A response-locking protocol to boost sensitivity for fMRI-based neurochronometry

The timeline of brain-wide neural activity relative to a behavioral event is crucial when decoding the neural implementation of a cognitive process. Yet, fMRI assesses neural processes indirectly via delayed and regionally variable hemodynamics. This method-inherent temporal distortion impacts the interpretation of behavior-linked neural timing. Here we describe a novel behavioral protocol that aims at disentangling the BOLD dynamics of the pre- and post-response periods in response time tasks. We tested this response-locking protocol in a perceptual decision-making (random dot) task. Increasing perceptual difficulty produced expected activity increases over a broad network involving the lateral/medial prefrontal cortex and the anterior insula. However, response-locking revealed a previously unreported functional dissociation within this network. preSMA and anterior premotor cortex (prePMV) showed post-response activity modulations while anterior insula and anterior cingulate cortex did not. Furthermore, post-response BOLD activity at preSMA showed a modulation in timing but not amplitude while this pattern was reversed at prePMV. These timeline dissociations with response-locking thus revealed three functionally distinct sub-networks in what was seemingly one shared distributed network modulated by perceptual difficulty. These findings suggest that our novel response-locked protocol could boost the timing-related sensitivity of fMRI.