Novel TMS-EEG indexes to investigate interhemispheric dynamics in humans

Abstract

Objective: To validate two indexes of interhemispheric signal propagation (ISP) and balance (IHB) by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG). Methods: We used TMS-EEG to non-invasively stimulate the two hemispheres of 50 healthy volunteers and measured interhemispheric dynamics in terms of ISP and IHB. We repeated our evaluation after three weeks to assess the reliability of our indexes. We also tested whether our TMS-EEG measures were correlated with traditional interhemispheric inhibition (IHI), as measured with motor-evoked potentials (MEPs). Results: Our main results showed that ISP and IHB (1) have a high reproducibility among all the participants tested; (2) have a high test-retest reliability (3) are linearly correlated with IHI, as measured with MEPs. Conclusions: The main contribution of this study lies in the proposal of new TMS-EEG cortical measures of interhemispheric dynamics and in their validation in terms of intra-and inter-subject reliability. We also provide the first demonstration of the correlation between ISP and IHI. Significance: Our results are relevant for the investigation of interhemispheric dynamics in clinical populations where MEPs are not reliable.

Evidence for interhemispheric imbalance in stroke patients as revealed by combining transcranial magnetic stimulation and electroencephalography

“…Surprisingly, the stimulation of the UH revealed, on the contrary, a preservation of the interhemispheric suppression mechanism, similarly to what we observed in the healthy brain. Then, we computed an index, that is, IHB, reflecting the balance between the two hemispheres, which we recently validated in a large sample of 50 old and young healthy volunteers (Casula et al, 2020). We found an abnormally higher IHB in stroke patients, compared to healthy volunteers, revealing an imbalance between the two hemispheres.…”

“…ISP has already been used by previous works (Jarczok et al, 2016; Määttä et al, 2017; Voineskos et al, 2010) even if these studies did not verify the sensitivity nor the reliability of this measure. We recently tested ISP in a large sample of healthy volunteers, founding an extremely low intersubject variability among the 50 participants tested (Casula et al, 2020). Although the physiological mechanism underlying ISP has not been fully elucidated, it is likely mediated by transcallosal inhibitory fibers, given its strict correlation with microstructural integrity of callosal fibers (Voineskos et al, 2010), a result that we confirmed in the present study.…”

“…To assess the balance between the two hemispheres, we computed the IHB as follows: where ISP AH and ISP UH are the ISP computed after the stimulation of M1 in the AH and AH, respectively (Casula et al, 2020). To assess the interhemispheric connectivity, we computed spectral coherence between the two M1 clusters of electrodes considering two epochs: a reference period, from 500 ms before to 20 ms before each TMS pulse, and an interest period, from 20 to 500 ms after each TMS pulse.…”

“…Recently, we introduced TMS–EEG as a valuable tool to investigate mechanisms of cortical reorganization early after stroke, even in the absence of recordable MEPs (Koch et al, 2019; Pellicciari et al, 2018). In another recent study of our group, we tested the sensitivity and reliability of two TMS–EEG indexes of interhemispheric interactions, that is, interhemispheric signal propagation (ISP) and interhemispheric balance (IHB) (Casula et al, 2020). Our results showed that these indexes have a low intersubject variability as well as a high test–retest reliability and, more importantly, showed a positive correlation with IHI, as measured with TMS–EMG.…”

Cortical oscillations to measure anti-epileptic drug activity in clinical trials

“…The small number of molecules that proceed through the pipeline into human research can encounter further failure due to lack of efficacy in clinical trials. These challenges to Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique which, in combination with electroencephalography (EEG), enables a fast and accurate assessment of human brain excitability in health 2,3 and pathological conditions 4 . TMS-EEG output measures can be interrogated in the time 5 and time-frequency domains 6 , providing different information about cortical processes 7 .…”