Despite extensive efforts to identify interhemispheric functional connectivity (FC) with resting-state (rs-) fMRI, correlated low-frequency rs-fMRI signal fluctuation across homotopic cortices originates from multiple sources. It remains challenging to differentiate circuit-specific FC from global regulation. Here, we developed a bilateral line-scanning fMRI method to detect laminar-specific rs-fMRI signals from homologous forepaw somatosensory cortices with high spatial and temporal resolution in rat brains. Based on spectral coherence analysis, two distinct bilateral fluctuation spectral features were identified: ultra-slow fluctuation (<0.04 Hz) across all cortical laminae versus Layer (L) 2/3-specific evoked BOLD at 0.05 Hz based on 4 s on/16 s off block design and resting-state fluctuations at 0.08–0.1 Hz. Based on the measurements of evoked BOLD signal at corpus callosum (CC), this L2/3-specific 0.05 Hz signal is likely associated with neuronal circuit-specific activity driven by the callosal projection, which dampened ultra-slow oscillation less than 0.04 Hz. Also, the rs-fMRI power variability clustering analysis showed that the appearance of L2/3-specific 0.08–0.1 Hz signal fluctuation is independent of the ultra-slow oscillation across different trials. Thus, distinct laminar-specific bilateral FC patterns at different frequency ranges can be identified by the bilateral line-scanning fMRI method.
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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.
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- Award ID(s):
- 2123970
- NSF-PAR ID:
- 10438534
- Date Published:
- Journal Name:
- Cerebral Cortex
- Volume:
- 32
- Issue:
- 20
- ISSN:
- 1047-3211
- Page Range / eLocation ID:
- 4492 to 4501
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Laminar-specific functional magnetic resonance imaging (fMRI) has been widely used to study circuit-specific neuronal activity by mapping spatiotemporal fMRI response patterns across cortical layers. Hemodynamic responses reflect indirect neuronal activity given the limitation of spatial and temporal resolution. Previously, a gradient-echo-based line-scanning fMRI (GELINE) method was proposed with high temporal (50 ms) and spatial (50 µm) resolution to better characterize the fMRI onset time across cortical layers by employing two saturation RF pulses. However, the imperfect RF saturation performance led to poor boundary definition of the reduced region of interest (ROI) and aliasing problems outside of the ROI. Here, we propose an α (alpha)-180 spin-echo-based line-scanning fMRI (SELINE) method in animals to resolve this issue by employing a refocusing 180˚ RF pulse perpendicular to the excitation slice (without any saturation RF pulse) and also achieve high spatiotemporal resolution. In contrast to GELINE signals which peaked at the superficial layer, we detected varied peaks of laminar-specific BOLD signals across deeper cortical layers using the SELINE method, indicating the well-defined exclusion of the large draining-vein effect using the spin-echo sequence. Furthermore, we applied the SELINE method with a 200 ms repetition time (TR) to sample the fast hemodynamic changes across cortical layers with a less draining vein effect. In summary, this SELINE method provides a novel acquisition scheme to identify microvascular-sensitive laminar-specific BOLD responses across cortical depth.
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Abstract We combined magnetoencephalography (MEG), 7 T proton magnetic resonance spectroscopy (MRS), and 7 T fMRI during performance of a task in a group of 23 first episode psychosis (FEP) patients and 26 matched healthy controls (HC). We recorded both the auditory evoked response to 40 Hz tone clicks and the resting state in MEG. Neurometabolite levels were obtained from the anterior cingulate cortex (ACC). The fMRI BOLD response was obtained during the Stroop inhibitory control task. FEP showed a significant increase in resting state low frequency theta activity (
p < 0.05; Cohend = 0.69), but no significant difference in the 40 Hz auditory evoked response compared to HC. An across-groups whole brain analysis of the fMRI BOLD response identified eight regions that were significantly activated during task performance (p < 0.01, FDR-corrected); the mean signal extracted from those regions was significantly different between the groups (p = 0.0006;d = 1.19). In the combined FEP and HC group, there was a significant correlation between the BOLD signal during task performance and MEG resting state low frequency activity (p < 0.05). In FEP, we report significant alteration in resting state low frequency MEG activity, but no alterations in auditory evoked gamma band response, suggesting that the former is a more robust biomarker of early psychosis. There were no correlations between gamma oscillations and GABA levels in either HC or FEP. Finally, in this study, each of the three imaging modalities differentiated FEP from HC; fMRI with good and MEG and MRS with moderate effect size. -
Brain network models (BNMs) have become a promising theoretical framework for simulating signals that are representative of whole-brain activity such as resting-state fMRI. However, it has been difficult to compare the complex brain activity obtained from simulations to empirical data. Previous studies have used simple metrics to characterize coordination between regions such as functional connectivity. We extend this by applying various different dynamic analysis tools that are currently used to understand empirical resting-state fMRI (rs-fMRI) to the simulated data. We show that certain properties correspond to the structural connectivity input that is shared between the models, and certain dynamic properties relate more to the mathematical description of the brain network model. We conclude that the dynamic properties that explicitly examine patterns of signal as a function of time rather than spatial coordination between different brain regions in the rs-fMRI signal seem to provide the largest contrasts between different BNMs and the unknown empirical dynamical system. Our results will be useful in constraining and developing more realistic simulations of whole-brain activity.more » « less
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ABSTRACT BACKGROUND AND PURPOSE Cognitive dysfunction is common in multiple sclerosis (MS). The dorsal anterior insula (dAI) is a key hub of the salience network (SN) orchestrating access to critical cognitive brain regions. The aim of this study was to assess whole‐brain dAI intrinsic functional connectivity (iFC) using resting‐state functional MRI (rs‐fMRI) in people with MS and healthy controls (HC) and test the relationship between cognitive reserve (CR) and dAI iFC in people with MS.
METHODS We studied 28 people with relapsing‐remitting MS and 28 HC. CR index was quantified by combining premorbid IQ, leisure activities, and education level. For whole‐brain iFC analyses, the bilateral dAI were used as seeds. Individual subject correlation maps were entered into general linear models for group comparison and to analyze the effect of CR index on dAI iFC, controlling for multiple comparisons. The correlation between CR index and iFC was assessed using a linear regression model.
RESULTS rs‐fMRI analyses revealed a negative relationship between CR index and iFC within the left dAI and a left occipital cluster in people with MS including regions of the cuneus, superior occipital gyrus, and parieto‐occipital sulcus. The regression analysis showed that people with MS and a higher CR index had a statistically significantly reduced iFC within the left dAI and the cluster.
CONCLUSIONS CR is relevant to functional connectivity within one of the main nodes of the SN, the dAI, and occipital regions in MS. These results have implications for how CR may modulate the susceptibility to cognitive dysfunction in MS.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/cercor/bhab497
