A Systematic Review of Long-Interval Intracortical Inhibition as a Biomarker in Neuropsychiatric Disorders

Abstract

Long-interval intracortical inhibition (LICI) is a paired-pulse transcranial magnetic stimulation (TMS) paradigm mediated in part by gamma-aminobutyric acid receptor B (GABAB) inhibition. Prior work has examined LICI as a putative biomarker in an array of neuropsychiatric disorders. This review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sought to examine existing literature focused on LICI as a biomarker in neuropsychiatric disorders. There were 113 articles that met the inclusion criteria. Existing literature suggests that LICI may have utility as a biomarker of GABAB functioning but more research with increased methodologic rigor is needed. The extant LICI literature has heterogenous methodology and inconsistencies in findings. Existing findings to date are also non-specific to disease. Future research should carefully consider existing methodological weaknesses and implement high-quality test-retest reliability studies.

Long-interval intracortical inhibition in primary motor cortex related to working memory in middle-aged adults

“…This research increases our knowledge of this association and suggests that greater intracortical inhibition, measured by LICI, is a possible marker of interindividual differences in working memory performance among healthy middle-aged adults, extending previous suggestions as a biomarker of neuropsychiatric disorders ( Fatih et al, 2021 ).…”

“…Long-Interval Intracortical Inhibition (LICI), where two suprathreshold stimuli separated by an interstimulus interval (ISI) between 50 and 200 ms are applied, has been used to study cortical inhibition ( Valls-Solé et al, 1992 ; Nakamura et al, 1997 ) and reflects the activity of GABA-B receptors ( McDonnell et al, 2006 ; Opie et al, 2017 ). While many studies have shown that RMT and LICI offer valuable biological markers in different neurological disorders ( Fatih et al, 2021 ; Guerra et al, 2021 ; Mimura et al, 2021 ; Versace et al, 2021 ), only a few have explored their association with brain health and cognitive performance in healthy, cognitive-unimpaired, middle-aged adults, and how biological sex affects the results ( Schicktanz et al, 2014 ; Akilan et al, 2020 ).…”

Deficient GABABergic and glutamatergic excitability in the motor cortex of patients with long-COVID and cognitive impairment

“…In addition, a trend for decreased LICI, although not significant, has also been observed in Mild Cognitive Impairment (MCI) due to FTD ( Benussi et al, 2021 ) and in pre-symptomatic genetic FTD ( Benussi et al, 2016 ). Abnormal LICI has also been considered a possible biomarker in different neuropsychiatric disorders such as mood disorder, schizophrenia, epilepsy, and amyotrophic lateral sclerosis ( Fatih et al, 2021 ).…”

“…For this reason, alterations in the regulation of the M1 output measured by ppTMS could be interpreted as a surrogate marker of activity happening elsewhere in the brain. In fact, alterations of ppTMS parameters in neurodegenerative and psychiatric diseases reflect alterations of cognitive rather than motor functions (Benussi et al, 2020, 2018, 2017, 2016; Fatih et al, 2021 ). Given the correlation between LICI and executive functions ( Redondo-Camós et al, 2022 ), whose heavy reliance on frontal processing has been extensively demonstrated ( Peters, 2006 ; Sanger et al, 2001), one could suspect that the Long COVID dysexecutive deficits that have been reported in our sample of patients could be partially explained by pathogenetic processes involving the frontal areas of the brain.…”

Advancements in Transcranial Magnetic Stimulation Research and the Path to Precision

“…LICF refers to the phenomenon where MEP amplitude is facilitated with an interstimulus interval of 50–200ms, whereas LICI induces inhibition with an interstimulus interval of 100–200ms. 21 , 22 SICF and SICI share a similar interstimulus interval of 1–5ms, but differ in their effects on excitatory circuits, with SICF reflecting facilitation mediated by facilitatory interneurons and SICI reflecting inhibition mediated by inhibitory interneurons. 23 , 24 IHI refers to the reduction of corticomotor excitability in the contralateral hemisphere following transcranial magnetic stimulation of the ipsilateral hemisphere.…”