Director of Centre
- Prof Tony Morland - Director of the Centre for Neuroscience
Academic and research staff
Exploring links between the EEG alpha rhythm and autism spectrum disorder
Autism spectrum disorder (ASD) affects over 1 in 100 people in the UK. Many theories have been proposed for the cause of ASD but none fully account for this prevalence and the range of observed alterations in cognitive ability and social behaviour. In addition, few quantitative markers exist beyond the complex, interview-based diagnostic procedures currently used. This project explores the use of subtle but highly robust changes in the EEG alpha rhythm in a task and context dependent-manner to attempt to better understand the changes in brain function underlying symptoms seen. We use MEG recordings from volunteers with ASD to provide a detailed map of alpha rhythm generation in the brain. We then combine this with experimental models to uncover the specific neuronal subtypes underlying the alpha rhythm and develop this model using known mutations in neuronal intrinsic conductances to predict subsequent alterations in patterns of communication between different brain areas.
Funded by: The Wellcome Trust
Uncovering the mechanisms underlying subtypes of absence-like seizures
Absence epilepsy is a common type of epilepsy – particularly in children – manifesting as brief loss of consciousness, often without any motor (movement) changes at all. While not as severe as many other forms of epilepsy, they do detrimentally affect qualify of life. Many patients respond well to anti-epileptic drugs (AEDs) but caution is needed in prescribing: Some drugs can be ineffective or even make the seizures worse depending on the type of absence epilepsy presented. Unfortunately spotting which subtype of absence epilepsy a patient has is not straightforward. This project aims to uncover the different mechanisms that can act alone, or in combination, to generate a picture of which neuronal processes underlie which types of absence seizures seen.
Absence epilepsy is associated with patterns of changes in EEG activity commonly termed ‘spike and wave’ (SPW) events. Subtle differences in the type of SPW event represent changes in the activity of different types of neuron in different regions of the brain. This project aims to map these neuronal subtypes and their connectivity profiles, construct experimental models of the different absence seizures associated with them and use these to test the current range of recommended AEDs.
Funded by: The Wellcome Trust
Linking neuronal plasticity to brain dynamics
Our brains are always active, irrespective of whether we are awake or asleep. This activity manifests as dynamic patterns of electrical activity generated by large populations of neurons communicating with each other. This pattern of communication represents the formation of a code for external sensory stimuli (sight, hearing, touch etc.), compare this against what we hold in memory, and ultimately construct appropriate motor output. However, the tasks our brain need to perform during wakefulness and sleep are very different: During the wake-state we have to cope with a bombardment of sensory stimuli. During sleep we ‘revisit’ these stimuli and sort them in a manner that allows us to understand and remember more efficiently our place in the world around us.
It is accepted that neuronal activity changes the strength of connections between neurons in a population – they are ‘plastic’. But the nature of this plasticity remains mysterious. In this project we monitor the expression of immediate early genes – genes that respond rapidly to neuronal activity and flag multiple aspects of plasticity – in neocortex during dynamic signatures associated with sleep (the ‘delta’ or slow-wave brain rhythm) or active sensing in the wake state (the ‘gamma’ or fast brain rhythm). The work is performed using animal and computational models.
Funded by: The Medical Research Council
Quantifying the consequences of neuroinflammation for brain function at the neuronal level
Acute neuroinflammation is an unavoidable consequence of many brain insults including physical trauma cancers and infection. Repeated episodes of neuroinflammation, or long-term activation of inflammatory pathways in the brain, is increasingly recognised as a precipitating factor in neurodegenerative brain disorders such as Alzheimer’s and Parkinson’s disease. There is considerable controversy over how changes in the amount of the many known inflammatory mediators in the brain leads to both acute changes in neuronal function and, ultimately, neuronal death.
In this study we quantify direct neuronal responses to experimentally-applied inflammatory mediators in brain tissue and compare with experimental models of brain metastases and chronic systemic infections. Direct neuronal affects are contrasted with indirect effects via microglial cell activation via a combination of specific pharmacological, electrophysiological and genetic manipulations.
Funded by: The Medical Research Council and Eisai inc.