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This study compared A\u2010SICI and T\u2010SICI for sensitivity and clinical usefulness as biomarkers for ALS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In all, 104 consecutive patients referred with suspicion of ALS were prospectively included and were subsequently divided into 62 patients with motor neuron disease (MND) and 42 patient controls (ALS mimics) by clinical follow\u2010up. T\u2010SICI and A\u2010SICI recorded in the first dorsal interosseus muscle (index test) were compared with recordings from 53 age\u2010matched healthy controls. The reference standard was the Awaji criteria. Clinical scorings, conventional nerve conduction studies and electromyography were also performed on the patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Motor neuron disease patients had significantly reduced T\u2010SICI and A\u2010SICI compared with the healthy and patient control groups, which were similar. Sensitivity and specificity for discriminating MND patients from patient controls were high (areas under the receiver operating characteristic curves 0.762 and 0.810 for T\u2010SICI and A\u2010SICI respectively at 1\u20133.5\u00a0ms). Paradoxically, T\u2010SICI was most reduced in MND patients with the fewest upper motor neuron (UMN) signs (Spearman<jats:italic>\u03c1<\/jats:italic>\u00a0=\u00a00.565,<jats:italic>p<\/jats:italic>\u00a0=\u00a04.3\u00a0\u00d7\u00a010<jats:sup>\u22126<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Amplitude\u2010based measure of cortical inhibition and T\u2010SICI are both sensitive measures for the detection of cortical involvement in MND patients and may help early diagnosis of ALS, with T\u2010SICI most abnormal before UMN signs have developed. The gradation in T\u2010SICI from pathological facilitation in patients with minimal UMN signs to inhibition in those with the most UMN signs may be due to progressive degeneration of the subset of UMNs experiencing facilitation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15010","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T19:12:30Z","timestamp":1625685150000},"page":"3030-3039","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Early diagnosis of amyotrophic lateral sclerosis by threshold tracking and conventional transcranial magnetic stimulation"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8495-9769","authenticated-orcid":false,"given":"Hatice","family":"Tankisi","sequence":"first","affiliation":[{"name":"Department of Clinical Neurophysiology Aarhus University Hospital Aarhus 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