Human brain networks
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2006 – 2009 Dr Hadwen Trust Postdoctoral Fellowship: Computational approaches to analysing human brain networks and their breakdown in diseaseDr H Johansen-Berg & Dr TE Behrens Prof D Higham |
Dr Heidi Johansen-Berg is a Wellcome Trust Career Development Fellow and University Research Lecturer at the University of Oxford. She and her research team study the relationship between brain structure and function using brain imaging techniques.
Dr Tim Behrens is a University Research Lecturer and an MRC Fellow in Computational Biology at the Department of Psychology, University of Oxford.
Prof Des Higham is Professor of Mathematics at the University of Strathclyde, Glasgow.
Dr Saad Jbabdi, who was supported by a Dr Hadwen Trust research fellowship for the duration of this grant, is a postdoctoral researcher at the Department of Clinical Neurology in Oxford.
This Dr Hadwen Trust-funded research project has advanced computational approaches to analysing data from non-invasive diffusion tensor magnetic resonance imaging (DTMRI) brain scans, to directly determine patterns of connections in human brains.
There are several neurological and psychiatric disorders in which connections between deep brain structures and cortical regions are damaged or disrupted. They include schizophrenia, chronic pain, and movement disorders such as Parkinson’s disease. Detailed knowledge of human brain circuitry is therefore crucial to understanding and treating these disorders.
So far much knowledge of brain connectivity has come from inferences based on invasive tracer studies in animals, including rodents, cats and monkeys. Recent developments in the field of non-invasive DTMRI allow tracing of fibre pathways in the living human brain and have the potential to replace certain invasive animal studies.
At Oxford, Dr Johansen-Berg’s research group is using DTMRI to scan healthy people and those with disorders such as stroke, multiple sclerosis, schizophrenia and pain disorders [1]. The brain scans can provide a huge amount of complex information and so sophisticated computational analytical techniques are needed to interpret this complex data [2].
Funding from the Dr Hadwen Trust enabled the development of new methods for analysing data from DTMRI brain scans to allow the study of brain fibre connections, and the application of these methods to study the connectivity of healthy and diseased brains.
Progress was made in three areas of method development:
- An improved method for tracing brain fibre connections using diffusion MRI, called global tractography, was developed that has the potential to solve some of the pitfalls of existing methodology [3]. This methodology helps us to understand how information flows between brain regions.
- A method that enhances our ability to segregate brain regions on the basis of their connections was developed [4]. The way a brain region is linked to others constitutes a fingerprint that provides information about its function.
- A method to quantify functional connections (as opposed to structural connections) between brain regions on the basis of functional MRI was developed. This work was presented at the Human Brain Mapping conference, San Francisco 2009.
These advanced imaging methods make it possible to study both the structure and function of brain regions at the same time in living people, and will help researchers to answer new types of scientific questions about the brain.
A method called diffusion-weighted imaging tractography was used to study the pre-motor cortex in human volunteers. Prior understanding of the anatomy and connectivity of the pre-motor cortex had been based on studies of macaque brains. Using advanced imaging our researchers were able to identify sub-regions within the pre-motor cortex based on their patterns of connections with other areas in the brains of healthy humans [5]. The pre-motor cortex is known to be involved in recovery from stroke, so these new approaches could help us to improve the outlook for stroke patients.
A parallel study explored connections of the respiratory centres in the brainstem in humans. All prior knowledge of these neuronal centres had come from studies of rodents. For the first time, the breathing centres of the brainstem were identified using functional MRI in healthy human subjects, and their connections to the cortex via the thalamus assessed using diffusion MRI [6].
A structural analysis was made of the visual connections in a brain injured patient with blindsight. Diffusion MRI revealed a pathway in this patient’s visual system that is not present in normal subjects and which could underlie his condition. This finding indicates a previously unsuspected plasticity of the visual system [7].
Finally, diffusion MRI was used to study brain connections in patients with Huntington’s disease. Crucially, degeneration of a specific group of neurons deep within the brain was observed, a finding previously only reported in post-mortem studies [8]. This finding is important as it offers a potential biomarker of selective neuro-degeneration in Huntington’s disease.
Future work will involve a study of the connectivity patterns of the insular cortex, a crucial region in pain processing, and the connectivity of the pre-frontal cortex and interactions occurring during pain perception.
These studies have shown that diffusion-weighted imaging tractography in human volunteers is a valid and powerful approach that could potentially replace certain animal studies in neuroscience research.
Summary
- New imaging methods are enabling the study of connections in the living human brain. This was not possible previously so research has involved invasive experiments on rodents, primates and cats
- Diffusion Magnetic Resonance Imaging (MRI) tractography can be used to explore human brain connections and to replace certain animal experiments.
- This Dr Hadwen Trust-funded project has developed novel methods for analysing data from diffusion MRI to provide more useful information and enable scientists to ask new questions about the human brain in health and disease.
- Connections in an area of the brain (pre-motor cortex) involved in recovery from stroke have been explored in human volunteers
- For the first time, centers in the human brain that are responsible for breathing, and their connections to other brain areas, have been explored
- A study of a patient with blind sight, as a result of brain damage, has revealed new information about their condition.
- The degeneration of a specific group of brain cells involved in the control of movements has been observed in patients with Huntington’s disease.
References
- Johansen-Berg H & Behrens TE (2006). Just pretty pictures? What diffusion tractography can add in clinical neuroscience.
Curr Opin Neurol 19:379-385 - Higham D (2003). Unravelling small world networks. J Comput Appl Math 158:61. Doi:10.1016/S0377-0427(03)00471-0
- Jbabdi S, Woolrich MW, Andersson JLR & Behrens TEJ (2007). A Bayesian framework for global tractography. NeuroImage 37:116-129
- Jbabdi S, Woolrich MW & Behrens TEJ (2009). Multiple-subjects connectivity-based parcellation using hierarchical Dirichlet process mixture models. NeuroImage 44:373-384
- Tomassini V, Jbabdi S, Klein J, et al (2007). Diffusion-weighted imaging tractography-based parcellation of the human lateral premotor cortex identifies dorsal and ventral subregions with anatomical and functional specializations. J Neurosci 27:10259-10269
- Pattinson KTS, Mitsis GD, Harvey AK, et al (2009). Determination of the human brainstem respiratory control network and its cortical connections in vivo using functional and structural imaging. NeuroImage 44:295-305
- Bridge H, Thomas O, Jbabdi S & Cowey A (2008). Changes in connectivity after visual cortical brain damage underlie altered visual function.
Brain 131:1433-1444 - Douaud G, Behrens TE, Poupon C, et al (2009). In vivo evidence for the selective subcortical degeneration in Huntington’s disease.
NeuroImage 46:958-966