Intracortical GABAergic dysfunction in patients with fatigue and dysexecutive syndrome after COVID-19

Viviana Versace, Luca Sebastianelli, Davide Ferrazzoli, Roberto Romanello, Paola Ortelli, Leopold Saltuari, Alessia D'Acunto, Francesco Porrazzini, Valentina Ajello, Antonio Oliviero, Markus Kofler, Giacomo Koch

Research output: Contribution to journalArticlepeer-review


Objective: A high proportion of patients experience fatigue and impairment of cognitive functions after coronavirus disease 2019 (COVID-19). Here we applied transcranial magnetic stimulation (TMS) to explore the activity of the main inhibitory intracortical circuits within the primary motor cortex (M1) in a sample of patients complaining of fatigue and presenting executive dysfunction after resolution of COVID-19 with neurological manifestations. Methods: Twelve patients who recovered from typical COVID-19 pneumonia with neurological complications and complained of profound physical and mental fatigue underwent, 9 to 13 weeks from disease onset, a psychometric evaluation including a self-reported fatigue numeric-rating scale (FRS, Fatigue Rating Scale) and the Frontal Assessment Battery (FAB). Intracortical activity was evaluated by means of well-established TMS protocols including short-interval intracortical inhibition (SICI), reflecting GABAA-mediated inhibition, long-interval intracortical inhibition (LICI), a marker of GABAB receptor activity, and short-latency afferent inhibition (SAI) that indexes central cholinergic transmission. TMS data were compared to those obtained in a control group of ten healthy subjects (HS) matched by age, sex and education level. Results: Post-COVID-19 patients reported marked fatigue according to FRS score (8.1 ± 1.7) and presented pathological scores at the FAB based on Italian normative data (12.2 ± 0.7). TMS revealed marked reduction of SICI, and disruption of LICI as compared to HS. SAI was also slightly diminished. Conclusions: The present study documents for the first time reduced GABAergic inhibition in the M1 in patients who recovered from COVID-19 with neurological complications and manifested fatigue and dysexecutive syndrome. Significance: TMS may serve as diagnostic tool in cognitive disturbances and fatigue in post-COVID-19 patients.

Original languageEnglish
Pages (from-to)1138-1143
Number of pages6
JournalClinical Neurophysiology
Issue number5
Publication statusPublished - May 2021


  • COVID-19
  • Executive functions
  • Fatigue
  • GABA
  • TMS

ASJC Scopus subject areas

  • Sensory Systems
  • Neurology
  • Clinical Neurology
  • Physiology (medical)


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