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The visual brain has the remarkable capacity to complete our percept of the world even when the information extracted from the visual scene is incomplete. This ability to predict missing information based on information from spatially adjacent regions is an intriguing attribute of healthy vision. Yet, it gains particular significance when it masks the perceptual consequences of a retinal lesion, leaving patients unaware of their partial loss of vision and ultimately delaying diagnosis and treatment. At present, our understanding of the neural basis of this masking process is limited which hinders both quantitative modeling as well as translational application. To overcome this, we asked the participants to view visual stimuli with and without superimposed artificial scotoma (AS). We used fMRI to record the associated cortical activity and applied model-based analyzes to track changes in cortical population receptive fields and connectivity in response to the introduction of the AS. We found that throughout the visual field and cortical hierarchy, pRFs shifted their preferred position towards the AS border. Moreover, extrastriate areas biased their sampling of V1 towards sections outside the AS projection zone, thereby effectively masking the AS with signals from spared portions of the visual field. We speculate that the signals that drive these system-wide population modifications originate in extrastriate visual areas and, through feedback, also reconfigure the neural populations in the earlier visual areas., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

How much of the functional organization of our visual system is inherited? Here we tested the heritability of retinotopic maps in human visual cortex using functional magnetic resonance imaging. We demonstrate that retinotopic organization shows a closer correspondence in monozygotic (MZ) compared to dizygotic (DZ) twin pairs, suggesting a partial genetic determination. Using population receptive field (pRF) analysis to examine the preferred spatial location and selectivity of these neuronal populations, we estimate a heritability around 10-20% for polar angle preferences and spatial selectivity, as quantified by pRF size, in extrastriate areas V2 and V3. Our findings are consistent with heritability in both the macroscopic arrangement of visual regions and stimulus tuning properties of visual cortex. This could constitute a neural substrate for variations in a range of perceptual effects, which themselves have been found to be at least partially genetically determined. These findings also add convergent evidence for the hypothesis that functional map topology is linked with cortical morphology., (Copyright © 2021. Published by Elsevier Inc.)

The extrastriate cortex in the human visual cortex is divided into two distinct clusters: the "what-information" processing area and the "where-information" processing area. It is widely accepted that the "what-information" cluster is processed through the ventral stream to the temporal cortex, and the "where-information" cluster through the dorsal stream to the parietal cortex. In human neuroanatomy, fiber bundles for the ventral stream (such as the inferior longitudinal fasciculus) are well defined, whereas fibers for the dorsal stream are poorly understood. In this study, we attempted to trace the dorsal stream fibers using a fiber tracking method using 7.0T diffusion-weighted MRI. We used data from a healthy male subject as well as from an unbiasedly selected nine-subject dataset in the Human Connectome Project. The surface of the visual area, including V1, V2, V3, V4, MT, was determined from the Brainnetome atlas (Fan et al., 2016), which is the connectivity-based parcellation framework of the human brain. The resulting visual pathway indicated that the putative pathway for the classical dorsal stream is unlikely to exist. Instead, we demonstrated that fiber connections exist between the angular gyrus with MT in the visual cortex, and between the angular gyrus and IT in the temporal cortex. Through that, we composed a two-pathway model for where-information processing that passes through the angular gyrus. Finally, we proposed a modified human visual pathway model based on our fiber tracking results in this report. The modified where-information pathway will provide a new aspect for the study of human visual processing., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The temporal monocular crescent (TMC) is the most peripheral portion of the visual field whose perception relies solely on input from the ipsilateral eye. According to a handful of post-mortem histological studies in humans and non-human primates, the TMC is represented visuotopically within the most anterior portion of the primary visual cortical area (V1). However, functional evidence of the TMC visuotopic representation in human visual cortex is rare, mostly due to the small size of the TMC representation (~6% of V1) and due to the technical challenges of stimulating the most peripheral portion of the visual field inside the MRI scanner. In this study, by taking advantage of custom-built MRI-compatible visual stimulation goggles with curved displays, we successfully stimulated the TMC region of the visual field in eight human subjects, half of them right-eye dominant, inside a 3 ​T MRI scanner. This enabled us to localize the representation of TMC, along with the blind spot representation (another visuotopic landmark in V1), in all volunteers, which match the expected spatial pattern based on prior anatomical studies. In all hemispheres, the TMC visuotopic representation was localized along the peripheral border of V1, within the most anterior portion of the calcarine sulcus, without any apparent extension into the second visual area (V2). We further demonstrate the reliability of this localization within/across experimental sessions, and consistency in the spatial location of TMC across individuals after accounting for inter-subject structural differences., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Studies of changes in cerebral neocortical thickness often rely on small control samples for comparison with specific populations with abnormal visual systems. We present a normative dataset for FreeSurfer-derived cortical thickness across 25 human visual areas derived from 960 participants in the Human Connectome Project. Cortical thickness varies systematically across visual areas, in broad agreement with canonical visual system hierarchies in the dorsal and ventral pathways. In addition, cortical thickness estimates show consistent within-subject variability and reliability. Importantly, cortical thickness estimates in visual areas are well described by a normal distribution, making them amenable to direct statistical comparison., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Advances in hardware, pulse sequences, and reconstruction techniques have made it possible to perform functional magnetic resonance imaging (fMRI) at sub-millimeter resolution while maintaining high spatial coverage and acceptable signal-to-noise ratio. Here, we examine whether sub-millimeter fMRI can be used as a routine method for obtaining accurate measurements of fine-scale local neural activity. We conducted fMRI in human visual cortex during a simple event-related visual experiment (7 T, gradient-echo EPI, 0.8-mm isotropic voxels, 2.2-s sampling rate, 84 slices), and developed analysis and visualization tools to assess the quality of the data. Our results fall along three lines of inquiry. First, we find that the acquired fMRI images, combined with appropriate surface-based processing, provide reliable and accurate measurements of fine-scale blood oxygenation level dependent (BOLD) activity patterns. Second, we show that the highly folded structure of cortex causes substantial biases on spatial resolution and data visualization. Third, we examine the well-recognized issue of venous contributions to fMRI signals. In a systematic assessment of large sections of cortex measured at a fine scale, we show that time-averaged T 2 *-weighted EPI intensity is a simple, robust marker of venous effects. These venous effects are unevenly distributed across cortex, are more pronounced in gyri and outer cortical depths, and are, to a certain degree, in consistent locations across subjects relative to cortical folding. Furthermore, we show that these venous effects are strongly correlated with BOLD responses evoked by the experiment. We conclude that sub-millimeter fMRI can provide robust information about fine-scale BOLD activity patterns, but special care must be exercised in visualizing and interpreting these patterns, especially with regards to the confounding influence of the brain's vasculature. To help translate these methodological findings to neuroscience research, we provide practical suggestions for both high-resolution and standard-resolution fMRI studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diffusion MRI tractography is essential for reconstructing white-matter projections in the living human brain. Yet tractography results miss some projections and falsely identify others. A challenging example is the optic radiation (OR) that connects the thalamus and the primary visual cortex. Here, we tested whether OR tractography can be optimized using quantitative T1 mapping. Based on histology, we proposed that myelin-sensitive T1 values along the OR should remain consistently low compared with adjacent white matter. We found that complementary information from the T1 map allows for increasing the specificity of the reconstructed OR tract by eliminating falsely identified projections. This T1-filtering outperforms other, diffusion-based tractography filters. These results provide evidence that the smooth microstructural signature along the tract can be used as constructive input for tractography. Finally, we demonstrate that this approach can be applied in a case of multiple sclerosis, and generalized to the HCP-available MRI measurements. We conclude that multimodal MRI microstructural information can be used to eliminate spurious tractography results in the case of the OR., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018. Published by Elsevier Inc.)

Brain regions are often topographically connected: nearby locations within one brain area connect with nearby locations in another area. Mapping these connection topographies, or 'connectopies' in short, is crucial for understanding how information is processed in the brain. Here, we propose principled, fully data-driven methods for mapping connectopies using functional magnetic resonance imaging (fMRI) data acquired at rest by combining spectral embedding of voxel-wise connectivity 'fingerprints' with a novel approach to spatial statistical inference. We apply the approach in human primary motor and visual cortex, and show that it can trace biologically plausible, overlapping connectopies in individual subjects that follow these regions' somatotopic and retinotopic maps. As a generic mechanism to perform inference over connectopies, the new spatial statistics approach enables rigorous statistical testing of hypotheses regarding the fine-grained spatial profile of functional connectivity and whether that profile is different between subjects or between experimental conditions. The combined framework offers a fundamental alternative to existing approaches to investigating functional connectivity in the brain, from voxel- or seed-pair wise characterizations of functional association, towards a full, multivariate characterization of spatial topography., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Functional MRI at ultra-high magnetic fields (≥ 7T) provides the opportunity to probe columnar and laminar processing in the human brain in vivo at sub-millimeter spatial scales. However, fMRI data only indirectly reflects the neuronal laminar profile due to a bias to ascending and pial veins inherent in gradient- and spin-echo BOLD fMRI. In addition, accurate delineation of the cortical depths is difficult, due to the relatively large voxel sizes and lack of sufficient tissue contrast in the functional images. In conventional depth-dependent fMRI studies, anatomical and functional data are acquired with different image read-out modules, the fMRI data are distortion-corrected and vascular biases are accounted for by subtracting the depth-dependent activation profiles of different stimulus conditions. In this study, using high-resolution gradient-echo fMRI data (0.7 mm isotropic) of the human visual cortex, we propose instead, that depth-dependent functional information is best preserved if data analysis is performed in the original functional data space. To achieve this, we acquired anatomical images with high tissue contrast and similar distortion to the functional images using multiple inversion-recovery time EPI, thereby eliminating the need to un-distort the fMRI data. We demonstrate higher spatial accuracy for the cortical layer definitions of this approach as compared to the more conventional approach using MP2RAGE anatomy. In addition, we provide theoretical arguments and empirical evidence that vascular biases can be better accounted for using division instead of subtraction of the depth-dependent profiles. Finally, we show that the hemodynamic response of grey matter has relatively stronger post-stimulus undershoot than the pial vein voxels. In summary, we show that the choice of fMRI data acquisition and processing can impact observable differences in the cortical depth profiles and present evidence that cortical depth-dependent modulation of the BOLD signal can be resolved using gradient-echo imaging., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Neuroimaging studies have identified multiple extra-striate visual areas that are sensitive to symmetry in planar images (Kohler et al., 2016; Sasaki et al., 2005). Here, we investigated which of these areas are directly involved in perceptual decisions about symmetry, by recording high-density EEG in participants (n = 25) who made rapid judgments about whether an exemplar image contained rotation symmetry or not. Stimulus-locked sensor-level analysis revealed symmetry-specific activity that increased with increasing order of rotation symmetry. Response-locked analysis identified activity occurring between 600 and 200 ms before the button-press, that was directly related to perceptual decision making. We then used fMRI-informed EEG source imaging to characterize the dynamics of symmetry-specific activity within an extended network of areas in visual cortex. The most consistent cortical source of the stimulus-locked activity was VO1, a topographically organized area in ventral visual cortex, that was highly sensitive to symmetry in a previous study (Kohler et al., 2016). Importantly, VO1 activity also contained a strong decision-related component, suggesting that this area plays a crucial role in perceptual decisions about symmetry. Other candidate areas, such as lateral occipital cortex, had weak stimulus-locked symmetry responses and no evidence of correlation with response timing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Which principles determine the organization of the intricate network formed by nerve fibers that link the primate cerebral cortex? We addressed this issue for the connections of primate visual cortices by systematically analyzing how the existence or absence of connections, their density as well as laminar patterns of projection origins and terminations are correlated with distance, similarity in cortical type as well as neuronal density or the thickness of cortical areas. Analyses were based on four extensive compilations of qualitative as well as quantitative data for connections of the primate visual cortical system in macaque monkeys (Felleman and Van Essen 1991; Barbas 1986; Barbas and Rempel-Clower 1997; Barone et al. 2000; Markov et al. 2014). Distance and thickness similarity were not consistently correlated with connection features, but similarity of cortical type, determined by qualitative features of laminar differentiation, or measured quantitatively as the areas' overall neuronal density, was a reliable predictor for the existence of connections between areas. Cortical type similarity was also consistently and closely correlated with characteristic laminar connection profiles: structurally dissimilar areas had origin and termination patterns that were biased to the upper or deep cortical layers, while similar areas showed more bilaminar origins and terminations. These results suggest that patterns of corticocortical connections of primate visual cortices are closely linked to the stratified architecture of the cerebral cortex. In particular, the regularity of laminar projection origins and terminations arises from the structural differences between cortical areas. The observed integration of projections with the intrinsic cortical architecture provides a structural basis for advanced theories of cortical organization and function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We studied a group of verbal memory specialists to determine whether intensive oral text memory is associated with structural features of hippocampal and lateral-temporal regions implicated in language processing. Professional Vedic Sanskrit Pandits in India train from childhood for around 10years in an ancient, formalized tradition of oral Sanskrit text memorization and recitation, mastering the exact pronunciation and invariant content of multiple 40,000-100,000 word oral texts. We conducted structural analysis of gray matter density, cortical thickness, local gyrification, and white matter structure, relative to matched controls. We found massive gray matter density and cortical thickness increases in Pandit brains in language, memory and visual systems, including i) bilateral lateral temporal cortices and ii) the anterior cingulate cortex and the hippocampus, regions associated with long and short-term memory. Differences in hippocampal morphometry matched those previously documented for expert spatial navigators and individuals with good verbal working memory. The findings provide unique insight into the brain organization implementing formalized oral knowledge systems., (Copyright © 2015. Published by Elsevier Inc.)

In the early visual cortex, information is processed within functional maps whose layouts are thought to underlie visual perception. However, the precise organization of these functional maps as well as their interrelationships remain unsettled. Here, we show that spatial frequency representation in cat early visual cortex exhibits singularities around which the map organizes like an electric dipole potential. These singularities are precisely co-located with singularities of the orientation map: the pinwheel centers. To show this, we used high resolution intrinsic optical imaging in cat areas 17 and 18. First, we show that a majority of pinwheel centers exhibit in their neighborhood both semi-global maximum and minimum in the spatial frequency map (i.e. extreme values of the spatial frequency in a hypercolumn). This contradicts pioneering studies suggesting that pinwheel centers are placed at the locus of a single spatial frequency extremum. Based on an analogy with electromagnetism, we proposed a mathematical model for a dipolar structure, accurately fitting optical imaging data. We conclude that a majority of orientation pinwheel centers form spatial frequency dipoles in cat early visual cortex. Given the functional specificities of neurons at singularities in the visual cortex, it is argued that the dipolar organization of spatial frequency around pinwheel centers could be fundamental for visual processing., (Copyright © 2015. Published by Elsevier Inc.)

A number of recent studies have established a link between behavior and the anatomy of the primary visual cortex (V1). However, one often-raised criticism has been that these studies provide little insight into the mechanisms of the observed relationships. As inhibitory neural interactions have been postulated as an important mechanism for those behaviors related to V1 anatomy, we measured the concentration of inhibitory gamma-amino butyric acid (GABA) in the medial occipital cortex where V1 is located using magnetic resonance spectroscopy (MRS) and estimated the surface area of V1 using fMRI retinotopic mapping. We found a significant positive relationship between GABA concentration and V1 surface area. This relationship was present irrespective of whether the MRS voxel had a fixed size across participants or was proportionally sized to each individual's V1 surface area. Hence, individuals with a larger V1 had a higher GABA concentration in the medial occipital cortex. By tying together V1 size and GABA concentration, our findings point towards individual differences in the level of neural inhibition that might partially mediate the relationships between behavior and V1 neuroanatomy. In addition, they illustrate how stable microscopic properties of neural activity and function are reflected in macro-measures of V1 structure., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Precise motor control requires the ability to scale the parameters of movement. Theta oscillations across the cortex have been associated with changes in memory, attention, and sensorimotor processing. What has proven more elusive is pinpointing the region-specific frequency band oscillations that are associated with specific parameters of movement during the acceleration and deceleration phases. We report a study using 3D analytic techniques for high density electroencephalography that examines electrocortical dynamics while participants produce upper limb movements to different distances at varying rates. During fast ballistic movements, we observed increased theta band activity in the left motor area contralateral to the moving limb during the acceleration phase of the movement, and theta power correlated with the acceleration of movement. In contrast, beta band activity scaled with the type of movement during the deceleration phase near the end of the movement and correlated with movement time. In the ipsilateral motor and somatosensory area, alpha band activity decreased with the type of movement near the end of the movement, and gamma band activity in visual cortex increased with the type of movement near the end of the movement. Our results suggest that humans use distinct lateralized cortical activity for distance and speed dependent arm movements. We provide new evidence that a temporary increase in theta band power relates to movement acceleration and is important during movement execution. Further, the theta power increase is coupled with desychronization of beta band power and alpha band power which are modulated by the task near the end of movement., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The maturation of cortical structures, and the establishment of their connectivity, are critical neurodevelopmental processes that support and enable cognitive and behavioral functioning. Measures of cortical development, including thickness, curvature, and gyrification have been extensively studied in older children, adolescents, and adults, revealing regional associations with cognitive performance, and alterations with disease or pathology. In addition to these gross morphometric measures, increased attention has recently focused on quantifying more specific indices of cortical structure, in particular intracortical myelination, and their relationship to cognitive skills, including IQ, executive functioning, and language performance. Here we analyze the progression of cortical myelination across early childhood, from 1 to 6 years of age, in vivo for the first time. Using two quantitative imaging techniques, namely T1 relaxation time and myelin water fraction (MWF) imaging, we characterize myelination throughout the cortex, examine developmental trends, and investigate hemispheric and gender-based differences. We present a pattern of cortical myelination that broadly mirrors established histological timelines, with somatosensory, motor and visual cortices myelinating by 1 year of age; and frontal and temporal cortices exhibiting more protracted myelination. Developmental trajectories, defined by logarithmic functions (increasing for MWF, decreasing for T1), were characterized for each of 68 cortical regions. Comparisons of trajectories between hemispheres and gender revealed no significant differences. Results illustrate the ability to quantitatively map cortical myelination throughout early neurodevelopment, and may provide an important new tool for investigating typical and atypical development., (Copyright © 2015. Published by Elsevier Inc.)

MRI, enabling in vivo analysis of cortical morphology, offers a powerful tool in the assessment of brain development and pathology. One of the most ubiquitous measures used-the thickness of the cortex-shows abnormalities in a number of diseases and conditions, but the functional and biological correlates of such alterations are unclear. If the functional connotations of structural MRI measures are to be understood, we must strive to clarify the relationship between measures such as cortical thickness and their cytoarchitectural determinants. We therefore sought to determine whether patterns of cortical thickness mirror a key motif of the cortex, specifically its structural hierarchical organisation. We delineated three sensory hierarchies (visual, somatosensory and auditory) in two species-macaque and human-and explored whether cortical thickness was correlated with specific cytoarchitectural characteristics. Importantly, we controlled for cortical folding which impacts upon thickness and may obscure regional differences. Our results suggest that an easily measurable macroscopic brain parameter, namely, cortical thickness, is systematically related to cytoarchitecture and to the structural hierarchical organisation of the cortex. We argue that the measurement of cortical thickness gradients may become an important way to develop our understanding of brain structure-function relationships. The identification of alterations in such gradients may complement the observation of regionally localised cortical thickness changes in our understanding of normal development and neuropsychiatric illnesses., (Copyright © 2015. Published by Elsevier Inc.)

In the absence of cognitive tasks and external stimuli, strong rhythmic fluctuations with a frequency ≈ 10 Hz emerge from posterior regions of human neocortex. These posterior α-oscillations can be recorded throughout the visual cortex and are particularly strong in the calcarine sulcus, where the primary visual cortex is located. The mechanisms and anatomical pathways through which local \alpha-oscillations are coordinated however, are not fully understood. In this study, we used a combination of magnetoencephalography (MEG), diffusion tensor imaging (DTI), and biophysical modeling to assess the role of white-matter pathways in coordinating cortical α-oscillations. Our findings suggest that primary visual cortex plays a special role in coordinating α-oscillations in higher-order visual regions. Specifically, the amplitudes of α-sources throughout visual cortex could be explained by propagation of α-oscillations from primary visual cortex through white-matter pathways. In particular, α-amplitudes within visual cortex correlated with both the anatomical and functional connection strengths to primary visual cortex. These findings reinforce the notion of posterior α-oscillations as intrinsic oscillations of the visual system. We speculate that they might reflect a default-mode of the visual system during which higher-order visual regions are rhythmically primed for expected visual stimuli by α-oscillations in primary visual cortex., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Acetylcholine modulates maturation and neuronal activity through muscarinic and nicotinic receptors in the primary visual cortex. However, the specific contribution of different muscarinic receptor subtypes in these neuromodulatory mechanisms is not fully understood. The present study evaluates in vivo the functional organization and the properties of the visual cortex of different groups of muscarinic receptor knock-out (KO) mice. Optical imaging of intrinsic signals coupled to continuous and episodic visual stimulation paradigms was used. Retinotopic maps along elevation and azimuth were preserved among the different groups of mice. However, compared to their wild-type counterparts, the apparent visual field along elevation was larger in M2/M4-KO mice but smaller in M1-KO. There was a reduction in the estimated relative receptive field size of V1 neurons in M1/M3-KO and M1-KO mice. Spatial frequency and contrast selectivity of V1 neuronal populations were affected only in M1/M3-KO and M1-KO mice. Finally, the neuronal connectivity was altered by the absence of M2/M4 muscarinic receptors. All these effects suggest the distinct roles of different subtypes of muscarinic receptors in the intrinsic organization of V1 and a strong involvement of the muscarinic transmission in the detectability of visual stimuli., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal and their underlying neurovascular origins have recently gained considerable interest. In this study a multi-echo, BOLD-corrected vascular space occupancy (VASO) functional magnetic resonance imaging (fMRI) technique was used to investigate neurovascular responses during stimuli that elicit positive and negative BOLD responses in human brain at 7 T. Stimulus-induced BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) changes were measured and analyzed in 'arterial' and 'venous' blood compartments in macro- and microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD responses is similar for tasks inducing positive and negative BOLD responses. Some aspects of the neurovascular coupling however, such as the temporal response, cortical depth dependence, and the weighting between 'arterial' and 'venous' contributions, are significantly different for the different task conditions. Namely, while for excitatory tasks the BOLD response peaks at the cortical surface, and the CBV change is similar in cortex and pial vasculature, inhibitory tasks are associated with a maximum negative BOLD response in deeper layers, with CBV showing strong constriction of surface arteries and a faster return to baseline. The different interplays of CBV, CBF and BOLD during excitatory and inhibitory responses suggests different underlying hemodynamic mechanisms., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Visual area MT is a model of choice in primate neurophysiological and human imaging research of visual perception, due to its considerable sensitivity to moving stimuli and the strong direction selectivity of its neurons. While the location of MT(V5) in the non-human primate is easily identifiable based on gross anatomy and appears consistent between animals, this is less the case in human subjects. Functional localisation of human MT+ with moving stimuli can identify a group of motion-sensitive regions, but defining MT proper has proved more challenging. In this review we consider approaches to studying the cyto- and myleoarchitecture of this cortical area that may, in the future, allow identification of human MT in vivo based on anatomy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

V1 is a canonical cortical area with clearly delineated architectonic boundaries and a continuous topographic representation of the visual hemifield. It thus serves as a touchstone for understanding what new mapping methods can tell us about cortical organization. By parcellating human cortex using local gradients in functional connectivity, Wig et al. (2014--in this issue) detected the V1 border with V2. By contrast, previously-published clustering methods that focus on global similarity in connectivity reveal a supra-areal organization that emphasizes eccentricity bands spanning V1 and its neighboring extrastriate areas; i.e. in the latter analysis, the V1 border is not evident. Thus the focus on local connectivity gradients emphasizes qualitatively different features of cortical organization than are captured by global similarity measures. What is intriguing to consider is that each kind of information might be telling us something unique about cortical organization. Global similarity measures may be detecting map clusters and other supra-areal arrangements that reflect a fundamental level of organization., (Copyright © 2013 Elsevier Inc. All rights reserved.)

High-resolution diffusion MRI (dMRI) is useful for resolving complex microstructures in the mouse brain, but technically challenging for in vivo studies due to the long scan time. In this study, selective excitation and a three-dimensional fast imaging sequence were used to achieve in vivo high-resolution dMRI of the mouse brain at 11.7Tesla. By reducing the field of view using spatially selective radio frequency pulses, we were able to focus on targeted brain structures and acquire high angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 0.1mm and 30 diffusion encoding directions in approximately 1h. We investigated the complex tissue microstructures of the mouse hippocampus, cerebellum, and several cortical areas using this localized dMRI approach, and compared the results with histological sections stained with several axonal and dendritic markers. In the mouse visual cortex, the results showed predominately radially arranged structures in an outer layer and tangentially arranged structures in an inner layer, similar to observations from postmortem human brain specimens., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The neural organization of person processing relies on brain regions functionally selective for faces or bodies, with a subset of these regions preferring moving stimuli. Although the response properties of the individual areas are well established, less is known about the neural response to a whole person in a natural environment. Targeting an area of cortex that spans multiple functionally-selective face and body regions, we examined the relationship among neural activity patterns elicited in response to faces, bodies, and people in static and moving displays. When both stimuli were static or moving, pattern classification analyses indicated highly discriminable responses to faces, bodies, and whole people. Neural discrimination transferred in both directions between representations created from moving or static stimuli. It transferred also to stimuli experienced across static and dynamic presentations (one static and the other dynamic). In both transfer cases, however, discrimination accuracy decreased relative to the case where the representations were both created and tested with static or moving forms. Next, we examined the relative contribution of activity pattern and response magnitude to discrimination by comparing classifiers that operated with magnitude-normalized scans with classifiers that retained pattern and magnitude information. When both stimuli were moving or static, response magnitude contributed to classification, but the spatially distributed activity pattern accounted for most of the discrimination. Across static and moving presentations, activity pattern accounted completely for the discriminability of neural responses to faces, bodies, and people, with no contribution from response magnitude. Combined, the results indicate redundant and flexible access to person-based shape codes from moving and static presentations. The transfer of shape information across presentation types that preferentially access dorsal and ventral visual processing streams indicates that a common shape code may ground functional divisions in the processing of face and body information., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn(2+) administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural-functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn(2+) injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn(2+) transfer but not intra- or inter-hemispheric monosynaptic Mn(2+) transport after Mn(2+) injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the neuroarchitecture, neurophysiology and structural-functional relationships of the visual brains in vivo. These may possess great potentials for effective monitoring and understanding of the basic anatomical and functional connections in the visual system during development, plasticity, disease, pharmacological interventions and genetic modifications in future studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In macaque monkeys, V6A is a visuomotor area located in the anterior bank of the POs, dorsal and anterior to retinotopically-organized extrastriate area V6 (Galletti et al., 1996). Unlike V6, V6A represents both contra- and ipsilateral visual fields and is broadly retinotopically organized (Galletti et al., 1999b). The contralateral lower visual field is over-represented in V6A. The central 20°-30° of the visual field is mainly represented dorsally (V6Ad) and the periphery ventrally (V6Av), at the border with V6. Both sectors of area V6A contain arm movement-related cells, active during spatially-directed reaching movements (Gamberini et al., 2011). In humans, we previously mapped the retinotopic organization of area V6 (Pitzalis et al., 2006). Here, using phase-encoded fMRI, cortical surface-based analysis and wide-field retinotopic mapping, we define a new cortical region that borders V6 anteriorly and shows a clear over-representation of the contralateral lower visual field and the periphery. As with macaque V6A, the eccentricity increases moving ventrally within the area. The new region contains a non-mirror-image representation of the visual field. Functional mapping reveals that, as in macaque V6A, the new region, but not the nearby area V6, responds during finger pointing and reaching movements. Based on similarity in position, retinotopic properties, functional organization and relationship with the neighboring extrastriate visual areas, we propose that the new cortical region is the human homologue of macaque area V6A., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Here we summarize the points raised in our dialog with Ales and colleagues on the cortical generators of the early visual evoked potential (VEP), and offer observations on the results of additional simulations that were run in response to our original comment. For small stimuli placed at locations in the upper and lower visual field for which the human VEP has been well characterized, simulated scalp projections of each of the visual areas V1, V2 and V3 invert in polarity. However, the empirically measured, earliest VEP component, "C1," matches the simulated V1 generators in terms of polarity and topography, but not the simulated V2 and V3 generators. We thus conclude that, 1) consistent with the title of Ales et al. (2010a), polarity inversion on its own is not a sufficient criterion for inferring neuroelectric sources in primary visual cortex; but 2) inconsistent with additional claims made in Ales et al. (2010a), the simulated topographies provide additional evidence for - not against - the tenet that the C1 component is generated in V1., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Fundamental understanding of higher cognitive functions can greatly benefit from imaging of cortical activity with high spatiotemporal resolution in the behaving non-human primate. To achieve rapid imaging of high-resolution dynamics of cortical representations of spontaneous and evoked activity, we designed a novel data acquisition protocol for sensory stimulation by rapidly interleaving multiple stimuli in continuous sessions of optical imaging with voltage-sensitive dyes. We also tested a new algorithm for the "temporally structured component analysis" (TSCA) of a multidimensional time series that was developed for our new data acquisition protocol, but was tested only on simulated data (Blumenfeld, 2010). In addition to the raw data, the algorithm incorporates prior knowledge about the temporal structure of the data as well as input from other information. Here we showed that TSCA can successfully separate functional signal components from other signals referred to as noise. Imaging of responses to multiple visual stimuli, utilizing voltage-sensitive dyes, was performed on the visual cortex of awake monkeys. Multiple cortical representations, including orientation and ocular dominance maps as well as the hitherto elusive retinotopic representation of orientation stimuli, were extracted in only 10s of imaging, approximately two orders of magnitude faster than accomplished by conventional methods. Since the approach is rather general, other imaging techniques may also benefit from the same stimulation protocol. This methodology can thus facilitate rapid optical imaging explorations in monkeys, rodents and other species with a versatility and speed that were not feasible before., (Copyright © 2013. Published by Elsevier Inc.)

Recently, a forward-model simulation study demonstrated that the upper and lower visual field projections to extrastriate visual cortical areas V2 and V3 have polarity-inverted electrical scalp projections, a property famously associated with potentials generated in primary visual cortex (V1) (Ales et al., 2010a). The authors use this finding, along with other findings from fMRI-constrained source modeling, to argue that the initial component "C1" of the human visual evoked potential may not be generated in V1 as has been widely believed, but may instead come from V2/V3. Here, we examine the validity of this claim with respect to the full set of anatomical and electrophysiological factors comprising the unabridged "cruciform" model linking C1 to V1. We find that the simulations in their current form do not present a valid test of the model, nor are their results inconsistent with it. We also review non-human primate neurophysiology findings that support the C1-V1 principle, and that can and should be taken into account in assessing the validity of constrained source models of human EEG in general., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Recent studies have identified large scale brain networks based on the spatio-temporal structure of spontaneous fluctuations in resting-state fMRI data. It is expected that functional connectivity based on resting-state data is reflective of - but not identical to - the underlying anatomical connectivity. However, which functional connectivity analysis methods reliably predict the network structure remains unclear. Here we tested and compared network connectivity analysis methods by applying them to fMRI resting-state time-series obtained from the human visual cortex. The methods evaluated here are those previously tested against simulated data in Smith et al. (Neuroimage, 2011). To this end, we defined regions within retinotopic visual areas V1, V2, and V3 according to their eccentricity in the visual field, delineating central, intermediate, and peripheral eccentricity regions of interest (ROIs). These ROIs served as nodes in the models we study. We based our evaluation on the "ground-truth", thoroughly studied retinotopically-organized anatomical connectivity in the monkey visual cortex. For each evaluated method, we computed the fractional rate of detecting connections known to exist ("c-sensitivity"), while using a threshold of the 95th percentile of the distribution of interaction magnitudes of those connections not expected to exist. Under optimal conditions - including session duration of 68min, a relatively small network consisting of 9 nodes and artifact-free regression of the global effect - each of the top methods predicted the expected connections with 67-85% c-sensitivity. Correlation methods, including Correlation (Corr; 85%), Regularized Inverse Covariance (ICOV; 84%) and Partial Correlation (PCorr; 81%) performed best, followed by Patel's Kappa (80%), Bayesian Network method PC (BayesNet; 77%), General Synchronization measures (67-77%), and Coherence (CohB; 74%). With decreased session duration, these top methods saw decreases in c-sensitivities, achieving 59-76% for 17min sessions. With a short resting-state fMRI scan of 8.5min, none of the methods predicted the real network well, with Corr (65%) performing best. With increased complexity of the network from 9 to 36 nodes, multivariate methods including PCorr and BayesNet saw a decrease in performance. Artifact-free regression of the global effect increased the c-sensitivity of the top-performing methods. In an overall evaluation across all tests we performed, correlation methods (Corr, ICOV, and PCorr), Patel's Kappa, and BayesNet method PC set themselves somewhat above all other methods. We propose that data-based calibration based on known anatomical connections be integrated into future network studies, in order to maximize sensitivity and reduce false positives., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The extrastriate body area (EBA) is located in the lateral occipito-temporal cortex, in the vicinity of the motion-sensitive region hMT/V5+. To investigate the relationship of EBA to the recently mapped retinotopic areas of the MT/V5 cluster (Kolster et al., 2010), we evaluated the proportion of voxels responsive to the presentation of static human bodies (EBA voxels) in each of the four areas of the MT/V5 cluster and neighboring LO and phPIT areas. We evaluated this proportion as both a function of the number of voxels in a given area and the total number of voxels in a broader lateral occipito-temporal cortex (LOTC) ROI. We observed that each of the four retinotopic areas of the MT/V5 cluster includes substantial fractions of EBA voxels, in contrast to the LO and phPIT areas. This proportion was slightly greater in the right than left hemisphere, and did not depend on the control condition. While most EBA voxels in MT/V5 were only body-sensitive, those in pMSTv and pFST were also motion-sensitive. The main locus of EBA voxels outside the MT/V5 cluster was in the LOTC cortex just rostral to the MT/V5 cluster. Although this region contained more EBA voxels than the MT/V5 cluster, the proportion as a function of areal size was much reduced compared to the MT/V5 cluster. Our results show that EBA is not a single cortical area as EBA voxels are located in all four areas of the MT/V5 cluster, and that body-sensitivity is a key feature of the MT/V5 cluster, in keeping with its exquisite sensitivity to observed actions of others., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Behavioral studies and single cell recordings in monkey inferotemporal cortex have documented greater sensitivity to differences in viewpoint invariant or nonaccidental properties (e.g., straight vs. curved), than metric properties (e.g., degree of curvature) of simple shapes. Are we similarly more sensitive to nonaccidental (NAP) than metric (MP) differences of the relations between objects? We addressed this question with sets of scene triplets that could, from a reference or "Base" scene (e.g., a brick slightly separated from a cylinder), undergo a NAP relational change (e.g., the brick attached to the cylinder) or an MP relational change (e.g., the brick further separated from the cylinder). Critically, both relational variations were matched in physical dissimilarity using pixel energy and the Gabor-jet system, a model of V1 similarity. In an adaptive staircase match-to-sample paradigm, subjects required more than double the presentation durations for detecting differences in MP than NAP relations to achieve equivalent levels of accuracy. In two fMRI experiments, NAP changes consistently produced greater responses in the lateral occipital cortex (LO), but not in earlier retinotopic stages, compared to MP changes, implicating LO as the potential neural locus for where the greater detectability of the differences of NAPs than MPs is made explicit. HMAX, a model of cell tuning in higher-level ventral visual areas, did not consistently reflect the marked NAP advantage witnessed in behavioral performance and in LO responses., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal resolution (4mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms temporal resolution (4×4×6 mm(3) voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: -52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5 min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75 s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In contrast to the limited use of functional magnetic resonance imaging (fMRI) in clinical diagnostics, it is currently a mainstay of neuroimaging in clinical and basic brain research. However, its non-invasive use in combination with its high temporal and spatial resolution would make fMRI a perfect diagnostic tool. We are interested in whether a pharmacological challenge imposed on the brain can be reliably traced by the blood oxygen level-dependent (BOLD) signal and possibly further exploited for diagnostics. We have chosen a systemic challenge with lactate and pyruvate to test whether the physiological formation of these monocarboxylic acids contributes to the BOLD signal and can be detected using fMRI. This information is also of interest because lactate levels in the cerebrospinal fluid rise concomitantly with reduced vascular responsiveness of the brain during the progression of Alzheimer disease (AD). We studied the BOLD response after a low-dose lactate challenge and monitored the induced plasma lactate levels in anesthetized non-human primates. We observed reliable lactate-induced BOLD responses, which could be confirmed at population and individual level by their strong correlation with systemic lactate concentrations. Comparable BOLD effects where observed after a slow infusion of pyruvate. We show here that physiological changes in lactate and pyruvate levels are indeed reflected in the BOLD signal, and describe the technical prerequisites to reliably trace a lactate challenge using BOLD-fMRI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In a widely used functional magnetic resonance imaging (fMRI) data analysis method, functional regions of interest (fROIs) are handpicked in each participant using macroanatomic landmarks as guides, and the response of these regions to new conditions is then measured. A key limitation of this standard handpicked fROI method is the subjectivity of decisions about which clusters of activated voxels should be treated as the particular fROI in question in each subject. Here we apply the Group-Constrained Subject-Specific (GSS) method for defining fROIs, recently developed for identifying language fROIs (Fedorenko et al., 2010), to algorithmically identify fourteen well-studied category-selective regions of the ventral visual pathway (Kanwisher, 2010). We show that this method retains the benefit of defining fROIs in individual subjects without the subjectivity inherent in the traditional handpicked fROI approach. The tools necessary for using this method are available on our website (http://web.mit.edu/bcs/nklab/GSS.shtml)., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This paper demonstrates the feasibility of real-time mapping of the visual field for clinical applications. Specifically, three aspects of this problem were considered: (1) experimental design, (2) statistical analysis, and (3) display of results. Proper experimental design is essential to achieving a successful outcome, particularly for real-time applications. A random-block experimental design was shown to have less sensitivity to measurement noise, as well as greater robustness to error in modeling of the hemodynamic impulse response function (IRF) and greater flexibility than common alternatives. In addition, random encoding of the visual field allows for the detection of voxels that are responsive to multiple, not necessarily contiguous, regions of the visual field. Due to its recursive nature, the Kalman filter is ideally suited for real-time statistical analysis of visual field mapping data. An important feature of the Kalman filter is that it can be used for nonstationary time series analysis. The capability of the Kalman filter to adapt, in real time, to abrupt changes in the baseline arising from subject motion inside the scanner and other external system disturbances is important for the success of clinical applications. The clinician needs real-time information to evaluate the success or failure of the imaging run and to decide whether to extend, modify, or terminate the run. Accordingly, the analytical software provides real-time displays of (1) brain activation maps for each stimulus segment, (2) voxel-wise spatial tuning profiles, (3) time plots of the variability of response parameters, and (4) time plots of activated volume., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Comprehensive information on the spatio-temporal dynamics of the vascular response is needed to underpin the signals used in hemodynamics-based functional imaging. It has recently been shown that red blood cells (RBCs) velocity and its changes can be extracted from wide-field optical imaging recordings of intrinsic absorption changes in cortex. Here, we describe a complete processing work-flow for reliable RBC velocity estimation in cortical networks. Several pre-processing steps are implemented: image co-registration, necessary to correct for small movements of the vasculature, semi-automatic image segmentation for fast and reproducible vessel selection, reconstruction of RBC trajectories patterns for each micro-vessel, and spatio-temporal filtering to enhance the desired data characteristics. The main analysis step is composed of two robust algorithms for estimating the RBCs' velocity field. Vessel diameter and its changes are also estimated, as well as local changes in backscattered light intensity. This full processing chain is implemented with a software suite that is freely distributed. The software uses efficient data management for handling the very large data sets obtained with in vivo optical imaging. It offers a complete and user-friendly graphical user interface with visualization tools for displaying and exploring data and results. A full data simulation framework is also provided in order to optimize the performances of the algorithm with respect to several characteristics of the data. We illustrate the performance of our method in three different cases of in vivo data. We first document the massive RBC speed response evoked by a spreading depression in anesthetized rat somato-sensory cortex. Second, we show the velocity response elicited by a visual stimulation in anesthetized cat visual cortex. Finally, we report, for the first time, visually-evoked RBC speed responses in an extended vascular network in awake monkey extrastriate cortex., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Resting-state networks derived from temporal correlations of spontaneous hemodynamic fluctuations have been extensively used to elucidate the functional organization of the brain in adults and infants. We have previously developed functional connectivity diffuse optical tomography methods in adults, and we now apply these techniques to study functional connectivity in newborn infants at the bedside. We present functional connectivity maps in the occipital cortices obtained from healthy term-born infants and premature infants, including one infant with an occipital stroke. Our results suggest that functional connectivity diffuse optical tomography has potential as a valuable clinical tool for the early detection of functional deficits and for providing prognostic information on future development., (Copyright © 2011. Published by Elsevier Inc.)

Recent developments in ultra high field MRI and receiver coil technology have opened up the possibility of laminar fMRI in humans. This could offer greater insight into human brain function by elucidating both the interaction between brain regions on the basis of laminar activation patterns associated with input and output, and the interactions between laminae in a specific region. We used very high isotropic spatial resolution (0.75 mm voxel size), multi-echo acquisition (gradient-echo) in a 7 T fMRI study of human primary visual cortex (V1) and novel data analysis techniques to quantitatively investigate the echo time dependence of laminar profiles, laminar activation, and physiological noise distributions over an extended region of cortex. We found T(2)* profiles to be explicable in terms of variations in myelin content. Laminar activation profiles vary with echo time (TE): at short TE the highest signal changes are measured at the pial surface; this maximum shifts into grey matter at longer TEs. The top layers peak latest as these have the longest transverse relaxation time. Theoretical simulations and experiment suggest that the intravascular contribution to functional signal changes is significant even at long TE. Based on a temporal noise analysis we argue that the (physiological) noise contributions will ameliorate differences in sensitivity between the layers in a statistical analysis, and correlates with laminar blood volume distribution. We also show that even at this high spatial resolution the physiological noise limit to sensitivity is reached within V1, implying that cortical sub-regions can be examined with this technique., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Variations of response time (RT) in selective attention tasks are often associated with variations of activity and functional connectivity in sensory cortices that process relevant stimuli. Here, we investigated whether such relationships are influenced by spatial attention. To investigate this hypothesis, we asked fourteen healthy adults to perform a covert spatial attention task, which made use of bilateral stimulus displays, while we recorded their brain activity using functional magnetic resonance imaging (fMRI). As expected, activity in the middle occipital gyrus increased when spatial attention was directed to the contralateral (versus the ipsilateral) visual field. Surprisingly, variations of RT were not associated with variations in the magnitude of this attentional enhancement. As predicted, however, they were linked to opposing variations of functional connectivity between middle occipital regions contralateral (but not ispilateral) to the attended visual field and the left fusiform gyrus, which is thought to figure prominently in the perceptual processing of visually presented letters. These findings suggest that trial-by-trial variations of RT reflect, at least partially, trial-by-trial variations in the extent to which spatial attention enhances functional connectivity between sensory regions that process relevant stimuli., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Although variations of response time (RT) within a particular experimental condition are typically ignored, they may sometimes reflect meaningful changes in the efficiency of cognitive and neural processes. In the present study, we investigated whether trial-by-trial variations of response time (RT) in a cross-modal selective attention task were associated with variations of functional connectivity between brain regions that are thought to underlie attention. Sixteen healthy young adults performed an audiovisual selective attention task, which involved attending to a relevant visual letter while ignoring an irrelevant auditory letter, as we recorded their brain activity using functional magnetic resonance imaging (fMRI). In line with predictions, variations of RT were associated with variations of functional connectivity between the anterior cingulate cortex and various other brain regions that are posited to underlie attentional control, such as the right dorsolateral prefrontal cortex and bilateral regions of the posterior parietal cortex. They were also linked to variations of functional connectivity between anatomically early and anatomically late regions of the relevant-modality visual cortex whose communication is thought to be modulated by attentional control processes. By revealing that variations of RT in a selective attention task are linked to variations of functional connectivity in the attentional network, the present findings suggest that variations of attention may contribute to trial-by-trial fluctuations of behavioral performance., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Although functional imaging of neuronal activity by magnetic resonance imaging (fMRI) has become the primary methodology employed in studying the brain, significant portions of the brain are inaccessible by this methodology due to its sensitivity to macroscopic magnetic field inhomogeneities induced near air-filled cavities in the head. In this paper, we demonstrate that this sensitivity is eliminated by a novel pulse sequence, RASER (rapid acquisition by sequential excitation and refocusing) (Chamberlain et al., 2007), that can generate functional maps. This is accomplished because RASER acquired signals are purely and perfectly T(2) weighted, without any T(2)*-effects that are inherent in the other image acquisition schemes employed to date. T(2)-weighted fMRI sequences are also more specific to the site of neuronal activity at ultrahigh magnetic fields than T(2)*-variations since they are dominated by signal components originating from the tissue in the capillary bed. The RASER based fMRI response is quantified; it is shown to have an inherently less noisy time series and to provide fMRI in brain regions, such as the orbitofrontal cortex, which are challenging to image with conventional techniques., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Coordination between glutamatergic excitatory neurons and gamma-aminobutyric acid (GABA)-ergic inhibitory interneurons is fundamental to the regulation of neuronal firing rates and is believed to have relevance to functional magnetic resonance imaging (fMRI) contrast. While much is known regarding the molecular behavior of excitatory and inhibitory processes, comparatively less is known regarding the role of such processes in explaining variations in fMRI and related hemodynamic imaging metrics. The relationship between baseline GABA levels, as measured by MR spectroscopy, and hemodynamic contrasts from four sequences in human visual cortex are investigated (n=12; field strength=3.0 T): blood oxygenation level-dependent (BOLD), cerebral blood flow (CBF)-weighted arterial spin labelling (ASL), cerebral blood volume (CBV)-weighted vascular-space-occupancy (VASO), and arterial CBV (aCBV)-weighted inflow VASO (iVASO). Results indicate that baseline GABA levels (GABA+ macromolecules normalized to creatine) inversely correlate with BOLD reactivity (R=-0.70; P=0.01) and magnitude CBV-weighted VASO reactivity (R=-0.71; P=0.01). A trend for significance was found between baseline aCBV-weighted iVASO (R=-0.50; P=0.10) and baseline GABA. A positive correlation was found between baseline CBF-weighted ASL signal and GABA (R=0.65; P=0.02) and ASL time-to-peak and baseline GABA (R=0.58; P=0.05). These findings demonstrate that both the dominant BOLD fMRI contrast, as well as other emerging MR hemodynamic contrasts, have signal variations that are linked to baseline GABA levels., (Copyright 2010 Elsevier Inc. All rights reserved.)

The visual cortex in each hemisphere is linked to the opposite hemisphere by axonal projections that pass through the splenium of the corpus callosum. Visual-callosal connections in humans and macaques are found along the V1/V2 border where the vertical meridian is represented. Here we identify the topography of V1 vertical midline projections through the splenium within six human subjects with normal vision using diffusion-weighted MR imaging and probabilistic diffusion tractography. Tractography seed points within the splenium were classified according to their estimated connectivity profiles to topographic subregions of V1, as defined by functional retinotopic mapping. First, we report a ventral-dorsal mapping within the splenium with fibers from ventral V1 (representing the upper visual field) projecting to the inferior-anterior corner of the splenium and fibers from dorsal V1 (representing the lower visual field) projecting to the superior-posterior end. Second, we also report an eccentricity gradient of projections from foveal-to-peripheral V1 subregions running in the anterior-superior to posterior-inferior direction, orthogonal to the dorsal-ventral mapping. These results confirm and add to a previous diffusion MRI study (Dougherty et al., 2005) which identified a dorsal/ventral mapping of human splenial fibers. These findings yield a more detailed view of the structural organization of the splenium than previously reported and offer new opportunities to study structural plasticity in the visual system., (Copyright 2010 Elsevier Inc. All rights reserved.)

It has been argued that changes in the relative sizes of visual system structures predated an increase in brain size and provide evidence of brain reorganization in hominins. However, data about the volume and anatomical limits of visual brain structures in the extant taxa phylogenetically closest to humans-the apes-remain scarce, thus complicating tests of hypotheses about evolutionary changes. Here, we analyze new volumetric data for the primary visual cortex and the lateral geniculate nucleus to determine whether or not the human brain departs from allometrically-expected patterns of brain organization. Primary visual cortex volumes were compared to lunate sulcus position in apes to investigate whether or not inferences about brain reorganization made from fossil hominin endocasts are reliable in this context. In contrast to previous studies, in which all species were relatively poorly sampled, the current study attempted to evaluate the degree of intraspecific variability by including numerous hominoid individuals (particularly Pan troglodytes and Homo sapiens). In addition, we present and compare volumetric data from three new hominoid species-Pan paniscus, Pongo pygmaeus, and Symphalangus syndactylus. These new data demonstrate that hominoid visual brain structure volumes vary more than previously appreciated. In addition, humans have relatively reduced primary visual cortex and lateral geniculate nucleus volumes as compared to allometric predictions from other hominoids. These results suggest that inferences about the position of the lunate sulcus on fossil endocasts may provide information about brain organization., (Copyright 2010 Elsevier Ltd. All rights reserved.)

There is increasing interest in the role gamma oscillations ( approximately 40 Hz) play in visual information processing. Despite this interest, and in contrast to the classically studied visual evoked potential, surprisingly little is known about the intra-individual repeatability of induced gamma oscillations. Similarly, little is known about inter-individual variability in terms of gamma oscillation frequency, bandwidth and amplitude with no extant normative data for these parameters. The purpose of the current study was therefore to examine the repeatability of visual gamma oscillations and to provide the first normative data on them. Our results demonstrate that evoked responses were highly repeatable across recording sessions whereas for induced visual gamma oscillations a large amount of inter-individual variability existed in terms of frequency, bandwidth and amplitude. However, these parameters and the general morphology of the gamma band response were stable within the same individuals for at least 4 weeks. The high degree of individual variability in gamma oscillations for gamma amplitude, bandwidth and frequency suggests that between-group studies on gamma oscillations will be difficult, requiring relatively large amounts of data to detect differences. However, the high degree of individual repeatability for gamma oscillation frequency, bandwidth and amplitude suggests that these dependent variables will be well suited for repeated-measure designs such as pharmacological studies. A number of individuals are described which show clear evoked responses yet a near absence of gamma oscillations and vice versa suggesting dissociations between the generative mechanisms of these responses. Our results also demonstrate that gamma frequency tends to decline with age and is positively correlated with the thickness of the pericalcarine cortex., (Copyright 2009 Elsevier Inc. All rights reserved.)

Primate neocortex contains over 30 visual areas. Recent techniques such as functional magnetic resonance imaging (fMRI) have successfully identified many of these areas in the human brain, but have been of limited value for revealing the temporal dynamics between visual areas. The electroencephalogram (EEG) provides information with high temporal precision, but has had limited success separating out the signals from individual neighboring cortical areas. Consequently, controversies exist over the temporal dynamics across cortical areas. In order to address this problem we developed a new method to identify the sources of the EEG. An individual's unique cortical pattern of sulci and gyri along with a visual area's functional retinotopic layout provides a folding fingerprint that predicts specific scalp topographies for stimuli presented in different parts of the visual field. Using this folding fingerprint with a 96 or 192 location stimulus severely constrains the solution space making it relatively easy to extract the temporal response of multiple visual areas to multiple stimulus locations. The large number of stimuli also provides a means to validate the waveforms by comparing across stimulus sets, an important feature not present in most EEG source identification procedures. Using this method our data reveal that both V1 and V2 waveforms have similar onset latencies, and their temporal dynamics provide new information regarding the response latencies of these areas in humans. Our method enables the previously unattainable separation of EEG responses from neighboring brain areas. While we applied the method to the first two cortical visual areas, V1 and V2, this method is also applicable to somatosensory areas that have defined mappings. This method provides a means to study the rapid information flow in the human brain to reveal top-down and bottom-up cognitive processes., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

This study shows that the spatial specificity of MEG beamformer estimates of electrical activity can be affected significantly by the way in which covariance estimates are calculated. We define spatial specificity as the ability to extract independent timecourse estimates of electrical brain activity from two separate brain locations in close proximity. Previous analytical and simulated results have shown that beamformer estimates are affected by narrowing the time frequency window in which covariance estimates are made. Here we build on this by both experimental validation of previous results, and investigating the effect of data averaging prior to covariance estimation. In appropriate circumstances, we show that averaging has a marked effect on spatial specificity. However the averaging process results in ill-conditioned covariance matrices, thus necessitating a suitable matrix regularisation strategy, an example of which is described. We apply our findings to an MEG retinotopic mapping paradigm. A moving visual stimulus is used to elicit brain activation at different retinotopic locations in the visual cortex. This gives the impression of a moving electrical dipolar source in the brain. We show that if appropriate beamformer optimisation is applied, the moving source can be tracked in the cortex. In addition to spatial reconstruction of the moving source, we show that timecourse estimates can be extracted from neighbouring locations of interest in the visual cortex. If appropriate methodology is employed, the sequential activation of separate retinotopic locations can be observed. The retinotopic paradigm represents an ideal platform to test the spatial specificity of source localisation strategies. We suggest that future comparisons of MEG source localisation techniques (e.g. beamformer, minimum norm, Bayesian) could be made using this retinotopic mapping paradigm.

Category selective regions in the ventral visual stream are considered to support higher-level representations of objects. The aim of this study was to determine the extent to which category selectivity in face and place regions can be explained by selectivity for low-level features of these complex objects. First, we compared the relative responses to intact and Fourier-scrambled images of faces and places. Next, we compared the magnitude of fMR adaptation to both intact and scrambled faces and places. The results revealed that global differences in the amplitude spectrum of face and place images can explain a small proportion of the category selectivity that is found in regions such as the fusiform face area (FFA) and parahippocampal place area (PPA). However, a whole-brain analysis revealed selectivity to scrambled images in more posterior regions of the ventral stream. Consistent with the pattern evident for intact images, more lateral regions responded selectively to scrambled faces, whereas more medial regions responded more strongly to scrambled places. These findings suggest that selectivity for object categories emerges from the differential processing of low-level features that are typical of different object categories in early visual areas.