Tuning Into the Brain

Oscillations as a mechanism of binding, routing, and selection of thoughts.

The brain is plastic, always wiring and rewiring its neurons, even generating new neurons in some areas. But this plasticity does not come near the speed and scale needed to manage brain function at the speed of thought. At that perspective and scale, our brains are static lumps, which somehow manage to dynamically assemble thoughts, visions, impressions, actions, and so much more as we go about our frenetic lives. It has gradually become clear that neural oscillations, or electrical brain waves, which are such a prominent feature of active brains, serve centrally to facilitate this dynamic organization, joining up some areas via synchrony for focused communication, while leaving others in the dark- unattended and waiting for their turn in the spotlight. 

The physical anatomy of the brain is obviously critical to organizing all the possible patterns of neural activity, from the most unconscious primary areas of processing and instinct to whatever it is that constitutes consciousness. But that anatomy is relatively static, so a problem is- how do some brain areas take precedence for some thoughts and activities, while others take over during other times? We know that, very roughly, the whole brain tends to be active most of the time, with only slight upticks during intensive processing, as seen in the induced blood flow detected by methods such as fMRI. How are areas needed for some particular thought brought into a dynamic coalition, which is soon after dissolved with the next thought? And how do such coalitions contribute to information flow, and ultimately, thought?

Oscillations seem to provide much of this selectivity, and the last decade of research has brought an increasingly detailed appreciation of its role in particular areas, and of its broad applicability to dynamic selection and binding issues generally. A recent paper describes a bunch of simulations and related analytical work on one aspect of this issue- how oscillations work at a distance, when there is an inevitable lag in communication between two areas. 

Originally, theories of neural oscillation just assumed synchrony and did not bother too much with spatial or time delay separations. Synchrony clearly offers the opportunity of activating one area of the brain based on the activity of a separate driving area. For instance, primary visual areas might synchronize rhythmically with downstream areas and thus drive their processing of a sequence of signals, thus generating higher level activations in turn that ultimately constitute visual consciousness. Adding in spatial considerations increases complexity, since various areas of the brain exist at widely different separations, potentially making a jumble of the original idea. But on the other hand, feedback is a common, even universal, phenomenon in the brain, and requires some amount of delay to make any sense. Feedback needs to be (and anatomically must be) offset in time to avoid instant shut-down or freezing. 

Perhaps one aspect of anatomical development is to tune the brain so that certain coalitions can form with useful sequentially delays, while others can not, setting in the anatomical concrete a certain time-delay characteristic for each anatomically connected group. Indeed, it is known that myelination- the process of white matter development during childhood and early adulthood- speeds up axonal conduction, thus greatly altering the delay characteristics of the brain. Keeping these delays tuned to produce usable coalitions for thought could be a significant hurdle as this development proceeds, and explain some of the deep alterations of cognition that accompany it. The opportunity to assemble more wide-ranging coalitions of entrained neurons is obviously beneficial to complex thought, but just how flexible are such relations? Could the speeding up of one possible coalition destroy a range of others?

The current paper simply makes the case that delays are perfectly conducive to oscillatory entrainment, and also that regions with higher frequencies tend to more effectively drive downstream areas with slightly lower intrinsic frequencies, though other relationships can also exist. Both phenomena contribute to assymmetric information flow, from one area to the next, given oscillatory entrainment. The computer simulations the authors set up were relatively simple- populations of a hundred neurons with some inhibitory and most excitatory, all behaving as closely as possible to natural neurons, modestly inter-connected, with some connections to another second similar population, and each given certain stable or oscillatory inputs. Each population showed a natural oscillation, given normal behavior of neurons (with inhibitory feedback) and a near-white noise input baseline that they injected for each population. On top of that, they injected oscillatory inputs as needed to drive each population's oscillations to perform the experiment, at particular frequencies and phases.

The authors manipulated the phase delay between the two populations (small delta), and also manipulated the frequency mismatch between them (called de-tuning, big delta). This led to a graph like shown above, where each has its own axis and leads to a regimes (red) of high entrainment (B) and information transfer (C). The degree of entrainment is apparent in the graphs in D, taken from the respective black points in B, with the driver population in red, the receiver population in blue, as diagramed in A. In this case, practically all the points are in red zones, and thus show substantial entrainment.

While this simulation method appears quite powerful, the paper was not well-written enough, and the experiments not clear enough, to make larger points out of this work. It is one small piece of a larger movement to pin down the capabilities and exact nature and role of neural oscillations in the brain- a role that has been tantalizing for a century, and is at last starting to be appreciated as central to cognition.

Based on the following articles:

• "Transmission delays and frequency detuning can regulate information flow between brain regions"
• "Rhythms for Cognition: Communication through Coherence"
• "Portraits of communication in neuronal networks"

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Who Can be a Shaman? Who Must be a Shaman?

Pasaquan and the modern Shamanism of St. EOM, Eddie Owens Martin.

While not religious, I am fascinated by religion. This mode of thought and experience is obviously instinctive, patently irrational, and strenuously defended and rationalized via theology, apologetics, and other formerly respectable modes of thought, not to mention jihad and other sorts of brute power. We are (mostly) in a much better position today than in the old days when every political system had its state religion, and woe betide anyone caught thinking crosswise. Yet in the even earlier days of our species, religion was much more free-form, and while the instinct of religion is/was shared universally, its expression varied widely among far-flung, isolated peoples. We may generally call it shamanism. The first ingredient was an acceptance that some people care a lot more about spiritual matters than others do. Typically this is because they are misfits, maybe mentally disturbed, and have a heightened appreciation of the unreality of this reality that we think inhabit. Mind-altering drugs provide a glimpse of this widened perspective, and naturally comprise a central part of many shamanistic sacraments.

It is striking how the shared appreciation of an alternate reality, whether though official scripture, traditional dogma, or via ecstatic worship practices or mind-altering drugs, contributes to social bonding and personal psychological healing- which are the ultimate positive impacts of religion. Maybe the starkest naturalistic reality, now that we have evolved to appreciate its full horror, is incompatible with psychic health. Maybe an alternate, colorful, humane, and supportive reality is essential, and is particularly binding and healing if everyone shares it, almost regardless of its particular nature or irrationality. But on the other hand, even religions of intolerance, war, human sacrifice and cannibalism have sustained long-lived cultures, so the binding may take precedence over the humane-ness.

Ideologies and value systems are in play as well. Societies run on particular views of what is right, who counts, what is meaningful, etc. While these touch on empirical reality in some respects, their values and social apparatus are relatively untethered, free to valorize some, deprecate others, and place values on obscure things and odd activities. A misfit will be, by definition, more likely to suffer under the ambient ideology and prone to seek an alternative. Whether the shaman supports the current culture or seeks to subvert it, her work is critical in framing a social ideology that most other members of society hardly even know exists, and are not generally capable of shaping or grappling with consciously.

At its best, shamanism provides more than a narrative or theory about the unseen forces that run the world. It also centers the society with a purposeful narrative of its existence and the essential part each member plays in its continuance. It can heal individuals via the power of this social cohesion- as even medical science is beginning to recognize- since even without any objective medicine whatsoever, the rituals of care, support, and confidence are themselves powerful expressions of our social nature and aids to healing.

But what about today? We are heading into a post-religious world, where neither shamanism nor mainline theology rings true, capitalist ideology reigns, and social atomization is in part the result. It was jarring and intriguing to run across an odd TV program about an autodidactic shaman in Georgia, Eddie Owens Martin, who died in 1986. As a gay man in rural Georgia of the early 1900's, he fled to New York and led an underground life, which led to a career in fortune telling. Eventually he inherited a property in Georgia, and moved back on his own terms, using the proceeds from his fortune telling to build a spiritual retreat / theme park, with ornate decoration throughout.

St. EOM painting from Pasaquan

The connection between fortune telling and other facets of free-form shamanism are obvious. Martin, who renamed himself St. EOM, was obviously a charismatic person, and attracted helpers who attended ceremonies and helped with the painting. There was a hair theme, where Martin thought that he received messages from the gods through hair that had to be pointed upward. After he went bald, he resorted to pointing the ends of his extensive beard to the sky in order to maintain this connection. And what about all the symbology? It seems to consist of benevolent faces and highly colorful geometric designs, as are common in other spiritual and ceremonial settings. It looks like an effort to capture positive and healing material from the archetypes, which are partly eternal, and partly influenced by the culture of the day, where multiracial themes of harmony were coming to prominence.

All this reminded me strongly of two other shamans of the day, Carl Jung and Walt Disney. Where Martin was a spontaneous and demotic shaman, Jung come at it from a scholarly, indeed logorrheic perspective, producing book after book of memories, dreams, reflections, and rationalizations by which he straddled the scientific and credulus approaches to spiritualism. Most evocative was his Red Book, which features highly colorful dreamscapes full of pregnant symbols and meaning, harvested from his forays into the inner world of his own fixations and archetypes.

Lastly, Disney obviously shared the fantasy and dream motivations of Martin, though seemingly without much of the spiritual baggage. Disney was also moved in some mysterious way to make these fantasies concrete by creating theme parks where this positive message of colorful suspension of reality was given relentless and popular expression. These are demotic shamanism on a vast scale, drained of any deeper significance other than the lightest symbology that fleetingly speaks to part of us that hopes for an escape from the humdrum and pressing constraints of reality.

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Mitochondria and the Ratchet of Doom

How do mitochondria escape Muller's ratchet, the genetic degradation of non-mating cells?

Muller's ratchet is one of the more profound concepts in genetics and evolution. Mutations build up constantly, and are overwhelmingly detrimental. So a clonal population of cells which simply divide and live out their lives will all face degradation, and no matter how intense the selection, will eventually end up mutated in some essential function or set of functions, and die out. This gives rise to an intense desire for organisms to exchange and recombine genetic information. This shuffling process can, while producing a lot of bad hands, also deal out some genetically good hands, purifying away deleterious mutations and combining beneficial ones.

This is the principle behind the meiotic sex of eukaryotes with large genomes, and also the widespread genetic exchange done by bacterial cells, via conjugation and other means. In this way, bacteria can stave off genetic obsolescence, and also pick up useful tricks like antibiotic resistance. But what about our mitochondria? These are also, in origin and essence, bacterial cells with tiny genomes which are critically essential to our well-being. They are maternally inherited, which means that the mitochondria from sperm cells, which could have provided new genetic diversity, are, without the slightest compunction, thrown away. This seriously limits opportunities for genetic exchange and improvement, for a genome that is roughly 16 thousand bases long and codes for 37 genes, many of which are central to our metabolism.

One solution to the problem has been to move genes to the nucleus. Most bacteria have a few thousand genes, so the 37 of the mitochondrial genome are a small remnant, specialized to keep local regulation intact, while the vast majority of needed proteins are encoded in the nucleus and imported through rather ornate mechanisms to take their places in one of the variety of the organelle's locations- inner matrix, inner membrane, inter-membrane space, or outer membrane.

The more intriguing solution, however, has been to perform constant and intensive quality control (with recombination) on mitochondria via a fission and fusion cycle. It turns out that mitochondria are constantly dividing and re-fusing into large networks in our cells. And there are a lot of them- typically thousands in our cells. Mitochondria are also capable of recombination and gene conversion, where parts of one DNA are over-written by copying another DNA molecule. This allows a modicum of gene shuffling among mitochondria in our cells. 

The fusion and fission cycle of mitochondria, where fissioned mitochondria are subject to evaluation for function, and disposal.

Lastly, there is a tight control process that eliminates poorly functioning mitochondria, called mitophagy. Since mitochondria function like little batteries, their charge state is a fundamental measure of health. A nuclear-encoded protein called PINK1 enters the mitochondria, and if the charge state is poor, it remains on the outer membrane to recruit other proteins, including parkin and ubiquitin, which jointly mark the defective mitochondrion for degradation through mitophagy. That means that it is engulfed in an autophagosome and fused with a lysozome, which are the garbage disposal / recycling centers of the cell, filled with acidic conditions and degradative enzymes.

The key point is that during the fission / fusion cycle of mitochondria, which happens over tens of minutes, the fissioned state allows individual or small numbers of genomes to be evaluated, and if defective, disposed of. Meanwhile, the fused state allows genetic recombination and shuffling, to recreate genetic diversity from the ambient mutation rate. Since mitochondria are the centers of metabolism, especially redox reactions, they are especially prone to high rates of mutation. So this surveillance is particularly essential. If all else fails, the whole cell may be disposed of via apoptosis, which is also quite sensitive to the mitochondrial state.

In oocytes, mitochondria appear to go through a particularly stringent period of fission, allowing a high level of quality control at this key point. Additionally, mitochondria then go through exponential growth and energy generation to make the oocyte, at which point those which more quality control discards the oocytes that are not up to snuff.

All this adds up to a pretty thorough method of purifying selection. Admittedly, little or no genetic material comes from outside the clonal maternal genetic lineage, but mutations are probably common enough that beneficial mutations arise occasionally, and one can imagine that there may be additional levels of selection for more successful mitochondria over less successful ones, in addition to the charge-dependent rough cut made by this mitophagy selection.

As the penetrating reader my guess, parkin is related to Parkinson's disease, as one of its causal genes, when defective. Neurons are particularly prone to mitochondrial dysfunction, due to their sprawled-out geography. The nuclear genes needed for mitochondria are made only in the cell body / nucleus, and their products (either as proteins, or sometimes as mRNAs) have to be ferried out to the axonal and dendritic periphery to supply their targets with new materials. Neurons have very active transport systems to do this, but still it is a significant challenge. Second, the local population of mitochondria in outlying processes of neurons is going to be small, making the fission/fusion cycle much less effective and less likely to eliminate defective genes and individual mitochondria, or make up for their absence if they are eliminated, leading to local energetic crises.

Cross-section of a neuronal synapse, with a sprinkling of mitochondria available locally to power local operations.

Papers reviewed here:

• "Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline"
• "Avoiding organelle mutational meltdown across eukaryotes with or without a germline bottleneck"
• "Germline selection shapes human mitochondrial DNA diversity"
• "Mitochondrial Fusion, Fission and Autophagy as a Quality Control Axis: The Bioenergetic View"
• "Optimizing mitochondrial maintenance in extended neuronal projections"

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This Starship has Gone off Course

Review of the Star Trek Discovery series.

At risk of outing myself, I do occasionally watch Star Trek franchise material. Their original series was incredibly hokey by today's standards, but contained a beloved kernel of curiosity and adventure, and the franchise later matured into a thoughtful and inspiring series in The Next Generation. The ensuing series, such as Deep Space Nine and Voyager, kept to similar themes, and had fine moments (such as the spiritual environment of Bajor, and its supernatural orbs, within their orb cabinets). The last series of the original franchise, Star Trek Enterprise, was sort of a dull affair, with particularly wooden acting, before it veered, in its last season, into total "war on terrorism" territory with torture and other gratitous violence. My watching of the movies has been spotty, and I won't comment on those, as they are not really at the heart of the franchise, as I see it.

What makes (or made) Star Trek special was its modicum of thoughtfulness and philosophy, in a medium and genre otherwise ridden with thoughtless stereotypes, plots, and action. Its genre originated in the Western, but evolved into something all its own, which now can be endlessly replicated, mocked, and spoofed. While fights, killing, and other elements of typical plots abound, there are also elements of curiosity, scientific pursuit, ethical conundrums, and genuine compassion. It is in some ways a workplace drama, but about people who are all passionate about the work they do, making its world one to look forward to, and its tasks ones of adventure. At its very best, it can interrogate relevant social dilemmas in a way that is distanced enough to be entertaining and novel, while incisive enough to pack a punch.

A lengthy and rich history, but what does the future hold?

The three more recent renditions of Star Trek have included an independent series by Seth McFarlane, (The Orville), and official reboots from Paramount including an animated series (Lower Decks), a Patrick Stewart vehicle (Star Trek: Picard), and its main series, Star Trek: Discovery. The Lower Decks offering has been delightful- a very snappy, funny, and intelligent spoof of the whole Star Trek concept,  (and those who watch it), located on the USS Cerritos, named after perhaps the most uninteresting city in California. Only one season has been put out so far, but it has been superb, and fundamentally consonant with the founding Star Trek ethos.

The Orville series has been perhaps the best of the new bunch, despite not being an official part of the franchise. All the names have been changed- such as a "Planetary Union", in place of the United Federation of Planets. While it was originally conceived as heavy on the humor- some quite juvenile- McFarlane was clearly (and perhaps invountarily) taken with the Star Trek concept, and has progressed, as the episodes went on, to more adventurous and serious plots, ending up with complex time travel and one of the most thrilling episodes of TV I have even experienced (season 2.20, concerning the Kaylons, whose name may derive from the Mary Kay franchise ... who knows?). With the third season, his ambitions may have outstripped his resources, in addition to running into a Covid-induced hiatus. That season may never appear.

Meanwhile, Paramount put most of its effort into the Star Trek: Discovery series. This is set slightly before the original series, and features tremendous production quality, and a typical mixed cast of aliens and ethnicities on the bridge. But something seems to have gotten lost along the way. We are immediately launched into a war with the Klingons, who are now so festooned with makeup that they look like giant toads. Rather than exploring strange new worlds and civilizations, we are cast right into a heart-pounding deathly fight with a baroque enemy, complete with gratuitous torture and operatic pomposity on both sides. It is like we have landed in a Die Hard 2 reboot instead of a Star Trek series. "Discovery", indeed!

One would think that, to an erstwhile fungal researcher, the mycelial spore drive central to the Discovery plots would be a welcome bit of fictional technology. The premise is that an invisible (if sparkly) fungal mycelium pervades the galaxy, allowing suitably tuned neural systems to map it out and then follow its paths by travel that is not warp 5, not warp 10, but instantaneous in time. The crew's first tuned neural system was a humble tardigrade microbe, blown up in the show to monster proportions and strength. Later they develop an interface to a crew member, who sacrifices his sanity to the need for speed. Even given the modest standards of Star Trek tech talk/science-y fiction, all this is absurdly ridiculous. While tardigrades may be able to stand exposure to space, they can hardly live there. Likewise with fungi and their mycelia, (not the same as spores), which need water like anyone else. These technologies are so transparently and carelessly grabbed from decade-old issues of Science News that it is embarrassing. If the writers could not come up with something even remotely plausible, it would have been better to devise a nonsense bit of techtalk, which has a storied history in the franchise.

On the whole, Discovery has been a severe disappointment, at least to someone with minimal tolerance for empty action plots. As of episode 9, I can only watch a few minutes at a time before hitting action-trauma overload. Thankfully, there is streaming. It would be unimaginable to watch this the old-fashioned way, as everyone did who was fortunate enough to see the original series over its first few decades of broadcast and syndication.

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