Ritobrato Datta

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.

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.

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).

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 Brocas 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.

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.

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.

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.

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.

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.

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.