Genetics is giving us, if you like, molecular markers that will allow us to begin to unpick the complexities of the disease process. We are perhaps some way behind the progress that has been made in cancer, for example, but nonetheless, we are making rapid and significant strides towards understanding some quite devastating conditions.The Wellcome Trust's Dr John Williams explains how developments in neuroscience are aiding the understanding of major health challenges...
Dr John Williams
With the potential to unlock important solutions to a huge range of health issues, advances in neurosciences are enhancing our ability to understand the functions of the brain and the nervous system. Neuroscience can thus provide tremendous insight, and some important strides have been made through recent research in the field, as Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust, explains to Public Service Review's Amy Caddick.
In addition to developing a better general understanding of basic brain functionality and the role of the nervous system in health, Williams begins by explaining that: "Neuroscience is crucial if we are going to be able to gain a real understanding of the major health challenges that we face in today's world. There are concerns around the impact of neurological disorders such as dementia, MS and epilepsy; and neuroscience is going to be integral in giving us the necessary insight to tackle mental
"If we define neuroscience very widely to include individuals who are using human brain imaging, those who are asking sophisticated questions about probing the fundamentals of the mechanisms underpinning things like thought – and not just as cellular neuroscience and molecular neuroscience – then this lies at the heart of how we are going to gain insight into normal function and also dysfunction of the brain and mind."
There is a wealth of ways in which this field is developing, and in order to consider advances in the research arena, it can be useful to take a thematic approach. For instance, Williams suggests that if we think about the impact that genetics has had on understanding the nervous system, it is necessary to look at the progress made in analysing brain circuits, and the importance of using tools such as neuro-imaging. This, in turn, leads to consideration of the impact that these methodologies have had in terms of enabling a greater understanding of disease phenotypes and mental health, for example.
The genetic impact on the drivers of mental health conditions, such as schizophrenia, are also linked to developments in other fields of genetic research for a variety of rare and more common disorders.
"Real breakthroughs have emerged from the study of autism, and the study of rare disorders such as Angelman syndrome," Williams comments. "These are currently beginning to inform how we approach the more complex disorders of emerging adolescence, such as schizophrenia. We have seen the emergence of what are called synaptopathies: dysfunction at the level of the circuit and in how cells come together and communicate."
There are many such examples of where improved understanding of one condition can make inroads into another arena. "We have seen similar progress made in terms of understanding the role of channel mutations – in particular ion channels – which underpin epilepsy," he continues. "Real advances have also been made in understanding the contribution of a plethora of autoimmune and inflammatory genes that underpin multiple sclerosis, and we have continued to make huge advances in figuring out the genetic mechanisms of neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's.
"Genetics is giving us, if you like, molecular markers that will allow us to begin to unpick the complexities of the disease process. We are perhaps some way behind the progress that has been made in cancer, for example, but nonetheless, we are making rapid and significant strides towards understanding some quite devastating conditions."
Looking in another direction at the influence of circuits, it is useful to consider the move beyond the communication at individual cell level to able to examine how large ensembles of cells interact with one another. "Genes allows us to unpick both functional and anatomical connectivity in a way that was not possible before," Williams says. "One of the most significant advances has been the development of optogenetics methods, which allow us to exert exquisite control over populations of cells, as well as giving us the opportunity to, potentially, unpick circuit function and correlate that with behavioural change of whatever your animal model is."
Williams suggests that with such transformative science taking place, incredible innovation can be brought about. This could enable large predictive models of brain circuits to be created, giving new insight into functionality and how behaviour emerges. Developments in neuroimaging, in particular, present a clearer view of the human brain.
"We are now able to study human brain function in a way that we could not before," Williams states. "We can get exquisitely detailed maps of human brain anatomy, correlate that with function, and combine that with information gleaned from other techniques such as MEG, EEG or PET.
"We are seeing incredibly innovative and significant steps in how imaging shows the ways in which the brain changes when challenged. For example, through increased understanding of how brain function might actually recover after stroke – such as how speech recovers – we can begin to take this information and use it in a predictive way to improve the rehabilitation of patients."
For all of the vast advances in recent years, there are still considerable difficulties to overcome. Williams believes that: "One of the major challenges that we face when we think about deciphering disease phenotypes is with neurodegenerative disorders.
"This tremendous burden of disease, particularly around dementia, is where innovative approaches to large-scale population studies – pulling out the genetic markers of disease – have allowed multidisciplinary groups to push forward on multiple fronts. This will allow the pharmaceutical companies to explore and exploit potential new targets."
Further issues arise in deciphering disease phenotypes in psychiatric disorders, where the challenges are perhaps even greater. With the ongoing development of more sophisticated behavioural models, it is possible to move beyond a simply descriptive approach to a disorder, to begin to look at definable traits that can be modelled and tested. "We are now beginning to see the full power of high-quality brain imaging, computational neuroscience and cognitive neuroscience being deployed on patient populations, which is starting to give new insight, over and above those that are currently used, to define the diagnosis of disorders," Williams clarifies.
Beyond the research methodologies, and the resulting improvement to stratifying patients, is a more practical end goal: to target new interventions more accurately and in novel ways, to help individuals and really improve the quality of care provision.This article first appeared on publicservice.co.uk: Down to a neuroscience.