Title: Looking Inside Your Brain
Abstract: Prof. Magistretti will outline current brain-imaging technology and explore the ethical and societal implications of how, in addition to conventional medical diagnostic applications, it might be sed. He is professor of Neuroenergetics and Cellular Dynamics at the Brain Mind Institute.
Magistretti began his talk by emphaising that despite major developments of neuroimaging techniques and the widespread applications of these technologies, we still have very little understanding of the mechanisms that generate the signals being detectde.
The talk focused mainly on functional magentic resonance imaging (fMRI), but also on positron emission tomography (PET). Both of these detect signals related to changes in the brain´s energy consumption, with fMRI detecting a change in the ration of deoxygenated to oxygenated blood.
Magistretti gave an interesting historical perspective into neuroimaging. He noted that the first imaging device was invented by the Italian 19th century physiologist Angelo Mosso, who invented a device which could detect the “brain pulsations” of patients who had undergone neurosurgery, and who inferred frmo using this device that blood flow to the brain increases during mental activity.
Subsequently, Roy and Sherrington published a paper in 1890 entitled “On the the regulation of the blood supply of the brain”, in the Journal of Physiology. Thus, early researchers were aware of the importance of the brain´s blood supply, and their work laid the foundations for modern neuroimaging.
Magistretti then described the classical mechanism by which the neuroimaging signal was until recently thought to be generated: neurons release vasodilators, which act on the capillaries that in turn transfer energy substrates to the nerve cells. We now know, however, that astrocytes have an important role in regulating cerebral blood flow. They couple neuronal activity with glucose uptake, by somehow detecting changes in nerve cell activity and communicating these changes to the capillaries in the brain via structures called endfeet.
He then described some of his own experiments, which have been conducted on the barrel cortex of rodents, and which clearly demonstrate some of these principles. For example, neuroimaging shows that mechanical deflection of a single whisker on a rodent´s face gives rise to increased acitivity in the corresponding part of the barrel cortex; on the other hand, this signal is completely abolished by decreasing the expression of a glutamate transporter expressed by astrocytes.
Research also shows that astrocytes, like neurons, are organized into functional networks. This can be shown by labelling an individual astrocyte in a cultured brain slice with a fluorescent dye; when the slice is later observed under the microscope, dozens of labelled cells can be observed.
Paradoxically, presentation of a visual stimulus causes an icnrease in visual cortical neuronal activity and an increase in blodo flow to that part of the brain, but there is no commensurate increase in oxygen use. This uncoupling occurs because there is actually a change in the ratio of oxygenated to deoxygenated blood.
This led to the most interesting part of the talk, about the brain´s “default regions”, which remain active when the brain is “offline” (i.e. not engaged in a goal-directed task). These regions, which include the medial prefrontal cortex, posterior cingulate gyrus and precuneus, become less active during mental activity focused on a specific task. This default activity may represent some kind of self’referential mental activity; it is absent in young children, and in patients with Alzheimer’s.
Thus Magistretti argues that the activation of various brain regions detected by fMRI may be just the tip of the iceberg. Basal activity, which occurs when teh brain is not engaged in a goal-directed task, may be equally as important. Exactly what it represents is unclear – it may be produced by the balance of excitation and inhibition, by synaptic plasticity (the activity- and experience-dependent biochemical and structural changes that are thought to underly learning and memory), or by some other non-conscious processes. This activity may be present in unconscious patients – e.g. those in a persistent vegetative state – or those with “locked-in” syndrome, it may encode some kind of internal unconscious reality, and could therefore be of potential use to clinicians who are treating these patients.
The talk concluded with a summary of the future challenges facing neuroimaging researchers: improving the spatial and temporal resolution of the techniques, and developing a way to visualize neuronal activity directly rather than indirectly by means of cerebral blood flow.