Fast automatic segmentation of thalamic nuclei from MP2RAGE acquisition at 7 Tesla.

PURPOSE: Thalamic nuclei are largely invisible in conventional MRI due to poor contrast. Thalamus Optimized Multi-Atlas Segmentation (THOMAS) provides automatic segmentation of 12 thalamic nuclei using white-matter-nulled (WMn) Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequence at 7T, but increases overall scan duration. Routinely acquired, bias-corrected Magnetization Prepared 2 Rapid Gradient Echo (MP2RAGE) sequence yields superior tissue contrast and quantitative T1 maps. Application of THOMAS to MP2RAGE has been investigated in this study. METHODS: Eight healthy volunteers and five pediatric-onset multiple sclerosis patients were recruited at Children's Hospital of Philadelphia and scanned at Siemens 7T with WMn-MPRAGE and multi-echo-MP2RAGE (ME-MP2RAGE) sequences. White-matter-nulled contrast was synthesized (MP2-SYN) from T1 maps from ME-MP2RAGE sequence. Thalamic nuclei were segmented using THOMAS joint label fusion algorithm from WMn-MPRAGE and MP2-SYN datasets. THOMAS pipeline was modified to use majority voting to segment bias corrected T1-weighted uniform (MP2-UNI) images. Thalamic nuclei from MP2-SYN and MP2-UNI images were evaluated against corresponding nuclei obtained from WMn-MPRAGE images using dice coefficients, volume similarity indices (VSIs) and distance between centroids. RESULTS: For MP2-SYN, dice > 0.85 and VSI > 0.95 was achieved for five larger nuclei and dice > 0.6 and VSI > 0.7 was achieved for seven smaller nuclei. The dice and VSI were slightly higher, whereas the distance between centroids were smaller for MP2-SYN compared to MP2-UNI, indicating improved performance using the MP2-SYN image. CONCLUSIONS: THOMAS algorithm can successfully segment thalamic nuclei in MP2RAGE images with essentially equivalent quality as WMn-MPRAGE, widening its applicability in studies focused on thalamic involvement in aging and disease.

Structural correlates of atypical visual and motor cortical oscillations in pediatric-onset multiple sclerosis.

We have previously demonstrated that pediatric-onset multiple sclerosis (POMS) negatively impacts the visual pathway as well as motor processing speed. Relationships between MS-related diffuse structural damage of gray and white matter (WM) tissue and cortical responses to visual and motor stimuli remain poorly understood. We used magnetoencephalography in 14 POMS patients and 15 age- and sex-matched healthy controls to assess visual gamma (30-80 Hz), motor gamma (60-90 Hz), and motor beta (15-30 Hz) cortical oscillatory responses to a visual-motor task. Then, 3T MRI was used to: (a) calculate fractional anisotropy (FA) of the posterior visual and corticospinal motor WM pathways and (b) quantify volume and thickness of the cuneus and primary motor cortex. Visual gamma band power was reduced in POMS and was associated with reduced FA of the optic radiations but not with loss of cuneus volume or thickness. Activity in the primary motor cortex, as measured by postmovement beta rebound amplitude associated with peak latency, was decreased in POMS, although this reduction was not predicted by structural metrics. Our findings implicate loss of WM integrity as a contributor to reduced electrical responses in the visual cortex in POMS. Future work in larger cohorts will inform on the cognitive implications of this finding in terms of visual processing function and will determine whether the progressive loss of brain volume known to occur in POMS ultimately contributes to both progressive dysfunction in such tasks as well as progressive reduction in cortical electrical responses in the visual cortex.

Human Visual Cortex Responses to Rapid Cone and Melanopsin-Directed Flicker.

Signals from cones are recombined in postreceptoral channels [luminance, L + M; red-green, L - M; blue-yellow, S - (L + M)]. The melanopsin-containing retinal ganglion cells are also active at daytime light levels and recent psychophysical results suggest that melanopsin contributes to conscious vision in humans. Here, we measured BOLD fMRI responses to spectral modulations that separately targeted the postreceptoral cone channels and melanopsin. Responses to spatially uniform (27.5° field size, central 5° obscured) flicker at 0.5, 1, 2, 4, 8, 16, 32, and 64 Hz were recorded from areas V1, V2/V3, motion-sensitive area MT, and the lateral occipital complex. In V1 and V2/V3, higher temporal sensitivity was observed to L + M + S (16 Hz) compared with L - M flicker (8 Hz), consistent with psychophysical findings. Area MT was most sensitive to rapid (32 Hz) flicker of either L + M + S or L - M. We found S cone responses only in areas V1 and V2/V3 (peak frequency: 4-8 Hz). In addition, we studied an L + M modulation and found responses that were effectively identical at all temporal frequencies to those recorded for the L + M + S modulation. Finally, we measured the cortical response to melanopsin-directed flicker and compared this response with control modulations that addressed stimulus imprecision and the possibility of stimulation of cones in the shadow of retinal blood vessels (penumbral cones). For our stimulus conditions, melanopsin flicker did not elicit a cortical response exceeding that of the control modulations. We note that failure to control for penumbral cone stimulation could be mistaken for a melanopsin response. SIGNIFICANCE STATEMENT: The retina contains cone photoreceptors and ganglion cells that contain the photopigment melanopsin. Cones provide brightness and color signals to visual cortex. Melanopsin influences circadian rhythm and the pupil, but its contribution to cortex and perception is less clear. We measured the response of human visual cortex with fMRI using spectral modulations tailored to stimulate the cones and melanopsin separately. We found that cortical responses to cone signals vary systematically across visual areas. Differences in temporal sensitivity for achromatic, red-green, and blue-yellow stimuli generally reflect the known perceptual properties of vision. We found that melanopsin signals do not produce a measurable response in visual cortex at temporal frequencies between 0.5 and 64 Hz at daytime light levels.

White matter lesion burden in migraine with aura may be associated with reduced cerebral blood flow.

Objective The objective of this study was to determine whether white matter hyperintensities (WMHs) in subjects with migraine are related to alterations in resting cerebral blood flow (CBF). Methods Migraine with aura (MWA), migraine without aura (MwoA), and control subjects were enrolled in a 1:1:1 ratio. WMH load was scored based on fluid-attenuated inversion recovery/T2-weighted magnetic resonance imaging (MRI) using a previously established semi-quantitative scale. Global and regional CBFs were quantified using arterial spin labelled perfusion MRI. Integrity of the circle of Willis was assessed with magnetic resonance angiography (MRA). Results A total of 170 subjects were enrolled (54 controls, 56 MWA, and 60 MwoA). There was no significant difference in subjects with ≥1 WMH across groups (22% controls, 29% MWA, 35% MwoA; p = NS). Similarly, high WMH load was not significantly different across groups (16.7% controls, 21.4% MWA, 25.0% MwoA; p = NS). High WMH load was strongly associated with increasing age (odds ratio: 1.08 per year, 95% confidence interval: 1.02-1.13, p = 0.01). Resting CBF was similar across groups, but was significantly higher in women. In MWA subjects with high WMH load, CBF was substantially lower ( p = 0.03). No association between WMH load and CBF was seen in control or MwoA subjects. Conclusions WHMs in MWA may be related to alterations in resting CBF.

Measurement of visual sensitivity in migraine: Validation of two scales and correlation with visual cortex activation.

OBJECTIVE: The objectives of this article are to compare interictal and ictal visual sensitivity between migraine and controls using two published questionnaires, and to correlate responses with a physiologic measure of visual cortex activation. METHODS: Migraine with (MWA, n = 51) and without (MwoA, n = 45) aura and control individuals (n = 45) were enrolled and underwent BOLD fMRI with a visual stimulus. The visual discomfort score (VDS) assessed interictal and the migraine photophobia score (MPS) assessed ictal visual sensitivity. RESULT: VDS was significantly higher both in MWA and MwoA vs controls (both p = 0.0001). MPS was greater in MWA vs MwoA (p = 0.008). Ictal and interictal visual sensitivity strongly correlated in MWA (p = 0.004) but not MwoA patients (p = 0.12). BOLD activation in visual cortex was greater in MWA vs controls (2.7% vs 2.3%, p = 0.003) but similar between MwoA and controls. Increasing VDS was associated with greater BOLD signal change in MWA (p = 0.03) but not MwoA (p = 0.65) or controls (p = 0.53). MPS did not correlate with BOLD activation in either group. CONCLUSION: Increased interictal visual sensitivity is present both in MWA and MwoA. However, the correlation with ictal visual sensitivity and with cortical hyper-responsivity varies between MWA and MwoA, suggesting underlying differences between groups.

The fine-scale functional correlation of striate cortex in sighted and blind people.

To what extent are spontaneous neural signals within striate cortex organized by vision? We examined the fine-scale pattern of striate cortex correlations within and between hemispheres in rest-state BOLD fMRI data from sighted and blind people. In the sighted, we find that corticocortico correlation is well modeled as a Gaussian point-spread function across millimeters of striate cortical surface, rather than degrees of visual angle. Blindness produces a subtle change in the pattern of fine-scale striate correlations between hemispheres. Across participants blind before the age of 18, the degree of pattern alteration covaries with the strength of long-range correlation between left striate cortex and Broca's area. This suggests that early blindness exchanges local, vision-driven pattern synchrony of the striate cortices for long-range functional correlations potentially related to cross-modal representation.

Interictal cortical hyperresponsiveness in migraine is directly related to the presence of aura.

OBJECTIVE: The objective of this study was to compare the interictal cortical response to a visual stimulus between migraine with aura (MWA), migraine without aura (MwoA), and control subjects. METHODS: In a prospective case-control study, blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to assess the response to a visual stimulus and arterial spin labeled perfusion MR to determine resting cerebral blood flow. A standardized questionnaire was used to assess interictal visual discomfort. RESULTS: Seventy-five subjects (25 MWA, 25 MwoA, and 25 controls) were studied. BOLD fMRI response to visual stimulation within primary visual cortex was greater in MWA (3.09 ± 0.15%) compared to MwoA (2.36 ± 0.13%, P = 0.0008) and control subjects (2.47 ± 0.11%, P = 0.002); responses were also greater in the lateral geniculate nuclei in MWA. No difference was found between MwoA and control groups. Whole brain analysis showed that increased activation in MWA was confined to the occipital pole. Regional resting cerebral blood flow did not differ between groups. MWA and MwoA subjects had significantly greater levels of interictal visual discomfort compared to controls ( P = 0.008 and P = 0.005, respectively), but this did not correlate with BOLD response. CONCLUSIONS: Despite similar interictal symptoms of visual discomfort, only MWA subjects have cortical hyperresponsiveness to visual stimulus, suggesting a direct connection between cortical hyperresponsiveness and aura itself.

Absence of changes in cortical thickness in patients with migraine.

OBJECTIVE: Previous studies have reported gray matter alterations in patients with migraine, particularly thinning of the cingulate gyrus, and thickening of the somatosensory cortex (SSC) and visual motion processing areas (V3A/MT+). We attempted to replicate these findings in a larger patient population. METHODS: Brain anatomy was collected with 3T MRI. Surface-based morphometry was used to segment each brain volume, reconstruct and inflate the cortical sheet, and estimate gray matter thickness. RESULTS: Eighty-four age and sex-matched participants (28 migraine with aura, 28 migraine without aura, and 28 controls) were studied. No significant differences in somatosensory, cingulate gyrus, or V3A/MT+ cortical thickness were found between the groups, including analysis of specific subregions previously reported to be affected. Whole brain analysis found no regions of differential gray matter thickness between groups. A highly significant inverse correlation between age and whole brain and regional cortical thickness was identified. Power analyses indicate that even a small difference (∼0.07 to 0.14 mm) in cortical thickness could have been detected between groups given the sample size. INTERPRETATION: Using highly sensitive surface-based morphometry, no differences in cortical thickness between patients with migraine and controls could be identified.

Memory, processing of emotional stimuli, and volume of limbic structures in pediatric-onset multiple sclerosis.

OBJECTIVE: The limbic system is involved in memory and in processing of emotional stimuli. We measured volume of the hippocampus, amygdala, and thalamus, and assessed their relative contribution to episodic memory and emotion identification in POMS. METHOD: Sixty-five POMS participants (Mage = 18.3 ± 3.9 years; 48 female (73.8%)), average disease duration = 3.8 ± 3.8 years) and 76 age- and sex-matched controls (Mage = 18.1 ± 4.6 years; 49 female (64.5%)) completed the Penn Computerized Neurocognitive Battery (PCNB); 59 of 65 POMS participants and 69 out of 76 controls underwent 3 T MRI scanning. We derived age-adjusted Z-scores on accuracy and response time (RT) measures of episodic memory and emotion identification of the PCNB. Magnetic resonance imaging (MRI) volumetrics were normalized using the scaling factor computed by SIENAx. On PCNB tests that differed between groups, we used multiple linear regression to assess relationships between regional brain volumes and either episodic memory or emotion identification outcomes controlling for age, sex, accuracy/RT, and parental education. RESULTS: POMS participants were slower and less accurate than controls on the episodic memory domain but did not differ from controls on emotion outcomes. At the subtest level, POMS participants showed reduced accuracy on Word Memory (p = .002) and slower performance on Face Memory (p = .04) subtests. POMS participants had smaller total and regional brain volumes of the hippocampus, amygdala, and thalamus (p values ≤ 0.01). Collapsing across groups, both hippocampal and thalamic volume were significant predictors of Word Memory accuracy; hippocampal volume (B = 0.24, SE = 0.10, p = .02) was more strongly associated with Word Memory performance than thalamic volume (B = 0.16, SE = 0.05, p = .003), though the estimate with was less precise. CONCLUSIONS: POMS participants showed reduced episodic memory performance compared to controls. Aspects of episodic memory performance were associated with hippocampal and thalamic volume. Emotion identification was intact, despite volume loss in the amygdala.

The Influence of Axial Length Upon the Retinal Ganglion Cell Layer of the Human Eye.

Purpose: Variation in retinal thickness with eye size complicates efforts to estimate retinal ganglion cell number from optical coherence tomography (OCT) measures. We examined the relationship among axial length, the thickness and volume of the ganglion cell layer (GCL), and the size of the optic chiasm. Methods: We used OCT to measure GCL thickness over 50 degrees of the horizontal meridian in 50 healthy participants with a wide range of axial lengths. Using a model eye informed by individual biometry, we converted GCL thickness to tissue volume per square degree. We also measured the volume of the optic chiasm for 40 participants using magnetic resonance imaging (MRI). Results: There is a positive relationship between GCL tissue volume and axial length. Given prior psychophysical results, we conclude that increased axial length is associated with increased retinal ganglion cell size, decreased cell packing, or both. We characterize how retinal ganglion cell tissue varies systematically in volume and spatial distribution as a function of axial length. This model allows us to remove the effect of axial length from individual difference measures of GCL volume. We find that variation in this adjusted GCL volume correlates well with the size of the optic chiasm. Conclusions: Our results provide the volume of ganglion cell tissue in the retina, adjusted for the presumed effects of axial length upon ganglion cell size and/or packing. The resulting volume measure accounts for individual differences in the size of the optic chiasm, supporting its use to characterize the post-retinal visual pathway. Translational Relevance: Variations in ametropia can confound clinical measures of retinal features. We present a framework within which the thickness and volume of retinal structures can be measured and corrected for the effects of axial length.

Effects of Optic Neuritis, T2 Lesions, and Microstructural Diffusion Integrity in the Visual Pathway on Cortical Thickness in Pediatric-Onset Multiple Sclerosis.

BACKGROUND AND PURPOSE: Pediatric-onset multiple sclerosis (POMS) is associated with focal inflammatory lesions and the loss of cortical and deep gray matter. Optic neuritis (ON) and white matter (WM) lesions in the visual pathway can directly contribute to visual cortical mantle thinning. We determine the relative contributions of MS insult on anterior and posterior visual pathway integrity. METHODS: High- and low-contrast visual acuity, optical coherence tomography (OCT), and 3T MRI scans were obtained from 20 POMS patients (10 with remote ON) and 22 age- and sex-matched healthy controls. Cortical mantle thickness was measured using FreeSurfer. Fractional anisotropy (FA) and mean diffusivity were calculated for postchiasmal optic radiations (with and without WM lesions). Groups were compared using Student's t-test (adjusted for multiple comparisons), and simple linear regression was used to investigate interrelationships between measures. RESULTS: Mean cortical thickness of the whole brain was reduced in patients (2.49 mm) versus controls (2.58 mm, P = .0432) and in the visual cortex (2.07 mm vs. 2.17 mm, P = .0059), although the foveal confluence was spared. Mean FA of the optic radiations was reduced in POMS (.40) versus controls (.43, P = .0042) and correlated with visual cortical mantle thickness in POMS (P = .017). Visual acuity, OCT measures, and lesion volumes in the optic radiations were not associated with cortical mantle thickness. CONCLUSIONS: POMS negatively impacts the integrity of the anterior visual pathway, but it is the loss of WM integrity that drives anterograde loss of the cortical mantle. Preserved visual acuity and foveal sparing imply some degree of functional and structural resilience.

7T MRI Visualization of Cortical Lesions in Adolescents and Young Adults with Pediatric-Onset Multiple Sclerosis.

BACKGROUND: Cortical pathology in multiple sclerosis (MS) has been associated with prolonged and progressive disease. 7T magnetic resonance imaging (MRI) provides enhanced visualization of cortical lesions (CLs). Hence, we conducted a pilot study to explore whether CLs occur early in MS, as evidenced by pediatric-onset patients. METHODS: A total of 8 pediatric-onset MS patients were imaged using 7T MRI. CLs were annotated on T1-weighted magnetization-prepared rapid acquisition of gradient echoes images as leukocortical (LC), intracortical, or subpial. Total CLs, age at onset, age at scan, disease duration, total relapses, and Expanded Disability Status Scale (EDSS) score were recorded. RESULTS: A median of 120 (range: 48-144) CLs was identified in 8 MS patients (3 female, all with relapsing remitting MS, mean age at scan 21 years ± 3.5 SD, mean age of disease onset 15 years ± 2.3 SD, mean disease duration 5.3 years ± 3.4 SD, median EDSS 2.0). Nearly all the lesions identified were LC. CONCLUSIONS: Many CLs are detectable using 7T MRI in patients with pediatric-onset MS despite relatively brief disease duration, absence of progressive disease, and very limited physical disability-supporting early cortical involvement in MS.

Postretinal Structure and Function in Severe Congenital Photoreceptor Blindness Caused by Mutations in the GUCY2D Gene.

Purpose: To examine how severe congenital blindness resulting from mutations of the GUCY2D gene alters brain structure and function, and to relate these findings to the notable preservation of retinal architecture in this form of Leber congenital amaurosis (LCA). Methods: Six GUCY2D-LCA patients (ages 20-46) were studied with optical coherence tomography of the retina and multimodal magnetic resonance imaging (MRI) of the brain. Measurements from this group were compared to those obtained from populations of normally sighted controls and people with congenital blindness of a variety of causes. Results: Patients with GUCY2D-LCA had preservation of the photoreceptors, ganglion cells, and nerve fiber layer. Despite this, visual function in these patients ranged from 20/160 acuity to no light perception, and functional MRI responses to light stimulation were attenuated and restricted. This severe visual impairment was reflected in substantial thickening of the gray matter layer of area V1, accompanied by an alteration of resting-state correlations within the occipital lobe, similar to a comparison group of congenitally blind people with structural damage to the retina. In contrast to the comparison blind population, however, the GUCY2D-LCA group had preservation of the size of the optic chiasm, and the fractional anisotropy of the optic radiations as measured with diffusion tensor imaging was also normal. Conclusions: These results identify dissociable effects of blindness upon the visual pathway. Further, the relatively intact postgeniculate white matter pathway in GUCY2D-LCA is encouraging for the prospect of recovery of visual function with gene augmentation therapy.

Patterns of Individual Variation in Visual Pathway Structure and Function in the Sighted and Blind.

Many structural and functional brain alterations accompany blindness, with substantial individual variation in these effects. In normally sighted people, there is correlated individual variation in some visual pathway structures. Here we examined if the changes in brain anatomy produced by blindness alter the patterns of anatomical variation found in the sighted. We derived eight measures of central visual pathway anatomy from a structural image of the brain from 59 sighted and 53 blind people. These measures showed highly significant differences in mean size between the sighted and blind cohorts. When we examined the measurements across individuals within each group we found three clusters of correlated variation, with V1 surface area and pericalcarine volume linked, and independent of the thickness of V1 cortex. These two clusters were in turn relatively independent of the volumes of the optic chiasm and lateral geniculate nucleus. This same pattern of variation in visual pathway anatomy was found in the sighted and the blind. Anatomical changes within these clusters were graded by the timing of onset of blindness, with those subjects with a post-natal onset of blindness having alterations in brain anatomy that were intermediate to those seen in the sighted and congenitally blind. Many of the blind and sighted subjects also contributed functional MRI measures of cross-modal responses within visual cortex, and a diffusion tensor imaging measure of fractional anisotropy within the optic radiations and the splenium of the corpus callosum. We again found group differences between the blind and sighted in these measures. The previously identified clusters of anatomical variation were also found to be differentially related to these additional measures: across subjects, V1 cortical thickness was related to cross-modal activation, and the volume of the optic chiasm and lateral geniculate was related to fractional anisotropy in the visual pathway. Our findings show that several of the structural and functional effects of blindness may be reduced to a smaller set of dimensions. It also seems that the changes in the brain that accompany blindness are on a continuum with normal variation found in the sighted.

Hierarchical and homotopic correlations of spontaneous neural activity within the visual cortex of the sighted and blind.

Spontaneous neural activity within visual cortex is synchronized by both monosynaptic, hierarchical connections between visual areas and indirect, network-level activity. We examined the interplay of hierarchical and network connectivity in human visual cortex by measuring the organization of spontaneous neural signals within the visual cortex in total darkness using functional magnetic resonance imaging (fMRI). Twenty-five blind (14 congenital and 11 postnatal) participants with equally severe vision loss and 22 sighted subjects were studied. An anatomical template based on cortical surface topology was used for all subjects to identify the quarter-field components of visual areas V1-V3, and assign retinotopic organization. Cortical visual areas that represent the same quadrant of the visual field were considered to have a hierarchical relationship, while the spatially separated quarters of the same visual area were considered homotopic. Blindness was found to enhance correlations between hierarchical cortical areas as compared to indirect, homotopic areas at both the level of visual areas (p = 0.000031) and fine, retinotopic scale (p = 0.0024). A specific effect of congenital, but not postnatal, blindness was to further broaden the cortico-cortico connections between hierarchical visual areas (p = 0.0029). This finding is consistent with animal studies that observe a broadening of axonal terminal arborization when the visual cortex is deprived of early input. We therefore find separable roles for vision in developing and maintaining the intrinsic neural activity of visual cortex.

Migraine with aura is associated with an incomplete circle of willis: results of a prospective observational study.

OBJECTIVE: To compare the prevalence of an incomplete circle of Willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of Willis variations with alterations in cerebral perfusion. METHODS: Migraine with aura, migraine without aura, and control subjects were prospectively enrolled in a 1∶1∶1 ratio. Magnetic resonance angiography was performed to examine circle of Willis anatomy and arterial spin labeled perfusion magnetic resonance imaging to measure cerebral blood flow. A standardized template rating system was used to categorize circle of Willis variants. The primary pre-specified outcome measure was the frequency of an incomplete circle of Willis. The association between circle of Willis variations and cerebral blood flow was also analyzed. RESULTS: 170 subjects were enrolled (56 migraine with aura, 61 migraine without aura, 53 controls). An incomplete circle of Willis was significantly more common in the migraine with aura compared to control group (73% vs. 51%, p = 0.02), with a similar trend for the migraine without aura group (67% vs. 51%, p = 0.08). Using a quantitative score of the burden of circle of Willis variants, migraine with aura subjects had a higher burden of variants than controls (p = 0.02). Compared to those with a complete circle, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow (p = 0.05). Specific posterior cerebral artery variants were associated with greater asymmetries of blood flow in the posterior cerebral artery territory. CONCLUSIONS: An incomplete circle of Willis is more common in migraine with aura subjects than controls, and is associated with alterations in cerebral blood flow.

The retinotopic organization of striate cortex is well predicted by surface topology.

In 1918, Gordon Holmes combined observations of visual-field scotomas across brain-lesioned soldiers to produce a schematic map of the projection of the visual field upon the striate cortex. One limit to the precision of his result, and the mapping of anatomy to retinotopy generally, is the substantial individual variation in the size, volumetric position, and cortical magnification of area V1. When viewed within the context of the curvature of the cortical surface, however, the boundaries of striate cortex fall at a consistent location across individuals. We asked whether the surface topology of the human brain can be used to accurately predict the internal, retinotopic function of striate cortex as well. We used fMRI to measure polar angle and eccentricity in 25 participants and combined their maps within a left-right, transform-symmetric representation of the cortical surface. These data were then fit using a deterministic, algebraic model of visual-field representation. We found that an anatomical image alone can be used to predict the retinotopic organization of striate cortex for an individual with accuracy equivalent to 10-25 min of functional mapping. This indicates tight developmental linkage of structure and function within a primary, sensory cortical area.

A digital atlas of the dog brain.

There is a long history and a growing interest in the canine as a subject of study in neuroscience research and in translational neurology. In the last few years, anatomical and functional magnetic resonance imaging (MRI) studies of awake and anesthetized dogs have been reported. Such efforts can be enhanced by a population atlas of canine brain anatomy to implement group analyses. Here we present a canine brain atlas derived as the diffeomorphic average of a population of fifteen mesaticephalic dogs. The atlas includes: 1) A brain template derived from in-vivo, T1-weighted imaging at 1 mm isotropic resolution at 3 Tesla (with and without the soft tissues of the head); 2) A co-registered, high-resolution (0.33 mm isotropic) template created from imaging of ex-vivo brains at 7 Tesla; 3) A surface representation of the gray matter/white matter boundary of the high-resolution atlas (including labeling of gyral and sulcal features). The properties of the atlas are considered in relation to historical nomenclature and the evolutionary taxonomy of the Canini tribe. The atlas is available for download (https://cfn.upenn.edu/aguirre/wiki/public:data_plosone_2012_datta).

I know where you are secretly attending! The topography of human visual attention revealed with fMRI.

Previous studies have described the topography of attention-related activation in retinotopic visual cortex for an attended target at one or a few locations within the subject's field of view. However a complete description for all locations in the visual field is lacking. In this human fMRI study, we describe the complete topography of attention-related cortical activation throughout the central 28 degrees of the visual field and compare it with previous models. We cataloged separate fMRI-based maps of attentional topography in medial occipital visual cortex when subjects covertly attended to each target location in an array of three concentric rings of six targets each. We combined the attentional maps for each of the 18 target locations for each subject into a unique composite display to identify common principles of attentional organization for different target locations. Attentional activation was universally highest at the attended target but spread to other segments in a manner depending on eccentricity and/or target size. For targets scaled in size with eccentricity, the attentional effects spread circumferentially as a gradient whose full width at half maximum was consistently 1.5 times the target width at each eccentricity. For targets in the inner (1.8-8.5 degrees) and middle (8.5-15.6 degrees) rings, attention also tended to spread outward, radially to other segments. For targets in the outer ring (15.6-28 degrees), the radial spread of attention was primarily inward to targets of the middle ring. We propose an "attentional landscape" model that is more complex than a "spotlight" or simple "gradient" model but includes aspects of both. Finally, we asked subjects to secretly attend to one of the 18 targets without informing the investigator. We then show that it is possible to determine the target of attentional scrutiny from the pattern of brain activation alone with 100% accuracy. Together, these results provide a comprehensive, quantitative and behaviorally relevant account of the macroscopic cortical topography of visuospatial attention. We also show the pattern of attentional enhancement as it would appear distributed within the observer's field of view thereby permitting direct observation of a neurophysiological correlate of a purely mental phenomenon, the "window of attention".

The topography of visuospatial attention as revealed by a novel visual field mapping technique.

Previously, we and others have shown that attention can enhance visual processing in a spatially specific manner that is retinotopically mapped in the occipital cortex. However, it is difficult to appreciate the functional significance of the spatial pattern of cortical activation just by examining the brain maps. In this study, we visualize the neural representation of the "spotlight" of attention using a back-projection of attention-related brain activation onto a diagram of the visual field. In the two main experiments, we examine the topography of attentional activation in the occipital and parietal cortices. In retinotopic areas, attentional enhancement is strongest at the locations of the attended target, but also spreads to nearby locations and even weakly to restricted locations in the opposite visual field. The dispersion of attentional effects around an attended site increases with the eccentricity of the target in a manner that roughly corresponds to a constant area of spread within the cortex. When averaged across multiple observers, these patterns appear consistent with a gradient model of spatial attention. However, individual observers exhibit complex variations that are unique but reproducible. Overall, these results suggest that the topography of visual attention for each individual is composed of a common theme plus a personal variation that may reflect their own unique "attentional style."