Читать книгу Philosophical Foundations of Neuroscience - P. M. S. Hacker - Страница 26

Neural activity in the cortex is reflected in vascular activity

Sherrington began his revolutionary research on the integrative action of the nervous system towards the end of the nineteenth century with an observation that was to have great impact on neuroscience research towards the end of the twentieth century. This was his discovery, with Charles Smart Roy (1854–1897), that there is an intrinsic ‘mechanism for controlling the cerebral circulation … by which the blood supply of various parts of the brain can be varied locally in accordance with local requirements’.⁹¹ They go on to say that ‘We conclude then, that the chemical products of cerebral metabolism contained in the lymph which baths the walls of the arteriole of the brain can cause variations of the calibre of the cerebral vessels: that in this reaction the brain possesses an intrinsic mechanism by which its vascular supply can be varied locally in correspondence with local variations of functional activity.’⁹² This vascular supply provides glucose and oxygen to the brain, in which glucose acts as a source of carbon for oxidization, necessary for the energy required to sustain neuronal electrical activity. Roy and Sherrington had thus discovered that a principal determinant of this energy supply was the activity of the neurons themselves.

Vascular activity can be measured using BOLD brain imaging

Exactly 100 years after this discovery Seiji Ogawa (1934– ) and his colleagues showed that brain nuclear magnetic resonance (NMR) spectroscopy could be used to determine proton signals from water molecules surrounding blood vessels in the brain. As these signals change in the presence of deoxyhemoglobin in the blood they could be used to determine blood-oxygen-level dependency (BOLD) contrast, allowing blood vessels to be imaged non-invasively.⁹³ As they state it, ‘the blood vessels in the image slice appear when the deoxyhemoglobin content in the red cells increases’; further that ‘the blood oxygen level development (BOLD) contrast follows blood oxygen changes induced by anesthetics … that alter metabolic demand of blood flow’.⁹⁴ Following Roy and Sherrington’ s insights, this immediately suggested that the BOLD signal in a particular volume of the brain should vary in proportion to the neurons in that volume that had been activated more or less during the normal workings of the brain. Ogawa and his colleagues immediately put this to the test and showed that the BOLD signals in the primary visual cortex increase when a human is engaged in visual perception.⁹⁵ So changes in local cerebral blood flow and oxygen consumption, indicating changes in metabolic responses, provide a non-invasive method of determining the local neural activity, through the use of what came to be known as functional magnetic resonance imaging (fMRI).

BOLD measurements during psychological tests

At the time of writing (2020) there are 556, 052 papers listed on PubMed that refer to this fMRI technique. These papers are overwhelmingly concerned with detection of BOLD changes in relation to various psychological tests presented to the subject whose head is in the MRI scanner. This procedure is carried out in order to determine the brain region engaged during the particular test, in the hope of providing a functional map of cortical areas supporting the psychological phenomena. It is of interest that Roy and Sherrington’ s comment that the ‘chemical products of cerebral metabolism contained in the lymph which baths the walls of the arteriole of the brain can cause variations of the calibre of the cerebral vessel’ (i.e. the mechanism by which changes in neuronal electrical activity produces changes in blood flow) has still not been elucidated in detail.

BOLD measurements in the absence of psychological tests

An exciting discovery made by Bharat Biswal and his colleagues in 1995 was that coupled BOLD signal variations between different areas of the brain could be detected when the subject was at rest in the scanner, that is when no psychological testing was taking place, indicating what they referred to as ‘manifesting a functional connectivity of the brain’ between these different areas using what is referred to as resting-state fMRI.⁹⁶ Some of these areas showing ‘functional connectivity’ with resting-state fMRI were later shown to be connected by identified nerve tracts. Resting-state measurements have been utilized extensively in the past twenty-five years, with one of the discoveries due to Marcus Raichle and colleagues generating intense interest.⁹⁷ They showed that when a subject in the scanner was lying quietly with eyes closed, particular areas of cortex displayed strong correlated activity, located in the posterior cingulate cortex, precuneus and medial prefrontal cortex; however these areas were depressed when the subject was engaged in goal-directed activity as in a psychological test. Raichle and his colleagues dubbed these areas as constituting a ‘default mode’ network. There has been much speculation concerning the purpose of this network, for example that it supports mind wandering. However this enthusiasm was dampened somewhat with the discovery that the network remains active not only during rest but also when the subject is anesthetized, that is unconsciousness.⁹⁸

Glucose consumption detected in the cortex as a measure of neuronal activity

Louis Sokoloff and his colleagues developed a method of introducing radiolabelled analogues of glucose [¹⁸F-2-deoxy-2-fluoro-D-glucose] at non-toxic levels into the brain so that the concentration of these analogues could serve as a quantitative measure of cerebral metabolism.⁹⁹ The analogue could be ‘used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation – local glucose consumption could be calculated’.¹⁰⁰ This technique now uses positron emission tomography (PET) to determine non-invasively brain regions with high levels of glucose metabolism and therefore of neuron excitability. The technique of using radiolabeled analogues of glucose to measure metabolism was developed well before that of fMRI, and has the advantage of giving a quantitative absolute measure of metabolism compared with the relative measures of activity provided by the BOLD technique, however the latter can follow activity with much better temporal resolution.