Pfaffenrot, V. | bioRxiv Science

bioRxiv2026

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.

neuroscience↗

bioRxiv2024

Characterizing BOLD activation patterns in the human hippocampus with laminar fMRI

The human hippocampus has been extensively studied at the macroscale using functional magnetic resonance imaging (fMRI) but the underlying microcircuits at the mesoscale (i.e., at the level of layers) are largely uninvestigated in humans. We target two questions fundamental to hippocampal laminar fMRI: How does the venous bias affect the interpretation of hippocampal laminar responses? And can we establish a benchmark laminar fMRI experiment which robustly elicits single-subject hippocampal activation utilizing the most widely applied GRE-BOLD contrast? We comprehensively characterized GRE-BOLD responses as well as T2*, tSNR and physiological noise as a function of cortical depth in individual subfields of the human hippocampus. Our results show that the vascular architecture differs between subfields leading to subfield-specific laminar biases of GRE-BOLD responses. Using an autobiographical memory paradigm, we robustly acquired depth-specific BOLD responses in hippocampal subfields. In the CA1 subregion, our results indicate a more pronounced trisynaptic path input rather than dominant direct inputs from entorhinal cortex during autobiographical memory retrival. Our study provides unique insights into the hippocampus at the mesoscale level, and will help interpreting hippocampal laminar fMRI responses and allow researchers to test mechanistic hypotheses of hippocampal function.

neuroscience↗