Layer-specific cortical processing dissociates sensory and cognitive influences on pain

Pain arises from the integration of nociceptive input with cognitive and affective processes, yet how these signals are organized within cortical circuits remains unclear. Here, using submillimeter-resolution 7T fMRI, we tested whether bottom-up (BU) and top-down (TD) influences on pain are segregated across cortical layers in human sensory-discriminative regions. Participants underwent a factorial manipulation of nociceptive input and cognitive modulation, enabling dissociation of BU and TD processes. BU processing was strongest in middle cortical layers. In contrast, TD modulation preferentially engaged superficial layers, consistent with cortico-cortical feedback mechanisms. Critically, individual differences in this laminar segregation predicted the magnitude of distraction-induced analgesia, linking circuit-level organization to behavior. These findings provide evidence that cognitive modulation of pain is implemented through layer-specific cortical computations and extend canonical microcircuit models to human pain processing. More generally, they establish laminar fMRI as a powerful approach for linking cortical circuit architecture to subjective experience.