Mark M. Schira

A novel in vivo atlas of human hippocampal subfields using high-resolution 3 T magnetic resonance imaging.

The hippocampus is a neuroanatomical structure that has been widely studied in the context of learning, memory, stress, and neurodegeneration. Neuroanatomically, the hippocampus is subdivided into several subfields with intricate morphologies and complex three-dimensional relationships. Recent studies have demonstrated that the identification of different subfields is possible with high-resolution and -contrast image volumes acquired using ex vivo specimens in a small bore 9.4 T scanner and, more recently, in vivo, at 7 T. In these studies, the neuroanatomical definitions of boundaries between subfields are based upon salient differences in image contrast. Typically, the definition of subfields has not been possible using commonly available magnetic resonance (MR) scanners (i.e.: 1.5 or 3T) due to resolution and contrast limitations. To overcome the limited availability of post-mortem specimens and expertise in state-of-the-art high-field imaging, we propose a coupling of MR acquisition and detailed segmentation techniques that allow for the reliable identification of hippocampal anatomy (including subfields). High-resolution and -contrast T1- and T2-weighted image volumes were acquired from 5 volunteers (2 male; 3 female; age range: 29-57, avg. 37) using a clinical research-grade 3T scanner and have final super-sampled isotropic voxel dimensions of 0.3mm. We demonstrate that by using these acquisition techniques, our data results in contrast-to-noise ratios that compare well with high-resolution images acquired with long scan times using post-mortem data at higher field strengths. For the subfields, the cornus ammonis (CA) 1, CA2/CA3, CA4/dentate gyrus, stratum radiatum/stratum lacunosum/stratum moleculare, and subiculum were all labeled as separate structures. Hippocampal volumes are reported for each of the substructures and the hippocampus as a whole (range for hippocampus: 2456.72-3325.02 mm(3)). Intra-rater reliability of our manual segmentation protocol demonstrates high reliability for the whole hippocampus (mean Dice Kappa of 0.91; range 0.90-0.92) and for each of the subfields (range of Dice Kappas: 0.64-0.83). We demonstrate that our reliability is better than the Dice Kappas produced by simulating the following errors: a translation by a single voxel in all cardinal directions and 1% volumetric shrinkage and expansion. The completed hippocampal atlases are available freely online (info2.camh.net/kf-tigr/index.php/Hippocampus) and can be coupled with novel computational neuroanatomy techniques that will allow for them to be customized to the unique neuroanatomy of different subjects, and ultimately be utilized in different analysis pipelines.

The foveal confluence in human visual cortex

The human visual system devotes a significant proportion of its resources to a very small part of the visual field, the fovea. Foveal vision is crucial for natural behavior and many tasks in daily life such as reading or fine motor control. Despite its significant size, this part of cortex is rarely investigated and the limited data have resulted in competing models of the layout of the foveal confluence in primate species. Specifically, how V2 and V3 converge at the central fovea is the subject of debate in primates and has remained “terra incognita” in humans. Using high-resolution fMRI (1.2 × 1.2 × 1.2 mm3) and carefully designed visual stimuli, we sought to accurately map the human foveal confluence and hence disambiguate the competing theories. We find that V1, V2, and V3 are separable right into the center of the foveal confluence, and V1 ends as a rounded wedge with an affine mapping of the foveal singularity. The adjacent V2 and, in contrast to current concepts from macaque monkey, also V3 maps form continuous bands (∼5 mm wide) around the tip of V1. This mapping results in a highly anisotropic representation of the visual field in these areas. Unexpectedly, for the centermost 0.75°, the cortical representations for both V2 and V3 are larger than that of V1, indicating that more neuronal processing power is dedicated to second-level analysis in this small but important part of the visual field.

Extended Concepts of Occipital Retinotopy

Retinotopic mapping is a key property of organization of occipital cortex, predominantly on the medial surface but increasingly being identified in lateral and ventral regions. The retinotopic organization of early visual areas V1-3 is well established, although anatomical landmarks can help to resolve ambiguities in poorly-defined functional maps. New morphing techniques are now available to define the metric mappings quantitatively within each retinotopic area. In the dorsal occipital regions, there is fair agreement that area V3A should be split into separate V3A and V3B maps, and that beyond them lies a further area, V7. We specify the eccentricity mapping of both V3B and V7 for the first time, showing how the latter is roughly parallel to the meridional mapping and offering formal accounts of such paradoxical behavior. In ventral occipital cortex, we support the analysis of Zeki and Bartels (1) and Wade et al. (2) that V4 maps the full hemifield, and show the existence of two more areas, a ventromedial map of the lower quadrant, emphasizing the upper vertical meridian, and an adjacent area with a dominant foveal representation. In lateral cortex, the motion area defined by a motion localizer shows pronounced retinotopy, particularly in the eccentricity parameter. A dorsolateral map between the motion area and V3B, which represents the lower quadrant with an emphasis the foveal part of the lower vertical meridian, may be a counterpart to the ventromedial map.

Don't look back in anger: neural correlates of reappraisal, analytical rumination, and angry rumination during recall of an anger-inducing autobiographical memory.

Despite the enormous costs associated with unrestrained anger, little is known about the neural mechanisms underlying anger regulation. Behavioral evidence supports the effectiveness of reappraisal in reducing anger, and demonstrates that rumination typically maintains or augments anger. To further understand the effects of different anger regulation strategies, during functional magnetic resonance imaging 21 healthy male and female undergraduates recalled an anger-inducing autobiographical memory. They then engaged in three counterbalanced anger regulation strategies: reappraisal, analytical rumination, and angry rumination. Reappraisal produced the least self-reported anger followed by analytical rumination and angry rumination. Rumination was associated with increased functional connectivity of the inferior frontal gyrus with the amygdala and thalamus. Understanding how neural regions interact during anger regulation has important implications for reducing anger and violence.

Future challenges for vection research: definitions, functional significance, measures, and neural bases.

This paper discusses four major challenges facing modern vection research. Challenge 1 (Defining Vection) outlines the different ways that vection has been defined in the literature and discusses their theoretical and experimental ramifications. The term vection is most often used to refer to visual illusions of self-motion induced in stationary observers (by moving, or simulating the motion of, the surrounding environment). However, vection is increasingly being used to also refer to non-visual illusions of self-motion, visually mediated self-motion perceptions, and even general subjective experiences (i.e., “feelings”) of self-motion. The common thread in all of these definitions is the conscious subjective experience of self-motion. Thus, Challenge 2 (Significance of Vection) tackles the crucial issue of whether such conscious experiences actually serve functional roles during self-motion (e.g., in terms of controlling or guiding the self-motion). After more than 100 years of vection research there has been surprisingly little investigation into its functional significance. Challenge 3 (Vection Measures) discusses the difficulties with existing subjective self-report measures of vection (particularly in the context of contemporary research), and proposes several more objective measures of vection based on recent empirical findings. Finally, Challenge 4 (Neural Basis) reviews the recent neuroimaging literature examining the neural basis of vection and discusses the hurdles still facing these investigations.

Modeling magnification and anisotropy in the primate foveal confluence.

A basic organizational principle of the primate visual system is that it maps the visual environment repeatedly and retinotopically onto cortex. Simple algebraic models can be used to describe the projection from visual space to cortical space not only for V1, but also for the complex of areas V1, V2 and V3. Typically a conformal (angle-preserving) projection ensuring local isotropy is regarded as ideal and primate visual cortex is often regarded as an approximation of this ideal. However, empirical data show systematic deviations from this ideal that are especially relevant in the foveal projection. The aims of this study were to map the nature of anisotropy predicted by existing models, to investigate the optimization targets faced by different types of retino-cortical maps, and finally to propose a novel map that better models empirical data than other candidates. The retino-cortical map can be optimized towards a space-conserving homogenous representation or a quasi-conformal mapping. The latter would require a significantly enlarged representation of specific parts of the cortical maps. In particular it would require significant enlargement of parafoveal V2 and V3 which is not supported by empirical data. Further, the recently published principal layout of the foveal singularity cannot be explained by existing models. We suggest a new model that accurately describes foveal data, minimizing cortical surface area in the periphery but suggesting that local isotropy dominates the most foveal part at the expense of additional cortical surface. The foveal confluence is an important example of the detailed trade-offs between the compromises required for the mapping of environmental space to a complex of neighboring cortical areas. Our models demonstrate that the organization follows clear morphogenetic principles that are essential for our understanding of foveal vision in daily life.

Hemodynamic traveling waves in human visual cortex.

Functional MRI (fMRI) experiments rely on precise characterization of the blood oxygen level dependent (BOLD) signal. As the spatial resolution of fMRI reaches the sub-millimeter range, the need for quantitative modelling of spatiotemporal properties of this hemodynamic signal has become pressing. Here, we find that a detailed physiologically-based model of spatiotemporal BOLD responses predicts traveling waves with velocities and spatial ranges in empirically observable ranges. Two measurable parameters, related to physiology, characterize these waves: wave velocity and damping rate. To test these predictions, high-resolution fMRI data are acquired from subjects viewing discrete visual stimuli. Predictions and experiment show strong agreement, in particular confirming BOLD waves propagating for at least 5–10 mm across the cortical surface at speeds of 2–12 mm s-1. These observations enable fundamentally new approaches to fMRI analysis, crucial for fMRI data acquired at high spatial resolution.

Endogenous testosterone and cortisol modulate neural responses during induced anger control.

Research with violent offenders and delinquent adolescents suggests that endogenous testosterone concentrations have the strongest positive correlations with violence among men who have low concentrations of cortisol. The present study tested the hypothesis that testosterone and cortisol would similarly interact to determine neural activation in regions supporting self-regulation in response to anger provocation. Nineteen healthy Asian male participants were insulted and asked to control their anger during functional magnetic resonance imaging (fMRI). When cortisol levels were low, testosterone positively correlated with activation in the dorsolateral prefrontal cortex (dlPFC) and thalamus, but not when cortisol levels were high. During induced anger control, functional connectivity was increased between the amygdala and a top-down prefrontal cortical control network. Moreover, the amygdala-PFC connectivity was strongest among those high in testosterone and low in cortisol. This research highlights a possible neural mechanism by which testosterone and cortisol may influence anger control.

A functional polymorphism of the maoa gene is associated with neural responses to induced anger control

Aggressiveness is highly heritable. Recent experimental work has linked individual differences in a functional polymorphism of the monoamine oxidase-A gene (MAOA) to anger-driven aggression. Other work has implicated the dorsal ACC (dACC) in cognitive-emotional control and the amygdala in emotional arousal. The present imaging genetics study investigated dACC and amygdala reactivity to induced anger control as a function of MAOA genotype. A research assistant asked 38 healthy male undergraduates to control their anger in response to an insult by a rude experimenter. Men with the low-expression allele showed increased dACC and amygdala activation after the insult, but men with the high-expression allele did not. Both dACC and amygdala activation independently mediated the relationship between MAOA genotype and self-reported anger control. Moreover, following the insult, men with the high-functioning allele showed functional decoupling between the amygdala and dACC, but men with the low-functioning allele did not. These results suggest that heightened dACC and amygdala activation and their connectivity are neuroaffective mechanisms underlying anger control in participants with the low-functioning allele of the MAOA gene.

Orientation-specific contextual modulation of the fMRI BOLD response to luminance and chromatic gratings in human visual cortex.

The responses of orientation-selective neurons in primate visual cortex can be profoundly affected by the presence and orientation of stimuli falling outside the classical receptive field. Our perception of the orientation of a line or grating also depends upon the context in which it is presented. For example, the perceived orientation of a grating embedded in a surround tends to be repelled from the predominant orientation of the surround. Here, we used fMRI to investigate the basis of orientation-specific surround effects in five functionally-defined regions of visual cortex: V1, V2, V3, V3A/LO1 and hV4. Test stimuli were luminance-modulated and isoluminant gratings that produced responses similar in magnitude. Less BOLD activation was evident in response to gratings with parallel versus orthogonal surrounds across all the regions of visual cortex investigated. When an isoluminant test grating was surrounded by a luminance-modulated inducer, the degree of orientation-specific contextual modulation was no larger for extrastriate areas than for V1, suggesting that the observed effects might originate entirely in V1. However, more orientation-specific modulation was evident in extrastriate cortex when both test and inducer were luminance-modulated gratings than when the test was isoluminant; this difference was significant in area V3. We suggest that the pattern of results in extrastriate cortex may reflect a refinement of the orientation-selectivity of surround suppression specific to the colour of the surround or, alternatively, processes underlying the segmentation of test and inducer by spatial phase or orientation when no colour cue is available.