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Chunk #43 — Open questions in layer-fMRI connectivity analyses — Lack of universal layer-dependent models

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Layer-dependent functional connectivity methods.
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The seminal meta-study from Felleman and van Essen (Felleman and Van Essen 1991) summarizes the layer-dependent feed-forward connections in layer IV vs. feedback connections mostly in superficial and deeper layers of the visual system. This simplified model is often considered to be canonical and evident across the entire neocortex (Douglas and Martin 2004), and thus, provides the basis of many layer-fMRI studies to date. The universal applicability of this simplified layer-dependent model, however, has been recently called into question (Constantinople and Bruno 2013; Harris et al. 2019). Recent neuroanatomical studies point to a more complicated layout of layer-dependent hierarchy-defining connections than previously assumed. Future insight of appropriate layer-dependent models needs to be taken into account (Markov and Kennedy 2013) when interpreting layer-dependent functional connectivity data. In any case, the discovery of more complex layer-specific pathway-models of inter-layer communication further underscores the importance of high-resolution laminar fMRI for elucidating principles of the cortical connectome. For more comprehensive discussions about the lack of accurate neural models for layer-fMRI interpretation, please see the discussion section of the layer-fMRI review article by Stephan et al. (2019).