Chen, Y.-A. A. | Search bioRxiv

bioRxiv2026

Active Escape or Active Change? Decomposing Pavlovian Bias into Non-emotional Components

Pavlovian bias, a motor bias driven by emotionally-valenced context, has long been considered a proxy for emotion-action processing, which may become aberrant in affective disorders and suicidality. The orthogonal valenced Go/NoGo paradigm was developed to isolate this bias and has been widely adopted in translational psychiatry research under this interpretation. However, several unresolved theoretical inconsistencies highlight the need to dissociate potential confounding factors within this paradigm before assigning mechanistic and clinical interpretations to its findings. Using a novel paradigm that fully orthogonalized valence, action, and aimed transition in a normative sample of 25 individuals, we found that the "active escape bias" previously observed in aversive contexts--and interpreted as reflecting suicidality in the clinical population--was reproduced in appetitive contexts using trials with the same transition structure. Furthermore, computational modeling indicated that the bias patterns isolated by the orthogonal paradigm are primarily explained by the combined effects of aimed transition and cue salience, without requiring emotional-valence modulation. These findings call for a fundamental reconsideration of how orthogonal Go/NoGo paradigms are interpreted in translational psychiatry, particularly how the behavior they isolate is mechanistically linked to affective symptoms.

neuroscience↗

bioRxiv2025

Evaluating the quality of brainstem ROI registration using structural and diffusion MRI

Accurate registration of regions of interest (ROIs) from standard atlases to participants native spaces is a critical step in fMRI studies, as it directly affects the reliability of sampled BOLD signals. While T1-weighted (T1w) image-based ROI registration is well validated and widely adopted in cortical fMRI, its performance degrades in brainstem studies due to the small size, dense packing, and poor visibility of brainstem nuclei on T1w contrast. We hypothesized that incorporating diffusion MR images, containing more information about internal brainstem architecture, should improve ROI registration accuracy. To test this, we developed four registration pipelines that either included or excluded diffusion-based alignment components and evaluated their performance using data from n=20 healthy participants. Registration accuracy was assessed using Dice coefficient for the red nucleus (RN) and the substantia nigra (SN), and mis-registration fraction--a metric developed for nuclei that cannot be manually delineated--for the dorsal raphe nucleus (DRN). The results showed that diffusion-based pipelines, using fractional anisotropy (FA) images, non-diffusion-weighted (b0) images, and multivariate combination, outperformed the T1w-only baseline. Probabilistic maps derived from inverse-transformed native ROIs further supported improved sensitivity to inter-individual anatomical variability in the diffusion-augmented pipelines. In addition, analysis of gradient magnitude maps from the Jacobian determinants revealed associations between localized deformation and image modality-specific landmarks. These findings demonstrate the potential of diffusion-augmented pipelines for improving brainstem ROI registration, which could enhance the robustness of fMRI studies on brainstem disorders characterized by functional dysregulation.

neuroscience↗