Laminar-specific interhemispheric connectivity mapping with bilateral line-scanning fMRI

Abstract

Despite extensive studies detecting blood-oxygen-level-dependent (BOLD) fMRI signals across two hemispheres to present cognitive processes in normal and diseased brains, the role of corpus callosum (CC) to mediate interhemispheric functional connectivity remains controversial. Several studies show maintaining low-frequency fluctuation of resting-state (rs)-fMRI signals in homotopic brain areas of acallosal humans and post-callosotomy animals, raising the question: how can we specify the circuit-specific rs-fMRI signal fluctuation from other sources? To address this question, we have developed a bilateral line-scanning fMRI (BiLS) method to detect bilateral laminar BOLD fMRI signals from symmetric cortical regions with high spatial (100 m) and temporal (100 ms) resolution in rodents under anesthesia. In addition to ultra-slow oscillation (0.01-0.02 Hz) patterns across all cortical layers, a layer-specific bilateral coherence pattern was observed with a peak at Layer (L)2/3, where callosal projection neurons are primarily located and reciprocal transcallosal projections are received. In particular, the L2/3-specific coherence pattern showed a peak at 0.05 Hz based on the stimulation paradigm, depending on the interhemispheric CC activation. Meanwhile, the L2/3-specific rs-fMRI coherence was peaked at 0.08-0.1Hz which was independent of the varied ultra-slow oscillation patterns (0.01-0.02 Hz) presumably involved with global neuromodulation. This work provides a unique laminar fMRI mapping scheme to characterize the CC-mediated evoked fMRI and frequency-dependent rs-fMRI responses, presenting crucial evidence to distinguish the circuit-specific fMRI signal fluctuations across two hemispheres. Significance statementLaminar fMRI is a promising method to better understand neuronal circuit contribution to functional connectivity (FC) across cortical layers. Here, we developed a bilateral line-scanning fMRI method, allowing the detection of laminar-specific BOLD-fMRI signals from homologous cortical regions in rodents with high spatial and temporal resolution. Laminar coherence patterns of both evoked and rs-fMRI signals revealed that CC-dependent interhemispheric FC is significantly strong at Layer 2/3, where callosal projection neurons are primarily located. The Layer 2/3-specific rs-fMRI coherence is independent of ultra-slow oscillation based on global neuromodulation, distinguishing the circuit-specific rs-fMRI signal fluctuation from different regulatory sources.