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.

MRI of acute Wiiitis

Magnetic resonance imaging of acute “wiiitis” of the upper extremity.

We present the first reported case of acute “wiiitis”, documented clinically and by imaging, of the upper extremity, caused by prolonged participation in a physically interactive virtual video-game. Unenhanced magnetic resonance imaging (MRI) demonstrated marked T2-weighted signal abnormality within several muscles of the shoulder and upper arm, without evidence of macroscopic partial- or full-thickness tearing of the muscle or of intramuscular hematoma.

Nett MP, Collins MS, Sperling JW. Skeletal Radiol. 2008 May;37(5):481-3. PMID 18259743.

It was really just a matter of time… the floodgates are now open. I expect that the musculoskeletal specialists are eagerly anticipating the release of the Wii Fit

Paul Lauterbur dies at age 77

The father of Magnetic Resonance Imaging passed away on Tuesday:

Physicist Paul C. Lauterbur, who received a 2003 Nobel Prize in Physiology or Medicine for giving physicians the ability to look inside the human body without using harmful radiation, died Tuesday at his home in Urbana, Ill.

He was 77 and had been suffering from kidney disease.

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?

PET and MRI

An editorial in the Journal of Nuclear Medicine (J Nucl Med. 2007 Mar;48(3):331. PMID: 17332606) argues that combination PET/MRI systems are the future and will supplant PET/CT:

In a number of ways, the path to PET/MRI has been reverse of that to PET/CT. The first PET/CT design emerged from industry–academia collaboration and was a prototype for human clinical use that eventually stimulated a commercial response and led to the development of PET/CT for imaging small animals. In contrast, PET/MRI began with the small-animal design and then, over a decade later, the first PET/MRI brain images were acquired on a dedicated prototype system, following an impressive industrial backing that far exceeded that of the early PET/CT developments.
[…]
A mere 2 y after the advent of commercial PET/CT, Johannes Czernin from UCLA, at the 2003 annual DGN meeting, commented that “PET/CT is a technical evolution that has led to a medical revolution.” Today, at the dawn of PET/MRI, it may be said that “PET/MRI is a medical evolution based on a technical revolution.” Although PET/CT appears to have replaced stand-alone PET for most oncologic indications, it is reasonable to assume that PET/MRI will be the preferred imaging option for neurologic and central nervous system indications. Without doubt, such dual-modality combinations are here to stay because they incorporate the diagnostic power of PET. Thus, PET/CT and PET/MRI, by virtue of their combined anatometabolic imaging, will lead to a “new-clear” medicine and the demise of “unclear” medicine.

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NSFW MRI: Sex at 1.5T

That’s “not safe for work”, not “national science foundation” up there in the acronym. It was surely inevitable that this amazing, subtle and elegant technology would eventually be applied to more scatological pursuits. The following paper is a classic in this genre.

Magnetic resonance imaging of male and female genitals during coitus and female sexual arousal.

OBJECTIVE: To find out whether taking images of the male and female genitals during coitus is feasible and to find out whether former and current ideas about the anatomy during sexual intercourse and during female sexual arousal are based on assumptions or on facts. DESIGN: Observational study. SETTING: University hospital in the Netherlands. METHODS: Magnetic resonance imaging was used to study the female sexual response and the male and female genitals during coitus. Thirteen experiments were performed with eight couples and three single women. RESULTS: The images obtained showed that during intercourse in the “missionary position” the penis has the shape of a boomerang and 1/3 of its length consists of the root of the penis. During female sexual arousal without intercourse the uterus was raised and the anterior vaginal wall lengthened. The size of the uterus did not increase during sexual arousal. CONCLUSION: Taking magnetic resonance images of the male and female genitals during coitus is feasible and contributes to understanding of anatomy.

Schultz et al, BMJ. 1999 Dec 18-25;319(7225):1596-600. PMID 10600954.

Continue reading “NSFW MRI: Sex at 1.5T”