National Antivisection Society
On the frontline of neuroscience
6 December 2007
Lord Dowding Fund’s support for the Magnetic Resonance Imaging facility at Aston University is currently our biggest annual grant and came about when we saw the rising trend of neurological research on primates and other animals. We are now seeing the fruits of this bold move with Aston’s first MRI graduates, and the work of the LDF-sponsored facility is starting to appear in the science journals. Whilst scientific dinosaurs may still want to put electrodes into the heads of rats and monkeys, the future of neurological research has arrived – and we are ensuring it becomes a reality.
It is predicted that there will be a rise in mental ill health and neurodegenerative diseases in our ageing population, as people are living longer. Therefore, increasing understanding of these conditions is considered to be vital. The neuroscience facility at Aston University utilises the very latest technology to enable real time noninvasive human studies. No more disastrous species differences. Welcome to the fast track to the human brain.
The human condition can be understood by linking brain changes to behaviour and determining how activities in nerve networks lead to behaviour. By studying the traits and attributes of neurodevelopmental disorders, such as Parkinson’s and Alzheimer’s, individual diagnoses and treatments can be developed. Neuroimaging can be carried out on humans without ill effect. It is also possible to monitor the progression of neurodegenerative disease in patients with brain imaging at different stages of the illness – something impossible in dissected animal brains.
The Neuroimaging Research Group at Aston University has gained an international reputation in developing novel approaches to modelling and analysing the biological processing of neuronal communication in the brain. The techniques apply to a wide range of human studies and aim to improve diagnosis, therefore aiding treatment and surgical intervention. The scope of the work is being expanded with links to clinicians in hospitals, including Great Ormond Street, Kings College, Sick Children’s (Toronto), Royal London and Barts.
Vision projects
These projects bridge the gap between microscopic descriptions of cell functioning and macroscopic, behavioural observations by relating behaviour to neural functioning in the cortex. Researchers achieve this by using tests involving physical stimuli and the resulting mental state and behaviour.Visual stimulus response in humans was then compared with published primate experiments: The study showed that behavioural responses to different visual stimuli in participants were distinct and representative of electrical brain activity measured in that subject. It had been assumed from previous primate research that such changes could only be detected by invasive microscopic observation of neurones (nerve cells). This means that not only can data be collected from the correct species (humans) but at a level of detail that the vivisectors had previously claimed was only possible with invasive animal tests.
Auditory, Speech, Language
These projects range from simple tone to complex speech experiments. Low-level auditory processing projects seek to make a correlation between magnetoencephalogram (MEG) data, which shows measures of the magnetic field in the brain, and the functions of the nerve network. Speech and language research looks at functions measurable only in the human brain.Auditory cortical responses to amplitude and frequency:
Researchers aimed to use MEG to demonstrate how networks of human neurons interact, when we process sound. By contrast, animal model auditory research has historically focused on single-unit responses to stimuli, not the interaction of neurones. An understanding of mental processing (cognition) and sensory perception may lead to an understanding of auditory and human speech perception.
Investigating the neurophysiology of speech perception:
Sinewave speech is a form of artificially degraded speech 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 how speech perception is biologically underpinned.
Cognition and Neuropharmacokinetics
Psychotropic agents are drugs which affect mental activity, perception or behaviour. Their effect on attention and working memory are being measured at Aston using cognitive tasks and their results. This information presents the opportunity to study the effects of nutritional supplements and drug activation.Cognitive function in anaemia:
Two groups of participants – excellent or poor performers in a visual information processing task (the Balkan task) – were compared to anaemic patients. MEG and MRI structural scans were studied and revealed higher magnitudes of brain activity consistently throughout the task in excellent performers, less activity in poor performers and considerably more reduction in anaemic people. It was found that anaemic people scored the worst. The results suggest that people with anaemia have a failing component of the working memory or a failure to bring together various cognitive components of the memory.
Investigating 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. The researchers now have an MEG drug profile of diazepam which can be compared to other studies – an entirely new approach to pharmacological imaging. The specifics of diazepam induced changes in therapy were also considered, as well as the potential application of this method in drug development, neuronal network investigation and microdosing.
Pain processing
Working with gastrointestinal physiologists, researchers at Aston University have characterised activation in the cortex of the brain in association 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.Measuring the influence of psychotropic drugs:
Developing techniques in MEG and Magnetic Resonance Spectroscopy (MRS), researchers are measuring the influence of psychotropic drugs on brain mechanisms and the functions underlying pain and pain relief medications. The mechanisms which cause the variation of pain experienced in people taking opioid pain killers, such as remefentanil, are unknown. It is hoped that the influences of pain perception, such as emotion, will be understood and the knowledge used to improve treatment for those who respond poorly to painkillers.
Neurodevelopment and clinical research
Studying neurodevelopment through linking brain changes to behaviour allows the improvement of diagnosis and treatment in illnesses unique to humans. In a case study of presurgery assessment of language and memory, a young patient undergoing temporal lobe brain surgery participated in functional imaging of brain areas involved in language and memory. This study showed the value of noninvasive imaging techniques in localising language and memory functions for preand post-surgical evaluation. This research allowed the team to assess the patient and find specific areas in the temporal lobe and avoid those which perform language and memory functions. They were then able to evaluate brain functioning in these after the operation. This technique may eventually replace techniques such as the Wada test, which creates a lesion in the patient’s brain with a risk of partial paralysis.Akanuma, N. et al (2003), “Presurgical assessment of memory-related brain structures: the Wada test and functional neuroimaging,” Seizure, 12: 346-358.
Desmond, J. E. et al (1995), “Functional MRI measurement of language lateralization in Wada-tested patients,” Brain, 118: 1411-149.
Replacing animals in education
Workshop takes computer simulations to Serbia, Bosnia/Herzegovina, Montenegro, Croatia, Macedonia and Greece.
Worldwide, hundreds of thousands of mice, rats, frogs and rabbits continue to be used in teaching each year, so we are committed to developing and promoting nonanimal resources. A two-day workshop was held at the University of Belgrade, entitled ‘Replacing Animal Use in teaching in Balkan Universities’, and attended by 110 professors, senior researchers and lecturers. Participants signed an agreement that each university would integrate at least one of the 17 computer-based alternatives into their teaching within one year and evaluate its usefulness. Data was gathered on animal use in teaching in Balkan universities via a questionnaire, which will be analysed and published in a Serbian scientific journal.
The workshop examined implementation of the alternatives and aimed to establish a network of teachers who are inclined to use them, with another meeting scheduled. The impact of the workshop should be widespread, as there were representatives from 14 universities from Serbia, Bosnia & Herzegovina, Montenegro, Croatia, Macedonia and Greece. Participants were provided with a software kit of the 17 computer programmes and printed material.
Promoting CAL in Japan
Professor David Dewhurst recently presented his Lord Dowding Fund-sponsored work on computer-aided learning (CAL) at the 6th World Congress on Alternatives and Animal Use in Life Sciences, in Japan.
Professor Dewhurst addressed whether it is possible to meet all the learning objectives of undergraduate pharmacology classes with nonanimal models. Professor Dewhurst has been developing creative solutions to improve the lifespan of computer alternatives as well as their ability to adapt to teachers’ needs. Computer simulation programmes are a viable alternative to traditional animal experiments. However, keeping them up-to-date and compatible with other methods can be expensive and resource-intensive.
The RECAL project, funded by our LDF since 2004, splits the present CAL programmes(CALs) into smaller learning objects (LOs), enabling easier modification, sharing and reuse of information. Nineteen CALs have been processed with RECAL, generating around 2,000 revitalised LOs. Authorised users can download Los, modify them and upload new LOs to share within the pharmacology academic community.
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