AUTHOR=Cui Brian , Mocchi Madaline M. , Metzger Brian A. , Kalva Prathik , Magnotti John F. , Fiedorowicz Jess G. , Waters Allison , Kovach Christopher K. , Reed Yvonne Y. , Mathura Raissa K. , Steger Camille , Pascuzzi Bailey , Kanja Kourtney , Veerakumar Ashan , Tiruvadi Vineet , Crowell Andrea , Denison Lydia , Rozell Christopher J. , Pouratian Nader , Goodman Wayne , Riva Posse Patricio , Mayberg Helen S. , Bijanki Kelly Rowe 

TITLE=Affective bias predicts changes in depression during deep brain stimulation therapy

JOURNAL=Frontiers in Human Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2025.1539857

DOI=10.3389/fnhum.2025.1539857

ISSN=1662-5161

ABSTRACT=IntroductionDeep brain stimulation (DBS) is a promising treatment for refractory depression, utilizing surgically implanted electrodes to stimulate specific anatomical targets within the brain. However, limitations of patient-reported and clinician-administered mood assessments pose obstacles in evaluating DBS treatment efficacy. In this study, we investigated whether an affective bias task, which leverages the inherent negative interpretation bias seen in individuals with depression, could serve as a reliable measure of mood changes during DBS therapy in patients with treatment-resistant depression.MethodsTwo cohorts of patients (n = 8, n = 2) undergoing DBS for treatment-resistant depression at different academic medical centers completed an affective bias task at multiple time points before and after DBS implantation. The affective bias task involved rating the emotional content of a series of static photographic stimuli of facial expressions throughout their DBS treatment. Patients' ratings were compared with those of non-depressed controls to calculate affective bias scores. Linear mixed-effects modeling was used to assess changes in bias scores over time and their relationship with depression severity measured by the Hamilton Depression Rating Scale (HDRS-17).ResultsWe observed significant improvements in total affective bias scores over the course of DBS treatment in both cohorts. Pre-DBS, patients exhibited a negative affective bias, which was nearly eliminated post-DBS, with total bias scores approaching those of non-depressed controls. Positive valence trials showed significant improvement post-DBS, while negative valence trials showed no notable change. A control analysis indicated that stimulation status did not significantly affect bias scores, and thus stimulation status was excluded from further modeling. Linear mixed-effects modeling revealed that more negative bias scores were associated with higher HDRS-17 scores, particularly for positive valence stimuli. Additionally, greater time elapsed since DBS implantation was associated with a decrease in HDRS-17 scores, indicating clinical improvement over time.DiscussionOur findings demonstrate that the affective bias task leverages the inherent negative interpretation bias seen in individuals with depression, providing a standardized measure of how these biases change over time. Unlike traditional mood assessments, which rely on subjective introspection, the affective bias task consistently measures changes in mood, offering potential as a tool to monitor mood changes and evaluate the candidacy of DBS treatment in refractory depression.