Human brain networks
Dr Heidi Johansen-Berg, Dr Tim Behrens & Prof Des Higham
Oxford University
2006 – 2009 Postdoctoral Fellowship
Computational approaches to analysing human brain networks and their breakdown in disease.
Dr Heidi Johansen-Berg is a Wellcome Trust Career Development Fellow and University Research Lecturer at the University of Oxford.
Dr Tim Behrens is a postdoctoral research assistant at the Centre for Functional Magnetic Imaging of the Brain, Oxford.
Prof Des Higham is Professor of Mathematics at the University of Strathclyde, Glasgow.
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 subcortical-cortical brain circuitry is therefore crucial to understanding and treating these disorders.
At present much knowledge of brain connectivity comes from inferences based on invasive tracer studies in animals, including rodents, cats and monkeys. Recent developments in the field of non-invasive diffusion tensor magnetic resonance imaging (DTMRI) allow tracing of fibre pathways in the living human brain.
The aim of this Dr Hadwen Trust-funded research project is to develop quantitative, computational approaches to analysing data from non-invasive DTMRI brain scans, to directly determine patterns of connections in human brains. This will provide a general framework in which to test hypotheses about breakdowns in subcortical-cortical network connectivity in brain disorders, with a focus on chronic pain.
This technique has the potential to replace invasive tracer studies in animals, as well as enhancing the quality of evidence concerning brain connectivity. The latter part of this research programme will focus specifically on chronic pain, although the framework developed could be applied to many different clinical brain disorders.
Publications
1. Tomassini V, Jbabdi S, Klein JC et al (2007). Diffusion-weighted imaging tractography-based parcellation of the human lateral premotor cortex identified dorsal and ventral subregions with anatomical and functional specialisations. J Neurosci 27:1059-1069.
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2. Jbabdi S, Woolrich WMW, Andersson JLR et al (2007). A Bayesian framework for global tractography. NeuroImage 37:116-129.
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3 Behrens TEJ, Johansen Berg H, Rushworth MFS et al (2007). Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? NeuroImage 34:144-155.
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Pathways in the human brain
A work in progress report by Dr Heidi Johansen-Berg
The brain includes many different regions, each with a specialised role to play in the functioning of the whole organism. Each region is connected by a variety of multidimensional nerve fibre pathways in order to communicate and orchestrate co-ordinated responses to the many needs which all living organisms have. Our research uses new scanning techniques to visualise these wiring patterns in the living human brain. It is not possible to see these pathways on conventional brain scans and, until recently, they could only be investigated by using animal studies. Now, however, a brain scanning technique, diffusion tensor magnetic resonance imaging (DTMRI), can provide images that allow us to visualise these pathways in living human brains. This opens up many new possibilities for testing how the pathways develop and age, and how they are disrupted in disease.
Using funding from the Dr Hadwen Trust, Heidi Johansen-Berg, Tim Behrens and Saad Jbabdi at the Department of Clinical Neurology in Oxford, are using DTMRI to scan healthy people and those with disorders such as stroke, multiple sclerosis, schizophrenia and pain disorders [1]. The brain scans can potentially provide a huge amount of information but this information is highly complex. Our team therefore also includes Professor Des Higham, at the Department of Mathematics, University of Strathclyde, who is helping us apply sophisticated analysis techniques to interpret this complex data [2].
These approaches have provided new developments in the study of the healthy brain as they enable the identification of specialised brain regions in living people [3-5]. For example, we have recently identified subregions within a brain area – the premotor cortex-based on their patterns of connections with other areas. Previously, this region could only be reliably identified by microscopically examining slices of post-mortem brain. The ability to identify the region in living people means that we can study both the structure and function of this area at the same time, for example, by using functional imaging to test how the region behaves when healthy people perform different tasks. This approach will also help us to tackle clinical challenges. For example, identifying brain regions in living subjects may be useful for accurately targeting these structures for medical interventions, such as brain surgery for Parkinson’s disease or brain stimulation for stroke.
Diffusion tensor MRI scanning techniques have the potential to reduce the need for invasive animal studies. Animal studies of brain connections involve injection of a tracer into a brain area of interest. The tracer will then be transported along the pathways connected to the area of interest. By looking at slices of this experimental animal’s brain post mortem, it is possible to reconstruct the route travelled by the tracer. Studies of brain connections using diffusion MRI however have the advantage that they can be performed in living human subjects and allow the visualisation of connections across the whole brain. Currently, however, the level of detail achievable in DTMRI scans is a long way from what can be visualised in animal studies. There is therefore much work still to be done in improving and developing the imaging technology and data analysis approaches in order to maximise the useful information which is available from scans of brain connections in human subjects. Such progress will also help replace some of the use of animal models in understanding patterns of connectivity in the brain.
Dr Heidi Johansen-Berg, who authored this article, 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.
References
1. Johansen-Berg H & Behrens TE (2006). Just pretty pictures? What diffusion tractography can add in clinical neuroscience. Curr Opin Neurol 19:379-385.
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2. Higham D (2003). Unravelling small world networks. J Comput Appl Math 158:61.
Doi:10.1016/S0377-0427(03)00471-0
3. Johansen-Berg H, Behrens TE, Robson MD et al (2004). Changes in connectivity profiles define functionally distinct regions in human medial frontal cortex. Proc Natl Acad USA 101:13335-13340.
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4. Klein JC, Behrens TE, Robson MD et al (2007). Connectivity-based parcellation of human cortex using diffusion MRI: Establishing reproducibility, validity and observer independence in BA 44/45 and SMA/pre-SMA. Neuroimage 34:204-211.
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5. Behrens TE & Johansen-Berg H (2005). Relating connectional architecture to grey matter function using diffusion imaging. Phil Trans R Soc Lond B Biol Sci. 360:903-911.
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