Trinity Researchers Harness New Technology to Find Improved ways of Understanding MND

Researchers combine EEG and MRI to monitor brain changes.

 

Our brains function by electrical and chemical signalling. Recording brain wave patterns can be very helpful in conditions like epilepsy, but the potential of this inexpensive and easily applied technology has not been fully recognised.Researchers in the Academic Unit of Neurology at Trinity College Dublin have been studying brain wave patterns in the neurodegenerative condition Motor Neuron Disease (MND). They have made the surprising discovery that some specific parts of the brain are “over-connected” in MND, while other parts show reduced activity as the brain networks disintegrate.

A previous study by the Trinity group had indicated the potential changes in EEG recordings. The new findings considerably advance our understanding of the brain regions that start to get overconnected as the disease progresses, and how they relate to the death of the motor neurons. These changes in comparison to the healthy brain indicated new dynamics of the disease in the brain and have revealed some previously unrecognised abnormalities in the brain.

Their findings, published in the recent issue of the journal Cerebral Cortexhttp://doi.org/10.1093/cercor/bhx301 imply that MND, along with other neurodegenerative conditions, are associated with important changes in neural communication between different brain networks, rather than changes in a single region of the brain. The new discoveries are pointing to the mechanisms in the brain that are associated with the disease, that were not previously taken into account, assuming that MND is simply a focal isolated degeneration in certain parts of the brain.

“Understanding how the networks in the human brain interact in health and disease is a very important area that has not been adequately researched” said Dr Bahman Nasseroleslami, Senior Research Fellow and Neural Engineer, who is the lead author of the study.

“Using EEG to decipher changes in brain function has not been possible until recently. The computational power, mathematical and statistical tools were just not available.  But our findings have shown that we can now explore the living human brain in a very sophisticated and non-invasive way, and that we can link our dynamic EEG changes with anatomical changes captured by MRI. This expands enormously our ability to understand how the brain is working in real-time, and how these changes in brain networking correlate with structural changes that we can see on MRI scans. This is breakthrough science”.

“These findings will change how we study MND” said Professor Hardiman, Head of the Academic Unit of Neurology in Trinity. “Our identification of specific changes in brain wave patterns in different forms of neurodegeneration will allow us to develop new drugs, and monitor the effects of these drugs in ways that have not been possible up to now.”

Professor Hardiman continued: “Our findings will revolutionise how we measure changes in brain function in MND and many other related neuro-degenerations such as frontotemporal dementia.  Our findings will also help in understanding the links we have shown previously between MND and schizophrenia. There is much to do, but this is the first step in developing new and innovative measurements that will have a major impact on how we conduct future clinical trials.”

There are 120 number of new cases of MND diagnosed in Ireland every year. 350 people are living with the condition in Ireland.

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Trinity Scientists discover shared genetic origin for MND and schizophrenia

Researchers from Trinity College Dublin have shown for the first time that Motor Neurone Disease (MND) — also known as Amyotrophic Lateral Sclerosis (ALS) — and schizophrenia have a shared genetic origin, indicating that the causes of these diverse conditions are biologically linked. The work has just been published in the prestigious journal Nature Communications.

By analysing the genetic profiles of almost 13,000 MND cases and over 30,000 schizophrenia cases, the researchers have confirmed that many of the genes that are associated with these two very different conditions are the same.

In fact, the research has shown an overlap of 14% in genetic susceptibility to the adult onset neuro-degeneration condition ALS/MND and the developmental neuropsychiatric disorder schizophrenia.

While overlaps between schizophrenia and other neuropsychiatric conditions including bipolar affective disorder and autism have been shown in the past, this is the first time that an overlap in genetic susceptibility between MND and psychiatric conditions has been shown.

Dr Russell McLaughlin, Ussher Assistant Professor in Genome Analysis at Trinity College Dublin, and lead author of the paper said: “This study demonstrates the power of genetics in understanding the causes of diseases.”

“While neurological and psychiatric conditions may have very different characteristics and clinical presentations, our work has shown that the biological pathways that lead to these diverse conditions have much in common.”

Professor of Neurology in Trinity and Consultant Neurologist at the National Neuroscience Centre at Beaumont Hospital Dublin, Orla Hardiman, is the senior author and lead investigator on the project.

Professor Hardiman said: “Our work over the years has shown us that MND is a much more complex disease than we originally thought. Our recent observations of links with psychiatric conditions in some families have made us think differently about how we should study MND. When combined with our clinical work and our studies using MRI and EEG, it becomes clear that MND is not just a disorder of individual nerve cells, but a disorder of the way these nerve cells talk to one another as part of a larger network.”

She continued: “So instead of thinking of MND as a degeneration of one cell at a time, and looking for a ‘magic bullet’ treatment that works, we should think about MND in the same way that we think about schizophrenia, which is a problem of disruptions in connectivity between different regions of the brain, and we should look for drugs that help to stabilise the failing brain networks.”

“The other significant issue that this research brings up is that the divide between psychiatry and neurology is a false one. We need to recognise that brain disease has many different manifestations, and the best way to develop new treatments is to understand the biology of what is happening. This will have major implications for how we classify diseases going forward, and in turn how we train our future doctors in both psychiatry and neurology. That in itself will have knock-on consequences for how society understands, approaches and treats people with psychiatric and neurological conditions.”

The new research was prompted by earlier epidemiological studies by researchers at Trinity, led by Professor Hardiman. These studies showed that people with MND were more likely than expected to have other family members with schizophrenia, and to have had another family member who had committed suicide.

This was first noted as family histories were ascertained from people with MND in the National ALS Clinic and was subsequently investigated as part of case control studies in Ireland in which over 192 families with MND and 200 controls participated. Details of over 12,000 relatives were analysed and the rates of various neurological and psychiatric conditions calculated in family member of those with MND and controls. This work was subsequently published in the prestigious American journal the Annals of Neurology in 2013.

This led the Trinity group to team up with European collaborators in MND including the University of Utrecht, Kings College London and members of the Project MinE and Psychiatric Genome Consortia to see if these epidemiological observations could be due to a genetic overlap between MND and schizophrenia.

The Trinity group, along with their partners in the University of Utrecht, will continue to study the links between MND and psychiatric conditions using modern genetics, epidemiology and neuroimaging, and in this way will develop new and more effective treatments that are based on stabilizing disrupted brain networks.

The full paper is available here: http://www.nature.com/articles/ncomms14774