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Using neurostimulation to understand the impact of pre-morbid individual differences on post-lesion outcomes

  1. Matthew A. Lambon Ralpha
  1. aNeuroscience and Aphasia Research Unit, Division of Neuroscience and Experimental Psychology, School of Biological Sciences, University of Manchester, Manchester, M13 9PL, England
  1. Edited by Robert D. Rafal, University of Delaware, Newark, DE, and accepted by Editorial Board Member Michael S. Gazzaniga September 6, 2017 (received for review May 4, 2017)


Data from patients with brain damage have provided unique insights into the neural bases of cognitive function. Yet interpretation of patient data is complicated by the possible influence of pre-morbid individual differences on performance. We addressed this issue by considering the impact of transcranial magnetic stimulation (TMS)-induced “virtual lesions” of the left anterior temporal lobe upon reading performance in healthy individuals who vary in their degree of semantic reliance during reading. TMS only disrupted performance in higher semantic reliance readers. These results establish a direct link between pre-morbid individual differences and post-damage outcomes. Our virtual lesion approach provides a methodology through which the impact of pre-morbid individual differences can be examined and their theoretical implications understood.


Neuropsychological data have proven invaluable in advancing our understanding of higher cognition. The interpretation of such data is, however, complicated by the fact that post-lesion behavioral abnormalities could reflect pre-morbid individual differences in the cognitive domain of interest. Here we exploited the virtual lesion methodology offered by transcranial magnetic stimulation (TMS) to explore the impact of pre-morbid individual differences on post-lesion performance. We applied this approach to the domain of reading, a crucial ability in which there are known to be considerable individual differences in the normal population. As predicted by neuropsychological studies of surface dyslexia in semantic dementia and the connectionist triangle model of reading, previous empirical work has shown that healthy participants vary in their reliance on meaning for reading words with atypical correspondences between spelling and sound. We therefore selected participants who varied along this dimension and applied a virtual lesion to the left anterior temporal lobe. As expected, we observed a significant three-way interaction between “pre-morbid” reading status, stimulation, and word type, such that TMS increased the disadvantage for spelling–sound atypical words more for the individuals with stronger semantic reliance. This successful test-case study provides an approach to understanding the impact of pre-morbid individual variation on post-lesion outcomes that could be fruitfully applied to a variety of cognitive domains.


  • ?1To whom correspondence should be addressed. Email: anna.woollams{at}manchester.ac.uk.
  • Author contributions: A.M.W. and M.A.L.R. designed research; A.M.W. and G.M. performed research; A.M.W. and G.M. analyzed data; and A.M.W. and M.A.L.R. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission. R.D.R. is a guest editor invited by the Editorial Board.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1707162114/-/DCSupplemental.

This is an open access article distributed under the PNAS license.

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