FSL analysis of structural, diffusion and functional connectivity as predictors of clinical response to transcranial direct current stimulation use in the treatment of unipolar major depressive disorder

Abstract

Major Depressive Disorder (MDD) causes important disabilities. Antidepressant drugs are the MDD most frequent treatment, but other ideal options are needed, and transcranial direct current stimulation (tDCS) is a promising one. TDCS is a non-invasive stimulation technique that injects low-intensity electrical current via electrodes located on the scalp, acting to facilitate or inhibit synaptic transmission. Although encouraging results have been reported, findings regarding the efficacy of tDCS are still heterogeneous, and the technique still needs to be optimized. Considering the core of tDCS mechanism is stimulating brain target(s) regions, the use of neuroimaging is particularly promising for comprehending how to enhance the effects of neuromodulation. Magnetic Resonance Imaging (MRI) studies aid to establish stimulation targets with greater precision and the identification of MRI-based biomarkers can possibly boost tDCS response. The most investigated neuroimaging modalities include the 1) structural MRI, that gives information about grey and white matter anatomical structure; 2) functional MRI (fMRI), for measuring brain activity by analyzing the blood-oxygen-level-dependent signal, and 3) diffusion MRI (DTI), which uses the diffusion of water molecules to provide insight into the microstructure integrity. Recently, all the three cited modalities have been investigated as potential biomarkers for MDD, but only our group has started to investigate MRI-based biomarkers and tDCS antidepressant effects. Our preliminary investigations were carried out in a sample of the ELECT-TDCS, a double-blinded, single centered, non-inferiority trial, that included patients with MDD randomly allocated to active tDCS plus placebo drug (tDCS group); sham tDCS plus escitalopram (escitalopram group), or sham tDCS plus placebo drug (placebo group). The images acquired at ELECT-TDCS include structural, functional and diffusion images (3T Phillips Scanner, HC-FMUSP). The tDCS (Soterix Medical, USA; electrodes = 25 cm2; sessions = 30 minutes of tDCS, with automatic shutdown after 30 seconds in the sham groups) was applied to areas involved in the physiopathology of the disorder, with anode on the left DPFC and cathode on right DPFC. The ELECT-TDCS (total n = 243, 52 with MRI) held 22 sessions. The present project aims to perform additional and more advanced neuroimaging analysis to the ELECT-TDCS MRI data using the FSL software, a comprehensive library of analysis tool developed by the renowned FMRIB group, Oxford, UK. Based on the preliminary results our hypothesis are: for 1) structural MRI, the brain volume of left Brodmann's areas 9, 10 and 46 and right Brodmann's area 9, suggested as possibly biomarkers, will be directly associated with tDCS antidepressant effects for MDD, for 2) fMRI the Default Mode Network (DMN) will be more hyper connected in individuals with more severe depressive symptoms, and for 3) DTI - higher fractional anisotropy of the prefrontal cortex will be associated with greater antidepressant response of tDCS. The neuroimaging skills acquired during the internship will be transferred to Prof. Brunoni's group. (AU)