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.

research money well spent

news flash: emotions sometime trump rational thought! Shocking, I know. Though I was intrigued at how the fMRI paradigm in this case provides a neat empirical example for why prisoner’s dilemma models don’t translate well into real-world practice:

A classic economic example is the “ultimatum game,” in which one participant gets 10 $1 bills (or loonies, in Canada). He chooses how many to offer to a second participant. If she accepts the offer, the money is split the way the first participant suggested; if she rejects the offer, nobody gets anything.

Logically, the first participant can maximize his money by offering a single dollar, because logically the second participant should accept that as being better than nothing. In real life, however, the second participant, if offered only a dollar or two, almost always rejects the offer.

Functional MRI scans of brain activity show that a low offer stimulates an area associated with negative emotions, including anger and disgust. It seems the second participant would rather punish the first participant for making such an insulting offer than make an easy buck. And usually, the person making the offer understands this and offers something close to an even split, averaging about $4.

I don’t really see why the above reasonable decision-making process is inherently non-rational or “emotional” though. Doesn’t it make good rational sense to “punish” someone making a lowball offer, so they are motivated to offer you more up front?

Scientists trying to read your mind?

Did anyone else see this article? I came across it on – “Scientists Try to Predict Intentions: using brain scans to read minds before thoughts turn into actions” (

I haven’t read anything Dr. Haynes has published in peer-reviewed journals on the topic (I’ll see what I can find) but this seems like another case of popular media grossly over-estimating (or mis-estimating?) the significance of the research. Take this excerpt:

But scientists are making enough progress to make ethicists nervous, since the research has already progressed from identifying the regions of the brain where certain thoughts occur to identifying the very content of those thoughts.

Although I think my favorite part is the opening paragraph, where the author writes:

At a laboratory in Germany, volunteers slide into a doughnut-shaped MRI machine and perform simple tasks, such as deciding whether to add or subtract two numbers, or choosing which of two buttons to press.

They have no inkling that scientists in the next room are trying to read their minds — using a brain scan to figure out their intention before it is turned into action.

Um…I think the first “inkling” that something is amiss is when these evil scientists ask you to step inside their big shiny machine. Perhaps I’m overly-critical. I still think articles like this are amusing, but it makes me cringe when I think that this is the public’s view of MR research. Any other opinions?

brain scans and superbowl ads

I am sure that this experiment was initially conceived by grad students:

FMRI scans while watching superbowl ads

FKF Applied Research and the UCLA Ahmanson Lovelace Brain Mapping Center have released their Second Annual Ranking of the most effective Super Bowl ads using fMRI (functional Magnetic Resonance Imaging) brain imaging. Many of the Super Bowl ads stoked regions of the brain associated with anxiety, including the amygdala.

Compared to last year’s ads there was much more anxiety, and far less positive emotion in these highly touted commercials. “This clearly was the year of the amygdala, the brain’s ‘threat detector,” said Dr. Joshua Freedman UCLA Clinical Assistant Professor of Psychiatry and a co-founder of FKF Applied Research. “Much of the anxiety seemed caused by violence, but was also rooted in economic fears. The Nationwide ad had a spike when Kevin Federline was revealed to be working in fast food, and also when the GM robot turned out to be OK but afraid for its job.”

FKF Applied Research and Dr. Marco Iacoboni’s group at the UCLA Ahmanson Lovelace Brain Mapping Center recruited men and women ages 18-34 to watch this year’s Super Bowl ads. The subjects viewed the ads while in UCLA’s high-field fMRI scanner, which monitors the activity in their brains.

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