A perspective on cortical layering and layer-spanning neuronal elements

This review article addresses the function of the layers of the cerebral cortex. We develop the perspective that cortical layering needs to be understood in terms of its functional anatomy, i.e., the terminations of synaptic inputs on distinct cellular compartments and their effect on cortical activity. The cortex is a hierarchical structure in which feed forward and feedback pathways have a layer-specific termination pattern. We take the view that the influence of synaptic inputs arriving at different cortical layers can only be understood in terms of their complex interaction with cellular biophysics and the subsequent computation that occurs at the cellular level. We use high-resolution fMRI, which can resolve activity across layers, as a case study for implementing this approach by describing how cognitive events arising from the laminar distribution of inputs can be interpreted by taking into account the properties of neurons that span different layers. This perspective is based on recent advances in measuring subcellular activity in distinct feed-forward and feedback axons and in dendrites as they span across layers

Laminar fMRI: applications for cognitive neuroscience

The cortex is a massively recurrent network, characterized by feedforward and feedback connections between brain areas as well as lateral connections within an area. Feedforward, horizontal and feedback responses largely activate separate layers of a cortical unit, meaning they can be dissociated by lamina-resolved neurophysiological techniques. Such techniques are invasive and are therefore rarely used in humans. However, recent developments in high spatial resolution fMRI allow for non-invasive, in vivo measurements of brain responses specific to separate cortical layers. This provides an important opportunity to dissociate between feedforward and feedback brain responses, and investigate communication between brain areas at a more fine- grained level than previously possible in the human species. In this review, we highlight recent studies that successfully used laminar fMRI to isolate layer-specific feedback responses in human sensory cortex. In addition, we review several areas of cognitive neuroscience that stand to benefit from this new technological development, highlighting contemporary hypotheses that yield testable predictions for laminar fMRI. We hope to encourage researchers with the opportunity to embrace this development in fMRI research, as we expect that many future advancements in our current understanding of human brain function will be gained from measuring lamina-specific brain responses

Cortical depth dependent population receptive field attraction by spatial attention in human V1

Visual spatial attention concentrates neural resources at the attended location. Recently, we demonstrated that voluntary spatial attention attracts population receptive fields (pRFs) toward its location throughout the visual hierarchy. Theoretically, both a feed forward or feedback mechanism could underlie pRF attraction in a given cortical area. Here, we use sub-millimeter ultra-high field functional MRI to measure pRF attraction across cortical depth and assess the contribution of feed forward and feedback signals to pRF attraction. In line with previous findings, we find consistent attraction of pRFs with voluntary spatial attention in V1. When assessed as a function of cortical depth, we find pRF attraction in every cortical portion (deep, center and superficial), although the attraction is strongest in deep cortical portions (near the gray-white matter boundary). Following the organization of feed forward and feedback processing across V1, we speculate that a mixture of feed forward and feedback processing underlies pRF attraction in V1. Specifically, we propose that feedback processing contributes to the pRF attraction in deep cortical portions

Point-spread function of the BOLD response across columns and cortical depth in human extra-striate cortex

Columns and layers are fundamental organizational units of the brain. Well known examples of cortical columns are the ocular dominance columns (ODCs) in primary visual cortex and the column-like stripe-based arrangement in the second visual area V2. The spatial scale of columns and layers is beyond the reach of conventional neuroimaging, but the advent of high field magnetic resonance imaging (MRI) scanners (UHF, 7 Tesla and above) has opened the possibility to acquire data at this spatial scale, in-vivo and non-invasively in humans. The most prominent non-invasive technique to measure brain function is blood oxygen level dependent (BOLD) fMRI, measuring brain activity indirectly, via changes in hemodynamics. A key determinant of the ability of high-resolution BOLD fMRI to accurately resolve columns and layers is the point-spread function (PSF) of the BOLD response in relation to the spatial extent of neuronal activity. In this study we take advantage of the stripe-based arrangement present in visual area V2, coupled with sub-millimetre anatomical and gradient-echo BOLD (GE BOLD) acquisition at 7 T to obtain PSF estimates and along cortical depth in human participants. Results show that the BOLD PSF is maximal in the superficial part of the cortex (1.78 mm), and it decreases with increasing cortical depth (0.83 mm close to white matter)

Linear systems analysis for laminar fMRI: evaluating BOLD amplitude scaling for luminance contrast manipulations

A fundamental assumption of nearly all functional magnetic resonance imaging (fMRI) analyses is that the relationship between local neuronal activity and the blood oxygenation level dependent (BOLD) signal can be described as following linear systems theory. With the advent of ultra-high field (7T and higher) MRI scanners, it has become possible to perform sub-millimeter resolution fMRI in humans. A novel and promising application of sub-millimeter fMRI is measuring responses across cortical depth, i.e. laminar imaging. However, the cortical vasculature and associated directional blood pooling towards the pial surface strongly influence the cortical depth-dependent BOLD signal, particularly for gradient-echo BOLD. This directional pooling may potentially affect BOLD linearity across cortical depth. Here we assess whether the amplitude scaling assumption for linear systems theory holds across cortical depth. For this, we use stimuli with different luminance contrasts to elicit different BOLD response amplitudes. We find that BOLD amplitude across cortical depth scales with luminance contrast, and that this scaling is identical across cortical depth. Although nonlinearities may be present for different stimulus configurations and acquisition protocols, our results suggest that the amplitude scaling assumption for linear systems theory across cortical depth holds for luminance contrast manipulations in sub-millimeter laminar BOLD fMRI

Systematic variation of population receptive field properties across cortical depth in human visual cortex

Receptive fields (RFs) in visual cortex are organized in antagonistic, center-surround, configurations. RF properties change systematically across eccentricity and between visual field maps. However, it is unknown how center-surround configurations are organized in human visual cortex across lamina. We use sub-millimeter resolution functional MRI at 7 Tesla and population receptive field (pRF) modeling to investigate the pRF properties in primary visual cortex (V1) across cortical depth. pRF size varies according to a U-shaped function, indicating smaller pRF center size in the middle compared to superficial and deeper intra-cortical portions of V1, consistent with non-human primate neurophysiological measurements. Moreover, a similar U-shaped function is also observed for pRF surround size. However, pRF center-surround ratio remains constant across cortical depth. Simulations suggest that this pattern of results can be directly linked to the flow of signals across cortical depth, with the visual input reaching the middle of cortical depth and then spreading towards superficial and deeper layers of V1. Conversely, blood-oxygenation-level-dependent (BOLD) signal amplitude increases monotonically towards the pial surface, in line with the known vascular organization across cortical depth. Independent estimates of the haemodynamic response function (HRF) across cortical depth show that the center-surround pRF size estimates across cortical depth cannot be explained by variations in the full-width half maximum (FWHM) of the HRF

Systematic variation of population receptive field properties across cortical depth in human visual cortex

Receptive fields (RFs) in visual cortex are organized in antagonistic, center-surround, configurations. RF properties change systematically across eccentricity and between visual field maps. However, it is unknown how center-surround configurations are organized in human visual cortex across lamina. We use sub-millimeter resolution functional MRI at 7Tesla and population receptive field (pRF) modeling to investigate the pRF properties in primary visual cortex (V1) across cortical depth. pRF size varies according to a U-shaped function, indicating smaller pRF center size in the middle compared to superficial and deeper intra-cortical portions of V1, consistent with non-human primate neurophysiological measurements. Moreover, a similar U-shaped function is also observed for pRF surround size. However, pRF center-surround ratio remains constant across cortical depth. Simulations suggest that this pattern of results can be directly linked to the flow of signals across cortical depth, with the visual input reaching the middle of cortical depth and then spreading towards superficial and deeper layers of V1. Conversely, blood-oxygenation-level-dependent (BOLD) signal amplitude increases monotonically towards the pial surface, in line with the known vascular organization across cortical depth. Independent estimates of the haemodynamic response function (HRF) across cortical depth show that the center-surround pRF size estimates across cortical depth cannot be explained by variations in the full-width half maximum (FWHM) of the HRF

Investigating visual and auditory scene feedback to early visual foveal and peripheral cortex using fMRI

No abstract available