Functional imaging of the brain has opened new avenues for answering questions about the underpinnings of human behavior. Current methods rely on measuring changes in blood oxygen levels in the brain, which is thought to correlate with neural activity. But now scientists have proposed measuring another factor that varies with brain activity: acid levels.

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When neuronal activity increases, pH-lowering lactic acid and carbon dioxide are produced. These pH fluctuations can have dramatic effects throughout the brain by acting on pH-sensitive receptors and channels, which play critical roles in synaptic plasticity, learning, memory, pain and neurodegeneration. John A. Wemmie and colleagues at the University of Iowa in Iowa City have previously shown that increased acidity, or low pH, in the brain is linked with panic disorders, anxiety and depression and that pH fluctuations are associated with normal brain activity as well. However, there are currently no non-invasive ways of measuring pH changes in the brain.

Using a magnetic resonance imaging (MRI) strategy, Wemmie and collaborator Vincent Magnotta have developed a technique that can detect pH changes in the live brain (Proc. Nat. Acad. Sci. 109, 8270–8273; 2012). First testing the method in mice, they systemically manipulated carbon dioxide or bicarbonate levels, which decrease and increase pH, respectively, and used a pH sensor implanted into the mouse amygdala to test the accuracy of their MRI measurements. The MRI-based imaging method was sufficiently sensitive to detect widespread pH changes in the mouse brain just as accurately as the implanted sensor. Later, they instructed a human subject to alter his brain pH levels by changing his breathing rate while in the MRI scanner, and the technique was accurate at detecting these pH changes as well.

Next, the researchers wanted to test the idea that local changes in brain activity could be measured using the pH-sensitive MRI technique just as well as when using methods that measure blood oxygenation levels. When human participants were shown a flashing checkerboard, both the pH-sensitive MRI signal and the blood oxygenation–sensitive signal were observed in the participants' visual cortex.

The scientists argue that pH measurement may be more accurate for quantifying neural activity than the blood oxygenation method, because only the pH-sensitive MRI signal changes in a linear fashion in response to change in pH level. Additionally, the technique is far more spatially and temporally accurate than current methods of measuring brain pH changes, making it crucial to advancing our knowledge of the role of pH dynamics in brain function.