Vogelstein, J. T. | Search bioRxiv

bioRxiv2018

On statistical tests of functional connectome fingerprinting

Fingerprinting of functional connectomes is an increasingly standard measure of reproducibility in functional magnetic resonance imaging connectomics. In such studies, one attempts to match a subjects first session image with their second, in a blinded fashion, in a group of subjects measured twice. The number or percentage of correct matches is usually reported as a statistic. In this manuscript, we investigate the statistical tests of matching based on exchangeability assumption in the fingerprinting analysis. We show that a nearly universal Poisson(1) approximation applies for different matching schemes. We theoretically investigate the permutation tests and explore the issue that the test is overly sensitive to uninteresting directions in the alternative hypothesis, such as clustering due to familial status or demographics. We perform a numerical study on two functional magnetic resonance imaging (fMRI) resting state datasets, the Human Connectome Project (HCP) and the Baltimore Longitudinal Study of Aging (BLSA). These datasets are instructive, as the HCP includes techinical replications of long scans and includes monozygotic and dyzogotic twins as well as non-twin siblings. In contrast, the BLSA study incorporates more typical length resting state scans in a longitudinal study. Finally, a study of single regional connections is performed on the HCP data.

neuroscience↗

bioRxiv2017

Whole-Brain Serial-Section Electron Microscopy In Larval Zebrafish

Investigating the dense meshwork of wires and synapses that form neuronal circuits is possible with the high resolution of serial-section electron microscopy (ssEM)1. However, the imaging scale required to comprehensively reconstruct axons and dendrites is more than 10 orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons2--some of which span nearly the entire brain. The difficulties in generating and handling data for relatively large volumes at nanoscale resolution has thus restricted all studies in vertebrates to neuron fragments, thereby hindering investigations of complete circuits. These efforts were transformed by recent advances in computing, sample handling, and imaging techniques1, but examining entire brains at high resolution remains a challenge. Here we present ssEM data for a complete 5.5 days post-fertilisation larval zebrafish brain. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management. The resulting dataset can be analysed to reconstruct neuronal processes, allowing us to, for example, survey all the myelinated axons (the projectome). Further, our reconstructions enabled us to investigate the precise projections of neurons and their contralateral counterparts. In particular, we observed that myelinated axons of reticulospinal and lateral line afferent neurons exhibit remarkable bilateral symmetry. Additionally, we found that fasciculated reticulospinal axons maintain the same neighbour relations throughout the extent of their projections. Furthermore, we use the dataset to set the stage for whole-brain comparisons of structure and function by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. We provide the complete dataset and reconstructions as an open-access resource for neurobiologists and others interested in the ultrastructure of the larval zebrafish.

neuroscience↗