Monday, July 27, 2015

Navigating through neuronal circuits in human brain

The Human Connectome Project is nearing its completion this year, casting light to the extensive structural and functional connectivity in brain.

Memories, speech, behavior, thoughts, emotions, experience, feelings; the quantum of functions managed by a human brain is tremendous. Deciphering the numerous neuronal circuits in brain has often left scientists and doctors equally puzzled. With more than 90 billion neurons and 150 trillion synapses, human brain has always been the object of awe and mystery over these years. When the Human Genome Project finally decoded the nearly 3 billion nucleotides of human DNA, researchers were energized to attempt a similar Herculean task to map the human brain. Two consortia of research institutions were formed in 2010, funded by National Institutes of Health (NIH) for The Human Connectome Project (HCP). Mapping of the long distance circuits of the whole brain (macro-connectome) is a five year $30 million project carried out by Washington University in St Louis- University of Minnesota- Oxford University (WashU-Minn) Consortium.  Simultaneously, mapping of every neuron, dendrite and synapse of the brain (micro-connectome) is a three year $8.5 million project executed by Harvard University- Massachusetts General Hospital- University of South Carolina (USC-MGH) Consortium. Discussing the progress of the HCP over the past five years with RGCB blog, David Van Essen PhD, the principal investigator of The Human Connectome Project remarked the extensive impact of HCP on neuroscience research.” The Human Connectome Project, now in its fifth and final year of funding, will soon complete its objective of acquiring high quality multimodal neuroimaging data from 1200 healthy young adults, along with extensive behavioral data.  By freely sharing these rich and complex datasets with the scientific community, we hope to accelerate analyses and improve our understanding of brain structure, function, and connectivity and its relation to behavior.”

The project utilizes cutting edge imaging techniques like functional Magnetic Resonance Imaging (fMRI) and Task MRI for analyzing functional connectivity and diffusion MRI (dMRI) for structural connectivity along with Magnetoencephalography (MEG) and High Angular Resolution Diffusion Imaging (HARDI) for crossing white fibers. 1200 healthy adults including twin and non-twin siblings were studied. The brain images at resting state and while undertaking different tasks like solving memory problems, playing gambling games, various physical movements were procured. The Blood Oxygen Level Dependent (BOLD) was used to represent the neural activity at each point and a dense functional connectivity matrix was recreated to show the spatial temporal orchestration of the brain.

One of the major challenges in the initial stages of compiling and making meaningful results out of the enormous amount of data was the inter subject variability in cortical folding pattern leading to blurring of images when population average is taken. This was solved by the perspicacious graduate student in Van Essen lab, Mathew Glasser. He developed Myelin maps by plotting heat maps of cortical region by calculating the ratio of intensity from T1 and T2 weighted images from the same individual. To tackle other challenges in the course of the HCP like noise and bias in the data, discordant results from different imaging modalities as well as subtle cortical boundaries, Salimi- Korishidi and Griffanti et al developed denoising by FMRIB's ICA-based X-noiseifier (FIX) and Robinson and Jenkinson et al developed inter subject alignment using Multimodal Surface Imaging (MSM), thus substantially reducing the average image distortion. The extensive and invaluable data procured over these years is analyzed by the Connectome Workbench and shared across the globe on the robust infrastructure XNAT developed by Marcus et al.

 “The improvements in data acquisition and analysis achieved by the HCP will have an impact on our understanding of brain development and aging and on the analysis of connectomes related to human disease, through projects soon to be funded by the National Institutes of Health”, David Van Essen PhD, the pioneer in neuroinformatics tools, shared with RGCB blog the impact of this much sought after venture and his pride in spearheading the project that unlatches the realm of neuronal circuits. ”The opportunity to help lead this exciting adventure and to work with an exceptionally talented and dedicated team of HCP investigators and staff has been a highlight of my scientific career.”

Neuroscience research in India has a long way to go. Studies in 2010 and 2013 analyze the status, flaws and refinements entailed for India to make our mark in Neuroscience research. Let the critical information newly available to us through the Human Connectome Project aid us in our mission to answer many questions in aging and diseases.

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