Layer-fMRI methods for applications in human neuroscience: beyond block designs and beyond primary brain areas
Creators: name: Huber, Laurentius
name: Finn, Emily
name: Goebel, Rainer
name: Bandettini, Peter
name: Poser, Benedikt
Publisher: name: F1000 Research Limited
Year: 2019

description: Methodological advancements of functional Magnetic Resonance Imaging (fMRI) in recent years allow researchers to approach the mesoscopic spatial regime of cortical layers and cortical columns. This revolutionizes the ability to tackle cortical information processing within brain systems. However, until now, most layer fMRI studies are confined to primary cortices in combination with basic fMRI task block-designs. Thus, to become an established method for user-friendly applicability in neuroscience practice, layer fMRI acquisition and analysis methods need to be extended to more sophisticated task designs and capture subtle changes in brain networks of higher-order cognitive areas too. In this study we aim to investigate the neuroscientific applicability of layer-fMRI across a wide spectrum of higher-order brain areas and task-designs.

	We describe the capabilities and challenges of layer-fMRI to generate participant specific directional connectomes with resting-state data in the visual and sensory motor system (Fig. 1). We find that it is possible pinpoint feed-forward and feedback connections between V1 and V5, as well as between BA3B and BA1 as off-diagonal connectivity elements (ellipses in Fig. 1). However, to account for shared sources of signal fluctuations across cortical depths (E.g. physiological noise), it is vital to normalize any measure of functional connectivity with a reference seed region.
	We discuss the sensitivity requirements for layer fMRI with naturalistic tasks of free movie watching compared to resting-state (Fig. 2). We find that the ability to perform signal averaging across multiple movie-watching runs is highly beneficial in layer-fMRI data to extract more neural driven ICA components. The improved sensitivity in movie watching tasks allows the extraction of unique brain networks, which differently engage different layers of the same brain area (blue and red voxels in right panel of Fig. 2).
	We assess the necessity of locally specific non-BOLD contrasts in the context of tasks with CNR-starved effect sizes (Fig. 3). When CBV- sensitive VASO contrasts are acquired in tandem with conventional GE-BOLD, the high-CNR of BOLD can be combined with the high localization specificity of VASO. When the ROI selection and seed time course extraction is guided by the high-CNR of BOLD signals, VASO fMRI can provide data with improved neuroscientific interpretability.
	We investigate the technical challenges of event related task designs. Compared to block-designs, event-related designs are applicable in human neuroscience studies with greater flexibility. However, in the context of layer fMRI, they can suffer from a reduced detection efficiency. We find that event related paradigms are particularly challenging in layer fMRI (1) due to cortical depth-dependent variable response times (HRFs), and (2) due to increased fMRI signal drifts, when MRI gradients are pushed to their limits.
	We discuss potential future analysis strategies to assess features of cortical hierarchy (Fig. 4).

We conclude: While layer fMRI comes along with technical acquisition and analysis challenges it is applicable for human neuroscience and provide valuable new insights.