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Functional networks in healthy and sick brains

Are disturbances to the brain, such as Alzheimer's or autism, linked to specific defects in the underlying communication networks in the brain? If this is the case, subtle changes in the networks can act as a marker for brain disturbances. Neuroscientist Serge Rombouts will be investigating this, together with a national consortium of researchers.

A new form of functional MRI has shown that an structural system of communication networks is active in the brain. With this imaging technique, known as Resting State fMRI, the researchers will not be studying which individual areas of the brain 'light up' with specific tasks or stimuli, but how patterns of functional relations between brain areas appear throughout the brain. This is known as functional connectivity.   

The same signals

‘Two brain areas can very systematically show the same signals. The left and right hemispheres of the brain can be shown to be functionally connected. If I raise my right arm, for example, you only see activity in the motor cortex in the left hemisphere, which comes as no surprise. But Resting State scans show that there is a definite connection between the left and right motor regions even when at rest. They show the same oscillations, which is something we didn't know until very recently.'  

Medicines

These are the words of neuroscientist Serge Rombouts, who introduced Resting State fMRI into Leiden University three years ago. Rombouts is Director of the interfaculty Leiden Institute for Brain and Cognition (LIBC). In 2007, he was awarded a Vidi subsidy by NWO to investigate whether Resting State fMRI can be used to observe what medicines actually do in the brain. This research is in full progress, and has already produced some promising results.

Diagnostic purposes

In parallel with this, he and an interdisciplinary team of Dutch researchers and non-scientific partner organisations are now intending to investigate whether you can use Resting State fMRI for diagnistic purposes and for monitoring brain diseases and disturbances. They will be looking at common conditions such as Alzheimer's and other forms of dementia, ADHD, autism, depression and schizophrenia.

Natural gas revenues

The consortium, with Rombouts as co-ordinator, will work under the flag of a major Dutch research programme on the brain and cognition, that was recently initiated with funding of 20 million euro from the natural gas revenues, the so-called FES funds (a fund for reinforcing the economic infrastructure). A condition for funding from this source is that the research has to generate results within a short period that will benefit society. Leiden researchers will be co-operating with researchers from different universities and university medical centres, as well as with other partners, such as Philips.  

Co-ordinated for the first time

Do Resting State brain scans allow you to see disturbances in communication patterns at an early stage? Can you follow the course of an illness using these scans? And does each separate condition have its own communication pattern? 'There are certainly indications that this is the case,' says Rombouts. 'But the necessary instruments for research in  this area still have to be developed. It is an important step forward that the five university medical centres taking part in the project all use the same measuring criteria. And, on top of that, you first have to know exactly what these functional networks look like in healthy brains and how they develop over the lifetime. We are now for the first time in the Netherlands going to take a co-ordinated approach to this research.'

Early stage

The social urgency of the research needs no explanation. The illnesses and conditions mentioned are constantly under discussion, they affect all stages of life and cause a great deal of personal suffering as well as representing a significant social and economic burden. And a sensitive and reliable diagnostic method for almost all these conditions is notoriously difficult. At the present time, for example it is not possible to diagnose Alzheimer's at an early stage. By the time brain scans detect changes in the structure of the brain, the condition is already far advanced. Resting State functional MRI, on the other hand, is very sensitive.  Rombouts: ‘There are indications that functional MRI, that doesn't show the structure but the activity of the brain, can detect subtle changes in the working of the brain at a much earlier stage.'

Dream for the future

Does every illness have its own specific changes in communication patterns? This is something else that the researchers want to know. 'The dream for the future is that we can recognise depression, Alzheimer's, autism, etc. from their disrupted pattern of functional connectivity,' explains Rombouts. 'We know, for example, that the hippocampus, that is responsible for many memory functions, is functionally linked to many other areas in the brain. If you can demonstrate using a standardised set of instruments that these lines of communication change in connection with particular sicknesses, such as depression, they you really do have somethign to offer.' 

This month, Serge Rombouts was awarded the C.J. Kok prize. This award by the C.J. Kok Fund, amounting to 2,500 euro, is made to individuals who have demonstrated a pronounced expertise in mathematical or medical problems.  

Project: Functional markers for cognitive disturbances
Scientific partners: Leiden Univesity Medical Center, UMC Utrecht, Maastricht University, VUMC, UMC Groningen. 
Societal partners: Philips, Alzheimer Nederland, Oudervereniging Balans. 

Official start Monday 23 November 2009 
National Initiative for Brain and Cognition (in Dutch)

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Research Profile Areas

Brain function and dysfunction over the lifespan

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