Posts Tagged ‘neurobiology’
dyslexia is not one thing 2: structural deficits
the human brain- a very very rough guide
Jacinta: So we’re going to look at earlier ideas about dyslexia, before the recent revolution in neurology, if that’s not being too hyperbolic. These ideas tended to focus on known systems, before there were well-identified or detailed neural correlates. ‘Word-blindness’ was an early term for dyslexia, highlighting the visual system. This was partly based on the 19th century case of a French businessman and musician who, after a stroke, could no longer read words or musical notes or name colours. A second stroke worsened the situation considerably, eventually causing his death.
Canto: An autopsy revealed that the first stroke had damaged the left visual area and part of the corpus callosum, which connects the two hemispheres. It appears that what the man was seeing with his right hemisphere was not able to be ‘backed up’ by the left visual area, and/or connected to the left language area. The second stroke struck mainly the angular gyrus, a complex and vital integrating and processing region towards the back of the brain.
Jacinta: Yes, and before we go on, what we’re doing here is looking in more detail at the four potential sources of dyslexia set down at the end of the previous post. So in this post we’re focusing on 1. a developmental, possibly genetic, flaw in the structures underlying language or vision.
Canto: Right, so there’ll be three more dyslexia posts after this. So this ‘Monsieur X’ case was one of ‘classic alexia’ or acquired dyslexia, and marked an important step forward in mapping regions in relation to the visual and processing aspects of language. Norman Geschwind described it as ‘disconnection syndrome’, when two brain regions essential to a function, in this case written language, are cut off from each other.
Jacinta: The auditory cortex became an important focus in the twentieth century, as researchers noted a problem with forming ‘auditory images’ – which sounds like a problem everyone would have! More specifically it means not being able to translate the images made by letters and phonemes into sounds.
Canto: Yes, so that a word like ‘come’ (which is actually quite complex – the hard ‘k’ followed by an ‘o’ which, orally, is neither the typically short nor long version, followed finally by the silent ‘e’ which has some quite strange effect on the previous vowel) would be quite a challenge. Perhaps the real surprise is that we have no trouble with it.
Jacinta: Yes, I prefer cum myself, but that’s a bit off-topic. Anyway, psycholinguistics, much derived from the work of Noam Chomsky, which came into prominence from the 1970s, tended to treat dyslexia more as specifically language-based rather than audio-visual. Taking this perspective, researchers found that ‘reading depended more on the linguistically demanding skills of phonological analysis and awareness than on sensory-based auditory perception of speech sounds’ (Wolf, p173). This was evidenced by the way impaired-reading children treated ‘visual reversal’ in letters (e.g p and q, b and d). They were able to draw the letters accurately, but had great trouble saying them (sounding them). This appears to be a spoken language problem, which carries over to writing.
Canto: Indeed, it highlighted a problem, which apparently had nothing to do with intelligence, or basic perception, but was more of a specific perception-within-language thing:
These children cannot readily delete a phoneme from the beginning or end of a word, much less from the middle, and then pronounce it; and their awareness of rhyme patterns (to decide whether two words like ‘fat’ and ’rat’ rhyme or not) develops much more slowly. More significantly, we now know that these children experience the most difficulties learning to read when they are expected to induce the rules of correspondence between letters and sounds on their own.
Phonological explanations of dyslexia have resulted in a lot of effective remedial work in recent decades, and a library of research in the field of reading deficits.
Jacinta: Yes, these are called structural hypotheses, noting deficits in awareness of phonemic structure, and phoneme-grapheme correspondences. And these deficits presumably have their home in specific neural regions and wiring. The executive processes of the frontal lobes may be at play, in terms of organised attention, the fixing of memory and the monitoring of comprehension, but also the more ‘basic’ processes of the cerebellum, involving timing and motor coordination. And co-ordination between these regions may also be an issue.
Canto: And, as Wolf points out, these structural hypotheses have sheeted home problems to so many brain regions – the frontal executive function region, the speech region close by, the central auditory region, the language and language/visual integration regions, the posterior visual cortex and the cerebellum – that it would be fair to say that ‘many of the collective hypothesised sources of dyslexia mirror the major component structures of the reading brain’ (Wolf, p176).
Jacinta: Which sounds pretty serious. Why is it happening? And why not for others…?
References
M Wolf, Proust and the squid: the story and science of the reading brain
https://www.kenhub.com/en/library/anatomy/angular-gyrus
20: bonobo and human families, early childhood and free will
ye olde nuclear family, and its enclosures
The bonobo reproduction rate is low, as is ours these days, though for different reasons. Bonobos don’t tend to go all the way, while humans have contraception even for naughty catholics. Muslim scholars seem a little confused about the issue, but are generally more accepting than their catholic counterparts. As to children, humans are rather more possessive about them than bonobos. Bonobo females are largely in charges of the kids, collectively, and paternity is unknown and undisputed. Think about how that would play out in human society, which for millennia has been largely patriarchal, patrilineal and even primogenitive.
This doesn’t mean male bonobos are hostile to kids, as it’s generally a caring and sharing society, and besides, humouring the kids is a good way of winning favours from their mothers and others. Think of how that would be as a kid – you wouldn’t just be able to run to dad when mum’s mad at you, you’d have any number of adults to run to. You’d also have a range of adults to learn from, to identify with, to consider as role models, as well as to play off against each other.
Modern, supposedly advanced human society is very different. We live in separate, securitised houses, in nuclear families – ideally mum, dad and 2⅓ kids – with a garden surrounded by a high fence, if we’re ‘lucky’. The grandparents live across town, or in another country, or a nursing home. Visitors are vetted by smartphone. Of course often it’s a single-parent situation, usually mum, and the odd long- or short-lived boyfriend. She works, so the kids spend a lot of time in day-care, meeting other kids and sharing with them one or two adults, who don’t get too close, wary of being accused of funny business. Rarely are these adults male. Still it’s pretty good, lots of toys and games and things to make and do, all in primary colours, but it’s not every day because it’s too expensive, you (the kid) sometimes get shipped around to aunties or friends or assorted baby-sitters, or you get switched to a new centre, with a whole bunch of strangers, or a kid you really like just disappears. But mostly you’re at home with your stupid brother, until school days arrive and you have to wear a uniform, and mum fusses over you and makes you feel nervous and watchful about whether you look different from the other kids, in a good or bad way. And you learn stuff and you like or hate the teacher and you start competing with the other kids and start thinking about how smart or dumb you are.
Modern human life is pretty regimented. At a certain tender age you go to school where you learn first of all the basics of numeracy and literacy as the first steps toward being civilised. You also learn about rules and regulations, time management and the difference between work and play. Thrown into the school pool of humanity, you’re driven to contemplate and come to terms with variety: fat and skinny, pretty and ugly, noisy and quiet, smart and dumb, friend and enemy and all in between. You learn to make judgments, who to trust, who to avoid, and what to pay attention to. The prefrontal cortex, that amazing human asset, is continuing on its great connective journey, as you negotiate yourself between the formal and the free, between regimentation and independence.
Yet all the research tells us that most of those judgments you make at school, and which you vaguely remember having made, are actually the product of that growth period before the laying down of memories, distorted or otherwise. And that includes your ability to make effective judgments.
In the first few years of life, we form more than a million new neural connections every second. In fact, so many that after this surge of connections comes a period of pruning for order and efficiency. But this early period of development requires stimulation, which comes in infinite varieties of ways, including, of course, the bonobo way (and I don’t mean tree-climbing and chomping on insects), the chimp way (watching adult males battling it out), the Tiwi Islander way or the Netherlands royal family way or whatever. And much of this guided stimulation forms our behaviour for the rest of our lives. And the lack of it can reduce our capacities for a lifetime, in spite of subsequent kindness and care, as the notorious case of the Romanian orphans kept in horrendous states of neglect under the Ceauşescu regime has shown, though interestingly, some 20% of those adopted orphans have grown up showing little or no damage. Stimulation can come from within as well as without, and neglect has many variables.
It stands to reason that we as individuals have little or no control over our development in this crucial period. Which brings me to the issue of free will. Philosophers have traditionally argued for free will on the ‘could have done otherwise’ basis. I could have drunk tea rather than coffee with brekky this morning (though I invariably drink coffee). I could’ve chosen x from the restaurant menu instead of y. So often these trivial examples are given, when it’s screamingly obvious that you don’t get to choose your parents, your genetic inheritance, your early childhood environment, the country or period you were born into, or even the species you were born as (I could’ve snuffed out your brief candle by treading on you in this morning’s walk). Given these restraints on your freedom, restaurant choices surely pale into insignificance.
But let’s stick with humanity. I won’t go into the neurological underpinnings of the argument against free will (as if I could), but if we treat no free will as a given, then the consequences for humanity, vis-à-vis our handling of crime and punishment, are stark, as the neurologist and primatologist Robert Sapolsky points out in the penultimate chapter of his book Behave, entitled ‘Biology, the criminal justice system, and (oh, why not?) free will’. This is a vital issue for me, in terms of a more caring and sharing bonoboesque society, so I’ll reserve it for another essay, or two, or more.
References
InBrief: The Science of Early Childhood Development
https://en.wikipedia.org/wiki/Romanian_orphans
Robert Sapolsky, Behave: the biology of humans at our best and worst. 2017
fountains 4: what’s a glial cell?
Here’s the transcript for the next podcast, which I won’t be putting online for another week or so, when I can afford to buy space to host podcasts directly from this site. Then I’ll be able to stick all the fountains podcasts in one place, with the new logo created by a friend of mine, Stuart Rose:
What’s a glial cell?
Today, I’m going to make my first, but hopefully not last, foray into neurobiology. And since neurobiology is about the most complicated subject imaginable, I’ve decided to enter it sideways, so to speak, by looking at glial cells, or neuroglia, as they’re sometimes called. Not that this will make it any easier.
Glial cells – ‘glia’ means glue in Greek – perform a whole range of tasks apart from holding neurons together. They also come in many different varieties, and there’s still a lot we don’t know about them. They make up about half the mass of the brain, and they outnumber neurons many times over, making up between 85% and 90% of brain cells.
Considering the great varieties of roles glial cells play in the central nervous system (CNS), the peripheral nervous system (PNS) and in neurogenesis or the development of the brain, it’s hard to start with a summary or overview. They’re generally a lot smaller than neurons, and the glia/neuron ratio varies greatly between species, with the human brain near the top end. Elephants, though, are much higher with 97% glial cells.
Glial cells emerge from the multipotent precursor cells of the neural crest and neural tube. Radial glial cells act as progenitors and also as scaffolding for the growth and migration of neurons in the brain. They play a role in the development and maintenance of synaptic plasticity in the cerebellum. This function of supporting neurons is typical of all glial cells, with some of them having their own quasi-neuronal tasks. In the vertebrate retina, for example, Muller cells or Muller glia have been found, quite recently, to play a role in the formation of synapses. They’ve also been shown, when the retina is damaged, to re differentiate into progenitor cells which can then become photoreceptor cells.
But I’m galloping forward a bit here. The three main types of glial cells in the CNS are the astrocytes, the oligodendrocytes and the microglia, and some of their functions have long been known, though the detail, as well as a growing number of other roles and functions, are only now being focused on, in what some are describing as a revolution in neurobiology. Dr. Douglas Fields, chief of the Nervous System Development & Plasticity Section of the National Institutes of Health in the USA, argues that our understanding of the brain has been overly influenced by what he calls ‘the neuron doctrine’, that’s to say, a relentless focus on the electrical activity of the brain in the form of action potentials between neurons. The fact that glial cells don’t communicate electrically has meant that their role in brain activity has been largely overlooked for the best part of a century, according to Dr Fields. My layman’s perspective suggests to me that, not being electrical, glial cells just aren’t as flashy or sexy as neurons. ‘I sing the body electric’, Walt Whitman memorably wrote, and maybe he wasn’t thinking about neurons, but he definitely wasn’t thinking about glial cells.
So let’s have a look at some of those glial cell types. Astrocytes – so-called because of their star-like shape and projections – perform lots of functions within the CNS, including providing physical support to neurons through the formation of a matrix, cleaning up chemical debris within the brain, and replenishing chemicals within neurons and so keeping them healthy and well-nourished. This clearly requires communication between neurons and glia. Astrocytes also monitor the fluid surrounding neurons and keep it chemically well maintained. They get rid of the flotsam and jetsam through a process called phagocytosis, which involves engulfing the unwanted particles and essentially digesting them, a process performed by dedicated cells throughout the body.
looks like an astrocyte
Astrocytes nourish the neurons by first obtaining glucose from capillaries, then breaking it down into lactate, the first product of glucose metabolism. The lactate is then released into the fluid surrounding the neurons. The neurons take up this lactate and transport it, as an energy source, to their mitochondria. Astrocytes also maintain a store of glycogen from this process, which may be used in times of high neuronal metabolism.
One of the essential functions of oligodendrocytes is myelination. Now I’m sorry for the polysyllabification there, but I’m talking about the production of myelin sheath, the insulating material that protects the axons of the CNS as well as substantially improving their electrical activity. Myelin is white in colour, and accounts for the white colour of the brain. It’s made up of 80% lipid and 20% protein and it increases, many times over, the strength and efficiency of electrical conduction down the axon. The axon is generally the only part of the neuron sheathed in myelin. The oligodendrocytes are able to sheath as many as 40 axons at once in myelin.
Microglia, the smallest of the glial cells, also engage in phagocytosis to clean up debris, but their most important role is immunological. The brain’s main protection against pathogens is the blood-brain barrier, a layer of endothelial cells similar to the types of cells that line blood vessels and internal organs. When somehow pathogens cross the blood-brain barrier or are introduced into the brain directly, microglia, which are ultra-sensitive to chemical imbalances in the brain, and particularly to extra-cellular potassium levels, move swiftly into action. Microglia perform a similar role in the CNS to that of macrophages in the blood system, but are not as easily replaceable as macrophages, due to the blood-brain barrier. However microglia are extremely plastic which allows them to perform a variety of immunological functions at short notice while also maintaining homeostasis in the brain.
Another type of glia, the Schwann cells, provide support to the nerve cells of the peripheral nervous system (PNS). They wrap themselves around axons, as with oligodendrocytes in the CNS, and in so doing produce myelin, though the process of myelin production is substantially different in the PNS, with one cell producing only one segment of myelin. Schwann cells also clean up debris and play a major role in the regrowth of PNS axons. They arrange themselves into cylinders which guide the tendrils of regenerating axons. When a functioning tendril comes into contact with one of these cylinders it will grow inside it a rate of up to 4mm a day.
There are other types of glia, and the glial cells already mentioned have their subsets and their developmental phases, which all play their part in the development and maintenance of the brain and the nervous systems, yet for a long time neurophysiologists considered the ‘white matter’ of the brain – the glia, predominantly – as passive, with the grey neuronal matter being the active component.
With the renewed interest in glia however, experiments are being conducted that show that when you remove or ablate relevant glial cells, it has a profound effect on an animal’s ability to sense its surroundings. This has been shown in worms and other creatures, and it raises many questions as to how glial cells communicate with neurons in facilitating an effective sense of our environment, without which, we wouldn’t last long.
We now know that the activation of calcium ions provides the principal means of chemical communication between neuroglia and neurons. An increase in calcium ions signals the release of what are now being called gliotransmitters, molecules that travel between cells in a manner similar to neurotransmitters. All this communication has a variety of purposes but it’s the immunological role of neuroglia that has researchers really excited. The neuroglia are able to pick up signals between neurons and respond by controlling neuronal activity, inhibiting or stimulating or refining the action potentials between nerve cells. All of this was completely unsuspected until recently. Their role in such diseases as Parkinson’s, Alzheimer’s, Lou Gehrig’s disease, cancer and AIDS, and even such disorders as OCD (Obsessive-Compulsive Disorder) are now being uncovered through a lot of experimental work. Communication between astrocytes and microglia and neurons are substantially altered in specific ways in each of these diseases. So important have glia become in contemporary neuro-research that there’s talk of ‘the other brain’ or ‘the glial brain’ as opposed to the neural brain. They of course work in tandem, but the point is that we have a lot of catching up to do in researching glia.
It’s worth noting that, though neurons in invertebrate animals are not substantially different from those in vertebrates, glial cells are far less numerous, in proportion to neurons, in invertebrates, where they don’t have the same myelin-producing role. Investigating the increasingly vital and diverse roles played by glia and how they came to evolve in more complex animals will no doubt be a focus of future research.