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News

Bringing brain functions into focus

Max Planck Society : 11 July, 2001  (Technical Article)
Scientists at T
Until now, researchers examining the active brains of humans and animals have been forced to go separate ways. Extremely fine electrodes have made it possible to record signals from small groups of neurons with excellent temporal resolution, but poor spatial coverage. In addition, the use of such invasive techniques is out of the question when dealing with human experimental subjects. On the other hand, functional magnetic resonance imaging, a non-invasive method for measuring brain activity, supplies information on a much larger spatial scale. However, it is still unknown exactly what kind of neural activity is reflected by the blood oxygen level dependent signal measured with this technique. Prof. Nikos K. Logothetis and his colleagues at the Max Planck Institute for Biological Cybernetics in Tübingen have now achieved a fundamental break-through. With a novel experimental set-up they were able to establish that BOLD fMRI provides a precise measure of changes in neural activity. In addition, they were able to show that, above all, the method reflects incoming signals from other brain regions and their local processing rather than outgoing signals to other brain regions. It is now possible to compare electrophysiological data collected from animals with findings in human subjects.

In brain cells, signal transduction always takes place via an incoming signal that is processed in the cell and passed on in a series of action potentials that lead to the release of a chemical neurotransmitter. This in turn acts as a transmission signal to stimulate the next nerve cell(s). Over the last century, progress made in our understanding of signal transmission in the brain has been largely based on the investigation of neuronal function using single electrode recording techniques. One disadvantage of this approach is its severely limited spatial coverage.

Functional magnetic resonance imaging overcomes this spatial restriction by simultaneously sensing activity changes in the whole brain. This technique measures the magnetic field fluctuations that come about when the concentration of deoxyhemoglobin in the blood vessels of the brain changes. This BOLD signal change is widely used to study cognitive brain functions and psychiatric and neurological disorders in humans. But until now, it was not known which physiological processes actually underlie the BOLD signal; ingoing or outgoing.

Nikos Logothetis' research group was able to determine precisely which signal is measured by BOLD fMRI. Until now, the interference between the strong magnetic field of the tomograph and the electrical currents measured at the electrodes has prevented the simultaneous use of electrophysiological recording and fMRI. The researchers were able to overcome this obstacle with a novel experimental set-up using special electrodes and sophisticated data processing methods. Their methodological innovations have enabled them to examine the visual cortex of anesthetized monkeys using three different methods at once: BOLD fMRI and measurements of multi-unit activity and local field potentials.

While fMRI measures changes in blood oxygenation in the brain triggered by increased neural activity, electrode recordings measure interactions between nerve cells in the vicinity of the electrodes. The MUA value largely reflects the outgoing signal of a relatively small group of neurons, while the LFP value is a measure of the incoming signal and signal processing of a substantially larger neuron population.

The data show that the BOLD-signal is more closely correlated with LFP than MUA. According to Logothetis, 'This indicates that a change in the oxygen content (of the blood) is not always connected with an outgoing signal (firing or spiking). On the contrary, BOLD-fMRI reveals stimulus-dependent changes in local field potentials and thus incoming signals from other brain regions and their processing in the corresponding cortical region.'

The combination of electrophysiology and fMRI developed by the Tübingen researchers represents a decisive step forward for both basic and clinical neuroscience. Logothetis comments, 'We won't really understand exactly what individual neurons do and how they do it until we are able to interpret their activity in the context of a task-specific, spatially distributed activation of neural networks - and we can only visualize these with high-resolution imaging methods.'

For the first time, fMRI and electrode recordings have been combined to yield information on two different spatial and temporal skills simultaneously. The combination of BOLD-fMRI and electrophysiology allows us to better understand the relationship between the different physiological parameters measured by these techniques.

But there is one more conclusion that can be drawn from these new findings. Statistically, neural activity is more reliable than the actual BOLD signal itself. 'The result of this is that the usual statistical analysis of human fMRI data underestimates the extent of neural activity in the brain', says Logothetis.
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