Lees, T. | Search bioRxiv

bioRxiv2026

Changes in anterior cingulate connectivity associated with response to antidepressant treatment for major depressive disorder

Background: Resting-state functional connectivity (rsFC) involving the anterior cingulate cortex (ACC) and the hippocampal formation has been implicated in major depressive disorder (MDD) and antidepressant response. However, it remains unclear whether connectivity changes in distinct ACC subdivisions and hippocampal formation reflect general antidepressant effects or are specifically associated with clinical improvement. Methods: Forty-one, unmedicated adults with MDD underwent functional MRI before and after 8 weeks of sertraline or bupropion treatment. Seed-based rsFC analyses examined subgenual ACC (sgACC), pregenual ACC (pgACC), dorsal ACC (dACC), and hippocampal formation connectivity. Linear mixed-effects models tested whether connectivity change was associated with treatment response, remission, and dimensional improvement in depressive symptoms. Results: Thirty individuals (73.2%) responded to treatment and 26 (63.4%) achieved remission. Overall, rsFC decreased pre- to post-treatment between (1) dACC and pgACC (but not sgACC and hippocampal formation) and (2) cortical regions primarily involving default mode and frontoparietal networks. When considering treatment response, differences in sgACC and pgACC connectivity with temporal and inferior frontal regions emerged (increased in responders vs. decreased in non-responders). Remission was similarly associated with increased sgACC connectivity with temporal and prefrontal regions, and increased sgACC connectivity with temporal cortical regions related to greater reductions in depressive symptoms. Conclusions: Antidepressant treatment was associated with distinct patterns of ACC connectivity change, with general reductions in dorsal and pregenual connectivity but increases in subgenual and pregenual connectivity associated with favorable clinical outcomes. Findings suggest that changes in sgACC/pgACC connectivity are particularly relevant to antidepressant treatment response. Keywords: Major depressive disorder; Resting-state functional connectivity; Anterior cingulate cortex; Antidepressant treatment; Treatment response; Subgenual anterior cingulate cortex.

neuroscience↗

bioRxiv2024

Test-Retest Reliability and repeatability of Behavioral and Electrophysiological Markers in an Eriksen Flanker Task

Cognitive control processes, specifically interference control and error monitoring, are often impaired across neuropsychiatric disorders and have been proposed as transdiagnostic markers of psychopathology and important treatment targets. Accurately probing them, however, requires understanding the psychometric properties of the measures used to assess cognitive control, including their intra- and interindividual stability over time. Using an Eriksen Flanker Task, we tested behavioral and electrophysiological readouts of cognitive control in 36 healthy individuals (26 female, 10 male, M age{+/-}SD=33.18{+/-}14.49, range=19-68) and evaluated their test-retest reliability across 48 hours by calculating Pearson correlations and Intraclass Correlation Coefficients (ICCs) to assess group-level stability. Moreover, we assessed repeatability through Coefficients of Variation (CVs) and Bland-Altman statistics, to investigate the degree of change in participants absolute scores. We found satisfactory-to-excellent test-retest reliability for most cognitive control measures, with condition-specific metrics generally being more reliable than difference scores. Regarding repeatability, we observed considerable intraindividual variability in absolute scores over time, which differed widely between participants. These results demonstrate that measurements of cognitive control may display substantial intraindividual variability across sessions despite demonstrating high test-retest reliability and vice versa. Our findings expand the current literature by providing novel information about the stability of behavioral and physiological markers of cognitive control over time. Moreover, they may have important implications for the application and evaluation of clinical interventions by highlighting the usefulness of considering repeatability measures in addition to the more commonly reported test-retest reliability metrics, when tracking changes over time in clinically relevant processes within single individuals.

neuroscience↗