Imaging Discord in the Brain

The advent of functional brain imaging has revolutionized the fashion in which psychologists and psychiatrists look at the brain. The pictures of behavior-related cerebral activation provide unprecedented information leading to new hypotheses about the workings of our mind.

However, it is of utmost importance to keep in mind that non-invasive functional brain imaging methods do not allow us to record nerve cell activity directly. With positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI), the most-frequently used procedures detect changes in local cerebral blood flow while the participants are exposed to sensory stimulation or execute tasks. Brain cells need sugar and oxygen to fuel the chemical reactions necessary for information processing. Both resources cannot be stored in the brain and thus have to be delivered on demand. Hence, local blood flow increases when nerve cells are activated, resulting in a tight association between nerve cell activity and blood flow under normal physiological conditions.

The molecular mechanisms that couple blood flow to nerve cells activity are not yet fully understood. Glutamate constitutes the predominant excitatory neurotransmitter in the cerebral cortex. This neurotransmitter, its precursors and metabolites as well as its cellular receptors may play a crucial role in the coupling of the two events. However, molecules unrelated to glutamate may also be important. Nitric oxide (NO) and adenosine are known to influence the blood flow response.

In addition to our lack of knowledge on the coupling between the nervous and the vascular response, blood flow measurements inherently cover a volume of brain tissue and do not permit us to identify precisely which nerve cells drive the observed change in flow.

In this week's issue of the journal Nature, Kerri Smith informs us on new findings relevant to the interpretation of functional brain imaging. Yevgeniy Sirotin and Aniruddha Das demonstrate the consequences of the uncertainties discussed above in a letter to Nature entitled "Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity" (Nature 457:475-479). The authors used optical imaging for the fine-grain mapping of changes in blood flow in exposed primary visual cortex of monkeys. The animals were trained to react to a small visual cue. As anticipated, blood flow increased locally in visual cortex after stimulus onset, and the researchers could record concomitantly increased nerve cell activity with wire electrodes inserted into the brain tissue at this location.

Remarkably, blood flow also increased, when the monkeys expected the visual cue to appear, but it was not presented. The anticipation alone was sufficient to significantly increase the local blood flow. By contrast, Sirotin and Das were not able to detect any increase in nerve cell activity that could be related to the anticipatory increase in blood flow.

The apparently discordant findings may not be entirely surprising. The monkeys were accustomed to treats as reward for their participation. Their readiness for the task may have activated neuromodulatory inputs to visual cortex that remain sub-threshold under ordinary conditions and do not trigger nerve cell activity directly, but facilitate the nerve cell response to the imminent stimulus. How such sub-threshold nerve cell signals may increase local blood flow remains an open question.

The discrepancy between blood flow and nerve cell activity Sirotin and Das observed suggests that blood-flow based brain imaging data must be considered with utter prudence, when complex behaviors are examined that involve the subjects' active participation and anticipation. The findings should caution those who strive to correlate patterns of cerebral blood flow with socio-affective mental disorders and criminality in the hope of developing novel predictors for our actions.

Neurolaw is an attempt to associate patterns of brain activity with criminal behavior. Terry Gross interviewed the eminent American neuroscientist Michael Gazzaniga on this issue on National Public Radio's Fresh Air broadcast July 28, 2008. I once wrote down my thoughts on this idea in secret ink. If you wish to spare a few minutes, click on the video, let the magic unfold and enjoy!