Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

Ars Technica has a nice writeup about a paper in Nature which isolates the BOLD signal from a specific type of neuron:

With everything in place, the researchers confirmed that firing an impulse in excitatory neurons produced a signal that matched nicely with the ones observed during regular experiments. Putting the channelrhodopsin into inhibitory neurons produced a small BOLD signal in the area where the light triggered an impulse, but it was surrounded by a halo of depressed activity, consistent with the neurons’ inhibitory role.

But the BOLD signals weren’t limited to the area where the light triggered activity. With a slight delay, signals started showing up in other areas of the brain, with the precise locations changing based on where exactly the activity was triggered. The authors indicate that these additional signals provide an indication of the brain’s wiring—the nerves at the site of the initial activity were simply doing what they normally did, and communicating with other areas of the brain. With enough time, they suggest, their technique could be used to map functional connections throughout the brain.

It’s impressive work that really takes aim at the foundation of fMRI and signal origin rather than most of the empirical neurologic applications that we usually see in the literature. I’m sure there must have been some work at this years’ ISMRM that went in a similar direction…

Here’s the full paper in Nature. Abstract:

Global and local fMRI signals driven by neurons defined optogenetically by type and wiring

Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD)1 signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons2. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications3. Using a novel integrated technology unifying optogenetic4, 5, 6, 7, 8, 9, 10, 11, 12, 13 control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKII?-expressing excitatory neurons, either in the neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (ofMRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that ofMRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations14 and fMRI with electrical stimulation that will also directly drive afferent and nearby axons, this ofMRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-used fMRI BOLD signal, and the features of ofMRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.