Functional MRI (fMRI) scans, long considered a direct window into brain activity, may provide an incomplete picture because blood flow signals are driven by two distinct, opposing populations of neurons. According to a study published in Nature by researchers at University College London, blood volume fluctuations represent the combined output of “Arousal+” neurons, which activate during excitement, and “Arousal-” neurons, which quiet down. This discovery suggests that while blood flow accurately tracks total neural energy, it cannot distinguish between these two underlying cellular states without additional data.
Why Does Blood Flow Not Always Equal Neural Activity?
For two decades, neuroscientists have used blood flow as a proxy for neural firing. While higher neural activity generally requires more oxygen—leading to increased blood flow—the relationship is more complex than previously assumed. Agnès Landemard, a postdoctoral fellow at University College London and the study’s first author, notes that earlier research relied on “bulk measures” of average firing rates. These averages often cause signals to cancel each other out, masking the richer, more nuanced dynamics occurring within specific brain regions.
How Do Arousal+ and Arousal- Neurons Influence Brain Mapping?
The study, conducted by Matteo Carandini and Kenneth Harris, identified that the brain contains two populations of neurons that react differently to arousal. As mice transitioned between rest and movement, these populations displayed inverse activity patterns. The team found that predicting blood flow based on an average firing rate was inaccurate. However, when they modeled the two populations separately, their predictions became “rock-solid,” according to Carandini. The variations in blood-flow-to-neural-activity ratios observed across different brain regions in past studies are likely caused by the varying proportions of these two neuron types in those specific areas.
What Are the Implications for Future Brain Imaging?
The inability to “work backward” from blood volume to specific neural activity presents a significant hurdle for fMRI research. Currently, scientists can observe an increase in blood flow and confirm that neurons are firing, but they cannot determine which population is responsible. Carandini compares this to listening to a crowd at a sports arena; while you can hear a roar, you cannot distinguish whether the home fans are cheering or the away fans are groaning. Without secondary information—such as the regional distribution of these two neuron types—fMRI data remains inherently ambiguous.
Pro Tip: Looking Beyond the Scan
Future brain mapping initiatives may need to integrate multi-modal data. By combining traditional fMRI with advanced techniques that measure neuromodulators like serotonin, researchers hope to better characterize the identity and function of these two distinct neuronal populations.
Frequently Asked Questions
- Why is it difficult to interpret fMRI scans?
Because blood flow is a one-dimensional signal that represents the combined activity of two different, often opposing, populations of neurons. - What are Arousal+ and Arousal- neurons?
These are two groups of brain cells identified by researchers at University College London. Arousal+ neurons increase activity during arousal, while Arousal- neurons decrease it. - Are these neurons only found in specific brain areas?
No, the study found these populations distributed throughout the entire brain, including in visual and auditory cortices.
The research was supported by the Simons Collaboration on the Global Brain and the International Brain Lab. For more updates on neuroscientific breakthroughs, subscribe to our weekly research newsletter or browse our archive of brain science reports.
