Local structure and global connectivity in the cerebral cortex: neuroinformatics, histology and ultra high resolution diffusion MRI in the rhesus and marmoset monkey brain

This thesis concerns the cortical connectivity in Primates. The efficacy of Diffusion weighted MRI (dMRI) is examined. White matter (“WM”) systems subjacent to cortex (“superficial WM” ) are found to be a limiting factor to dMRI tractography. Superficial WM systems are examined with dMRI itself, and with analysis of histological data from the scanned brains. dMRI data was acquired ex-vivo at exceptional spatial and angular resolution (250μm in Rhesus, 150μm in Marmoset). The superficial WM was found to be complex, and with current dMRI methods, an effective barrier to tracking to and from around 50% of cortex in Rhesus. The quality of our data allowed Gray matter seeding, so that penetration both into and out of cortex was examined. We summarize the history of cortical connectivity and current work in tractography. We present an account of the formation and properties of the superficial WM. We compare tracking behaviors to tracer results, and develop a series of scalar maps on cortical surface models to summarize tracking behaviors. We attempt to explain these maps by examining the underlying tracking behavior and the brain tissue itself, revealing the intricate nature of the superficial WM. Chapter 4 contains a separate but related project in which a histologically accurate high resolution 3D and surface atlas of the Rhesus cortex is constructed with unprecedented accuracy. A method to rapidly and accurately non-linearly transform the atlas to a scan of another animal is developed, thus labelling its cortex. accuracy is by comparison to histology of the scanned animals

Three-dimensional digital template atlas of the Macaque brain

We present a new 3D template atlas of the anatomical subdivisions of the macaque brain, which is based on and aligned to the magnetic resonance imaging (MRI) data set and histological sections of the Saleem and Logothetis atlas. We describe the creation and validation of the atlas that, when registered with macaque structural or functional MRI scans, provides a straightforward means to estimate the boundaries between architectonic areas, either in a 3D volume with different planesof sections, or on an inflated brain surface (cortical flat map). As such, this new template atlas is intended for use as a reference standard for macaque brain research. Atlases and templates are available as both volumes and surfaces in standard NIFTI and GIFTI formats

Virtual Partner Interaction (VPI): Exploring Novel Behaviors via Coordination Dynamics

Inspired by the dynamic clamp of cellular neuroscience, this paper introduces VPI—Virtual Partner Interaction—a coupled dynamical system for studying real time interaction between a human and a machine. In this proof of concept study, human subjects coordinate hand movements with a virtual partner, an avatar of a hand whose movements are driven by a computerized version of the Haken-Kelso-Bunz (HKB) equations that have been shown to govern basic forms of human coordination. As a surrogate system for human social coordination, VPI allows one to examine regions of the parameter space not typically explored during live interactions. A number of novel behaviors never previously observed are uncovered and accounted for. Having its basis in an empirically derived theory of human coordination, VPI offers a principled approach to human-machine interaction and opens up new ways to understand how humans interact with human-like machines including identification of underlying neural mechanisms

GM_PROJECT

Code & preprocessed data from reveley et al 2022 " Diffusion MRI Anisotropy in the Cerebral Cortex is Determined by Unmyelinated Tissue Features"  </p

SourceData

Source histology image data from reveley et al 2022 " Diffusion MRI Anisotropy in the Cerebral Cortex is Determined by Unmyelinated Tissue Features" </p

Local structure and global connectivity in the cerebral cortex: neuroinformatics, histology and ultra high resolution diffusion MRI in the rhesus and marmoset monkey brain

This thesis concerns the cortical connectivity in Primates. The efficacy of Diffusion weighted MRI (dMRI) is examined. White matter (“WM”) systems subjacent to cortex (“superficial WM” ) are found to be a limiting factor to dMRI tractography. Superficial WM systems are examined with dMRI itself, and with analysis of histological data from the scanned brains. dMRI data was acquired ex-vivo at exceptional spatial and angular resolution (250µm in Rhesus, 150µm in Marmoset). The superficial WM was found to be complex, and with current dMRI methods, an effective barrier to tracking to and from around 50% of cortex in Rhesus. The quality of our data allowed Gray matter seeding, so that penetration both into and out of cortex was examined. We summarize the history of cortical connectivity and current work in tractography. We present an account of the formation and properties of the superficial WM. We compare tracking behaviors to tracer results, and develop a series of scalar maps on cortical surface models to summarize tracking behaviors. We attempt to explain these maps by examining the underlying tracking behavior and the brain tissue itself, revealing the intricate nature of the superficial WM. Chapter 4 contains a separate but related project in which a histologically accurate high resolution 3D and surface atlas of the Rhesus cortex is constructed with unprecedented accuracy. A method to rapidly and accurately non-linearly transform the atlas to a scan of another animal is developed, thus labelling its cortex. accuracy is by comparison to histology of the scanned animals

Diffusion MRI Anisotropy in the Cerebral Cortex is Determined by Unmyelinated Tissue Features

AbstractDiffusion magnetic resonance imaging (dMRI) is commonly used to assess the tissue and cellular substructure of the human brain. In the white matter, myelinated axons are the principal neural elements that shape dMRI through the restriction of water diffusion; however, in the gray matter the relative contributions of myelinated axons and other tissue features to dMRI are poorly understood. Here we investigate the determinants of diffusion in the cerebral cortex. Specifically, we ask whether myelinated axons significantly shape dMRI fractional anisotropy (dMRI-FA), a measure commonly used to characterize tissue properties in humans. We compared ultra-high resolution ex vivo dMRI data from the brain of a marmoset monkey with both myelin- and Nissl-stained histological sections obtained from the same brain after scanning. We found that cortical diffusion was only minimally related to the density and arrangement of myelinated fibers. Instead, the spatial pattern of dMRI-FA in the cortex was more closely related to anisotropy of tissue features indicated in the Nissl stained sections. Our results suggest that unmyelinated neurites such as large caliber apical dendrites are the primary features shaping dMRI measures in the cerebral cortex.</jats:p

Experimental conditions defined by the direction of coupling or information flow.

<p>In human-to-VP condition (A), the display is switched off but kinematic information about the subject's movement is received by the virtual partner. In the bidirectional condition (B), the subject sees the virtual partner's movements and the virtual partner receives kinematic information of the subject's movements. In the VP-to-human condition (C), a subject has vision of the virtual partner's movements but the virtual partner is decoupled (coupling term set to zero) from the subject.</p

Selection of experimental frequencies guided by the HKB collective variable dynamics.

<p>Humans have shown remarkably consistent coordinative (relative phase) behavior in a wide variety of coordination tasks with rhythmic stimuli, a fact captured by the elementary HKB dynamics <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005749#pone.0005749-Haken1" target="_blank">[11]</a> illustrated here. When asked to synchronize at the same frequency with the stimulus, stable phase patterns are invariably present at (or close to) anti-phase and in-phase for low movement frequencies (typically <2 Hz). This is indicated by the solid lines of fixed points () when and for <i>f</i> below a critical frequency <i>f*</i>. For frequencies <i>f</i>><i>f*</i>, only the fixed point at is stable. In the VPI experiment, a separate scaling trial in which the frequency is systematically increased is used to determine <i>f*</i>. The value of <i>f*</i> is then used as an upper bound for the choice of frequency parameter, ensuring that pattern instability is not only due to the effect of high frequency in the subject but also comes from conflicting tasks.</p

The Virtual Partner Interaction (VPI) paradigm.

<p>Subject coordinates finger movement with a virtual partner visually via an animated display. Subject's behavior is digitized and fed to a real-time HKB computational circuit. The circuit computes corresponding virtual partner position and velocity which is then used to animate the hand of the virtual partner. Circuit is coupled to the subject via the digitized inputs. Subject is coupled to the circuit visually via the display.</p