¹The First Affiliated Hospital of Chongqing Medical University, Psychiatric Center, Chongqing, China, ²University of Leicester, School of Psychology & Vision Sciences, Leicester, United Kingdom

Background: Attentional bias towards negative stimuli is a core mechanism in Major Depressive Disorder (MDD), yet objective biomarkers to quantify it are lacking. Steady-State Visual Evoked Potentials (SSVEP) provide a robust neural measure of attentional allocation. This study investigates SSVEP as a biomarker in adolescent MDD and its sensitivity to neuromodulation-enhanced treatment.

Aims & Objectives: 

1. To validate the sensitivity of the SSVEP paradigm for detecting emotional attentional bias in adolescents with MDD at both the group and individual level.
2. To investigate whether high-frequency transcranial alternating current stimulation (tACS), combined with standard SSRI pharmacotherapy, is more effective than SSRIs alone in normalizing this attentional bias.
3. To evaluate the SSVEP-based attentional bias index (Competition Index) as a potential biomarker for predicting and monitoring clinical treatment response.

Method: We recruited 66 unmedicated adolescents with DSM-5 MDD in a randomized controlled trial. Participants received either SSRIs plus active high-frequency transcranial alternating current stimulation (tACS) targeting the prefrontal cortex, or SSRIs plus sham tACS. The tACS parameters (77.5 Hz) were selected based on emerging evidence linking high-frequency stimulation to the modulation of cortical networks involved in cognitive control. Attentional bias was assessed with an SSVEP task where participants monitored Gabor patches superimposed on task-irrelevant faces (neutral, emotional). The primary outcome was the Competition Index (CI), a ratio of SSVEP power that directly quantifies the neural competition for attention between emotional faces and the primary task. Assessments occurred at baseline, week 4 (post-tACS), and week 8.

Results: Preliminary data (N=7) confirms the paradigm's sensitivity, with the CI reliably capturing a spectrum of individual attentional preferences. Our primary analysis will test the hypothesis that the active tACS group shows a significantly greater reduction in the emotional bias CI (i.e., a normalized attentional allocation) compared to the sham group, using Linear Mixed Effects models. We will further test if this neurophysiological change mediates clinical improvement (HAMD-24).

Discussion & Conclusions: This study aims to validate a sensitive and objective SSVEP-based biomarker for attentional bias in adolescent MDD. By integrating a novel neuromodulation approach with a direct neural measure of cognition, our findings have the potential to guide future development of precise and individualized therapeutic strategies for depression.