Title: Development of human EEG-ASL-BOLD neuroimaging and math modelling framework to quantify neuronal, haemodynamic and metabolic responses to stimulation
Funder: Engineering and Physical Sciences Research Council

Abstract: Human neuroimaging is the science of measuring brain function non-invasively, meaning without physically entering the body in any way. This collaboration between researchers at the Universities of Birmingham and Nottingham will develop new imaging techniques and mathematical models to improve understanding of the biological meaning of human brain imaging measurements.Studying the function of the healthy human brain is vitally important. Improving knowledge of normal brain function helps the understanding of what goes wrong in the diseased brain and aids medical diagnoses, drug design and treatment for disorders such as stroke, epilepsy, Parkinson's, and Alzheimer's.The functional magnetic resonance imaging (FMRI) technique is crucially important because it can accurately pinpoint the brain regions that are active when we experience sensations and feelings, or perform an action such as grasping a cup or watching a movie. Conventional FMRI uses a method that is sensitive to changes in both blood flow and the level of oxygen in the brain's blood (BOLD). A second less-common FMRI method, called ASL, provides absolute measurements of the delivery of nutrient blood to the brain's signalling cells, called neurons. However, both BOLD and ASL responses take 5 seconds to reach their maximum level. Obviously, brain processes occur on a much shorter timescale. A third technique called electroencephalography (EEG) directly records the electrical activity of neurons from electrodes on the patient's scalp. EEG provides information on when different parts of the brain are active with millisecond precision.These three techniques are widely used in brain research and increasingly in clinical practise. However, none of them alone provides a conclusive measurement of brain activity. Accurately identifying unique brain sources of the EEG signal is often not possible. Changes in BOLD signal can be measured that are caused only by differences in blood flow without any change in electrical signaling. Without an EEG measurement of that event the researcher would not know that it was a 'false' BOLD response, and without an ASL measurement of blood flow the researcher would not know why it was a 'false' BOLD response.This research project will overcome these limitations by developing combined EEG-BOLD-ASL as a multi-dimensional imaging technique. Simultaneous EEG-BOLD-ASL measurement will provide a more complete picture of the changes in blood flow, energy usage and electrical activity that occur when neurons are signaling.Mathematical models of the coupling between changes in blood flow, neuronal activity and brain energy usage will be used to re-create brain imaging results on computers. These models are simplified versions of the biological reality but are based on well-founded assumptions from scientific literature. The models output will be compared to real EEG and fMRI data to help understand the significance of individual biological variables in creating the observed brain signals.The proposed imaging development is crucial as EEG and ASL measurements are required so that models can be used to extract physiological variables from the combined signals. Only by combining multi-dimensional imaging with modelling can we untangle some of the factors that influence the BOLD signal, enabling a much more detailed description of the processes accompanying neuronal activity to be made.This project ultimately aims to answer two very important questions that are currently poorly understood: 1) What common aspects of brain activity are represented in the measurements made by EEG and FMRI? 2) What is the relationship between the brain's energy usage and the neuronal activity measured by EEG?A better understanding of the relationship between EEG and FMRI signals will help all researchers and clinicians that use these methods individually and improve our interpretation of healthy brain imaging signals and how they change with aging and disease.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: NEUROLOGICAL