I just love books like this. In the shape of the greats, this series from the Dana Foundation allow for quick and easy, but erudite reading of exciting ideas and progress in neuroscience. So paging through, we bump into Chris Nowinski’s Hit Parade, the future of the sports concussion crisis, which of course is a real issue in an America dedicated to its sentinel sports, even when the risks are emerging as so high. Traumatic encephalopathies are so troubling, leading young men to commit suicide, and yet to be thoughtful enough to donate their brains to science, asking science to explain what went wrong, what destroyed their lives.  As the author says, looking at the implication of the studies coming out now for our children, that they should play sports built around the limitations of their brains, not their will to bash others senseless or just rub some dirt in it.

Stephen Lisberger addresses the other side of the coin in neuroscience, that of fraud. We all know of the limitations that have been discussed recently, that of evaluating all of what has gone before as poorly replicated or perhaps all invalid for one reason or another, plagued by difficult methodologies and the limits of neuroimaging, but what of blatant fraud in neuroscience? One actually needs some Yiddish phrases which sound a lot better than the English words shock and horror, but we really do need more dramatic phrases in even contemplating what Lisberger is saying. Psychiatry has produced a lot of discontent, but its old alter ego, Neuroscience was supposed to be more concrete in its neuroepistemology, and not demonstrate flaws in ontological sensibilities. Lisberger notes that fraud is easy to hide, hard to detect, and he has the credentials as an editor to practice this detection. We would all understand the benefits of fraud, and the benefits of being an author of something one’s students may have produced, in a competitive and stressful environment, more intense over the years. The fault is not with the guys who advertise the jobs and demand a long list of prestigious publications, says Lisberger, but with ourselves as scientists, as how we evaluate value in scientists. And of course reviewers are themselves competitive in the field, and so may have subtle biases in what they regard as a threat to their own careers which may emerge from a paper they are reviewing. The answers are suggested to lie in the realm followed by animal experiment activists, with protocols evolving and a different culture emerging to reduce the incidence, small though it may be.

Jane Foster has produced something here that really gets me going, namely all the recent work on the biome of the gut and its effect on the brain. It’s not that this is a new field, with nearly 200 years of work passing by so far since Beaumont noted that mood changes and gut content altered in sync with each other.  So the gut microbiota as a whole, in syncing with multiple other systems in the body and brain, become in the last decade a valued source of data on the top down and bottom up processing of information and the health of the overall system.

Speaking of mood, Raison and Miller take a look at inflammatory processes in depression, since inflammatory biomarkers in the blood attend inflammation, and mainline journals have been engaged in speculation of this for a while (for instance take a look at what Miller and his colleagues wrote in 2009 in Biological Psychiatry Vol 65). And so the cytokines, in particular two of them, Tumor Necrosis Factor and Interleukin VI are the current bogey men, and to a lesser extent CRP, C-reactive protein.  The bug in this system is that inflammatory responses and elevated measures are neither necessary nor sufficient to warrant a judgment about mood, whether elevated markers are present or not. Whilst inflammation may or may not be present, there is a relationship with depression, although depression is NOT an inflammatory disorder. Thus there will be a subgroup of patients with elevated inflammatory markers within their depressive episode and needing some work on those, it seems.  Minor increases in inflammatory markers are sufficient to predict the danger of a whole host of diseases associated with higher inflammatory markers, not just (but including) depressive illness.

Philip Shaw talks about ADHD “ten years later”. This refers to the first findings about 11 years ago now, that there were changes in the brains of kids with ADHD. The cerebellum, some bits of the striatum, and the prefrontal cortex, are the ‘hubs’ in the brain affected by this condition. Whilst ADHD studies with newer methods, e.g. fractional anisotropy have illuminated further on the tracts connecting these hubs, and the difficulties that may arise, something that hides even further is the subject of the next chapter, namely, Lewy Body Disease.

Galvin and Balasubramaniam look at this under-recognized but most common foe, a dementia second in incidence only to Alzheimer’s.  LBD also shares much of the features in many cases, as does Alzheimer’s share some features of LBD and many of the other 98-odd dementias, blurring further in terms of differentiation as the patient declines further. This has implications for medication however, and other interventions, as Parkinson’s Dementia shares the platform with LBD and vice versa. Given 57% of LBD patients will have memory issues, compared to 99% of Alzheimer’s, and with a verbal-non-verbal discrimination between the two illnesses amongst other issues, the differential can be made, although the first diagnoses of LBD I recall coming out in 1961, with full descriptions only in 1996, after which we realized it was NOT a rare disorder at all.  There are no drugs for it as of yet, but given the similarities to PDD, it is a matter of time the authors suggest.

Speaking of drug development, what of psychiatry? Given the STAR-D and CATIE studies demonstrating limitations in success rates of new vs. old drugs, this is a hot topic perennially.  Steve Hyman, past boss of the NIMH, is an ideal writer for this topic, and you might recall his seminal plea for the DSM-V to be enhanced by neuroscience, which fell it seems on deaf ears, leading perhaps to the NIMH vilifying it on its publication. Now he writes of newer drugs. As we all know now, the production of new drugs in Phase IV trials is in serious decline, and the blockbuster drug boom is all but over it seems, apart from companies like Astrazeneca buying new ideas from small competitors. Hyman discusses the past, how accidentally dirty, deliberately clean, and now deliberately dirty medications target various neurotransmitter receptors and uptake mechanisms, but little is advancing in that respect.

Since this book was written, John Freeman’s comment about a relatively unknown diet being a great way to treat some epilepsy is probably moot. The Paleo Diet, high in fat and low in carbs means that protein is burned in the absence of glucose, causing a ketone ‘hum’ or smell, common to those who are now producing ketones. Not just for epilepsy, patients with cancer that I know are also on high fat diets, twice the fat of a McDonald’s happy meal, with good effect, as the Sloan-Kettering Cancer Centre has demonstrated: some cells just love their sugar, and if they can’t get it, don’t function as they used to.  Episodic fasting is also a great help, so the issue is that of glucose-reduction more than the use of the fat in the diet. How does this work in brain tumours such as my friends endure? Cancer cells cannot utilize ketones for energy, but the brain can use glucose and ketones, so functions as usual while the tumour struggles.

The book also takes close peeks at Migraine and Sleep, the endocannabinoid system, the effect on the brain of literacy, and the value of the evolution of risk takers vs the rest of us, all interesting and valuable reading for everyone who picks up this book. A great enhancer of dinner conversation, as well as a great stimulant for reading further, following the authors’ works, and inspiring researchers to make further advances, it comes highly recommended.

© 2014 Roy Sugarman

Roy Sugarman PhD, Director: Applied Neuroscience, Performance Innovation Team, EXOS USA