Lord Dowding Fund for humane research

 

National Antivisection Society

The Mindís Eye: The present and future of Neuroscience

15 February 2008

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Neuroimaging is contributing to the detailed mapping of the human brain, providing unprecedented understanding of functioning and development of mental ill health and neurodegenerative diseases1. The neuroscience facility at Aston University utilises cutting edge technology allowing static and real time brain imaging, including an LDF-sponsored Magnetic Resonance Imaging (MRI) scanner.

Aston was the UKís first location to combine the emerging scanning technologies Ė with scientists in Japan and Germany taking the same bold step. Several years on, and the Aston Neuroimaging Research Group has gained an international reputation and as more and more research data emerges from other facilities using these techniques, these approaches are already surpassing their promise. Behold the future of neuroscience......

Aston actively seeks to provide more appropriate modes of research in the study of human perception and cognition than animal models. The study of neuroscience is important in both characterisation of neurodevelopmental disorders and is improving differential diagnostic and treatment strategies.
By studying single cell physiology and their networks, researchers at Aston University seek to determine principles of functional behaviour with non-invasive human studies. Examining the traits and attributes of neurodevelopmental disorders, such as Parkinsonís and Alzheimerís, enables individual diagnostic and treatment strategies to be tailored to patients. Such studies offer increased clarity without the imprecision and misleading results caused by species differences during animal experiments. It is also possible to monitor the progression of neuro-degenerative disease in patients by carrying out brain imaging at different points of the illness, something which is not possible in a dissected animal brain.

There are some animal experimenters now advocating MRI to study primate brains, which illustrates the resistance in some quarters to actually shift away from the animal research habit Ė even when a technique for human study is available.

The Neuroimaging Research Group have gained an international reputation in developing novel approaches to modelling and analysing the biological processing of neuronal communication in the brain. These are being applied to a wide range of human studies, with the aim of improving diagnosis and aiding surgical intervention and are validated during surgery by evaluation of cortical localisation.

Aston University has secured a five year research fellowship from the Research Council UK (RCUK) allowing them to explore alternatives to pharmaceutical and physiological brain research in animals. As a result of this funding the Neuroimaging Research Group at Aston is in a unique position to make important progressions in the field of advanced research solutions.

The Lord Dowding Fund is sponsoring the annual running costs of the fMRI facility at Aston Life Sciences Academy, for the five years up to 2009. We have also supported a range of individual neuroscience research projects at Aston and elsewhere.

Vision research

A series of projects is providing a bridge between microscopic descriptions of cell functioning and macroscopic, behavioural observations, by relating behavioural performance to neural functioning in the cortex. Researchers achieved this by using tests involving visual stimuli and the resulting mental state and behaviour. In order to achieve high temporal and high spatial resolution for cortical processes, MEG and fMRI are used in combination. Modelling of cellular level networks can then be designed using the observation of this dynamic activity.

This research has provided the opportunity to compare measures of visual brain activity in humans to published data collected in invasive primate procedures. The recorded gamma activity can be reconstructed from MEG using sophisticated processing techniques which show the stimulus related dynamics over time in a human subject.

It has been claimed that certain detailed readings cannot be obtained from non-invasive human study, but can be obtained for example using micro-electrodes in the heads of primates. This human research has shown that comparable readings can be obtained from the human studies. The human-based data is immeasurably superior to the monkey data because it is from the correct species.

Investigating neuronal networks in visual information processing tasks: Concordance between fMRI and MEG scanning

In order to study the neuronal networks involved in sustained attention and vigilance, participants carrying out the Rapid Visual Information Processing (RVIP) task were measured with MEG and fMRI. A previous study using fMRI found two networks, one involved in sustained attention and one corresponding to working memory. Results of this study, in agreement with previous work, found various areas of the brain significantly active during the RVIP task. The images resulting from the two neuroimaging techniques were found to be concordant.

Auditory, Speech and Language

Speech and language research looks at functions measurable only in the human brain. Research at Aston has ranged from simple tone to complex higher level speech experiments involving semantic processing. Low level auditory processing projects seek to make a correlation between Magneto-encephalogram (MEG) data, which shows measures of the magnetic field in the brain, and the functions of the neuronal network.

One project has been investigating the neurophysiology of speech perception. Sinewave speech is a form of artificially degraded speech which is used as a tool for measuring speech perception. Once familiarised with the phonetic content the participant can recognise it as speech. Participants listening to sinewave speech were measured using MEG to explore the characteristics of the neurophysiological networks involved in the perception of phonetic information in auditory stimuli. Adding to knowledge from functional Magnetic Resonance Imaging (fMRI) research, it is possible to begin to understand the biological underpinnings of speech perception Ė a uniquely human process.

The brain and pharmaceuticals

We are also gaining a remarkable insight into the impacts of drugs on the human brain.

Psychotropic agents are drugs which affect mental activity, perception or behaviour. In a study of cognition and neuropharmacokinetics, the effects of these drugs on attention and working memory are being measured at Aston. These can be monitored for changes extensively using tasks which measure rapid visual information and offers much for the future study of nutrition and drug development and testing.

Another project has investigated brain changes as a result of drug uptake. Using a combination of MEG and structural MRI, neuronal changes were studied in relation to administration of a low dose of the tranquilliser diazepam with a focus on finding which loci of the brain are affected in all participants. Researchers also monitored neuronal changes in response to diazepam over the whole cortex. The researchers now have an MEG drug profile of diazepam which can be compared to other studies in order to discuss and hopefully develop an entirely new approach to pharmacological imaging. The specifics of diazepam induced changes in therapy were considered as well as the potential application of this method in drug development, neuronal network investigation and microdosing.

Pain processing

One of the earliest LDF projects utilising neuro-imaging, was an examination of the areas of the brain connected with pain in the gut. The result of the collaboration between Hope Hospital, Salford and Aston University was a new brain imaging technique to non-invasively record nerve cell activity in the human brain Ė known as Synthetic Aperture Magnetometry (SAM). This important field of research remains high on the agenda at Aston.
Working with gastro intestinal (GI) physiologists, researchers have characterised activation in the cortex of the brain, associated with abdominal pain such as in the gut. This information can provide a valuable model for the evaluation of pain incorporating autonomic nervous system measures. These can then be used to further explore measures of pain sensitisation and regulation.

Around a tenth of the UK population suffer Functional Gastrointestinal Disorder (FGD) the commonest symptom of which is GI pain. However differences between members of this group and a lack of clinical investigation mean that the origin of the pain often goes undiscovered. It has been suggested that these pains are a result of either an actual sensitivity which exists due to previous injury or inflammation in the gut, or that there is abnormal processing of abdominal sensation in the brain as a result of psychological abnormalities. Researchers plan to test, using models of oesophageal hypersensitivity, for the individual differences between patients with unexplained GI pain in whole human studies. MEG will be used to measure cortical activity in order to distinguish activity evoked by an actual stimulus from outside the body, from activity which is induced in anticipation of a stimulus.

Neurodevelopment and clinical research

The Aston University Neuroimaging Research Centre considers two aspects of translational research; to apply basic research to address clinical questions and to seek alternative approaches to animal experimentation. Studying neurodevelopment through linking brain changes to behaviour allows the improvement of diagnosis and treatment in disorders unique to humans.
Studying cortical networks which underlie languages and assessing language functions in both the left and right hemispheres would prove valuable in pre-surgical evaluation. Current invasive techniques cause temporary paralysis and speech arrest which can be distressing and complications do occur in a small percentage of patients. The need for individual evaluation of patients is evident as large differences were detected between adult participants in a word generation task when analysed with SAM. This method allows easy estimates of laterality in brain hemispheres by simple visual inspection of SAM analysis without having to rely on a calculated index. This is valuable to safeguard the language areas during brain surgery.
1.Human brain: The next frontier: http://humanitieslab.stanford.edu/2/372 (accessed 9/1/08)

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