The Effects of Intermittent Theta Burst Stimulation on Functional Brain Network Following Stroke: An Electroencephalography Study

Abstract

Objective: Intermittent theta burst stimulation (iTBS) is a special form of repetitive transcranial magnetic stimulation (rTMS), which effectively increases cortical excitability and has been widely used as a neural modulation approach in stroke rehabilitation. As effects of iTBS are typically investigated by motor evoked potentials, how iTBS influences functional brain network following stroke remains unclear. Resting-state electroencephalography (EEG) has been suggested to be a sensitive measure for evaluating effects of rTMS on brain functional activity and network. Here, we used resting-state EEG to investigate the effects of iTBS on functional brain network in stroke survivors.Methods: We studied thirty stroke survivors (age: 63.1 ± 12.1 years; chronicity: 4.0 ± 3.8 months; UE FMA: 26.6 ± 19.4/66) with upper limb motor dysfunction. Stroke survivors were randomly divided into two groups receiving either Active or Sham iTBS over the ipsilesional primary motor cortex. Resting-state EEG was recorded at baseline and immediately after iTBS to assess the effects of iTBS on functional brain network.Results: Delta and theta bands interhemispheric functional connectivity were significantly increased after Active iTBS (P = 0.038 and 0.011, respectively), but were not significantly changed after Sham iTBS (P = 0.327 and 0.342, respectively). Delta and beta bands global efficiency were also significantly increased after Active iTBS (P = 0.013 and 0.0003, respectively), but not after Sham iTBS (P = 0.586 and 0.954, respectively).Conclusion: This is the first study that used EEG to investigate the acute neuroplastic changes after iTBS following stroke. Our findings for the first time provide evidence that iTBS modulates brain network functioning in stroke survivors. Acute increase in interhemispheric functional connectivity and global efficiency after iTBS suggest that iTBS has the potential to normalize brain network functioning following stroke, which can be utilized in stroke rehabilitation.

Intermittent Theta Burst Stimulation Increases Natural Oscillatory Frequency in Ipsilesional Motor Cortex Post-Stroke: A Transcranial Magnetic Stimulation and Electroencephalography Study

“…RMT was determined as the minimum intensity required to evoke 5 out of 10 MEPs greater than 50 μV at rest ( Chen et al, 1998 ). A neuronavigation system (Visor2, ANT Neuro, Hengelo, Netherlands) was used to ensure consistent coil positioning over the optimal scalp position (i.e., motor hotspot) throughout the experiment ( Ding et al, 2021a , c ). For the individuals in whom MEPs in the IH cannot be elicited even with 100% MSO ( n = 6 in the Active iTBS group and n = 5 in the Sham iTBS group), RMT in the IH was considered as 100% maximum stimulator output (MSO).…”

“…iTBS was applied over the motor hotspot in the ipsilesional M1. The iTBS stimulation intensity was set at 70% RMT in the IH ( Volz et al, 2016 ; Ding et al, 2021c ). During the application of iTBS, participants were instructed to remain static.…”

“…Motor impairment following stroke has been suggested to arise from disruptions of structural and functional integrity at both local and global scales ( Bonkhoff et al, 2020 ). Intermittent theta burst stimulation (iTBS) is a specific form of repetitive transcranial magnetic stimulation (rTMS) that can effectively enhance cortical excitability and modulate oscillatory dynamics in both stimulated area and remote brain regions ( Suppa et al, 2016 ; Ding et al, 2021c ). iTBS has been considered as a promising approach for stroke rehabilitation ( Corti et al, 2012 ; Suppa et al, 2016 ).…”

Excitatory-Inhibitory Homeostasis and Diaschisis: Tying the Local and Global Scales in the Post-stroke Cortex

“…Indeed, connectivity can also be modulated with neurostimulation techniques usually targeted at regulation of excitability (Grefkes and Fink, 2012). TBS has been shown to modulate both excitability (Ackerley et al, 2010;Boddington et al, 2020) and connectivity (Ding et al, 2021) in stroke patients and healthy controls (Nettekoven et al, 2014), although results in the latter showed that, even though both processes happen simultaneously, a correlation between them could not be found.…”

“…Not only that, but TBS is thought to potentiate cortical excitability ( Huang et al, 2005 ) and, when applied to stroke rehabilitation, can be used to stimulate increases in excitability of the ipsilesional cortex that relate to clinical recovery ( Di Lazzaro et al, 2008 ; Ackerley et al, 2010 ; Boddington et al, 2020 ), although the specific contribution of each particular area (e.g., somatosensory and motor cortices) to motor recovery is not yet fully understood ( Meehan et al, 2011 ). Interestingly, recent results suggest that TBS further acts on functional connectivity, contributing to the recovery of important properties such as interhemispheric connectivity and global efficiency ( Ding et al, 2021 ). Taking that into consideration, it is reasonable to believe that mesoscale excitability and large-scale connectivity are synergetic processes and can be simultaneously modulated by the same techniques, fitting the hypothesis that EI homeostasis is an underlying driver of cortical reorganization.…”