Throughout history, humans have been asking questions about thinking and behavior. The phenomena that people aimed to study greatly surpassed the verbiage and knowledge that was available. This disconnect between what humans want to know and actual understanding drives progress. In light of the brain’s amazing capabilities, endless supply of mysteries and intricate complexities, the brain is humans’ acclaimed black box. After generations of ceaseless probing, the key to this black box may finally be within our grasp; the Human Connectome Project has developed unprecedented tools for uncovering the human brain.
The Human Connectome Project (HCP) began in 2010 after the National Institutes of Health contributed about $40 million to two separate consortia to create better neuroimaging protocols (2). The goal of the Project was to map the healthy human macroscale connectome—the network of connections between all areas of the brain. Not only would the scientific community better understand the healthy brain, researchers could also deepen their ability to comprehend and treat neurological disorders. The WU-Minn-Ox HCP consortium is based at WUSTL, University of Minnesota and Oxford University. WU-Minn-Ox collected data on adult twins and their non-twin siblings in order that neuroscientists can systematically study the genetics and connectivity of neural networks. Before acquiring data, the consortium of scientists spent two years developing novel approaches of data acquisition, analysis and distribution (3). The changes that resulted from the efforts of HCP scientists were unparalleled because they altered traditional brain study protocol.
Traditionally, localized brain lesions were detected to identify the functions of specific brain regions. Scientists who studied individuals who displayed abnormal symptoms after a traumatic brain injury could establish a causal link between the injured brain area and the impaired function. The problem with the traditional method of brain study is its reliance on case studies that mainly demonstrate correlation rather than prove causality. More importantly, many neurological and psychiatric behaviors reflect networks of connected regions as opposed to one specific location in the brain. The current conceptualizations of brain regions have been mainly constructed from exemplary historical cases that are often cited in psychology and neuroscience. For example, H.M. suffered from medial temporal injuries to the brain, revealing the medial temporal region’s fundamental importance in memory. Through this type of single-lesion analysis, Wernicke’s Area was determined to be responsible for speech comprehension and Broca’s Area was linked to speech production. As imaging technology became available, computed tomography and Magnetic Resonance Imaging (MRI) were adopted to infer causality between abnormalities in the brain to symptoms displayed by the patient. While studying each symptom and brain region individually provides uncomplicated clarity and simplicity, the relationship between symptoms and lesions cannot be captured so clearly. Similar symptoms can manifest from lesions in different brain locations and many complex behaviors result without identifiable brain lesions. A brain map that reflected the interconnectedness of the brain was needed.
Instead of isolated lesion studies, HCP uses large-scale functional neuroimaging, which detects changes in brain metabolism, blood flow and oxygenation, water flow and electrical activity. The healthy brain can be studied because physiological changes can be identified in anatomically intact brain regions. With more advanced technology, maps of interactions are created through measurements of brain connections. Unlike anatomical connectivity, functional connectivity is mapped with MRI sequences that are sensitive to spontaneous deviations in blood oxygen levels. When the spontaneous activity of two regions is correlated, the regions are said to be functionally connected. Combining anatomical and functional connectivity maps, “complex symptoms that transcend localization to single brain regions can be mapped to larged distributed brain networks” (1). Nevertheless, image acquisition is often difficult because patients can be uncomfortable and nervous, which leads to blurry images. The differences between individual anatomy also produces inconsistent results that need to be interpreted and cross-linked. While functional neuroimaging minimizes some of the shortcomings of traditional lesion analyses, it does not eliminate all complications since the brain interacts in ways that are not always visible.
The Human Connectome is used in conjunction with lesion analysis to provide more precise information about the commonalities of impairments in different regions. Areas of the brain can interact by producing similar symptoms because they are linked in the same network. Using this method, scientists discovered that the location of a lesion in the corticospinal tract correlates with the degree of motor impairment in the patient. This anatomical connection can be visualized with the connectome, explaining why injuries to the brain stem, midbrain, pons and cerebral cortex can all cause paralysis. Single-lesion analysis has now expanded to lesion network mapping, which reverses the analysis process by tracing back the locations of lesions to a standard brain atlas. Connectome maps are then used to determine the related network. This method will facilitate the discovery of symptom-based treatment targets and more accurate therapeutic brain stimulation.
HCP not only aimed to map the brain, but also to create a paradigm that “span the domains of acquisition, analysis and sharing of MRI-based data” (2) and surpassed traditional models. Adopting this upgraded prototype will accelerate progress in finding therapeutic approaches to brain diseases. Neurodevelopmental disorders begin onset at birth, many psychiatric disorders develop throughout the human lifespan, and neurodegenerative diseases tend to debilitate older adults. HCP focused on the study of the healthy brain in order to better equip scientists to decipher the abnormal brain. Though the original five-year Human Connectome Project may have ended, the goals and vision of the Project are far from complete. Currently, imaging protocols are being adopted for the Lifespan Development and Aging projects, which aim to characterize brain connectivity changes in human childhood and aging.
The human brain is an open book and its mysteries may never be fully unveiled. Just as the famous Human Genome Project has enabled research into cell therapies, the Human Connectome Project has broadened psychiatric and neurological treatment and research possibilities. The Human Connectome Project was one giant step towards opening the black box, providing the means for more progress in the future. The key to mapping the human black box has been found, now it is up to scientists to continue the quest for answers.
Edited by: Morgan Leff
Illustrated by: Jennifer Broza