Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI

Abstract

Despite extensive studies detecting laminar functional magnetic resonance imaging (fMRI) signals to illustrate the canonical microcircuit, the spatiotemporal characteristics of laminar-specific information flow across cortical regions remain to be fully investigated in both evoked and resting conditions at different brain states. Here, we developed a multislice line-scanning fMRI (MS-LS) method to detect laminar fMRI signals in adjacent cortical regions with high spatial (50 μm) and temporal resolution (100 ms) in anesthetized rats. Across different trials, we detected either laminar-specific positive or negative blood-oxygen-level-dependent (BOLD) responses in the surrounding cortical region adjacent to the most activated cortex under the evoked condition. Specifically, in contrast to typical Layer (L) 4 correlation across different regions due to the thalamocortical projections for trials with positive BOLD, a strong correlation pattern specific in L2/3 was detected for trials with negative BOLD in adjacent regions, which indicated brain state-dependent laminar-fMRI responses based on corticocortical interaction. Also, in resting-state (rs-) fMRI study, robust lag time differences in L2/3, 4, and 5 across multiple cortices represented the low-frequency rs-fMRI signal propagation from caudal to rostral slices. In summary, our study provided a unique laminar fMRI mapping scheme to better characterize trial-specific intra- and inter-laminar functional connectivity in evoked and resting-state MS-LS.

Identifying the distinct spectral dynamics of laminar-specific interhemispheric connectivity with bilateral line-scanning fMRI

“…97 Besides CC, there are a few brain structures connecting the two cerebral hemispheres such as anterior commissure, cingulum, interhemispheric thalamic connections. Major thalamocortical input target L4 of FP-S1 regions, 50,52,53,112,113 leading to synchronized neuronal activity 72,114 (Figure 2(f), e.g., L4 has higher coherence values in Group 1 besides L2/3). A future study to combine the callosal circuit-specific optogenetic stimulation with BiLS will further elucidate the causal relationship, of which thalamocortical circuit optogenetic stimulation can be used as a control condition for laminar BOLD responses mapping with BiLS.…”

“…To study laminar-specific intrahemispheric FC, we developed a multi-slice line-scanning fMRI method to detect evoked and rs-fMRI signals from multiple line profiles with ultra-high spatiotemporal resolution. 72 Here, a bilateral line-scanning fMRI (BiLS) method was used to record laminar fMRI signals in bilateral forepaw somatosensory cortex (FP-S1) and CC of anesthetized rats. In both evoked and resting states, we detected ultra-slow oscillation (<0.04 Hz) across all cortical layers, which can be directly differentiated from callosal circuit-specific bilateral coherent oscillation at Layer (L) 2/3, where callosal projection neurons are mainly located.…”

Alpha-180 spin-echo based line-scanning method for high resolution laminar-specific fMRI

“…Significant effort with high magnetic field fMRI has been made to explore laminar fMRI responses corresponding to distinct information flows (e.g., top-down/bottom-up or feedforward/feedback) at high spatial and temporal scales in both animals and humans. Among these efforts, cortical depth-dependent fMRI, detecting BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) signals with both SE and GRE methods, has identified hemodynamic regulation, blood volume distribution, circuit-specific laminar responses, and hierarchical information streams across cortical layers in animal 1,2,5,8,15,16,25–29 and human brains 30–34 . In particular, the high resolution CBV-fMRI (based on the VASO mapping scheme) has been used to measure layer-specific directional functional connectivity across human motor cortex and somatosensory and premotor regions 30 .…”

“…Line-scanning fMRI has been successfully applied to investigate circuit-specific neuronal activity by measuring dynamic hemodynamic responses across cortical layers with high spatiotemporal resolution [1][2][3][4][5][6][7][8][9] . This is initially originated from Mansfield's line-profile mapping studies in early 1970s 10,11 .…”

“…Typical gradient echo (GRE)-based line-scanning fMRI (GELINE) method needs to dampen signals outside of the region of interest (ROI) to avoid aliasing artifacts along the phase encoding direction 1,2,4,5,[7][8][9] . Two saturation slices with additional RF exposure are applied for this purpose.…”