Natalia Castillo Dutor

Catholic University of Valencia San Vicente Martir, Spain

Abstract Title: Enhancing Brain Resilience Mechanisms to Improve Treatment Outcomes in Depression: A TMS-EEG Approach

Biography:

Natalia Castillo is a PhD candidate at the Doctoral School of the Catholic University of Valencia (UCV). She holds a degree in Biomedical Engineering and a master’s in Neuroengineering and Rehabilitation. With two years of experience in clinical trial management and neuroimaging processing, she is currently part of the Brain Health and Resilience Challenge project at UCV. Her research is in collaboration with Dr. Álvaro Pascual-Leone, MD, PhD, a world-renowned neurologist from Harvard Medical School, and Dr. Tormos, MD, PhD, from the University of Valencia, focusing on brain resilience and non-invasive brain stimulation.

Research Interest:

Major depressive disorder (MDD) is a leading cause of disability worldwide, with nearly 30% of patients failing to respond to conventional treatments. Non-invasive brain stimulation, such as transcranial magnetic stimulation (TMS), offers an alternative with response rates ranging from 33% to 48% in treatment-resistant patients, yet many remain unresponsive. Recent evidence suggests that brain resilience—the capacity to resist or adapt to stressors—may influence treatment outcomes. This study examines brain resilience mechanisms in treatment- resistant depression (TRD), using transcranial direct current stimulation (tDCS) as a treatment and electroencephalography (EEG) and TMS-EEG as tools to evaluate neurophysiological changes. The treatment protocol includes 20 tDCS sessions targeting resilience-related neural nodes (cathodes at F3 and P3, anodes at Cz and T7, per the 10-20 EEG system). Baseline resting- state EEG and TMS-EEG measurements focus on the dorsolateral prefrontal cortex (dLPFC), inferior parietal lobule (IPL), and primary motor cortex. After treatment, participants complete a stress-inducing task involving moving circles (Limbachia et al., 2021), followed by post-task EEG and TMS-EEG assessments to capture changes in cortical excitability/inhibition balance. Preliminary resting-state EEG findings reveal increased alpha activity and reduced theta and delta power in frontal regions, along with decreased asymmetries across all frequency bands. TMS-EEG results show increased amplitudes in early-latency evoked potentials (P25, N45, P70), predominantly in the stimulated hemisphere, suggesting improved intracortical inhibition, facilitation, and enhanced effective connectivity. With TMS serving as an artificial stressor, individuals showing less adaptive responses may have less efficient networks for handling unexpected stress. These preliminary findings suggest that neurophysiological resilience markers, as captured by EEG and TMS-EEG, could inform targeted approaches for enhancing therapeutic outcomes in TRD, with observed improvements in participants' executive function and emotional regulation post-treatment.