Combined effects of theta-burst stimulation with transcranial direct current stimulation of the prefrontal cortex: study protocol of a randomized, double-blinded, sham-controlled trial using 99mTc-ECD SPECT

Abstract

Introduction: Non-invasive brain stimulation (NIBS) as monotherapy has been increasingly used to enhance the activity of brain networks. However, it is unclear whether a combination of distinct NIBS approaches could enhance prefrontal cortical (PFC) activity. Objective: We propose to investigate the combined and standalone effects of two NIBS modalities on the PFC through a working memory task, single photon emission computed tomography (SPECT), and salivary cortisol. We hypothesize that the combined protocol will provoke greater changes in the collected measures compared to the remining protocols. Methods: A randomized, double-blind, sham-controlled, full-factorial design will be conducted. The effects of transcranial direct current stimulation (tDCS) and intermittent theta-burst stimulation (iTBS) will be investigated over four different sessions (sham tDCS + sham iTBS, anodal tDCS + sham iTBS, anodal tDCS + active iTBS and sham tDCS + active iTBS) in 30 healthy adult volunteers. A 99mTcethylene cysteine dimer (99mTC-ECD) will be administered during the NIBS session and neuroimaging will be acquired within one hour. Salivary cortisol will be collected before and after each session and an n-back working memory task will be applied after the end of each NIBS session. The outcomes will be cerebral perfusion alterations (99mTC-ECD SPECT), accuracy and reaction time in the n-back task, and changes in salivary cortisol level. Conclusion:The results from this trial can guide future therapeutic protocols for NIBS treatments stimulating the PFC by demonstrating that the combination of NIBS techniques is feasible, tolerable, and can lead to greater enhancement of PFC activity.

Transcranial direct current stimulation versus intermittent theta-burst stimulation for the improvement of working memory performance

“…It was approved by the local and national Ethics Committee (CAAE: 89310918.8.0000.0068) and participants provided written, informed consent. We used a factorial, double-blinded, within-subjects design, in which participants received, once a week and in a randomized order: sham tDCS/sham iTBS (placebo) ; active tDCS/active iTBS (combined protocol) , sham tDCS/active iTBS (iTBS-only) ; and active tDCS/sham iTBS (tDCS-only) ( Razza et al, 2021 ) (Sup. Material - Appendix A).…”

“…All results were considered significant at a p-value < 0.05. More information regarding sample size calculation can be found elsewhere ( Razza et al, 2021 ).…”

Brain Perfusion Alterations Induced by Standalone and Combined Non-Invasive Brain Stimulation over the Dorsolateral Prefrontal Cortex

“…We used a factorial (2 × 2 design), within-subjects, double-blinded design in which participants were assigned to receive, in a randomized order: (a) sham tDCS plus sham iTBS (placebo), (b) active tDCS plus active iTBS (double active), (c) sham tDCS plus active iTBS (iTBS-only) and (d) active tDCS plus sham iTBS (tDCS-only). The sessions were applied once a week for four consecutive weeks [ 18 ]. For more details, the protocol of this study has been published previously [ 18 ].…”

“…The sessions were applied once a week for four consecutive weeks [ 18 ]. For more details, the protocol of this study has been published previously [ 18 ].…”

Efficacy of Intermittent Theta-Burst Stimulation and Transcranial Direct Current Stimulation in Treatment of Post-Stroke Cognitive Impairment

“…Few studies have explored the role of neuroplasticity in the use of iTBS and tDCS to improve cognitive function, and the mechanism remains unclear [24]. Func-tional near-infrared spectroscopy (fNIRS) is a non-invasive optical imaging technology that relies on the principle of neurovascular coupling.…”