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Previous transcranial magnetic stimulation (TMS) studies have assessed cortical dysfunction from the hand. The aim of the present study was to determine whether cortical dysfunction was evident across representations of three body regions, and to relate these changes to clinical features of ALS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this cross\u2010sectional study, threshold tracking TMS was undertaken in 60 sporadic ALS patients, with motor evoked potential (MEP) responses recorded over the hand (abductor pollicis brevis), lower limb (tibialis anterior), and bulbar (trapezius) regions. The cross\u2010sectional findings were compared to 28 age\u2010 and gender\u2010matched controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cortical dysfunction was evident across the representation of the three body regions, although the degree and nature of the dysfunction varied. Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI), was evident in all cortical regions (hand, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01; leg, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05; bulbar, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) in ALS patients when compared with healthy control subjects. Importantly, features of cortical hyperexcitability seemed more prominent in clinically affected body regions and correlated with functional disability and muscle weakness. Cortical inexcitability was more prominent in the leg (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and bulbar regions (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) when compared with controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The nature of cortical dysfunction varied across the body regions in ALS, with cortical hyperexcitability being more prominent in the upper limbs while cortical inexcitability was more evident in the lower limbs and bulbar regions. The findings suggest a heterogeneity of cortical pathophysiological processes in ALS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50819","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T09:38:15Z","timestamp":1561714695000},"page":"1373-1382","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Regional motor cortex dysfunction in amyotrophic lateral sclerosis"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-5852","authenticated-orcid":false,"given":"Parvathi","family":"Menon","sequence":"first","affiliation":[{"name":"Westmead Hospital Sydney New South Wales Australia"},{"name":"University of Sydney Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Con","family":"Yiannikas","sequence":"additional","affiliation":[{"name":"University of Sydney Sydney New South Wales Australia"},{"name":"Concord 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