topographical-estimation-of-visual-population-receptive-fields-by-fmri

Topographical Estimation of Visual Population Receptive Fields by fMRI

Visual cortex is retinotopically organized so that neighboring populations of cells map to neighboring parts of the visual field. Functional magnetic ...

Neurons in area V4 of the macaque are generally not selective for direction of motion, as judged from their response to directional stimuli presented after a baseline condition devoid of movement. We used motion adaptation to investigate whether stimulation history influences direction-of-motion selectivity. We found that classically nondirectional V4 neurons develop direction-of-motion selectivity after adaptation, an observation that underscores the dynamic nature of functional cortical architecture.

Neurons in macaque area V4 acquire directional tuning after adaptation to motion stimuli.

Functional MR imaging of the alert, behaving monkey is being used more and more often to detect activation patterns and guide electrophysiological research investigating the neural basis of behavior. Several labs have reported fMRI data from the awake monkey, but none of them has studied and systematically corrected the effects of monkeys' motion on fMRI time series. In this study, a significant refinement of acquisition and correction strategies is reported that can be used to minimize magnetic susceptibility artifacts induced by respiration and by jaw and body movement. Real-time acquisition of sensor signals (e.g., signals induced by jaw and body movement) and MR navigator data were combined to optimize fMRI signal-correction strategies. Within trials, the artifact-induced off-resonance changes were small and mainly reflected the effects of respiration; between trials, movements caused major changes of global frequency and shim (>20 Hz/cm). Several methods were used to assess the stability of the fMRI series: k-space analysis ('dynamic intensity and off-resonance changes in k-space', dubbed DICK and DORK) and image analysis using a Laplace operator and a center-of-mass metric. The variability between trials made it essential to correct for inter-trial variations. On the other hand, images were sufficiently stable with our approach to perform fMRI evaluations on single trials before averaging of trials. Different motion correction strategies were compared: DORK, McFLIRT (rigid body model with three translations and three rotations) and 2D image alignment based on a center-of-mass detection (in-plane translation). The latter yielded the best results and proved to be fast and robust for intra- and inter-trial alignment. Finally, fMRI in the behaving monkey was tested for spatial and temporal reproducibility on a trial-to-trial basis. Highly activated voxels also displayed good reproducibility between trials. On average, the BOLD amplitude response to a short 3-s visual stimulus was close to 2%.

Functional MR imaging in the awake monkey: effects of motion on dynamic off-resonance and processing strategies.

The use of functional magnetic resonance imaging (fMRI) in alert non-human primates is of great potential for research in systems neuroscience. It can be combined with invasive techniques and afford better understanding of non-invasively acquired brain imaging signals in humans. However, the difficulties in optimal application of alert monkey fMRI are multi-faceted, especially at high magnetic fields where the effects of motion and of changes in B0 are greatly amplified. To overcome these difficulties, strict behavioral controls and elaborate animal-training are needed. Here, we introduce a number of hardware developments, quantify the effect of movements on fMRI data, and present procedures for animal training and scanning for well-controlled and artifact-reduced alert monkey fMRI at high magnetic field. In particular, we describe systems for monitoring jaw and body movements, and for accurately tracking eye movements. A link between body and jaw movement and MRI image artifacts is established, showing that relying on the immobilization of an animal's head is not sufficient for high-quality imaging. Quantitative analysis showed that body and jaw movement events caused large instabilities in fMRI time series. On average, body movement events caused larger instabilities than jaw movement events. Residual baseline brain image position and signal amplitude shifts were observed after the jaw and body movement events ended. Based on these findings, we introduce a novel behavioral paradigm that relies on training the monkeys to stay still during long trials. A corresponding analysis method discards all data that were not obtained during the movement-free periods. The baseline position and amplitude shifts are overcome by motion correction and trial-by-trial signal normalization. The advantages of the presented method over conventional scanning and analysis are demonstrated with data obtained at 7 T. It is anticipated that the techniques presented here will prove useful for alert monkey fMRI at any magnetic field.

Robust controlled functional MRI in alert monkeys at high magnetic field: effects of jaw and body movements.

Understanding the mechanisms of learning requires characterizing how the response properties of individual neurons and interactions across populations of neurons change over time. To study learning in vivo, we need the ability to track an electrophysiological signature that uniquely identifies each recorded neuron for extended periods of time. We have identified such an extracellular signature using a statistical framework that allows quantification of the accuracy by which stable neurons can be identified across successive recording sessions. Our statistical framework uses spike waveform information recorded on a tetrode's four channels to define a measure of similarity between neurons recorded across time. We use this framework to quantitatively demonstrate for the first time the ability to record from the same neurons across multiple consecutive days and weeks. The chronic recording techniques and methods of analyses we report can be used to characterize the changes in brain circuits due to learning.

Recording chronically from the same neurons in awake, behaving primates.

The local field potential (LFP), comprised of low-frequency extra-cellular voltage fluctuations, has been used extensively to study the mechanisms of brain function. In particular, oscillations in the gamma-band (30-90 Hz) are ubiquitous in the cortex of many species during various cognitive processes. Surprisingly little is known about the underlying biophysical processes generating this signal. Here, we examine the relationship of the local field potential to the activity of localized populations of neurons by simultaneously recording spiking activity and LFP from the primary visual cortex (V1) of awake, behaving macaques. The spatial organization of orientation tuning and ocular dominance in this area provides an excellent opportunity to study this question, because orientation tuning is organized at a scale around one order of magnitude finer than the size of ocular dominance columns. While we find a surprisingly weak correlation between the preferred orientation of multi-unit activity and gamma-band LFP recorded on the same tetrode, there is a strong correlation between the ocular preferences of both signals. Given the spatial arrangement of orientation tuning and ocular dominance, this leads us to conclude that the gamma-band of the LFP seems to sample an area considerably larger than orientation columns. Rather, its spatial resolution lies at the scale of ocular dominance columns.

Comparing the feature selectivity of the gamma-band of the local field potential and the underlying spiking activity in primate visual cortex.

Extracellular voltage fluctuations (local field potentials, LFPs) reflecting neural mass action are ubiquitous across species and brain regions. Numerous studies have characterized the properties of LFP signals in the cortex to study sensory and motor computations as well as cognitive processes like attention, perception and memory. In addition, its extracranial counterpart - the electroencephalogram - is widely used in clinical applications. However, the link between LFP signals and the underlying activity of local populations of neurons remains largely elusive. Here, we review recent work elucidating the relationship between spiking activity of local neural populations and LFP signals. We focus on oscillations in the gamma-band (30-90 Hz) of the LFP in the primary visual cortex (V1) of the macaque that dominate during visual stimulation. Given that in area V1 much is known about the properties of single neurons and the cortical architecture, it provides an excellent opportunity to study the mechanisms underlying the generation of the LFP.

Feature selectivity of the gamma-band of the local field potential in primate primary visual cortex.

Correlated trial-to-trial variability in the activity of cortical neurons is thought to reflect the functional connectivity of the circuit. Many cortical areas are organized into functional columns, in which neurons are believed to be densely connected and to share common input. Numerous studies report a high degree of correlated variability between nearby cells. We developed chronically implanted multitetrode arrays offering unprecedented recording quality to reexamine this question in the primary visual cortex of awake macaques. We found that even nearby neurons with similar orientation tuning show virtually no correlated variability. Our findings suggest a refinement of current models of cortical microcircuit architecture and function: Either adjacent neurons share only a few percent of their inputs or, alternatively, their activity is actively decorrelated.

Decorrelated neuronal firing in cortical microcircuits.

The role of primary visual cortex (area V1) in subjective perception has intrigued students of vision for decades. Specifically, the extent to which the activity of different types of cells (monocular versus binocular) and electrophysiological signals (i.e., local field potentials versus spiking activity) reflect perception is still debated. To address these questions we recorded from area V1 of the macaque using tetrodes during the paradigm of binocular flash suppression, where incongruent images presented dichoptically compete for perceptual dominance. We found that the activity of a minority (20%) of neurons reflect the perceived visual stimulus and these cells exhibited perceptual modulations substantially weaker compared with their sensory modulation induced by congruent stimuli. Importantly, perceptual modulations were found equally often for monocular and binocular cells, demonstrating that perceptual competition in V1 involves mechanisms across both types of neurons. The power of the local field potential (LFP) also showed moderate perceptual modulations with similar percentages of sites showing significant effects across frequency bands (18-22%). The possibility remains that perception may be strongly reflected in more elaborate aspects of activity in V1 circuits (e.g., specific neuronal subtypes) or perceptual states might have a modulatory role on more intricate aspects of V1 firing patterns (e.g., synchronization), not necessarily altering the firing rates of single cells or the LFP power dramatically.

The role of the primary visual cortex in perceptual suppression of salient visual stimuli.

Functional magnetic resonance imaging (fMRI) experiments with awake nonhuman primates (NHPs) have recently seen a surge of applications. However, the standard fMRI analysis tools designed for human experiments are not optimal for NHP data collected at high fields. One major difference is the experimental setup. Although real head movement is impossible for NHPs, MRI image series often contain visible motion artifacts. Animal body movement results in image position changes and geometric distortions. Since conventional realignment methods are not appropriate to address such differences, algorithms tailored specifically for animal scanning become essential. We have implemented a series of high-field NHP specific methods in a software toolbox, fMRI Sandbox (http://kyb.tuebingen.mpg.de/~stoewer/), which allows us to use different realignment strategies. Here we demonstrate the effect of different realignment strategies on the analysis of awake-monkey fMRI data acquired at high field (7 T). We show that the advantage of using a nonstandard realignment algorithm depends on the amount of distortion in the dataset. While the benefits for less distorted datasets are minor, the improvement of statistical maps for heavily distorted datasets is significant.

Realignment strategies for awake-monkey fMRI data.

fMRI experiments with awake non-human primates (NHP) have seen a surge of applications in recent years. However, the standard fMRI analysis tools designed for human experiments are not optimal for analysis of NHP fMRI data collected at high fields. There are several reasons for this, including the trial-based nature of NHP experiments, with inter-trial periods being of no interest, and segmentation artefacts and distortions that may result from field changes due to movement. We demonstrate an approach that allows us to address some of these issues consisting of the following steps: 1) Trial-based experimental design. 2) Careful control of subject movement. 3) Computer-assisted selection of trials devoid of artefacts and animal motion. 4) Nonrigid between-trial and rigid within-trial realignment of concatenated data from temporally separated trials and sessions. 5) Linear interpolation of inter-trial intervals and high-pass filtering of temporally continuous data 6) Removal of interpolated data and reconcatenation of datasets before statistical analysis with SPM. We have implemented a software toolbox, fMRI Sandbox (http://code.google.com/p/fmri-sandbox/), for semi-automated application of these processing steps that interfaces with SPM software. Here, we demonstrate that our methodology provides significant improvements for the analysis of awake monkey fMRI data acquired at high-field. The method may also be useful for clinical applications with subjects that are unwilling or unable to remain motionless for the whole duration of a functional scan.

An analysis approach for high-field fMRI data from awake non-human primates.

PURPOSE: Animal models are powerful tools to broaden our understanding of disease mechanisms and to develop future treatment strategies. Here we present detailed structural and functional findings of a rhesus macaque suffering from a naturally occurring bilateral macular dystrophy (BMD), partial optic atrophy and corresponding reduction of central V1 signals in visual fMRI experiments when compared to data in a healthy macaque (CTRL) of similar age. METHODS: Retinal imaging included infrared and autofluorescence recordings, fluorescein and indocyanine green angiography and spectral domain optical coherence tomography (OCT) on the Spectralis HRA + OCT platform. Electroretinography included multifocal and Ganzfeld-ERG recordings. Animals were killed and eyes analyzed by immunohistochemistry. RESULTS: Angiography showed reduced macular vascularization with significantly larger foveal avascular zones (FAZ) in the affected animal (FAZ(BMD) = 8.85 mm(2) vs. FAZ(CTRL) = 0.32 mm(2)). OCT showed bilateral thinning of the macula within the FAZ (total retinal thickness, TRT(BMD) = 174 ± 9 µm) and partial optic nerve atrophy when compared to control (TRT(CTRL) = 303 ± 45 µm). Segmentation analysis revealed that inner retinal layers were primarily affected (inner retinal thickness, IRT(BMD) = 33 ± 9 µm vs. IRT(CTRL) = 143 ± 45 µm), while the outer retina essentially maintained its thickness (ORT(BMD) = 141 ± 7 µm vs. ORT(CTRL) = 160 ± 11 µm). Altered macular morphology corresponded to a preferential reduction of central signals in the multifocal electroretinography and to a specific attenuation of cone-derived responses in the Ganzfeld electroretinography, while rod function remained normal. CONCLUSION: We provided detailed characterization of a primate macular disorder. This study aims to stimulate awareness and further investigation in primates with macular disorders eventually leading to the identification of a primate animal model and facilitating the preclinical development of therapeutic strategies.

Detailed functional and structural characterization of a macular lesion in a rhesus macaque.

Introduction to research topic - binocular rivalry: a gateway to studying consciousness.

We introduce a new method for measuring visual population receptive fields (pRF) with functional magnetic resonance imaging (fMRI). The pRF structure is modeled as a set of weights that can be estimated by solving a linear model that predicts the Blood Oxygen Level-Dependent (BOLD) signal using the stimulus protocol and the canonical hemodynamic response function. This method does not make a priori assumptions about the specific pRF shape and is therefore a useful tool for uncovering the underlying pRF structure at different spatial locations in an unbiased way. We show that our method is more accurate than a previously described method (Dumoulin and Wandell, 2008) which directly fits a 2-dimensional isotropic Gaussian pRF model to predict the fMRI time-series. We demonstrate that direct-fit models do not fully capture the actual pRF shape, and can be prone to pRF center mislocalization when the pRF is located near the border of the stimulus space. A quantitative comparison demonstrates that our method outperforms the direct-fit methods in the pRF center modeling by achieving higher explained variance of the BOLD signal. This was true for direct-fit isotropic Gaussian, anisotropic Gaussian, and difference of isotropic Gaussians model. Importantly, our model is also capable of exploring a variety of pRF properties such as surround suppression, receptive field center elongation, orientation, location and size. Additionally, the proposed method is particularly attractive for monitoring pRF properties in the visual areas of subjects with lesions of the visual pathways, where it is difficult to anticipate what shape the reorganized pRF might take. Finally, the method proposed here is more efficient in computation time than direct-fit methods, which need to search for a set of parameters in an extremely large searching space. Instead, this method uses the pRF topography to constrain the space that needs to be searched for the subsequent modeling.

A new method for estimating population receptive field topography in visual cortex.

The visual field is retinotopically represented in early visual areas. It has been suggested that when adult primary visual cortex (V1) is deprived of normal retinal input it is capable of large-scale reorganisation, with neurons inside the lesion projection zone (LPZ) being visually driven by inputs from intact retinal regions. Early functional magnetic resonance imaging (fMRI) studies in humans with macular degeneration (MD) report > 1 cm spread of activity inside the LPZ border, whereas recent results report no shift of the LPZ border. Here, we used fMRI population receptive field measurements to study, for the first time, the visual cortex organisation of one macaque monkey with MD and to compare it with normal controls. Our results showed that the border of the V1 LPZ remained stable, suggesting that the deafferented area V1 zone of the MD animal has limited capacity for reorganisation. Interestingly, the pRF size of non-deafferented V1 voxels increased slightly (~20% on average), although this effect appears weaker than that in previous single-unit recording reports. Area V2 also showed limited reorganisation. Remarkably, area V5/MT of the MD animal showed extensive activation compared to controls stimulated over the part of the visual field that was spared in the MD animal. Furthermore, population receptive field size distributions differed markedly in area V5/MT of the MD animal. Taken together, these results suggest that V5/MT has a higher potential for reorganisation after MD than earlier visual cortex.

Visual cortex organisation in a macaque monkey with macular degeneration.

Investigations of topographic cortical plasticity following peripheral nervous injury predominantly report receptive field (RF) shifts toward the intact periphery. A recent study on visual cortex plasticity following retinal lesions by Botelho et al.[1] finds RF coverage of the lesion affected space when global retinotopic mapping strategies are used.

Filling-in versus filling-out: patterns of cortical short-term plasticity.

Injury to the primary visual cortex (V1) typically leads to loss of conscious vision in the corresponding, homonymous region of the contralateral visual hemifield (scotoma). Several studies suggest that V1 is highly plastic after injury to the visual pathways, whereas others have called this conclusion into question. We used functional magnetic resonance imaging (fMRI) to measure area V1 population receptive field (pRF) properties in five patients with partial or complete quadrantic visual field loss as a result of partial V1+ or optic radiation lesions. Comparisons were made with healthy controls deprived of visual stimulation in one quadrant ["artificial scotoma" (AS)]. We observed no large-scale changes in spared-V1 topography as the V1/V2 border remained stable, and pRF eccentricity versus cortical-distance plots were similar to those of controls. Interestingly, three observations suggest limited reorganization: (i) the distribution of pRF centers in spared-V1 was shifted slightly toward the scotoma border in 2 of 5 patients compared with AS controls; (ii) pRF size in spared-V1 was slightly increased in patients near the scotoma border; and (iii) pRF size in the contralesional hemisphere was slightly increased compared with AS controls. Importantly, pRF measurements yield information about the functional properties of spared-V1 cortex not provided by standard perimetry mapping. In three patients, spared-V1 pRF maps overlapped significantly with dense regions of the perimetric scotoma, suggesting that pRF analysis may help identify visual field locations amenable to rehabilitation. Conversely, in the remaining two patients, spared-V1 pRF maps failed to cover sighted locations in the perimetric map, indicating the existence of V1-bypassing pathways able to mediate useful vision.

Population receptive field analysis of the primary visual cortex complements perimetry in patients with homonymous visual field defects.

Primary visual cortex (V1) was implicated as an important candidate for the site of perceptual suppression in numerous psychophysical and imaging studies. However, neurophysiological results in awake monkeys provided evidence for competition mainly between neurons in areas beyond V1. In particular, only a moderate percentage of neurons in V1 were found to modulate in parallel with perception with magnitude substantially smaller than the physical preference of these neurons. It is yet unclear whether these small modulations are rooted from local circuits in V1 or influenced by higher cognitive states. To address this question we recorded multi-unit spiking activity and local field potentials in area V1 of awake and anesthetized macaque monkeys during the paradigm of binocular flash suppression. We found that a small but significant modulation was present in both the anesthetized and awake states during the flash suppression presentation. Furthermore, the relative amplitudes of the perceptual modulations were not significantly different in the two states. We suggest that these early effects of perceptual suppression might occur locally in V1, in prior processing stages or within early visual cortical areas in the absence of top-down feedback from higher cognitive stages that are suppressed under anesthesia.

Article	Year
Neurons in macaque area V4 acquire directional tuning after adaptation to motion stimuli. Nature neuroscience\| PubMed ID: 15834417	2005
Functional MR imaging in the awake monkey: effects of motion on dynamic off-resonance and processing strategies. Magnetic resonance imaging\| PubMed ID: 17451900	2007
Robust controlled functional MRI in alert monkeys at high magnetic field: effects of jaw and body movements. NeuroImage\| PubMed ID: 17509896	2007
Recording chronically from the same neurons in awake, behaving primates. Journal of neurophysiology\| PubMed ID: 17942615	2007
Comparing the feature selectivity of the gamma-band of the local field potential and the underlying spiking activity in primate visual cortex. Frontiers in systems neuroscience\| PubMed ID: 18958246	2008
Feature selectivity of the gamma-band of the local field potential in primate primary visual cortex. Frontiers in neuroscience\| PubMed ID: 19225593	2008
Decorrelated neuronal firing in cortical microcircuits. Science (New York, N.Y.)\| PubMed ID: 20110506	2010
The role of the primary visual cortex in perceptual suppression of salient visual stimuli. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 20844131	2010
Realignment strategies for awake-monkey fMRI data. Magnetic resonance imaging\| PubMed ID: 21664781	2011
An analysis approach for high-field fMRI data from awake non-human primates. PloS one\| PubMed ID: 22238636	2012
Detailed functional and structural characterization of a macular lesion in a rhesus macaque. Documenta ophthalmologica. Advances in ophthalmology\| PubMed ID: 22923360	2012
Introduction to research topic - binocular rivalry: a gateway to studying consciousness. Frontiers in human neuroscience\| PubMed ID: 23055962	2012
A new method for estimating population receptive field topography in visual cortex. NeuroImage\| PubMed ID: 23684878	2013
Visual cortex organisation in a macaque monkey with macular degeneration. The European journal of neuroscience\| PubMed ID: 24033706	2013
Filling-in versus filling-out: patterns of cortical short-term plasticity. Trends in cognitive sciences\| PubMed ID: 24568929	2014
Population receptive field analysis of the primary visual cortex complements perimetry in patients with homonymous visual field defects. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 24706881	2014
Binocular flash suppression in the primary visual cortex of anesthetized and awake macaques. PloS one\| PubMed ID: 25216188	2014

Georgios A. Keliris

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