Identifying informative voxels is a critical, yet challenging step in functional magnetic resonance imaging (fMRI), particularly for multivariate analyses involving multiple related conditions. Existing approaches often rely on predefined regions of interest (ROIs) or activation-based criteria, which may be insufficient for capturing fine-grained representational differences. This challenge becomes particularly relevant in experimental settings and interventions such as neurofeedback training, where voxels are not only measured as neural responses but also used as targets for intervention based on their previously observed activity patterns. In this study, we propose a subject-level searchlight optimization framework that integrates voxel-wise general linear model (GLM)-based univariate analysis with representational similarity analysis (RSA)-based multivariate refinement to identify voxels that are both task-relevant and condition-sensitive. To enhance practical applicability, the framework further incorporates a data-driven hyperparameter tuning step based on Bayesian optimization, enabling efficient identification of high-performing configurations from small pilot datasets, with consistent performance when applied to larger samples. The proposed framework was evaluated using an emotion imagery fMRI dataset with four affective conditions. Results demonstrate that the multivariate refinement improves alignment between empirical and target representational structures compared with univariate selection alone. Compared with a classifier-based voxel selection approach, the RSA-based approach better preserves the representational geometry of emotional states while maintaining discriminative capacity. These findings highlight the effectiveness, efficiency, and robustness of the proposed RSA framework, providing a practical solution for identifying condition-sensitive voxels and supporting more precise multivariate investigation of affective brain states in multi-condition fMRI studies.
Wang, X., Zweerings, J., Lührs, M., Cong, F., Mathiak, K., Linden, D. E. J., Goebel, R., Ciarlo, A., Mehler, D. M. A.
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