experiment 1 tested naming of items with either multiple synonymous labels (“Alternate Names,” e.g., gift/present) or closely semantically related but non-equivalent responses (“Near Semantic Neighbors,” e.g., jam/jelly). Picture naming was fastest and most accurate for pictures with only one label (“High Name Agreement”), slower and less accurate in the Alternate Names condition, and slowest and least accurate in the Near Semantic Neighbors condition. These results suggest that selection mechanisms in picture naming operate at two distinct levels of processing: selecting between similar but non-equivalent names requires two selection processes (semantic and lexical), whereas selecting among equivalent names only requires one selection at the lexical level. Experiment 2 examined how these selection mechanisms are affected by normal aging and found that older adults had significantly more difficulty in the Near Semantic Neighbors condition, but not in the Alternate Names condition. This suggests that aging affects semantic processing and selection more strongly than it affects lexical selection. Experiment 3 examined the role of the left inferior frontal gyrus (LIFG) in these selection processes by testing individuals with aphasia secondary to stroke lesions that either affected the LIFG or spared it. Surprisingly, there was no interaction between condition and lesion group: the presence of LIFG damage was not associated with substantively worse naming performance for pictures with multiple acceptable labels. These results are not consistent with a simple view of LIFG as the locus of lexical selection and suggest a more nuanced view of the neural basis of lexical and semantic selection.

In sign languages, the task of communicating a shape involves drawing in the air with one moving hand (Method One) or two (Method Two). Since the movement path is iconic, method choice might be based on the shape. In the present studies we aimed to determine whether geometric properties motivate method choice. In a study of 17 deaf signers from six countries, the strongest predictors of method choice were whether the shape has any curved edges (Method One), and whether the shape is symmetrical across the Y‐axis (Method Two), where the default was Method One. In a second study of ASL dictionary entries for which the movement path of the sign is iconic of an entity's shape, the same predictors surfaced. These tendencies are captured in the Lexical Drawing Principle, which is coherent with biological constraints on movement in general. Drawing in the air with two hands, however, is costly, both cognitively and biomechanically. Furthermore, it distinguishes signers from non‐signers, who draw shapes with only one hand. Signers assume this extra cost in the lexicon because of the enhanced iconicity the possibility of two hands offers; they assume it in drawing shapes in the air because they apply the same linguistic principle they use in the lexicon. Additionally, having a choice of methods allows the signer to benefit from over‐specification in providing redundant information about the shape, enhancing comprehensibility and resolving ambiguity.

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