Montreal Brain Injury Vision Screening Test for General Practitioners.

Visual disturbances are amongst the most commonly reported symptoms after a traumatic brain injury (TBI) despite vision testing being uncommon at initial clinical evaluation. TBI patients consistently present a wide range of visual complaints, including photophobia, double vision, blurred vision, and loss of vision which can detrimentally affect reading abilities, postural balance, and mobility. In most cases, especially in rural areas, visual disturbances of TBI would have to be diagnosed and assessed by primary care physicians, who lack the specialized training of optometry. Given that TBI patients have a restricted set of visual concerns, an opportunity exists to develop a screening protocol for specialized evaluation by optometrists-one that a primary care physician could comfortably carry out and do so in a short time. Here, we designed a quick screening protocol that assesses the presence of core visual symptoms present post-TBI. The MOBIVIS (Montreal Brain Injury Vision Screening) protocol takes on average 5 min to perform and is composed of only "high-yield" tests that could be performed in the context of a primary care practice and questions most likely to reveal symptoms needing further vision care management. The composition of our proposed protocol and questionnaire are explained and discussed in light of existing protocols. Its potential impact and ability to shape a better collaboration and an integrative approach in the management of mild TBI (mTBI) patients is also discussed.

Blur Representation in the Amblyopic Visual System Using Natural and Synthetic Images.

Purpose: Amblyopia is diagnosed as a reduced acuity in an otherwise healthy eye, which indicates that the deficit is not happening in the eye, but in the brain. One suspected mechanism explaining these deficits is an elevated amount of intrinsic blur in the amblyopic visual system compared to healthy observers. This "internally produced blur" can be estimated by the "equivalent intrinsic blur method", which measures blur discrimination thresholds while systematically increasing the external blur in the physical stimulus. Surprisingly, amblyopes do not exhibit elevated intrinsic blur when measured with an edge stimulus. Given the fundamental ways in which they differ, synthetic stimuli, such as edges, are likely to generate contrasting blur perception compared to natural stimuli, such as pictures. Because our visual system is presumably tuned to process natural stimuli, testing artificial stimuli only could result in performances that are not ecologically valid. Methods: We tested this hypothesis by measuring, for the first time, the perception of blur added to natural images in amblyopia and compared discrimination performance for natural images and synthetic edges in healthy and amblyopic groups. Results: Our results demonstrate that patients with amblyopia exhibit higher levels of intrinsic blur than control subjects when tested on natural images. This difference was not observed when using edges. Conclusions: Our results suggest that intrinsic blur is elevated in the visual system representing vision from the amblyopic eye and that distinct statistics of images can generate different blur perception.

Intersubject Spatial Pattern Correlations During Movie Viewing Are Stimulus-Driven and Nonuniform Across the Cortex.

A fundamental step to predicting brain activity in healthy and diseased populations is characterizing the common spatio-temporal response to a shared experience. Multivoxel pattern analysis allows us to investigate information encoding through these patterns; however, we have yet to explore local, stimulus-driven, patterns of cortical activity during naturalistic stimulation. We sought to examine these patterns with minimum interpolation-excluding functional alignment-to characterize the most basic degree of shared response between subjects. We used an unbiased analytic approach, combined with rich, naturalistic, and nonsemantic stimulation to estimate shared spatial patterns in functional magnetic resonance imaging responses across a large group. We found that meso-scale spatial patterns were shared nonuniformly across the visual cortex and represent information distinct from the shared temporal response. Shared spatial patterns were stimulus-driven, modulated by pattern size, and more sensitive to the contrast of 3D versus 2D stimulus differences than the temporal signals. Although the grand functional structure of the brain is understood to be common, these results suggest that even at a meso-scale, we share common spatial structures with anatomical alignment alone. The strength of this similarity varies across the cortex, suggesting some spatial structures are innately organized, whereas others are shaped by factors such as learning and plasticity.

Natural scene representations in the gamma band are prototypical across subjects.

Prototypical brain responses describe similarity in neural representations between subjects in response to a natural stimulus. During natural movie viewing, for example, inter-subject correlation (ISC) measured by fMRI is high in visual areas (Hasson et al., 2004). But the electrophysiological basis for this fMRI ISC has been controversial. Previous reports have only found ISC in low frequency bands-below 12 â€‹Hz (Chang et al., 2015). These findings stand in contrast to reports that gamma band oscillations-30 to 90 â€‹Hz-are highly stimulus-driven in visual cortex (Perry et al., 2015). To resolve this discrepancy, we carried out both ISC estimation and a novel inter-subject representational correlation analysis across six frequency bands extracted from MEG data of 24 subjects who each viewed four 5-min clips of an underwater documentary. Region-of-interest-based and vertex-based temporal ISC estimates confirmed that low-frequency bands are significantly synchronized in visual areas and that gamma band has low temporal correlation. We also found the representational geometry of movie scenes were related to structural statistics from the stimuli. Crucially, our results show that the gamma band oscillations also reflect prototypical brain response in scene representations formed in response to naturalistic stimuli as revealed by inter-subject representational correlation.

Long-Range Interocular Suppression in Adults with Strabismic Amblyopia: A Pilot fMRI Study.

Interocular suppression plays an important role in the visual deficits experienced by individuals with amblyopia. Most neurophysiological and functional MRI studies of suppression in amblyopia have used dichoptic stimuli that overlap within the visual field. However, suppression of the amblyopic eye also occurs when the dichoptic stimuli do not overlap, a phenomenon we refer to as long-range suppression. We used functional MRI to test the hypothesis that long-range suppression reduces neural activity in V1, V2 and V3 in adults with amblyopia, indicative of an early, active inhibition mechanism. Five adults with amblyopia and five controls viewed monocular and dichoptic quadrant stimuli during fMRI. Three of five participants with amblyopia experienced complete perceptual suppression of the quadrants presented to their amblyopic eye under dichoptic viewing. The blood oxygen level dependant (BOLD) responses within retinotopic regions corresponding to amblyopic and fellow eye stimuli were analyzed for response magnitude, time to peak, effective connectivity and stimulus classification. Dichoptic viewing slightly reduced the BOLD response magnitude in amblyopic eye retinotopic regions in V1 and reduced the time to peak response; however, the same effects were also present in the non-dominant eye of controls. Effective connectivity was unaffected by suppression, and the results of a classification analysis did not differ significantly between the control and amblyopia groups. Overall, we did not observe a neural signature of long-range amblyopic eye suppression in V1, V2 or V3 using functional MRI in this initial study. This type of suppression may involve higher level processing areas within the brain.

Increased Noise in Cortico-Cortical Integration After Mild TBI Measured With the Equivalent Noise Technique.

The bulk of deficits accompanying mild traumatic brain injury (mTBI) is understood in terms of cortical integration-mnemonic, attentional, and cognitive disturbances are believed to involve integrative action across brain regions. Independent of integrative disturbances, mTBI may increase cortical noise, and this has not been previously considered. High-level integrative deficits are exceedingly difficult to measure and model, motivating us to utilize a tightly-controlled task within an established quantitative model to separately estimate internal noise and integration efficiency. First, we utilized a contour integration task modeled as a cortical-integration process involving multiple adjacent cortical columns in early visual areas. Second, we estimated internal noise and integration efficiency using the linear amplifier model (LAM). Fifty-seven mTBI patients and 24 normal controls performed a 4AFC task where they had to identify a valid contour amongst three invalid contours. Thresholds for contour amplitude were measured adaptively across three levels of added external orientation noise. Using the LAM, we found that mTBI increased internal noise without affecting integration efficiency. mTBI also caused hemifield bias differences, and efficiency was related to a change of visual habits. Using a controlled task reflecting cortical integration within the equivalent noise framework empowered us to detect increased computational noise that may be at the heart of mTBI deficits. Our approach is highly sensitive and translatable to rehabilitative efforts for the mTBI population, while also implicating a novel hypothesis of mTBI effects on basic visual processing-namely that cortical integration is maintained at the cost of increased internal noise.

Radio-Frequency Coil Array for Improved Concurrent Transcranial Magnetic Stimulation and Functional Magnetic Resonance Imaging.

PURPOSE: To perform concurrent TMS-fMRI on difficult targets, such as the occipital lobe. METHODS: a 3-channel flexible, thin RF coil was constructed that allows for whole head image coverage without impeding TMS placement. A custom MR-safe patient table which mates with typical 3T MR scanners was constructed for the purpose of face-down subject positioning to allow for access to posterior TMS targets. To counterbalance the loading effect of the TMS coil on the RF coil circuits "Dummy Loads" are introduced, which mimic the loading conditions of the TMS coil when it is not present. RESULTS: the designed RF coil performed as expected, achieving acceptable SNR values at depths equal to the center of the average human head, and high SNR values near the surface. CONCLUSION: The system allows for concurrent TMS-fMRI, targeting any area of the being while imaging the entire volume.

Two cortical deficits underlie amblyopia: A multifocal fMRI analysis.

Amblyopia is a relatively common (incidence 3%) developmental disorder in which there is loss of vision as a consequence of a disruption to normal visual development. Although the deficit is monocular and known to be of cortical origin, the nature of the processing deficit is controversial. Human behavioral studies have identified two main deficits - a loss of contrast sensitivity and perceived spatial distortions. Here we use a multifocal fMRI approach to ascertain, in a group of anisometropic amblyopes, whether these two deficits have a single common cause or whether they are the result of two underlying independent cortical disorders. We found that fMRI magnitudes were attenuated in amblyopic eye stimulation, and that there was poor fidelity for co-localization of the activity clusters between the amblyopic and fellow-fixing eye stimulation. These effects varied across eccentricities and correlate with the degree of amblyopia but not with one another, suggesting two independent cortical deficits: a reduced responsiveness as well as reduced fidelity of spatial representation. These deficits are independent of eccentricity within the central field and consistent across early cortical visual areas.

Magnetoencephalography adaptation reveals depth-cue-invariant object representations in the visual cortex.

Independent of edges and 2-D shape that can be highly informative of object identity, depth cues alone can also give rise to vivid and effective object percepts. The processing of different depth cues engages segregated cortical areas, and an efficient object representation would be one that is invariant to depth cues. Here, we investigated depth-cue invariance of object representations by measuring the category-specific response to faces-the M170 response measured with magnetoencephalography. The M170 response is strongest to faces and is sensitive to adaptation, such that repeated presentation of a face diminishes subsequent M170 responses. We used this feature of the M170 and measured the degree to which the adaptation effect is affected by variations in depth cue and 3-D object shape. Subjects viewed a rapid presentation of two stimuli-an adaptor and a test stimulus. The adaptor was either a face, a chair, or a face-like oval surface, and rendered with a single depth cue (shading, structure from motion, or texture). The test stimulus was always a shaded face of a random identity, thus completely controlling for low-level influences on the M170 response to the test stimulus. In the left fusiform face area, we found strong M170 adaptation when the adaptor was a face regardless of its depth cue. This adaptation was marginal in the right fusiform and negligible in the occipital regions. Our results support the presence of depth-cue-invariant representations in the human visual system, alongside size, position, and viewpoint invariance.

Mapping of neuron soma size as an effective approach to delineate differences between neural populations.

BACKGROUND: A single histological marker applied to a slice of tissue often reveals myriad cytoarchitectonic characteristics that can obscure differences between neuron populations targeted for study. Isolation and measurement of a single feature from the tissue is possible through a variety of approaches, however, visualizing the data numerically or through graphs alone can preclude being able to identify important features and effects that are not obvious from direct observation of the tissue. NEW METHOD: We demonstrate an efficient, effective, and robust approach to quantify and visualize cytoarchitectural features in histologically prepared brain sections. We demonstrate that this approach is able to reveal small differences between populations of neurons that might otherwise have gone undiscovered. RESULTS & COMPARISON WITH EXISTING METHOD(S): We used stereological methods to record the cross-sectional soma area and in situ position of neurons within sections of the cat, monkey, and human visual system. The two-dimensional coordinate of every measured cell was used to produce a scatter plot that recapitulated the natural spatial distribution of cells, and each point in the plot was color-coded according to its respective soma area. The final graphic display was a multi-dimensional map of neuron soma size that revealed subtle differences across neuron aggregations, permitted delineation of regional boundaries, and identified small differences between populations of neurons modified by a period of sensory deprivation. CONCLUSIONS: This approach to collecting and displaying cytoarchitectonic data is simple, efficient, and provides a means of investigating small differences between neuron populations.

The equivalent internal orientation and position noise for contour integration.

Contour integration is the joining-up of local responses to parts of a contour into a continuous percept. In typical studies observers detect contours formed of discrete wavelets, presented against a background of random wavelets. This measures performance for detecting contours in the limiting external noise that background provides. Our novel task measures contour integration without requiring any background noise. This allowed us to perform noise-masking experiments using orientation and position noise. From these we measure the equivalent internal noise for contour integration. We found an orientation noise of 6° and position noise of 3 arcmin. Orientation noise was 2.6x higher in contour integration compared to an orientation discrimination control task. Comparing against a position discrimination task found position noise in contours to be 2.4x lower. This suggests contour integration involves intermediate processing that enhances the quality of element position representation at the expense of element orientation. Efficiency relative to the ideal observer was lower for the contour tasks (36% in orientation noise, 21% in position noise) compared to the controls (54% and 57%).

Sensitivity to Binocular Disparity is Reduced by Mild Traumatic Brain Injury.

Purpose: The impairment of visual functions is one of the most common complaints following mild traumatic brain injury (mTBI). Traumatic brain injury-associated visual deficits include blurred vision, reading problems, and eye strain. In addition, previous studies have found evidence that TBI can diminish early cortical visual processing, particularly for second-order stimuli. We investigated whether cortical processing of binocular disparity is also affected by mTBI. Methods: In order to investigate the influence of mTBI on global stereopsis, we measured the quick Disparity Sensitivity Function (qDSF) in 22 patients with mTBI. Patients with manifest strabismus and double vision were excluded. Compared with standard clinical tests, the qDSF is unique in that it offers a quick and accurate estimate of thresholds across the whole spatial frequency range. Results: Results show that disparity sensitivity in the mTBI patients were significantly reduced compared with the normative dataset (n = 61). The peak spatial frequency was not affected. Conclusions: Our results suggest that the reduced disparity sensitivity in patients with mTBI is more likely caused by cortical changes (e.g., axonal shearing, or reduced interhemispheric communication) rather than oculomotor dysfunction.

Gaze behavior during 3-D face identification is depth cue invariant.

Gaze behavior during scene and object recognition can highlight the relevant information for a task. For example, salience maps-highlighting regions that have heightened luminance, contrast, color, etc. in a scene-can be used to predict gaze targets. Certain tasks, such as face recognition, result in a typical pattern of fixations on high salience features. While local salience of a 2-D feature may contribute to gaze behavior and object recognition, we are perfectly capable of recognizing objects from 3-D depth cues devoid of meaningful 2-D features. Faces can be recognized from pure texture, binocular disparity, or structure-from-motion displays (Dehmoobadsharifabadi & Farivar, 2016; Farivar, Blanke, & Chaudhuri, 2009; Liu, Collin, Farivar, & Chaudhuri, 2005), and yet these displays are devoid of local salient 2-D features. We therefore sought to determine whether gaze behavior is driven by an underlying 3-D representation that is depth-cue invariant or depth-cue specific. By using a face identification task comprising morphs of 3-D facial surfaces, we were able to measure identification thresholds and thereby equate for task difficulty across different depth cues. We found that gaze behavior for faces defined by shading and texture cues was highly comparable, but we observed some deviations for faces defined by binocular disparity. Interestingly, we found no effect of task difficulty on gaze behavior. The results are discussed in the context of depth-cue invariant representations for facial surfaces, with gaze behavior being constrained by low-level limits of depth extraction from specific cues such as binocular disparity.

Non-uniform phase sensitivity in spatial frequency maps of the human visual cortex.

KEY POINTS: Just as a portrait painting can come from a collection of coarse and fine details, natural vision can be decomposed into coarse and fine components. Previous studies have shown that the early visual areas in the brain represent these components in a map-like fashion. Other studies have shown that these same visual areas can be sensitive to how coarse and fine features line up in space. We found that the brain actually jointly represents both the scale of the feature (fine, medium, or coarse) and the alignment of these features in space. The results suggest that the visual cortex has an optimized representation particularly for the alignment of fine details, which are crucial in understanding the visual scene. ABSTRACT: Complex natural scenes can be decomposed into their oriented spatial frequency (SF) and phase relationships, both of which are represented locally at the earliest stages of cortical visual processing. The SF preference map in the human cortex, obtained using synthetic stimuli, is orderly and correlates strongly with eccentricity. In addition, early visual areas show sensitivity to the phase information that describes the relationship between SFs and thereby dictates the structure of the image. Taken together, two possibilities arise for the joint representation of SF and phase: either the entirety of the cortical SF map is uniformly sensitive to phase, or a particular set of SFs is selectively phase sensitive - for example, greater phase sensitivity for higher SFs that define fine-scale edges in a complex scene. To test between these two possibilities, we constructed a novel continuous natural scene video whereby phase information was maintained in one SF band but scrambled elsewhere. By shifting the central frequency of the phase-aligned band in time, we mapped the phase-sensitive SF preference of the visual cortex. Using functional magnetic resonance imaging, we found that phase sensitivity in early visual areas is biased toward higher SFs. Compared to a SF map of the same scene obtained using linear-filtered stimuli, a much larger patch of areas V1 and V2 is sensitive to the phase alignment of higher SFs. The results of early areas cannot be explained by attention. Our results suggest non-uniform sensitivity to phase alignment in population-level SF representations, with phase alignment being particularly important for fine-scale edge representations of natural scenes.

Surface phosphonation enhances hydroxyapatite coating adhesion on polyetheretherketone and its osseointegration potential.

Polyetheretherketone (PEEK) has excellent mechanical properties, biocompatibility, chemical resistance and radiolucency, making it suitable for use as orthopedic implants. However, its surface is hydrophobic and bioinert, and surface modification is required to improve its bioactivity. In this work, we showed that grafting phosphonate groups via diazonium chemistry enhances the bioactivity of PEEK. Decreased contact angle indicated reduced hydrophobicity as a result of the treatment and X-ray photoelectron spectroscopy (XPS) confirmed the attachment of phosphonate groups to the surface. The surface treatment not only accelerated hydroxyapatite (HA) deposition after immersion in simulated body fluid but also significantly increased the adhesion strength of HA particles on PEEK. MC3T3-E1 cell viability, metabolic activity and deposition of calcium-containing minerals were also enhanced by the phosphonation. After three months of implantation in a critical size calvarial defect model, a fibrous capsule surrounded untreated PEEK while no fibrous capsule was observed around the treated PEEK. Instead, mineral deposition was observed in the region between the treated PEEK implant and underlying bone. This work introduces a simple method to improve the potential of PEEK-based orthopedic implants. STATEMENT OF SIGNIFICANCE: We have introduced phosphonate groups on the surface of PEEK substrates using diazonium chemistry. Our results show that the treatment not only increased the adhesion strength of hydroxyapatite particles deposited on PEEK in vitro by approximately 40% compared to unmodified PEEK, but also improved the metabolic activity and mineralization of MC3T3-E1 cells. When implanted in cranial defects in rats, the phosphonate coating enhanced the osseointegration of PEEK by successfully preventing the formation of a fibrous capsule and favoring mineral deposition between the implant and the surrounding bone. This work introduces a simple method to improve the potential of PEEK-based orthopedic implants, particularly those with complex shapes.

Construction and Operation of a High-Speed, High-Precision Eye Tracker for Tight Stimulus Synchronization and Real-Time Gaze Monitoring in Human and Animal Subjects.

Measurements of the fast and precise movements of the eye-critical to many vision, oculomotor, and animal behavior studies-can be made non-invasively by video oculography. The protocol here describes the construction and operation of a research-grade video oculography system with ~0.1° precision over the full typical viewing range at over 450 Hz with tight synchronization with stimulus onset. The protocol consists of three stages: (1) system assembly, (2) calibration for both cooperative, and for minimally cooperative subjects (e.g., animals or infants), and (3) gaze monitoring and recording.

Three-Dimensional Face Recognition in Mild Cognitive Impairment: A Psychophysical and Structural MR Study.

OBJECTIVES: Mild cognitive impairment (MCI) has been associated with a high risk of conversion to Alzheimer's dementia. In addition to memory complaints, impairments in the visuospatial domain have been reported in this condition. We have previously shown that deficits in perceiving structure-from-motion (SFM) objects are reflected in functional reorganization of brain activity within the visual ventral stream. Here we aimed to identify structural correlates of psychophysical complex face and object recognition performance in amnestic MCI patients (n=30 vs. n=25 controls). This study was, therefore, motivated by evidence from recent studies showing that a combination of visual information across dorsal and ventral visual streams may be needed for the perception of three-dimensional (3D) SFM objects. METHODS: In our experimental paradigm, participants had to discriminate 3D SFM shapes (faces and objects) from 3D SFM meaningless (scrambled) shapes. RESULTS: Morphometric analysis established neuroanatomical evidence for impairment in MCI as demonstrated by smaller hippocampal volumes. We found association between cortical thickness and face recognition performance, comprising the occipital lobe and visual ventral stream fusiform regions (overlapping the known location of face fusiform area) in the right hemisphere, in MCI. CONCLUSIONS: We conclude that impairment of 3D visual integration exists at the MCI stage involving also the visual ventral stream and contributing to face recognition deficits. The specificity of such observed structure-function correlation for faces suggests a special role of this processing pathway in health and disease. (JINS, 2016, 22, 744-754).

Are face representations depth cue invariant?

The visual system can process three-dimensional depth cues defining surfaces of objects, but it is unclear whether such information contributes to complex object recognition, including face recognition. The processing of different depth cues involves both dorsal and ventral visual pathways. We investigated whether facial surfaces defined by individual depth cues resulted in meaningful face representations-representations that maintain the relationship between the population of faces as defined in a multidimensional face space. We measured face identity aftereffects for facial surfaces defined by individual depth cues (Experiments 1 and 2) and tested whether the aftereffect transfers across depth cues (Experiments 3 and 4). Facial surfaces and their morphs to the average face were defined purely by one of shading, texture, motion, or binocular disparity. We obtained identification thresholds for matched (matched identity between adapting and test stimuli), non-matched (non-matched identity between adapting and test stimuli), and no-adaptation (showing only the test stimuli) conditions for each cue and across different depth cues. We found robust face identity aftereffect in both experiments. Our results suggest that depth cues do contribute to forming meaningful face representations that are depth cue invariant. Depth cue invariance would require integration of information across different areas and different pathways for object recognition, and this in turn has important implications for cortical models of visual object recognition.

First- and second-order contrast sensitivity functions reveal disrupted visual processing following mild traumatic brain injury.

Vision is disrupted by traumatic brain injury (TBI), with vision-related complaints being amongst the most common in this population. Based on the neural responses of early visual cortical areas, injury to the visual cortex would be predicted to affect both 1(st) order and 2(nd) order contrast sensitivity functions (CSFs)-the height and/or the cut-off of the CSF are expected to be affected by TBI. Previous studies have reported disruptions only in 2(nd) order contrast sensitivity, but using a narrow range of parameters and divergent methodologies-no study has characterized the effect of TBI on the full CSF for both 1(st) and 2(nd) order stimuli. Such information is needed to properly understand the effect of TBI on contrast perception, which underlies all visual processing. Using a unified framework based on the quick contrast sensitivity function, we measured full CSFs for static and dynamic 1(st) and 2(nd) order stimuli. Our results provide a unique dataset showing alterations in sensitivity for both 1(st) and 2(nd) order visual stimuli. In particular, we show that TBI patients have increased sensitivity for 1(st) order motion stimuli and decreased sensitivity to orientation-defined and contrast-defined 2(nd) order stimuli. In addition, our data suggest that TBI patients' sensitivity for both 1(st) order stimuli and 2(nd) order contrast-defined stimuli is shifted towards higher spatial frequencies.

Dense, shape-optimized posterior 32-channel coil for submillimeter functional imaging of visual cortex at 3T.

PURPOSE: Functional neuroimaging of small cortical patches such as columns is essential for testing computational models of vision, but imaging from cortical columns at conventional 3T fields is exceedingly difficult. By targeting the visual cortex exclusively, we tested whether combined optimization of shape, coil placement, and electronics would yield the necessary gains in signal-to-noise ratio (SNR) for submillimeter visual cortex functional MRI (fMRI). METHOD: We optimized the shape of the housing to a population-averaged atlas. The shape was comfortable without cushions and resulted in the maximally proximal placement of the coil elements. By using small wire loops with the least number of solder joints, we were able to maximize the Q factor of the individual elements. Finally, by planning the placement of the coils using the brain atlas, we were able to target the arrangement of the coil elements to the extent of the visual cortex. RESULTS: The combined optimizations led to as much as two-fold SNR gain compared with a whole-head 32-channel coil. This gain was reflected in temporal SNR as well and enabled fMRI mapping at 0.75 mm resolutions using a conventional GRAPPA-accelerated gradient echo echo planar imaging. CONCLUSION: Integrated optimization of shape, electronics, and element placement can lead to large gains in SNR and empower submillimeter fMRI at 3T. Magn Reson Med 76:321-328, 2016. © 2015 Wiley Periodicals, Inc.