Preoperative Transcranial Direct Current Stimulation in Glioma Patients: A Proof of Concept Pilot Study

Abstract

Background: Transcranial direct current stimulation (tDCS) has been used extensively in patient populations to facilitate motor network plasticity. However, it has not been studied in patients with brain tumors. We aimed to determine the feasibility of a preoperative motor training and tDCS intervention in patients with glioma. In an exploratory manner, we assessed changes in motor network connectivity following this intervention and related these changes to predicted electrical field strength from the stimulated motor cortex. Methods: Patients with left-sided glioma (n=8) were recruited in an open label proof of concept pilot trial and participated in four consecutive days of motor training combined with tDCS. The motor training consisted of a 60-min period where the subject learned to play the piano with their right hand. Concurrently, they received 40 min of 2 mA anodal tDCS of the left motor cortex. Patients underwent task and resting state fMRI before and after this intervention. Changes in both the connectivity of primary motor cortex (M1) and general connectivity across the brain were assessed. Patient specific finite element models were created and the predicted electrical field (EF) resulting from stimulation was computed. The magnitude of the EF was extracted from left M1 and correlated to the observed changes in functional connectivity. Results: There were no adverse events and all subjects successfully completed the study protocol. Left M1 increased both local and global connectivity. Voxel-wide measures, not constrained by a specific region, revealed increased global connectivity of the frontal pole and decreased global connectivity of the supplementary motor area. The magnitude of EF applied to the left M1 correlated with changes in global connectivity of the right M1. Conclusion: In this proof of concept pilot study, we demonstrate for the first time that tDCS appears to be feasible in glioma patients. In our exploratory analysis, we show preoperative motor training combined with tDCS may alter sensorimotor network connectivity. Patient specific modeling of EF in the presence of tumor may contribute to understanding the dose-response relationship of this intervention. Overall, this suggests the possibility of modulating neural networks in glioma patients.

How structural and functional MRI can inform dual-site tACS parameters: A case study in a clinical population and its pragmatic implications

“…One of the earliest studies was [101] that reported a significant positive correlation between tDCS-induced electric fields and changes in task-based fMRI data(post tDCS minus pre tDCS) in a single subject. Significant associations between electric fields and changes in functional activity/connectivity has been also reported in some other previous studies [50][51][52]54]. This information would also help to determine where and to what extent targeted brain regions should be stimulated (e.g., in FPS) in a group of participants (e.g., SUD group).…”

“…Previous fMRI-computational head modeling studies reported relationships between computed field measures (e.g., electric field strength) and functional outcomes [47,50]. Results revealed that electric field intensity generated by a specific electrode montage correlated with changes in functional activity/connectivity patterns in targeted brain areas [50][51][52][53][54][55]. Therefore, determining the ideal configuration of electrodes to optimally target a specific brain function and distinct network nodes is important and choice of suited stimulation montage and dose to enhance cortico-cortical coupling is not straightforward [45].…”

Applications of open-source software ROAST in clinical studies: A review

“…Ref. [ 29 ] used ROAST to model N = 8 glioma patients in their study of TES feasibility on these patients. They showed that patient-specific modeling of electric field in the presence of tumor may contribute to understanding the dose-response relationship of this intervention.…”

“…Note that for those studies that involved subjects with pathological head anatomies (e.g., tumor or lesion), customized segmentation was performed and integrated into the ROAST pipeline to account for these anatomies [ 25 , 29 ]. This is because the segmentation function in ROAST [ 116 ] was developed for normal head anatomy only.…”

“…For the primary motor cortex, Ref. [ 29 ] used bipolar montage C3-FP1 with conventional electrodes and achieved an average electric field of 0.12 V/m at the left M1 with 1 mA stimulating current. Ref.…”