Sunday, August 12, 2018

Improved Brain Health for All! (update on the BRAIN initiative)


adapted from Figure 3 (Koroshetz et al., 2018). Magnetic resonance angiography highlighting the vasculature in the human brain in high resolution, without the use of any contrast agent, on a 7T MRI scanner. Courtesy of Plimeni & Wald (MGH). [ed. note: here's a great summary on If, how, and when fMRI goes clinical, by Dr. Peter Bandettini.]


The Journal of Neuroscience recently published a paywalled article on The State of the NIH BRAIN Initiative. This paper reviewed the research and technology development funded by the “moonshot between our ears” [a newly coined phrase]. The program has yielded a raft of publications (461 to date) since its start in 2014. Although the early emphasis has not been on Human Neuroscience, NIH is ramping up its funding for human imaging and neuromodulation.



They've developed a Neuroethics Division, because...
...neuroscience research in general and the BRAIN Initiative specifically, with its focus on unraveling the mysteries of the human brain, generate many important ethical questions about how these new tools could be responsibly incorporated into medical research and clinical practice.

I don't think most of the current grant recipients are focused on “unraveling the mysteries of the human brain”, however. They're interested in cell types, circuit diagrams, and monitoring and manipulating neural activity in model organisms such as Drosophila, zebrafish, and mice. There are aspirations for a Human Cell Atlas, but many of the other tools are very far away (or impossible) for use in humans.

- click on image to enlarge -



Some aspects of the terminology used by Koroshetz et al., (2018) are vague to the savvy but non-expert eye. What is a neural circuit? The authors never actually define the term. You'll get different answers depending on who you ask. We know that “individual neuroscientists have chosen to work at specific spatial scales, ranging from .. ion channels ... to systems level” and we know there is a range of temporal scales, “from the millisecond of synaptic firing to the entire lifespan” (Koroshetz et al., 2018):
Within this diverse set of scales, the circuit is a key point of focus for two primary reasons: (1) neural circuits perform the calculations necessary to produce behavior; and (2) dysfunction at the level of the circuit is the basis of disability in many neurological and psychiatric disorders.

So maybe key point #1 is a generic working definition of a neural circuit, and is the focus of many NIH BRAIN-funded neuroscientists. But there's a huge leap from the impressive work on e.g. mapping, manipulating, and controlling stress-related feeding behaviors in rodents, and key point #2: isolating circuit dysfunction and ultimately treating eating disorders in humans. There is a lot of “promise” and many “aspirational goals”, but the concluding sentence is just too aspirational and promises too much:
With diverse scientists jointly working in novel team structures, often in partnership with industry, and sharing unprecedented types and quantities of data, the BRAIN Initiative offers a unique opportunity to open the door to a golden age in brain science and improved brain health for all.

The research that gets closest to bridging this gap is electocorticography (ECoG) and deep brain stimulation (DBS) in human patients.1 The exemplar cited in the NIH paper is by Swann et al. (2018), and involved testing a closed-loop DBS system in two Parkinson's patients. The Activa PC + S system (Medtronic) is able to both stimulate the brain target region (subthalamic nucleus, STN) and record neural activity at the same time. The local field potential (LFP) activity is then fed back to the stimulator, which adjusts its parameters based on a complex control algorithm derived from the neural data.

Fig. 4 (Swann et al., 2018). Adaptive DBS.


The unique aspect here is that the authors recorded gamma oscillations (60–90 Hz in this case) from a subdural lead over motor cortex to adjust stimulation. In earlier work, they showed this gamma power was indicative of dyskinesia (abnormal, uncontrolled, involuntary movement), so STN stimulation was adjusted when gamma was above a certain threshold. The study demonstrated feasibility, and its greatest benefit at this early point was energy savings that preserved the battery.

It's cool work that has been promoted by NIH, but unfortunately the first author was not mentioned in the press release, not featured in the accompanying video, and her name isn't even visible on a shot of the poster that appears in the video.2  [the last author gets all the credit.]

Future NIH BRAIN studies will address essential tremor, epilepsy, obsessive-compulsive disorder, major depressive disorder, traumatic brain injury, stroke, tetraplegia, and blindness (apparently).


Returning to key point #1, some have criticized the distinct lack of emphasis on behavior, which echos recent papers (see An epidemic of "Necessary and Sufficient" neurons).


The next tweet is critical too, and an interesting discussion ensued.


And given all the technology development funded by BRAIN, it's a great time to be a neuroengineer, but not a neuropsychologist, ethologist, or behavioral specialist.
Indeed, the BRAIN Initiative funded an equal number of investigators trained in engineering relative to those trained in neuroscience in 2016 (Koroshetz et al., 2018).

Footnotes

1 DARPA is the biggest investor here.

2 We interrupt the NIH press coverage of this paper to acknowledge the first author, Dr. Nicki Swann. Dr. Swann and many of her female colleagues have described the difficulties of traveling and attending conferences while being a new mother, and offered some possible solutions. If the BRAIN Initiative is serious about addressing Neuroethics (for animals and futuristic sci-fi applications to human patients), they should also be actively involved in issues affecting women and minority researchers. And I imagine they are, it just wasn't apparent here.


References

Koroshetz W, Gordon J, Adams A, Beckel-Mitchener A, Churchill J, Farber G, Freund M, Gnadt J, Hsu N, Langhals N, Lisanby S. (2018). The State of the NIH BRAIN Initiative. Journal of Neuroscience Jun 19:3174-17.  NOTE: this should really be open access...

Swann NC, de Hemptinne C, Thompson MC, Miocinovic S, Miller AM, Gilron R, Ostrem JL, Chizeck HJ, Starr PA. (2018). Adaptive deep brain stimulation for Parkinson's disease using motor cortex sensing. J Neural Eng. 15(4):046006.

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