Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

Nature in motion: The tuning of the visual system to the spatiotemporal properties of natural scenes.

Natural scenes contain several statistical regularities despite their superficially diverse appearances (e.g., mountains, rainforests, deserts). First, they exhibit a unique distribution of luminance intensities decreasing across spatial frequency, known as the 1/fα amplitude spectrum (α ≈ 1). Additionally, natural scenes share consistent geometric properties, comprising similar densities of structure across multiple scales-a property classifying them as fractal (e.g., how the branching patterns of rivers and trees appear similar irrespective of scale). These two properties are intimately related and correlate strongly in natural scenes. However, research using thresholded noise images suggests that spatially, the human visual system is preferentially tuned to natural scene structure more so than 1/fα spectra. It is currently unclear whether this dependency on natural geometry extends to the temporal domain. We used a psychophysics task to measure discrimination sensitivity toward two types of synthetic noise movies: gray scale and thresholded (N = 60). Each movie type shared the same geometric properties (measured fractal D), but substantially differing spectral properties (measured α). In both space and time, we observe a characteristic dependency on stimulus structure across movie types, with sensitivity peaking for stimuli with natural geometry despite having altered 1/fα spectra. Although only measured behaviorally, our findings may imply that the neural processes underlying this tuning have developed to be sensitive to the most stable signal in our natural environment-structure (e.g., the structural properties of a tree are consistent from morning to night despite illumination changes across time points).

Correcting Susceptibility Artifacts of MRI Sensors in Brain Scanning: A 3D Anatomy-Guided Deep Learning Approach.

Echo planar imaging (EPI), a fast magnetic resonance imaging technique, is a powerful tool in functional neuroimaging studies. However, susceptibility artifacts, which cause misinterpretations of brain functions, are unavoidable distortions in EPI. This paper proposes an end-to-end deep learning framework, named TS-Net, for susceptibility artifact correction (SAC) in a pair of 3D EPI images with reversed phase-encoding directions. The proposed TS-Net comprises a deep convolutional network to predict a displacement field in three dimensions to overcome the limitation of existing methods, which only estimate the displacement field along the dominant-distortion direction. In the training phase, anatomical T1-weighted images are leveraged to regularize the correction, but they are not required during the inference phase to make TS-Net more flexible for general use. The experimental results show that TS-Net achieves favorable accuracy and speed trade-off when compared with the state-of-the-art SAC methods, i.e., TOPUP, TISAC, and S-Net. The fast inference speed (less than a second) of TS-Net makes real-time SAC during EPI image acquisition feasible and accelerates the medical image-processing pipelines.

Fine-Grained Mapping of Cortical Somatotopies in Chronic Complex Regional Pain Syndrome.

It has long been thought that severe chronic pain conditions, such as complex regional pain syndrome (CRPS), are not only associated with, but even maintained by a reorganization of the somatotopic representation of the affected limb in primary somatosensory cortex (S1). This notion has driven treatments that aim to restore S1 representations in CRPS patients, such as sensory discrimination training and mirror therapy. However, this notion is based on both indirect and incomplete evidence obtained with imaging methods with low spatial resolution. Here, we used fMRI to characterize the S1 representation of the affected and unaffected hand in humans (of either sex) with unilateral CRPS. The cortical area, location, and geometry of the S1 representation of the CRPS hand were largely comparable with those of both the unaffected hand and healthy controls. We found no differential relation between affected versus unaffected hand map measures and clinical measures (pain severity, upper limb disability, disease duration). Thus, if any map reorganization occurs, it does not appear to be directly related to pain and disease severity. These findings compel us to reconsider the cortical mechanisms underlying CRPS and the rationale for interventions that aim to "restore" somatotopic representations to treat pain.SIGNIFICANCE STATEMENT This study shows that the spatial map of the fingers in somatosensory cortex is largely preserved in chronic complex regional pain syndrome (CRPS). These findings challenge the treatment rationale for restoring somatotopic representations in complex regional pain syndrome patients.

Manipulating the structure of natural scenes using wavelets to study the functional architecture of perceptual hierarchies in the brain.

Functional neuroimaging experiments that employ naturalistic stimuli (natural scenes, films, spoken narratives) provide insights into cognitive function "in the wild". Natural stimuli typically possess crowded, spectrally dense, dynamic, and multimodal properties within a rich multiscale structure. However, when using natural stimuli, various challenges exist for creating parametric manipulations with tight experimental control. Here, we revisit the typical spectral composition and statistical dependences of natural scenes, which distinguish them from abstract stimuli. We then demonstrate how to selectively degrade subtle statistical dependences within specific spatial scales using the wavelet transform. Such manipulations leave basic features of the stimuli, such as luminance and contrast, intact. Using functional neuroimaging of human participants viewing degraded natural images, we demonstrate that cortical responses at different levels of the visual hierarchy are differentially sensitive to subtle statistical dependences in natural images. This demonstration supports the notion that perceptual systems in the brain are optimally tuned to the complex statistical properties of the natural world. The code to undertake these stimulus manipulations, and their natural extension to dynamic natural scenes (films), is freely available.

Feasibility of functional magnetic resonance imaging of ocular dominance and orientation preference in primary visual cortex.

A recent hemodynamic model is extended and applied to simulate and explore the feasibility of detecting ocular dominance (OD) and orientation preference (OP) columns in primary visual cortex by means of functional magnetic resonance imaging (fMRI). The stimulation entails a short oriented bar stimulus being presented to one eye and mapped to cortical neurons with corresponding OD and OP selectivity. Activated neurons project via patchy connectivity to excite other neurons with similar OP in nearby visual fields located preferentially along the direction of stimulus orientation. The resulting blood oxygen level dependent (BOLD) response is estimated numerically via the model's spatiotemporal hemodynamic response function. The results are then used to explore the feasibility of detecting spatial OD-OP modulation, either directly measuring BOLD or by using Wiener deconvolution to filter the image and estimate the underlying neural activity. The effect of noise is also considered and it is estimated that direct detection can be robust for fMRI resolution of around 0.5 mm, whereas detection with Wiener deconvolution is possible at a broader range from 0.125 mm to 1 mm resolution. The detection of OD-OP features is strongly dependent on hemodynamic parameters, such as low velocity and high damping reduce response spreads and result in less blurring. The short-bar stimulus that gives the most detectable response is found to occur when neural projections are at 45 relative to the edge of local OD boundaries, which provides a constraint on the OD-OP architecture even when it is not fully resolved.

Manual segmentation of the fornix, fimbria, and alveus on high-resolution 3T MRI: Application via fully-automated mapping of the human memory circuit white and grey matter in healthy and pathological aging.

Recently, much attention has been focused on the definition and structure of the hippocampus and its subfields, while the projections from the hippocampus have been relatively understudied. Here, we derive a reliable protocol for manual segmentation of hippocampal white matter regions (alveus, fimbria, and fornix) using high-resolution magnetic resonance images that are complementary to our previous definitions of the hippocampal subfields, both of which are freely available at https://github.com/cobralab/atlases. Our segmentation methods demonstrated high inter- and intra-rater reliability, were validated as inputs in automated segmentation, and were used to analyze the trajectory of these regions in both healthy aging (OASIS), and Alzheimer's disease (AD) and mild cognitive impairment (MCI; using ADNI). We observed significant bilateral decreases in the fornix in healthy aging while the alveus and cornu ammonis (CA) 1 were well preserved (all p's<0.006). MCI and AD demonstrated significant decreases in fimbriae and fornices. Many hippocampal subfields exhibited decreased volume in both MCI and AD, yet no significant differences were found between MCI and AD cohorts themselves. Our results suggest a neuroprotective or compensatory role for the alveus and CA1 in healthy aging and suggest that an improved understanding of the volumetric trajectories of these structures is required.

The neural correlates of alcohol-related aggression.

Alcohol intoxication is implicated in approximately half of all violent crimes. Over the past several decades, numerous theories have been proposed to account for the influence of alcohol on aggression. Nearly all of these theories imply that altered functioning in the prefrontal cortex is a proximal cause. In the present functional magnetic resonance imaging (fMRI) experiment, 50 healthy young men consumed either a low dose of alcohol or a placebo and completed an aggression paradigm against provocative and nonprovocative opponents. Provocation did not affect neural responses. However, relative to sober participants, during acts of aggression, intoxicated participants showed decreased activity in the prefrontal cortex, caudate, and ventral striatum, but heightened activation in the hippocampus. Among intoxicated participants, but not among sober participants, aggressive behavior was positively correlated with activation in the medial and dorsolateral prefrontal cortex. These results support theories that posit a role for prefrontal cortical dysfunction as an important factor in intoxicated aggression.

The tuning of human visual cortex to variations in the 1/fα amplitude spectra and fractal properties of synthetic noise images.

Natural scenes share a consistent distribution of energy across spatial frequencies (SF) known as the 1/fα amplitude spectrum (α≈0.8-1.5, mean 1.2). This distribution is scale-invariant, which is a fractal characteristic of natural scenes with statistically similar structure at different spatial scales. While the sensitivity of the visual system to the 1/f properties of natural scenes has been studied extensively using psychophysics, relatively little is known about the tuning of cortical responses to these properties. Here, we use fMRI and retinotopic mapping techniques to measure and analyze BOLD responses in early visual cortex (V1, V2, and V3) to synthetic noise images that vary in their 1/fα amplitude spectra (α=0.25 to 2.25, step size: 0.50) and contrast levels (10% and 30%) (Experiment 1). To compare the dependence of the BOLD response between the photometric (intensity based) and geometric (fractal) properties of our stimuli, in Experiment 2 we compared grayscale noise images to their binary (thresholded) counterparts, which contain only black and white regions. In both experiments, early visual cortex responded maximally to stimuli generated to have an input 1/f slope corresponding to natural 1/fα amplitude spectra, and lower BOLD responses were found for steeper or shallower 1/f slopes (peak modulation: 0.59% for 1.25 vs. 0.31% for 2.25). To control for changing receptive field sizes, responses were also analyzed across multiple eccentricity bands in cortical surface space. For most eccentricity bands, BOLD responses were maximal for natural 1/fα amplitude spectra, but importantly there was no difference in the BOLD response to grayscale stimuli and their corresponding thresholded counterparts. Since the thresholding of an image changes its measured 1/f slope (α) but not its fractal characteristics, this suggests that neuronal responses in early visual cortex are not strictly driven by spectral slope values (photometric properties) but rather their embedded geometric, fractal-like scaling properties.

The spatiotemporal hemodynamic response function for depth-dependent functional imaging of human cortex.

The gray matter of human cortex is characterized by depth-dependent differences in neuronal activity and connections (Shipp, 2007) as well as in the associated vasculature (Duvernoy et al., 1981). The resolution limit of functional magnetic resonance imaging (fMRI) measurements is now below a millimeter, promising the non-invasive measurement of these properties in awake and behaving humans (Muckli et al., 2015; Olman et al., 2012; Ress et al., 2007). To advance this endeavor, we present a detailed spatiotemporal hemodynamic response function (HRF) reconstructed through the use of high-resolution, submillimeter fMRI. We decomposed the HRF into directions tangential and perpendicular to the cortical surface and found that key spatial properties of the HRF change significantly with depth from the cortical surface. Notably, we found that the spatial spread of the HRF increases linearly from 4.8mm at the gray/white matter boundary to 6.6mm near the cortical surface. Using a hemodynamic model, we posit that this effect can be explained by the depth profile of the cortical vasculature, and as such, must be taken into account to properly estimate the underlying neuronal responses at different cortical depths.

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.

Derivation of high-resolution MRI atlases of the human cerebellum at 3T and segmentation using multiple automatically generated templates.

The cerebellum has classically been linked to motor learning and coordination. However, there is renewed interest in the role of the cerebellum in non-motor functions such as cognition and in the context of different neuropsychiatric disorders. The contribution of neuroimaging studies to advancing understanding of cerebellar structure and function has been limited, partly due to the cerebellum being understudied as a result of contrast and resolution limitations of standard structural magnetic resonance images (MRI). These limitations inhibit proper visualization of the highly compact and detailed cerebellar foliations. In addition, there is a lack of robust algorithms that automatically and reliably identify the cerebellum and its subregions, further complicating the design of large-scale studies of the cerebellum. As such, automated segmentation of the cerebellar lobules would allow detailed population studies of the cerebellum and its subregions. In this manuscript, we describe a novel set of high-resolution in vivo atlases of the cerebellum developed by pairing MR imaging with a carefully validated manual segmentation protocol. Using these cerebellar atlases as inputs, we validate a novel automated segmentation algorithm that takes advantage of the neuroanatomical variability that exists in a given population under study in order to automatically identify the cerebellum, and its lobules. Our automatic segmentation results demonstrate good accuracy in the identification of all lobules (mean Kappa [κ]=0.731; range 0.40-0.89), and the entire cerebellum (mean κ=0.925; range 0.90-0.94) when compared to "gold-standard" manual segmentations. These results compare favorably in comparison to other publically available methods for automatic segmentation of the cerebellum. The completed cerebellar atlases are available freely online (http://imaging-genetics.camh.ca/cerebellum) and can be customized to the unique neuroanatomy of different subjects using the proposed segmentation pipeline (https://github.com/pipitone/MAGeTbrain).

Lifestyle management and brain MRI metrics in female Australian adults living with multiple sclerosis: a feasibility and acceptability study.

BACKGROUND: Limited studies of multiple sclerosis (MS) exist whereby magnetic resonance imaging (MRI) of the brain with consistent imaging protocols occurs at the same time points as collection of healthy lifestyle measures. The aim of this study was to test the feasibility, acceptability and preliminary efficacy of acquiring MRI data as an objective, diagnostic and prognostic marker of MS, at the same time point as brain-healthy lifestyle measures including diet. METHODS: Participants living with relapsing remitting MS partook in one structural MRI scanning session of the brain, completed two online 24-hour dietary recalls and demographic and self-reported lifestyle questionnaires (e.g. self-reported disability, comorbidities, physical activity, smoking status, body mass index (BMI), stress). Measures of central tenancy and level of dispersion were calculated for feasibility and acceptability of the research protocols. Lesion count was determined by one radiologist and volumetric analyses by a data analysis pipeline based on FreeSurfer software suite. Correlations between white matter lesion count, whole brain volume analyses and lifestyle measures were assessed using Spearman's rank-order correlation coefficient. RESULTS: Thirteen female participants were included in the study: eligibility rate 90.6% (29/32), recruitment rate 46.9% (15/32) and compliance rate 87% (13/15). The mean time to complete all required tasks, including MRI acquisition was 115.86 minutes ( ± 23.04), over 4 days. Conversion to usual dietary intake was limited by the small sample. There was one strong, negative correlation between BMI and brain volume (rs = -0.643, p = 0.018) and one strong, positive correlation between physical activity and brain volume (rs = 0.670, p = 0.012) that were both statistically significant. CONCLUSIONS: Acquiring MRI brain scans at the same time point as lifestyle profiles in adults with MS is both feasible and accepted among adult females living with MS. Quantification of volumetric MRI data support further investigations using semi-automated pipelines among people living with MS, with pre-processing steps identified to increase automated feasibility. This protocol may be used to determine relationships between elements of a brain-healthy lifestyle, including dietary intake, and measures of disease burden and brain health, as assessed by T1-weighted and T2-weighted lesion count and whole brain volume, in an adequately powered sample. TRIAL REGISTRATION: The study protocol was retrospectively registered in the Australia New Zealand Clinical Trials Registry (ACTRN12624000296538).

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.

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.

HumanBrainAtlas: an in vivo MRI dataset for detailed segmentations.

We introduce HumanBrainAtlas, an initiative to construct a highly detailed, open-access atlas of the living human brain that combines high-resolution in vivo MR imaging and detailed segmentations previously possible only in histological preparations. Here, we present and evaluate the first step of this initiative: a comprehensive dataset of two healthy male volunteers reconstructed to a 0.25 mm isotropic resolution for T1w, T2w, and DWI contrasts. Multiple high-resolution acquisitions were collected for each contrast and each participant, followed by averaging using symmetric group-wise normalisation (Advanced Normalisation Tools). The resulting image quality permits structural parcellations rivalling histology-based atlases, while maintaining the advantages of in vivo MRI. For example, components of the thalamus, hypothalamus, and hippocampus are often impossible to identify using standard MRI protocols-can be identified within the present data. Our data are virtually distortion free, fully 3D, and compatible with the existing in vivo Neuroimaging analysis tools. The dataset is suitable for teaching and is publicly available via our website (hba.neura.edu.au), which also provides data processing scripts. Instead of focusing on coordinates in an averaged brain space, our approach focuses on providing an example segmentation at great detail in the high-quality individual brain. This serves as an illustration on what features contrasts and relations can be used to interpret MRI datasets, in research, clinical, and education settings.

Cannabidiol as a Treatment for Neurobiological, Behavioral, and Psychological Symptoms in Early-Stage Dementia: A Double-Blind, Placebo-Controlled Clinical Trial Protocol.

Rationale: The slowing of disease progression in dementia in the early stages of diagnosis is paramount to improving the quality of life for those diagnosed and their support networks. Accumulating evidence suggests that CBD, a constituent of Cannabis sativa, is associated with neuroprotective, neuroendocrine, and psychotherapeutic effects, suggesting that it may be beneficial to dementia treatment. However, no published human study to date has examined this possibility. This trial aims to determine whether daily treatment with CBD over a 12-week period is associated with improved neurobiological, behavioral, and psychological outcomes in individuals living with early-stage dementia. Methods: Sixty participants with early-stage dementia will be recruited for a randomized, double-blind, placebo-controlled clinical trial. Participants will be randomized into either 99.9% pure CBD or placebo treatment conditions and administered two capsules per day for 12 weeks. Participants will commence a 200 mg/day dose for 2 weeks before escalating to 300 mg/day for the remaining 10 weeks. Neuroimaging and blood-based neuroendocrine profiles will be assessed at baseline and post-treatment. Psychological and behavioral symptoms will be assessed at baseline, 6 weeks, and post-treatment. Monitoring of health and side-effects will be conducted through weekly home visits. Discussion: This study is among the first to investigate the effects of isolated CBD in improving neuroanatomical and neuroendocrine changes, alongside psychological symptoms, during the early stages of dementia diagnosis. The outcomes of this trial have the capacity to inform a potential novel and accessible treatment approach for individuals living with early-stage dementia, and in turn, improve quality of life, prognoses, and treatment outcomes. Trial Registration: This trial has been registered with the Therapeutic Goods Administration (CT-2020-CTN-03849-1v2) and the Australian and New Zealand Clinical Trials Registry (ACTRN12621001364864).

Neurodesk: An accessible, flexible, and portable data analysis environment for reproducible neuroimaging.

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.

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.

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.