Monday, March 24, 2008

Brain Oscillations: Ten part series

This series of blogposts is based on Ginger Campbell's interview with Dr. György Buzsáki in Feb. 08, and released as a podcast, #31 of her series of BrainScience Podcasts. It was written mostly as a study effort, to help me better understand how the brain works, to help me get more from reading the book itself - Rhythms of the Brain.

INTRO: Oscillatory Matters

Part I: Where do brain oscillations come from?

Part II: Input/Output

Part III: Why write a book?

Part IV: Complex Systems

Part V: Strength and efficiency in numbers

Part VI: Origins and interactions

Part VII:Inhibition, excitation and balance

Part VIII: Deep brain function or "noise"

Part IX: References and suggested reading

Link to transcript of episode #31

Oscillations Part IX: References and Suggested Reading

(This is a final post in the series "Oscillations" based on notes taken from Ginger Campbell's podcast #31 with György Buzsáki, and a continuation from Part VIII):


1. Stephen Strogatz: (homepage ) known for his discovery of “small world” architecture
His 2003 bestseller Sync: The emerging science of spontaneous order is aimed at a general audience

2. Nancy Kopell: mathematician
Buzsáki recommends her review of the analytical approaches to neuronal oscillators: We got Rhythm: Dynamical Systems of the Nervous System. (pdf 11 pages) N Am Math Soc 47: 6-16 (2000).

3. Zoltán Néda (Bebes-Bolyai University Romania): the spontaneous synchronization of hand clapping
Self-organizing processes: The sound of many hands clapping Nature 403, 849-850 (24 February 2000)

4. Hermann Haken (his homepage ): German laser physicist who studies bidirectional causation
The Science of Structure: Synergetics (1984)
* His Scholarpedia articles on self-organization and on synergetics

5. John O’Keefe (University College, London): along with Lynn Nadel he discovered how the hippocampus forms a cognitive map of the world.
He has shown how the timing of oscillations in the hippocampus are important
* “Independent rate and temporal coding in hippocampal pyramidal cells ” by John Huxter, Neil Burgess, and John O’Keefe. Nature 425, 828-832 (23 October 2003)

6. David McCormick (Yale University): showed that neurons from the thalamus can oscillate spontaneously
Neocortical Network Activity In Vivo Is Generated through a Dynamic Balance of Excitation and Inhibition (11-page pdf)
He has also studied the oscillations of place cells in the hippocampus
List of publications

7. David Hubel and Torston Wiesel recieved a 1981 Nobel Prize for their discoveries concerning information processing in the visual system, based on work done by Vernon Montcastle on the use of single neuron recordings.
Montcastle, VB (1997) “The Columnar Organization of the Neocortex.” Brain 102:01-722.
*Montcastle's biography

8. Claude E. Shannon : Founder of Information Theory

9. Jan Born (University of Lübeck, Germany): experiments with how sleep improves both memory and problem solving
*list of publications

10. The Handbook of Brain Theory and Neural Networks, Michael Arbib 2003

11. Scholarpedia Encyclopedia of Dynamical Systems

August 6/08
Added: When Neurons Fire Up: Study Sheds Light on Rhythms of the Brain

Oscillations Part VIII: Deep Brain Function or "Noise"

(This is a continuation of notes taken from Ginger Campbell's podcast #31 with György Buzsáki, and a continuation from Part VII):

Independence of "deep" brain function

* the brain maintains its own excitability, activity, in the absence of external information, or external perturbations
* what is it good for?
* physicists and computational neuroscientists like noise, because many of the systems they study wouldn't be able to operate without some energy which is usually supplied with the mechanism of noise
* this noise is generated by the internal activity of the brain at a time when the brain cannot rely on outside sources
* this is the time when brain activity moves forward independently
* sometimes it coincides with sleep - it's very difficult to understand what kind of processes go on in sleep but one of them seems to be consolidation: e.g., remember a conversation with someone - you will:
"recall that information with just one single question and you go through a whole long process of thinking, and that implies that there are cell assemblies that produce self-organized and perpetuating sequences without any further input. And you can think and talk about these events for a long time. And this is all maintained by internally generated activity."

Why is brain "noise" necessary?
"(Deep brain activity) is the internally-generated activity that is independent from the outside world and that is the one that interferes with the incoming inputs. This is the source of noise that is annoying when you are trying to understand the impact of a stimulus on the brain. So this noise, which is considered noise for many, is my most important signal. That's in fact the only source of cognitions - the self-generated or inside-generated activity or internally generated activity of the brain is an absolute requirement for cognition. And there has been very little thought about this, and they are very difficult experiments."

* self-generated, inside-generated activity, or internally generated activity of the brain is an absolute requirement for cognition
* it is very difficult to approach this experimentally, especially in animals
* but if you are seriously interested about how cognitive information is transferred around from one place to the other in the brain, then we have to consider seriously how self-generated activity is serving important functions

* various things must be energy efficient, volume-efficient, wiring-efficient etc., but certain problems must be solved - a balance becomes struck between needs and goals and energy efficiency
* it seems a waste of energy to maintain spontaneous activity - why do we have a lot of neurons firing when we are drowsy?
* this activity/noise makes:
"perception less effective, the inputs are not the same so in fact when you are driving on the highway and getting tired, then your brain takes control and your input is becoming less efficient. So from this point of view it's a disaster. But we have to understand and give some good rationale why is it good in the long run for the brain that it has its own fluctuations."

Some benefits of sleep:

* activity during sleep is not a random useless activity
* in many structures where this has been looked at, it turns out that the activity of sequences and patterns in the neurons that are being active in our sleep processes are pretty much the same as the ones that have been used in our waking experience
* a recent book about creativity discusses what could be the mechanism of creativity in the brain; many creative people reported to the author that they try to create in an environment which is peaceful, calm, and they try to fall asleep, but not quite sleep, and whenever the associations occur in an interesting and random manner they can bring it back to wakefulness.
"I have fantastic associations every single night in my dreams, but I don't have the ability to bring them back to the waking states. These are the states when the activity of the previous day dominate, but at the same time, other things that happened in our previous life will also emerge, and mix with the recently acquired information. Sleep is the best mixing phase because it's noisier so to speak, but perhaps this noisiness is creating, is using something or serving something very important."

Does sleep make you 'smarter'?

* sleep seems to be very important for consolidating memories
* Jan Born, in Lübeck, Germany has done work on this:
* students are given a puzzle to solve
* the puzzles are of sufficient difficulty that it takes more than two or three times to solve them
* they go and sleep on it:
"...when they wake up, a fairly high percentage of students can solve the task right away, compared with those students who have been engaged doing something else, implying that during sleep, those representations about the unsolved problem went through various synapses and various parts of the brain, and in the morning, they were, so to speak, consolidated, and the answer was available."

* many examples show that sleep provides an advantage - there may be a savings of 10, maybe 15% (more information retained)
* interestingly this can be enhanced beautifully by oscillations
* the same lab followed up the idea that there is a slow oscillation in the neo-cortex capable of entraining these fast ripples that seems critical for storing and consolidating episodic memories
* the rationale was, if this is the case, then we should be able to enhance the magnitude of these slow oscillations during sleep
* EEG electrodes were placed on the scalp, electrical currents were applied while the students were in stage 4 sleep
" a result of the electrical sinusoid stimulation, the power of the slow oscillation increased, and perhaps this enhanced activity increased the probability and timing of hippocampal ripples (although this hasn't been shown...). But this entrainment of oscillations enhanced the ability of sleep for an additional 10% or so (more information retained).

* students whose brains were stimulated during stage 4 sleep remembered the memorized items even better than those who had just had a regular sleep

* a counter-argument might be: oscillations not only produce oscillations but they made neurons fire more synchronously, contact with the balancing partners were discharged more effectively
* if perturbations did not occur in an oscillatory manner but in a random manner, perhaps the outcome would be the same

* it's a very difficult issue to answer -
"... it's a bi-directional causation, and the system that oscillates uses every ingredient, and every ingredient when it works perfectly together produces an oscillation. So whether it's an epiphenomenon or not, it doesn't have a trivial solution. However, it does not matter. If you are looking at the practical aspects of this, because they are there, they can be used, they can be useful for a researcher who is interested in how internal activity of the brain or internal generated activity of the brain is generated, and whether oscillations are epiphenomena or not doesn't really matter as long as he understands the processes that underlie behavior and commission."


So ends the interview. I will bring a list of references and further suggested reading here in a separate blogpost, then I will hook all these posts together and post a single link in the menu.

This has been a great few weeks of soaking in this information. I want to thank Ginger Campbell and György Buzsáki for having such a good informative conversation about oscillations.

Sunday, March 23, 2008

Oscillations Part VII: Inhibition, Excitation and Balance

(This is a continuation of notes taken from Ginger Campbell's podcast #31 with György Buzsáki, and a continuation from Part VI):

In the brain, inhibition and excitation operate as opposing forces

* inhibitory neurons on a single pyramidal cell from the neocortex are in the minority ... about 15 - 20%.
* however, they are located strategically - most of these inhibitory terminals are near the soma and the axon initial segment, parts of the neurons that are critical for generating action potential output
* inhibitory terminals make sure that the timing of the neuron is optimal - that's what happens in many cases of oscillations

Balance between excitation and inhibition

* even though the number of inhibitory terminals are smaller, the inhibitory terminals are very active, about 5 times more active than the principal cells: i.e., way fewer inhibitory terminals and inhibitory neurons, but activity is higher; the result is that the total number of EPSPs and IPSPs, i.e., the excitatory inputs and inhibitory inputs per unit time, are exactly the same or almost exactly the same, resulting in a balanced system

How fluctuation creates balance
"However, this balance is brought about by fluctuation... if you zoom in in small time windows then we always see that either inhibition or excitation dominates. And the easiest thing to balance the two opposing forces is through oscillations. So that is the reason why inhibition is so important. Without inhibition there would be no computation in the brain. Why? Well, the second law of thermodynamics clearly states that in physical system if you have only collisions then collisions will produce more collisions and the entropy of the system will increase and there will be no order. This applies also to the brain, of course, and any other physical systems, and the brain is a physical system, is that if we had only excitation, and then excitation would produce only further excitation. In fact, in principle, the action potential of one neuron would lead to the discharge of every single neuron in the brain."


* Shannon's information theory approach works perfectly - at the periphery - at the first senses
* it works good at the retina, at the cochlea, perhaps even at the first relay station in the thalamus

* as one goes deeper and deeper into the brain the variability increases; not because the reliability of the brain isn't good, but because other sources of "noise" come into the picture; this "noise" is generated by the brain itself

* the deeper we go into the brain, the more we find independence from the environment
"The deepest structure in the brain, if there is such a thing as deep, is the hippocampus, or the prefrontal cortex, because they are multiple synaptic connections, far from either the motor output or the sensory inputs, and, they maintain their activity. But this maintained activity is observed almost everywhere. Visual cortical neurons are active, a little bit less perhaps, but they are still active when we close our eyes or when we fall asleep. Many parts of the brain, for example, again, the hippocampus, they are as active during sleep as in the waking state. The number of action potentials of all neurons, that is, the energy they use, is pretty much constant, independent of what happens out in the environment."

Oscillations Part VI: Origins and Interactions

(This is a continuation of notes taken from Ginger Campbell's podcast #31 with György Buzsáki, and a continuation from Part V):

How do oscillators get themselves synchronized?

It's simple to link oscillators together:
- every neuron is an oscillator - the issue is how they get synchronized into an oscillation activity
- one can make an oscillator where none of the elements individually serve as an oscillator - e.g., a mechanical clock is a perfect example - a mechanism that ties all the elements together to make the clock tick is all that is needed
"...if you record from single neurons, you can record from them for long long long times, and you will never see that there is an underlying oscillation. And this is the main reason perhaps, this explains the skepticism of many investigators in neuroscience that deal usually with one neuron at a time. For example, the ripple oscillations that I just mentioned is a perfect illustration of that. If we would be looking at single neurons for five years, there would be no moment in time, perhaps, when we would say, aha - there is a population output here. But if we begin to look at 50 or 100 together, then it becomes absolutely obvious, and we won't miss any of these events. So, in this case, none of the neurons oscillate, but their cooperative activity produces a perfect sinusoid oscillator."

Is there a pacemaker, something in the brain that controls these oscillations?

- there are pacemakers: e.g., our respiration rhythm is determined by a group of neurons in the brainstem responsible for maintaining or pacing respiration
- in hippocampal theta activity it has been thought that there is a pacemaker in the medial septum
- many neurons in the medial septum, cholinergic and gabenergic neurons can be recorded when in slice preparation, in in vitro conditions, when they are disconnected from the hippocampus and every part of the brain, they maintain oscillating activity
- David McCormick has shown that isolated neurons can oscillate perfectly
"Now, calling many of these or some of these 'true' pacemakers comes with some burden, because in many cases, like in the thalamus, even in the medial septum, it turns out that yes, individual neurons have the propensity to oscillate, and under certain circumstances they do, but when they are embedded into a physiological substrate or physiological activity their timing is coordinated by various feedbacks. And even if we have an independent set of neurons, let's say in the medial septum, that can fire at 5 Hz, somehow their activity must be coordinated. And in many cases that kind of coordination comes from their target structures, in our case the hippocampus."

- in terms of energy, it may be cheaper to have neurons that can transform information, affect the firing patterns of neurons, and simultaneously in cooperation with others, produce an oscillation, than it would be to have a set of neurons which did nothing but keep time

How does an isolated neuron (without excitation or inhibition) oscillate independently?

- inhibition and excitation are very important in the brain, but not required for an oscillation
- ocean waves don't have inhibition and excitation in this exposit sense - oscillation always emerges
- it's inevitable when you have opposing forces - a push and a pull, like in the swing, is perfect enough to maintain oscillations
- in the brain opposing forces include potassium and sodium going in opposite directions in the membrane - this is perfectly sufficient to maintain oscillation in a single neuron
- no inhibitory neurotransmitter is needed for this but there is inhibition in the sense that one force tends to counteract the other force

This last part is important because it suggests that no outside agency is required to make a brain or to keep it oscillating, other than energy from ordinary, thermodynamically congruent energy sources, utilized through ordinary metabolic pathways; this is supported by other observations as noted in the post Oscillatory Matters where different concepts regarding "movement" are listed. There is a bit more on this in the next post.

Saturday, March 22, 2008

Oscillations Part V: Strength and efficiency in numbers

(This is a continuation of notes taken from Ginger Campbell's podcast #31 with György Buzsáki, and a continuation from Part IV):

So what is it that changes during synchronization?

* individual neurons don't change their firing rate at all
* when synchrony emerges through oscillations, it's the timing of the neurons relative to each other that changes
* the result is that now the impact of the same neurons when they are firing in synchrony is much more effective
* in fact these ripple patterns have been associated later on in several laboratories with the transferring of information from the hippocampus to the neocortex
* this was just one single oscillator

What happens when you have two oscillators?

* when two oscillators come together with slightly different frequencies, we get an interference pattern
* the best example for this interference pattern has been provided by John O'Keefe from the University College London
* he observed that individual place cells in the hippocampus oscillate at a frequency slightly faster than the ongoing so-called theta frequency oscillation
* the result of this is very precise timing - the importance of this that was translated into behaviour is that the phase position of the action potential relative to the ongoing clock cycle, reliably predicted the position of the animal
"'s a convincing case where we go from the basic features of oscillators through physiology all the way to behavioural significance. And then you can pose other questions - how would this be possible without an oscillator? And I can come up with some scenarios that could be done without oscillators, but it would be very expensive energetically and it would involve a lot more computation and would be a lot more complex."

What about when many oscillators come together?

Simple rule that applies to oscillations of various frequencies:
* the brain is a physical system
* information from one place to another goes through
1. axonal conduction delays
2. refractory delays:
"...when one neuron discharges, its target neuron will discharge later, not only because it takes time for the action potential to go through the axon, but it also, when the neuronal transmitter is released, on the post-synaptic neuron, the neural transmitter has to charge the membrane to threshold - so there is a time delay - a finite time delay of how fast the information can go from one place to another."


Brains are very slow mechanisms compared to computers:
* if it generates a fast oscillation that has a short time period, the number of neurons, or the proportion of neurons that can be involved in these fast oscillations, are relatively small
* the oscillation is typically local
* when the time period is long, there is time for activity to propagate from one area, from one set of neurons to many other sets of neurons
* a large volume is involved, the result of which is that the synchrony of the population or the proportion of the neurons that are engaged in this rhythmic activity is much larger:
"This explains the common observation that slow oscillations are always high in amplitude, or almost always high in amplitude, whereas fast oscillators are small in amplitude. But the important consequence for the purpose of our conversation is that slow oscillators can affect fast ones, in such a way that the phase of the slow oscillator, because it involves very large areas, can organize the activity of the faster ones that emerge locally."

* though other possibilities also exist to coordinate activity, oscillations provide the cheapest possible solution:
"If you talk to anybody who works in this field he'll remind you that our brain uses 20% of our energy; with a newborn it's actually 50% and if you look at the smallest mammal, the tree shrew, the tree shrew uses continuously even during sleep, 50% of all the energy to sustain brain activity. It's very expensive. Evolution must be very careful how it allocates resources."

Oscillations Part IV: Complex Systems

(This is a continuation of notes taken from Ginger Campbell's podcast #31 with György Buzsáki, and a continuation from Part III:)

Complex systems

* science progresses when it understands ideas from other disciplines and finds the commonalities
* neuroscience has progressed in one direction and physics and statistics and certain parts of engineering progressed almost independently and made large movements forward in an area that is called today complex systems.
"The "complex system" offered a very rich toolkit for neuroscience to think about interactions in the brain in a new way."
"..ideas and principles that have a common thread across different disciplines are substrate free. But whenever we want to understand the mechanisms we have to translate these interesting principles into mechanisms on a given substrate."

* mechanisms have to be understood and broken down into pieces.
* responsibility of neuroscientists lie in translating interesting explanations into neuronal mechanisms
"..the new field of neuronal computation and experimental neuroscience must work together to see how the ideas that spring out from your brain, from your head, can be really tied to reality rather than just express imagination."

The sound of many hands clapping:

* provides convincing example of synchronization
* clapping can slowly change from random noise - "clapclapclapclapclapclap" - to synchronized: "CLAP!.... CLAP!.... CLAP!"

* after a few seconds the clapping of the entire audience can become rhythmic
* what is the cause of the emergence of the rhythm? That's a very tough question, because there is no real "cause" as such
*"emergence" is the word being used - it starts with a random interaction of a few: some people just happen to clap their hands in synchrony, and with the same rhythmicity, and the surge of the sound of these individuals influence their neighbours, and eventually the rhythmic clapping becomes dominant


1. Bi-directionality:

* once the pattern or the rhythm emerges, it captures every single individual in the room - their degree of freedom decreases: i.e., their tendency is to stop doing their self-organized activity and become part of the synchronized clap sound formation

* Hermann Haken, laser physicist from Germany, talks about "bi-directional causation"
* the elements of the system emerge and produce, give rise to a new quality - we can call it an "order parameter", or the rhythm in this case
* the rhythm will then cause or effect the elements to do one thing, and not another

* the rhythm is a very fundamental property - it makes the questions of the skeptics so difficult to answer
* what many brain scientists ask is, if brain oscillations are important, remove them and see what happens, remove oscillations without affecting anything else and see how the brain will be affected
* it is not possible, because the reason why the oscillation emerges is because of the behaviour of the individual elements
* the two of them are tied in an interesting bi-directional manner

2. Cost effectiveness of single oscillators:

* the goal of hand-clapping is to generate as much impact with sound as possible
* if hand-clapping is rhythmic, the surge of the sound is several orders of magnitude stronger than.. at least it's louder ... than compared to the random clapping
* this increase of the output can be achieved at no cost - if you count the number of claps, or the rhythm of the clapping, during rhythmic clapping compared to random clapping, the frequency of the individuals is actually slower - individual investment and the energy that's being invested is less, yet the outcome is much stronger.

* with regard to systems of neurons, if the goal of computation is to not only compute something but to transfer that information to target neurons, the best way to do that is synchronize them
* synchrony through oscillations comes for free:
- e.g., during a particular type of epilepsy, called petit mal or generalized epilepsy, many neurons in the thalamus and the neocortex become entrained into 3 Hz spike and wave.
- this synchrony can be measured, and it's very obvious by recordings, but because it's epilepsy we thought for a long time that epileptic activity is extremely energy consuming
- it came as a surprise when the methods for measuring energy use with fMRI was applied to these epileptic episodes, many investigators in several laboratories almost simultaneously found that both signals became negative when the spike and wave epilepsy emerged, meaning that less energy was used.

* if you understand the mechanisms of how oscillations come about, and what of a single neuron invests into it, then it is not surprising at all - it is almost obvious.
* in 1992 we described a phenomenon, hippocampal ripples, at 200 Hz, very fast oscillation; we showed that we can get synchrony, very nice, tight synchrony, without any change of the firing rate.

Further reading:
1. Synergetics:
"The connection with chaos theory and catastrophe theory is in particular established by the concept of order parameters and the slaving principle, according to which close to instabilities the dynamics even of complex systems is governed by few variables only."

2. Self-organization of brain function
3. Zoltán Néda (Bebes-Bolyai University Romania): the spontaneous synchronization of hand clapping

Wednesday, March 19, 2008

Oscillations Part III: Why write a book?

(This is a continuation of notes taken from Ginger Campbell's podcast #31 with György Buzsáki, and a continuation of Part I and Part II):


Scientific reasons

- debate, exaggeration, denial, and misunderstanding exist regarding the brain rhythms and brain oscillations

- oscillations were considered a mere byproduct in physics, engineering, architecture and neuroscience

- many questioned how the brain can perform despite the fact that there are these oscillators at all levels of neuron organization.

- Buzsáki began to look at what kind of advantages oscillators provide to the nervous system - lots of fundamental things that can be solved very effectively with oscillators:

1. Codification

- messages in the brain from one place to another must first be coded

- information coding entails that every message that is transmitted from one place to another must have a beginning and an end;
"It's the same with coding for DNA; you have to have a beginning code and an ending one."

- this is not trivial in a brain which is interconnected and continuously active:
"For example, if you are looking at events at the periphery, such as the cochlea, then the beginning of the sound and the end of the sound perfectly signals the messages because these are coded or signaled by extrinsic physical stimuli. But these stimuli are not available in the brain especially during cognitive processes when there are no external timers, so the brain has to come up with these internal timers. So, oscillations are perhaps the best solutions for marking the beginning and the end of the messages, because, as we may be talking about a little bit later, every single oscillation reflects or is associated with the fluctuation of excitability. There is always the period or phase of the oscillator when the activity is maximum and when it is minimum. So, when you go from minimum to minimum, then these time periods can beautifully mark the beginning and the end of a message. So this is one attractive feature."

2. Existence of Oscillator systems

- people acknowledge that there are oscillators in the brain - e.g., sleep spindles, alpha oscillations, Parkinsonian tremor

- not only are there a few oscillators with different frequencies in the brain but there is a system of oscillators:
"What I mean by that, is that several orders of magnitude of time starting let's say with the high frequencies - 3, 4, 500 Hz, which is only a few milliseconds of time window - all the way to tens of seconds, or minutes, are covered by neuronal oscillators. And there is no gap. And if you look at the mean frequencies, and the variability of the range of these oscillation generators, they are overlapping in a regular way, and their mean frequencies happen to coincide with a number of life's natural logarithms. And that was an interesting revelation.. that oscillators exist together, or can exist together; they don't have an integer relationship - in other words one oscillator cannot entrain the other one permanently - but because they are related to each other through irrational relationships, irrational numbers, they can never sustain some permanent activities. For the interference between oscillators, between natural brain oscillators, is always transitional. And this was an attractive feature for many, because it's led to the recognition that this is probably the way how you can generate pictures that look like noise, as well as this is a force that keeps the brain going permanently, and it never comes back to the same state. These are the scientific arguments behind trying to write a book."

Practical reason

- different departments: biomedical engineering, physics departments, neurosciences departments, molecular biology - much of the knowledge about oscillators is available only in various specific publications

- people in various disciplines are exploiting information about oscillators; physics, mathematics, engineering, and membrane physiology, systems neuroscience, even clinical neuroscience, but such information has never been bound together into a coherent whole

- discussion about a specific oscillator is assumed to be very specific to a favorite structure, or to a favorite species, but there was no comprehensive overview:
"to present a coherent synthesized picture, all this scattered information should come together in a single brain, and cross reference across the information, and somehow simplify it. So my goal was to simplify the existing knowledge and to explain it not necessarily to the layman but to those people who have some background in neuroscience or some serious interest in neuroscience and see how a neglected area of dynamics can represent something very important and fundamentally in the brain."


Further reading:
1. Information on sleep cycles, including sleep spindles.
2. Memory and Brain Dynamics: Oscillations, Integrating Attention, Perception, Learning and Memory, by Erol Basar (large portions of this book can be read online)

More about Oscillations - Part II:

In reference to More About Oscillations Part I:


*most of the oscillators in the brain belong to the family of relaxation oscillators

*a single neuron is a very typical pulse type of oscillator: if the neuron is depolarized, if certain channels that prevent the neuron from habituation or from adaptation are blocked, then the neuron will spike forever

*there is one period (action potential) and a longer period, the "in between", the charging phase or the incremental phase

*if large numbers of these neurons are considered together and their mean or average field activity measured, they can become very sinusoid - their collective behavior looks like a harmonic oscillator

*the elements that are critical in generating the oscillations are made up from relaxation oscillators: however they are tied together in a monolithic form, such that they form a harmonic oscillator

*it has features of both - the good features of both: they can be perturbed effectively, but they are also good timekeepers.

A useful INPUT/OUTPUT feature:

*relaxation oscillators can be separated into "input phase" and "output phase"
output phase means when an effect is going out; in the faucet example - the drop of water is the "output"

*the incremental (charging) phase is the "input", the phase in which water accumulates, the phase when the system or the oscillator can be perturbed

*separation of the input/output highlights the relatively long time when the oscillator can be perturbed, or input can be put into the system

*the internal mechanisms of the oscillator determine when the output occurs

*when effects are combined/synchronized, outputs can be enhanced, can become more than just the sum of the parts

*output phase includes refractory phase, when perturbation has no effect

Tuesday, March 18, 2008

More about oscillations- Part I: Where do brain oscillations come from?

In reference to Oscillatory Matters:
If the reader goes back through all the posts linked in the post I've linked to here, he or she will learn that György Buzsáki has studied the hippocampus and brain rhythms all his research life. I completed an entire transcript of the Buzsáki interview by Ginger Campbell of Brain Science Podcast and sent it to her to do with as she wishes. I'm sure she will find good use for it. My main objective in writing a transcript was to understand the material in greater depth.

I plan to bring a series of notes here, based on the interview. This is Part I - Where do brain oscillations come from?

His opening statement in the interview is:
"Synchrony is an important mechanism to bring elements of a system together in time - it's critical - then I think everybody agrees that it's a pretty important mechanism. The only thing we can add to it is that oscillations do a fantastic job of doing that and they do it almost for free."

That "almost for free" aspect is important given that the nervous system is an expensive system to maintain metabolically.

What are oscillations?
*Nature is full of cyclic phenomena - movement of heavenly bodies, the calendar, the life cycles in biology, respiration, heart beat, menstrual cycles.. these are all rhythmic phenomena.

*Many man made objects are also based on rhythms or oscillations, such as clocks, radios, TVs, computers, cell phones, even electrical line transmission

*What is the use of all this repetitive phenomena? Artifact (side effect of how things are put together), or essential parts of the mechanism?

*A one or five megahertz clock could be built using random timing, but it would be incredibly difficult.

Oscillations synchronize events

*Imagine a car designed to not move smoothly; it speeds up and slows down irregularly. The average speed of this car and a regular car may be identical. On a smooth terrain both would take about the same length of time to get to the goal. When the terrain is difficult the car would be harder to drive.

Types of oscillators

1. "Harmonic" oscillators: predictability

* e.g. pendulum clock with motion almost perfectly sinusoid
* e.g. orbit of the moon around the earth
* "predictability" is that one need only look at motion of the moon for a short period of time to extract the phase information then one can predict the phase of the moon tomorrow or a million years from now
* harmonic oscillators are very useful for predicting events in time
* there are many examples in the brain of harmonic oscillators, exploited for exactly this purpose

2. "Relaxation" or "pause" : easy perturbation

* discrete events repeat with long or less predictable intervals
* e.g. clapping of hands: a discrete event is followed by silent period which may vary in length
* e.g. a dripping faucet: drips (discrete events) repeat at certain intervals; if observation period is short, within two drops, one cannot predict the occurrence of next event
* no timing precision, but they can be perturbed easily - tap on the faucet will produce a premature drop, determined exactly by the timing of the perturbation

* very effective to synchronize in large numbers if they are identical:

Imagine hundreds or thousands of faucets, simultaneously perturbed: phase reset means to start them all with the same phase (tap on the tap): if they are identical this need be done only once - they will drip simultaneously thereafter, demonstrating synchrony and phase reset-ability.

So where do oscillations come from? The short answer Buzsáki provides is that they seem to come from nature itself.

This next thought doesn't come from the interview, but I want to point out that even a glass of water sitting unperturbed will contain "oscillation" in the form of Brownian movement of the water molecules - and life contains a lot of water molecules.

This inherent atomic motion is unlikely to be completely stilled by being bound in a cell. In fact those who study motility in single-cell organisms have to separate out Brownian movement as a potential confounding factor.

What are neurons? They seem to be many things to many fields, but first of all they are long skinny single cells containing water, very easily perturbed, whose job seems primarily to be to signal - to chatter continuously. This entire interview, and the book Rhythms of the Brain, explains how this chatter appears to be organized into patterns.

1. Stephen Strogatz: known for his discovery of “small world” architecture. Sync: The emerging science of spontaneous order (2003) is for a general audience

2. Nancy Kopell: mathematician
We got Rhythm: Dynamical Systems of the Nervous System (pdf). N Am Math Soc 47: 6-16 (2000). (Buzsáki recommends her review of the analytical approaches to neuronal oscillators)

Wednesday, March 12, 2008

Always right?

This is from a certain ortho blog which shall remain nameless and linkless, because I'm not interested in supporting it by sending traffic its way. The author (who I met and had a discussion with online) starts out with some nice thoughts nicely couched, quotes Kipling, then by paragraph three gets to his point, which is to lump dermoneuromodulation (my approach) in with quack-based manual therapy treatments.

Here is the paragraph:
"Yet some in our profession would speak as if this weren't the if some are indeed always right or always wrong. Most notably, these ideologues tend to speak in absolutes with very little equivocation. They will actively recruit easily led individuals and defend the faith at any cost. Questioning is met with often harsh admonishment that you must be part of some central orthopedic conspiracy designed to bring them down. It's the behavior expected of someone who always got picked last for kickball. We've seen it in our daily practice from subluxation-based chiropractors, myofascial release providers, and recently dermoneuromodulation."

So, I get that he thinks I'm an "ideologue", speaking in "absolutes". In that I give the nervous system 100% of the credit for arranging:

a) all autonomous movement of, and

b) all actions (including physiological and pain-reducing) taken in response to perturbation of the conscious human organism in a manual therapy context,

... then I agree, yes I am. Guilty. There's no "faith" to defend at my end. None whatsoever.

I can't help it that this is the only reasonable position that science supports. I can't help it that an "ectodermal derivative"/nervous system-friendly manual approach will always trump any "mesodermal derivative"/ bone-shoving/ muscle-bending/ fascia-stretching/ joint-mobe-ing approach whenever pain and movement dysfunction are chief complaints. These complaints are, after all, what we are supposed to be treating. He still thinks he's treating anatomy, not physiology. It was Butler (author of The Sensitive Nervous System) who first said (in a discussion thread several years ago) "We don't treat anatomy - we treat physiology!" Matthias, the Neurotopian, calls it treating "functionally" as opposed to "structurally".

The blogger reads quite a bit into my conceptualization of what I call the ortho/chiro/meso-digm; I have not ever claimed it is a "conspiracy" - first, it's not that bright, and second, it's identifiable as a collective largely by its collective lack of understanding that science has moved on - really, really moved on!.. in the last 30 or so years when it comes to understanding pain and nervous system function. It's not my fault that manual therapy (with a few notable exceptions) hasn't caught up yet. The mass of PTs out there are still drenched in the same sets of assumptions we were all drenched in a hundred years ago. And they are still producing masses of papers based on those same out-dated assumptions. And they are so proud of this "science" that they won't listen to any voice that suggests to them, however kindly, that perhaps their assumptions are lacking in any way. Again, it's not my fault that the body is set up in such a way that certain specialized portions of it are built for signalling speed and other parts are built merely for structure. I want to work with the signalling part, thank you, not the structure. I want the system I treat to self-correct, because it's a lot less work for me and less confusing to it.

He is insinuating there is a "cult" at work, that there are members actively recruited. Or at least that's the conceptual slag he's providing his readers, in an effort to head them back into his own conceptual fold, perhaps. Or maybe he's truly paranoid.. There is no dermoneuromodulation cult as far as I know. If there is one, I'm it. The only follower and the only teacher.

As far as kickball goes, I never played it, so never was picked last for it. Or for anything else. Perhaps he was, since he seems to know something about the behavior.

Lumping dermoneuromodulation in with subluxation-based chiro and MFR providers is his idea of having the last word, I guess. It's a meaningless statement which only shows his defensiveness and how little he learned from our little encuentro.

He goes on to talk about "science" (by and for the orthodigm), ending with an admonition for his readers not to listen to anything else. A former teacher of mine described this sort of attitude as "Don't think or you'll weaken the team." I maintain that certain pervasive ideology needs to be weakened, deserves to be weakened, and that I have not only full right, but a scientific duty to the profession, to do precisely that, here in my humble blog and anywhere else I might go.

To be fair, I see a ray of hope here and there. Here is an abstract of a paper, Paradigm shift in manual therapy? Evidence for a central nervous system component in the response to passive cervical joint mobilisation, by Annina Schmid et al., in Switzerland, published in Manual Therapy, that with great scientific delicacy exposes the chiro/ortho/mesodigm to some nervous system reality, carefully weaning them away from the idea that what they do with their hands somehow directly translates into improvement for the patient. It actually points out that there are a few papers out there that would suggest that just perhaps other perspectives on the matter may just possibly (but without any of those annoying 100% declarations of course).. exist. Perspectives that include a consideration that a patient's CNS might actually be a willing and participatory and cooperative change agent itself.


Segmental neurological modulation, neural hysteresis and biomechanical effects have been proposed as mechanisms underpinning the effects of manual therapy. An increasing number of studies hypothesise activation of the central nervous system resulting in a non-segmental hypoalgesic effect with concurrent activation of other neural pathways as a potential mechanism of action. Whether this model is consistent with the current literature is unknown.

This systematic review aims to assess the consistency of evidence supporting an involvement of supraspinal systems in mediating the effects of passive cervical joint mobilisation.

We searched randomised trials in three electronic databases from inception to November 2007, without language restriction, and checked reference lists of included studies. We assessed study validity and extracted salient features in duplicate.

Fifteen studies met our inclusion criteria. The overall quality was high. We found consistency for concurrent hypoalgesia, sympathetic nervous system excitation and changes in motor function. Pooling of data suggested that joint mobilisation improved outcomes by approximately 20% relative to controls. This specific pattern suggests that descending pathways might play a key role in manual therapy induced hypoalgesia.

Our review supports the existence of an alternative neurophysiological model, in which passive joint mobilisation stimulates areas within the central nervous system.

Keywords: Treatment outcome; Cervical pain; Neck; Manipulation spinal; Joint mobilisation techniques; Physical therapy" (speciality)

Once joint mobilization can be shown to not do a whole lot as such, then it should be more plausible for the joint mobers to see that it's the contact itself that stirs the brain and accounts for the changes. If they care to include work by Collins, Gandevia etc., in their reading. Which is unlikely to happen probably, unless those authors start to publish in Manual Therapy.

So, there you go ortho-boy. My best to you. As far as I'm concerned this ship left the dock ages ago.

Dec 15/08 Update: As of today, this individual and I have buried the hatchet. He agreed to remove the offending bits from his post, and for that I thank him. He has, of late, come to appreciate the role the nervous system plays in pain, turned a new leaf and apologized for his former attitude. He is forgiven. The tiff has ended.

Another quackbuster

This post features Victor Stenger, particle physicist, atheist, and deconstructionist extraordinaire of healthquack and "alt med" ideas about "quantum physics" and "quantum energy". Here is a link to his webpage.

1. Here is his paper, Is the Brain a Quantum Device?
The answer is no. In the paper he explains the relationship between Penrose and Hammeroff (among the subjects interviewed in that gaggy film, What the Bleep), and discusses how their microtubule notion is off by at least two orders of magnitude. His conclusion:
"The brain is simply too large and too hot to be a quantum device, coherent or not."

2. He has written a number of books, including God: The failed Hypothesis (most recent), and many more.

3. This is an article written for Skeptical Inquirer magazine, Quantum Quackery, from way back in 1997. It debunks attempts by Goswami and Chopra to insinuate quantum physics into a frame of reality that supports dualism:
"Quantum physics is claimed to support the mystical notion that the mind creates reality. However, an objective reality, with no special role for consciousness, human or cosmic, is consistent with all observations."

4. This paper called The Anthropic Coincidences: A Natural Explanation, systematically lays out arguments against the idea of "supernatural purpose."
"Anthropic Design: Does the Cosmos Show Evidence of Purpose?
Claims that scientists have uncovered supernatural purpose to the universe have been widely reported recently in the media. The so-called anthropic coincidences, in which the constants of nature seem to be extraordinarily fine-tuned for the production of life, are taken as evidence. However, no such interpretation can be found in scientific literature. All we currently know from fundamental physics and cosmology remains consistent with a universe that evolved by purely natural processes."

5. A list of quotations. My fave so far:
"People are entitled to their opinions, but when the opinion is in disagreement with the data -- with the facts -- when that opinion does not stand up under critical or rational scrutiny, I think we have a right to point that out. We shouldn't be stepping on anybody's toes when we do that. If they're going to be spouting off nonsense, then we should say that -- not as a matter of opinion, but as a matter of scientific fact. When someone says science says something, and science doesn't say something ("It doesn't say that! That's a misrepresentation of what science says."), then I think we can state that. And if it ruffles some feathers, so what?"

6. An interview with Victor Stenger from 1999, on atheism.

Go Victor.

Saturday, March 01, 2008

Oscillatory Matters

Ginger Campbell at Brain Science Podcasts has put out a very nice podcast interviewing György Buzsáki (pronounced Yuri Bu-shock-i) about his book, Rhythms of the Brain. I have read this book, and posted about it here a number of times here and also here.

My favorite line in the book is still the very first sentence -
"The short punch line of this book is that brains are foretelling devices and their predictive powers emerge from the various rhythms they perpetually generate. At the same time, brain activity can be tuned to become an ideal observer of the environment, due to an organized system of rhythms."

In the interview, Buzsáki points out that oscillations are part of nature, and that neurons, being part of nature, are just doing what comes naturally. In his interview, he stresses that oscillations are economical for the nervous system to produce, that they provide a means by which the whole system can synchronize itself "almost for free."

The reason I found his book and this podcast so riveting is because my line of work (Physical Therapy/Physiotherapy) has always been to do with "movement" at every level of the human system. I have read lots about it, tracking "movement":

1. all the way in to the motor cortex, then premotor, where firing patterns precede "awareness", conscious will, decision-making,

2. embryology, "movement" of cells to destinations through mechanisms of chemo-attraction/repulsion,

3. evolution or "movement" of life through time and form,

4. "movement" that occurs in organisms without nervous systems,

5. "movement" generated in humans (and other multicellular creatures) that do have nervous systems,

6. remembering that "movement" begins before the nervous system ever gets any sensory perturbation at all (e.g., chicks etc. pecking their way out of an egg, fetuses "kicking"),

... all presumably because life can stir, can "move" of its own accord, simply because of biochemical processes.

I loved hearing that oscillation (or neural "movement") seems to be so inherent, so fundamental, such an energy saver for an oxygen-expensive system like the nervous system - a means by which it can "perturb" itself.

Buzsáki used a clapping example in the podcast and in his video as well. My understanding is that this illustrates that any signal (including any neuronal signal) can be perturbed, amplified, sharpened, synchronized, stretched into greater contrast without wasting energy.

Logically then, neuroplasticity is merely an outcome, therefore, a simple function of this inherent oscillatory "movement", taking advantage of this ability "nature"/neuron cell assembly/ brains have to be able to talk to "it"self/ themselves. Do neurons see a chance to save some energy and go for it? or is it a completely passive process like woodchips being washed up on a beach by ocean waves? I'd bank on the latter but who knows, maybe Varela/Maturana are right about "living" cells having "cognition" of a sort, maybe "cognition" that boils down to a simple proclivity for being "lazy" thermodynamically. Get enough of these lazy cells together and you have a functional multicellular organism that runs on "almost free" oscillatory synchrony, by cooperating to rectify/enhance the signal.