fMRI, BOLD and the Beautiful

When we want to examine the brain of a person noninvasively by Computed Tomography (CT) or MRI, we get a ‘snapshot’ of the anatomy (or pathology, if any) of the subject’s brain. We are however clueless as to its functional aspect. fMRI or Functional Magnetic Resonant Imaging allows us to do just that. The difference is not unlike a ‘still picture’ versus a ‘video of a moving train’. PET scans, previously described, also can asses the functional state of the brain.

Whenever we do a task, think, dream, memorize, speak or see things, the brain is not activated as a whole; but only certain portions of it are activated. Activation, here, means increased metabolic activity of neurons in certain areas of the brain. Naturally, these ‘metabolically active’ neurons would demand more energy which would power them. The blood supply to these areas increases as a result of this metabolically driven vasodilation. The arteries then bring in glucose and oxygen with them, with Oxygen being transported in the form of Oxyhemoglobin (oxygenated hemoglobin or HbO2). Neurons on the other hand use up the oxygen contained in the blood, thereby reducing it to de-oxyhemoglobin or simply Hb. However, the alteration in tissue perfusion exceeds the extraction of oxygen by the neurons, so the concentration of deoxyhemoglobin within ‘the areas’ decreases. This causes molecular inhomogeneities in the magnetic field.

Oxyhemoglobin is diamagnetic, meaning that they align perpendicularly to magnetic field lines. On the other hand, deoxyhemoglobin is paramagnetic, i.e. it aligns parallely and proportinately with the intensity of the magnetic field. This causes the inhomogeneity within the magnetic field (magnetic susceptibility) in the tissue sampled. This inhomogeneity is exploited in fMRI in terms of decay of transverse magnetization, T2*, with longer T2* values in HbO2 blood and shorter values in Hb (paramagnetic) blood.Since this stems from the oxygen content in blood, fMRI is also known as the BOLD ((blood oxygenation level dependent) effect.

The machine is essentially the same as the MRI machine with echo planar imaging technology that permits faster imaging due to faster gradient switching, improved algorithm and faster CPU processing power. The patient/subject is placed inside the magnetic chamber and MRI signals are acquired, Fourier transformed and corrected for artifacts. Finally the computer reconstructs a 3D fMRI image out of this.

As is obvious, we can learn about the motor areas of a patient by asking him to grasp an object or giving him any motor task and noticing which area(s) of the brain lights up. A neurosurgeon can then be cautious about not hurting these areas. Similarly, the mapping will help spare motor and other vital areas like auditory, visual and language areas from damage in radiotherapy procedures, in addition to neurosurgery. It can also detect occult Alzheimer’s disease and cognitive deficits including those of the autism spectrum and dyslexia (reading disorder).

fMRI can also be employed to ‘read peoples’ minds’, thoughts, intentions including lie detection. Watch the video below which explains how an fMRI scan is done and interpreted.


Thus the legal and forensic implications are obvious. However, in fMRI, correlation doesn't always mean causation. Whatever it may be, it seems that fMRI is very much here to stay, both in the clinics as well as in cognitive neuroscience research. It may also be combined with tractography, MRI or other diagnostic radiologic modalities.

Hardenbergh et al combined Tractography techniques with fMRI, using a technique capable of rendering multiple color-coded functional activation volumes and fiber tract bundles. Many pharmacologically active drugs have effect on memory impairment, which can be seen in ‘telltale’ fMRI scans. Sperling et al studied the effects of lorazepam (a benzodiazepine) and scopolamine (an anticholinergic drug once used as ‘truth serum’ by the CIA) on healthy volunteers and found that they did impair memory and their functional coordinates could be reproducively mapped on fMRI scans (see figure on the left). I still shudder at the thought of what happened during my PG exam when I took a benzodiazepine.

Last modified: Mar 09, 2014
Reference: Integrated 3D Visualization of fMRI and DTI tractography
Gore, J. (2003). Principles and practice of functional MRI of the human brain Journal of Clinical Investigation, 112 (1), 4-9 DOI: 10.1172/JCI200319010

Relaxation in the Nuclear Microcosm

All of us want to give themselves a hard earned ‘rest’ after a “hard day’s night”, don’t we? So do the protons, perturbed by the destabilizing magnetic component of the radio-frequency pulse [which previously ‘happily’ aligned themselves to the externally applied magnetic field; one way (parallel) or the other (antiparallel)] applied at the Larmor frequency. It is like slapping an individual in a “merry go round” each time he came near a person who is paid just for slapping that person. But, when we call ‘spin’, we do not mean ‘spin’ the way we see them in a classical world. [We’ve given various names to the ‘quarks’: up, down, strange, bottom etc. depending on ‘something’ called ‘flavor’; and red, green and blue depending on ‘something’ called ‘color’.However, spin, flavor, color etc.‘in the quantum world’ have ‘no relevance’ to what we usually attribute to them in our everyday life. Things are a bit crazy in the quantum world, but I will take recourse to some ‘classical world’ analogies to make the description lucid.]

Thus, the already aligned nuclei (parallel or anti-parallel to the applied steady external magnetic field B0), has now been perturbed owing to the ‘knocking’ by the ‘magnetic component’ (B1) of the electromagnetic RF pulse. The nuclei gain energy and sway away from the perpendicular to the horizontal (90 degree) depending on how long the RF pulse is applied. So, now the nuclei behave like ‘punch-drunk’( like a person who’s been reeling due to a strong blow to the head!). Remember, that this new angular momentum is also a vector quantity having magnitude and direction. It can be resolved in terms of a horizontal component (Mxy) and a vertical component Mz. Anyway, the proton does recover from this situation, after some time, once the external RF field has stopped. Typically, Mxy component decays faster than the recovery of Mz.

The excited proton recovers in two ways and both forms occur simultaneously: (1) The excited nuclei which now have been ‘forced’ to lie horizontally (90 degree), ‘re-align’ themselves back to their ‘original position’ as they were before the RF pulse (perpendicularly towards the field of externally applied field B0); and (2) the energized protons dissipate their energies to the surrounding nuclei (horizontally) at their level. The first example, obviously, is called the (spin-lattice, or longitudinal) relaxation; while the second one, transverse relaxation (T2). There is little energy loss due to RF emission.

T1 relaxation, also known as, longitudinal relaxation or spin-lattice relaxation can be best understood if you see the following Youtube video. [The spiral trajectory, in this case, reminds me of the laser experiment I did to satisfy my lesser friends. Analogically, the trajectory would be such, if the power supply were switched off.] In T1 relaxation, the proton loses energy to the surrounding lattice, by interacting with nuclei in the lattice which are in vibrational, translational and rotational motion. Clearly, the surrounding nuclei (lattice) having the same (or nearly same) Larmor frequency will efficiently absorb energy of the excited proton, resulting in a tiny rise of temperature.

T2 relaxation (transverse or spin-spin relaxation) on the other hand, does not involve exchange of energy with the lattice.
The magnetic moments of the protons merely changes phase. Here, the nuclei exchange “quantum states” (kind of, what Einstein called ‘spooky action at a distance’): an excited nucleus (proton) will transfer its energy and relax, while the neighboring nucleus in the lower energy state that absorbs it becomes excited. This loss of phase coherence of spins can be clearly seen in this beautiful video.

It can be understood easily that T1 and T2 values would depend on the surrounding molecular environment (tissues, for example). Hence, the values differ in different tissues. Again, since Mxy decays faster, as described, it may be understood why T1 is greater than T2 (usually, T1=5T2). Both T1 and T2 contribute toward contrast in tissues. T1 relaxation time is the time needed for 63% of protons to return to their previous equilibrium state. Likewise, T2 relaxation time is the time needed for 63% of protons to become dephased owing to their interaction with nearby protons. The contrast, naturally depends on the water content of the tissues. Grey matter has about 10% more water than white matter and this creates a contrast. We can also create contrast by varying TR and TE times.

TR (Repetition Time) refers to the time gap at which consecutive RF pulses are applied; while TE (Echo Time) refers to the time delay between the applied RF pulse and its reception (echo). T1 weighted images (T1W) are produced by keeping TR and TE relatively short, while T2 weighted images (T2W) are produced by keeping TR and TE relatively long. Water molecules being relatively light spins much faster than the Larmor frequency, making energy transfer rather tough (exchanging of packets of energy becomes more efficient as the relative angular velocity narrows). Consequently, water has a long T1 time. Proteins and nucleic acids being rather heavy, spin slowly. They also have problem with energy exchanging, and thus have a long T1. Cholesterol, a medium sized molecule, precesses near the Larmor frequency, efficiently absorbing the energy and giving a small T1 value.Thus (fat) liquid cholesterol in craniopharyngiomas, a benign tumor, appears bright on T1W images (T1 being small, the rate at which RF energy is released is fast. Hence, the signal intensity in NMR is high).

Subacute hemorrhage also has shorter T1, due to the presence of paramagnetic iron in methemoglobin present in the tissue, hence high signal intensity. Cerebrospinal fluid (CSF), edema (collection of fluid in tissue space or ECF) having more water content have both long T1 & T2 relaxation time. They give low signal intensity in T1 (dark) but higher signal intensity (bright) in T2W images. T2W images are superior to their T1 counterparts in case of infarction, edema, demyelination etc. Contrast agents like the heavy metal Gadolinium, a paramagnetic substance, has been used to reduce both T1 and T2 times by introducing inhomogeneity in the magnetic field. Gadolinium is complexed (chelated) with a substance called DTPA to prevent toxic build-up inside body tissues. This gives high signal in T1W but a low signal in T2W. It (the complex) does not cross the blood brain barrier (BBB); but disruption in the BBB or parts of the brain where it is deficient (circumventricular organs), take-up the substance and affects relaxation properties.

Below is an MRI showing changes in Subacute Sclerosing Panencephalitis, a complication of measles. Note: Panels A and C are T1-weighted images; B and D are T2-weighted images. The hypointense (darker) signal on the T1-weighted image (arrow in A) and a hyperintense (bright) signal on the T2-weighted image (arrow in B) can be clearly seen.

Given all these, it can be said that relaxation parameters of nuclei have enabled us in visualizing biological tissues nonivasively, identifying chemicals spectroscopically and a lot more as we shall see later.

• References: Magnetic Resonance Imaging: David D. Stark, William. G. Bradley, Jr.

• NMR spectroscopy
• Magnetic Resonance Imaging
• Principles of NMR
• William P. Dillon. Neuroimaging in Neurologic Disorders. In: Harrison's Principles of Internal Medicine, 17th Ed., Volume 2, McGraw Hill; 2008. p. 2491-2497.
• Ian L. Pykett, Ph.D., Jeffrey H. Newhouse, M.D., Ferdinando S. Buonanno, M.D., Thomas J. Brady, M.D., Mark R. Goldman, M.D., J. Philip Kistler, M.D., & Gerald M. Pohost, M.D. (1982). Principles of Nuclear Magnetic Resonance Imaging Radiology
• Time constants

Last Modified: Aug 19, 2010

Toward An Objective Correlate Of Pain

While taking a hot water bag to find relief for a severe spondylosis pain, I wondered why pain could not be expressed in a way different from the generally used Visual analog scale. The patient is asked to look at a chart (shown in the figure) and told to rate his sensation, that tallies most well with his pain. If that hot bag were to be applied to a person not having any pain, he would jump almost instantly. The fact that I tolerated it so well (and benefited from it), only shows its countering (counter irritant property) property, which should be somewhat proportional to the severity of one's pain. The relationship of a counter-irritant to pain severity, whether linear, logarithmic or exponential, needs to be established and quantified.

A patient's own account of pain may be subjectively modified according to the personality of the patient and many other factors. As such, this type of quantification is liable to be erroneous. Pain should better be measured in an objective manner, free of bias. In this instance cited above, one could use the formula: Q(heat)=m(mass) x s(specific heat of the substance) x t(temperature), to know the amount of heat energy transferred to the patient. I am assuming that the pain relieving techniques will, kind of, obey Newton's Third law. Amount (intensity) of counterirritant that just suffices pain relief will be equal to the degree of pain. But it is not actually so, as we will see later.

By noting the difference in local temperatures before and after the procedure, one could get "t".
Mass or "m" could be measured by estimating the volume of the body tissue that was actually heated by infrared mapping, for example; and the expected density of that area. Specific heat for the tissue in question could be easily known and standardized using some cross-sectional studies. A suitable nomogram may later be drawn by plotting values obtained from such observations, for quick estimates. It seems logical that pain so measured, will have its units in British Thermal Units (btu), calories or their work (mechanical) equivalents like ergs, Joules, foot-pounds etc..

In pain therapies using mechanical energies (Ultrasound), electromagnetic devices (laser, short wave diathermy, high frequency photons such as X rays) , a similar formula may be used to obtain the pain equivalent. For example, in laser or short wave therapy, we may design a device that will measure the amount of energy in Watt.seconds/Joules the given area of tissue is supposed to absorb, over a given period of time. The chemical analgesics (pharmaceuticals e.g. Non Steroidal Anti Inflammatory Drugs or steroids; counter irritants such as capsaicin) may be quantified using Scoville scale or by evaluation on the degree of relief from algesia.

Calculating pain may be quite painful in itself. Pain sensation does not tally linearly with noxious stimulus. Rather, a logarithmic relationship was proposed in the Weber Fechner law, which held that the magnitude of pain (or a sensation) felt, was proportional to the log of the intensity of a stimulus. In other words, to feel twice as much pain, you needed to hurt 10 times! To complicate matters further, our present knowledge suggests that the magnitude of a sensation is related by a power factor to the intensity of that sensation. R=KS^A; where R is the sensation felt, S the intensity of stimulus, K and A are constants for that particular tissue. The brighter side is, we get a preformulated relationship for pain calculation.

Pain (musculo skeletal/ visceral, exogenous/endogenous) is generally of two types: fast pain and slow pain. Fast pains such as sharp pain of pricks, stabs are usually carried by Ad (A delta) nerve fibres, while slow aching pains are carried by type C nerve fibers. Ad fibres can carry impulses rapidly as these fibers are myelinated and are of large caliber. C fibers, on the other hand, are unmyelinated and narrow. A-delta fibres release glutamate and C fibers secrete substance-P. A way to measure these chemicals could be a step closer to quantifying pain.

The signals from these fibers travel to the thalamus, a part of the lower brain, on their way to the cerebrum for the localization of pain. Measuring the metabolic activity in thalamus, arising out of increased neural discharges there, by fMRI or PET scan may also shed some light on the intensity of pain stimuli (the stimulus at this level is unmodified by the higher brain) that reaches thalamus. We can also measure the blood levels of endogenous opioids (enkephalins, endorphins) which are secreted in body's response to the pain and adrenaline, secreted in response to increased sympathetic discharge, which is an usual accompaniment of pain. Their blood/plasma levels may correspond with pain severity. Other pain markers like bradykinin, histamine, potassium ions and proteolytic enzymes could be probed too.

True, that the patient may or may not feel as much pain as has been measured this way, because pain perception may not be proportional to the physical/chemical parameters thus described and it is not uniform in all subjects. The brain sees pain in its own mathematical terms, and everyones' brain is different in this regard. A soldier may overlook his gushing wounds, whereas pampered girls of rich persons may feel a lot of pain from an apparently trivial injury. But, quantification of pain in this way (by measuring the physical/chemical yardsticks) may correctly establish the severity of pain in silent myocardial infarction of neuropathy (pain sensation is dulled here due to neural malfunction), decubitus ulcers, trophic ulcers, malingering and in similar situations. In this way we may be able to find a better and objective correlate of pain in clinical practice and develop more efficient analgesics.

P.S. In a recent development, some objective physiological correlates of pain has been tracked. These include measurements from the nonlinear composite of heart rate, heart rate variability, amplitude of the photoplethysmogram, skin conductance, fluctuations in skin conductance, and their time derivatives.  Algorithms can then convert the data into a real-time, continuous index on a bedside monitor. This has resulted in the fabrication of a wearable sensing device can be mounted on a finger.

Last modified: Nov 28, 2015
Reference: hyper-links, unless specifically mentioned

Tobacco Trouble ?

For centuries this substance, obtained from the plant Nicotiana tabacum has entertained (or rather haunted) the human race. After Colombus's introduction of this habit into the new world, a tobacco epidemic has gripped the entire world. The addictive ingredient in tobacco is mostly nicotine, while its adverse effects on human bodies are largely attributable to its tar content. When smoked, about 4,000 different molecules are released and this includes the radioactive substance Polonium 210.

Not only the active smoker inhales it but also the 'sidestream smoke' it generates, makes passive smoking a reality. Nicotine is then rapidly absorbed from the lungs. The vast capillary networks surrounding the pulmonary alveoli aid its absorption directly into the blood stream. The onset of its action is very quick, since it takes only a few seconds to pass across the blood brain barrier. The blood-brain barrier acts as a frontier of defense in the brain, against many molecules thus protecting the brain.

Nicotine then liberates a long list of neurotransmitters including, noradrenaline, adrenaline (they make the heart race, pump more blood into the circulation, makes you alert, increases the blood glucose level and many related actions responsible for 'fight or flight reaction'), beta endorphin (a pleasure chemical in the brain, which binds to the opioid/morphine receptors), dopamine (a substance released from the 'reward center' of the brain ) and many others. These substances make smokers feel alert, cool and all the effects a smoker feels. These are the same chemicals that cause the serious cravings when one tries to kick the habit.

Nicotine, in addition, stimulates nicotinic cholinergic receptors in small doses, but depresses them in larger amounts. Tobacco causes a plethora of diseases. Cardiovascular diseases including peripheral arterial diseases; pulmonary diseases like emphysema, chronic bronchitis and cancers are just a few of them. It also decreases the sperm count, and even causes impotency (due to its vasoconstricting action).

But not all of us know that it guards against some diseases too. The frequency of ulcerative colitis, Alzheimer's disease, Parkinson's disease, and even breast cancers (in women harboring the BRCA gene =BReast CAncer) are statistically less in smokers than in non smokers. But the risks far outweigh the benefits it offers. Hence, kicking the habit is a more sensible option than to carry on smoking.

The Ubiquitous Symmetry

Ever wondered why our bodies are so symmetrical? I mean, if you cut our (and also other animals') bodies in half (don't do a Jack the Ripper though!), through a line that passes through the nose, navel, the perineum (i.e., a sagittal section); you get two halves, left and right, which exhibit a near perfect mirror image symmetry. Not only are they found in the animal kingdom; in a molecular level (e.g. in crystal lattices), and subatomic level (electron spins) too they exist.

The question naturally arises why nature exhibits this mathematical expression. A complacent and plausible explanation would be that it was an act of the evolutionary selection process (in the case of animals). A symmetrical body would give us the advantage in standing upright, against gravity. Assymetricality would mean a 'couple' (the couple/torque of physics: and not husband and wife!) working on the body, thus making it fall.

We should not nevertheless, ignore the plants' own aptitude in mathematics too. They are expert in number theories, in that, they exhibit Fibonacci sequence ( 0, 1, 1, 2, 3, 5, 8, 13, 21, 34......every number is the sum of the previous two numbers), fractal geometry (image to the left) and many others. Another interesting thing that amazes me about plants is the way the tree trunks so faithfully point towards the center of the earth, even on a sloping hill. In other words, the tree trunks could be considered as an extension of the earth's radius.

Lets discuss the point why and how we are symmetrical. When a sperm meets and combines an ovum, a zygote is formed. The cells in this zygote multiplies resulting in a ball kind of stuff, called the blastocyst. In this sphere like stuff, only the central portion remains, in the form of a disk, while the rest of the sphere disappears. This central disk then differentiates (=evolves into different kinds of tissues) into three layers: an outer ectoderm, an inner endoderm and an intervening mesoderm sandwiched between them. Now this three layered disk then folds in such a way so that the edges of the disks appose and merge. This merging point is the navel or umbilicus (and other midline structures), via which the fetus gets nutrition from the placenta, via the umbilical cord. The limbs like arms or legs form as an offshoot from this folded structure. No wonder then, that the growing fetus will be symmetric, since the left and the right halves including the limbs are forming almost identically from a single entity.

Dysmorphisms do occur though, despite all this. In the case of other animals too, this same kind of embryogenesis is seen (and expected too), as ontogeny repeats phylogeny.

Of Lightning, Photosynthesis and Electron Transport Chain

We all know that plants use solar energy to form chemical energy in the form of carbohydrates. The suns rays (photons) impinge on the chlorophyll of the green leaves. This excites them and raises them to a higher energy level. These electrons in turn, transfer their energies to another electron nearby and this process goes on till the energy is transferred to the reaction center, where actual conversion of energy is occurring. This energy transfer occurs at a phenomenal efficiency of about 95%. In order to achieve such unprecedented (compared to about 40% in the most efficient solar cells) efficiency, the electrons should 'change hands' in an efficient way and not merely by a random walk.

The electrons do this by 'sensing' and sorting of the energy levels of different electrons (without ever actually having to go to these places for sensing: what Einstein called spooky action at a distance). How the electrons found the right path so as to reach the destination (to electrons with a lower energy level) quickly and efficiently remained elusive. Now scientists perhaps know the reason. These electrons do some kind of quantum computing to arrive at their destinations with unprecedented efficiency.

This premonition of 'unsorted databases' is characteristic of the quantum computing algorithm. Like gamma synchrony, regular patterns of signals lasting several femtoseconds were found, when the chlorophyll molecules were mapped by using electronic spectroscopy. As in dendritic networks, these 'quantum beats' 'bind' (synchronize) all the energy levels of electrons together. Thus these quantum beats help electrons find out the 'path of least resistance' in such an astonishing efficiency. It is as if the energy status of the electrons were indexed as in a computer search algorithm, so that they could be found out faster.

A similar mechanism may be involved in our mitochondria where electron transport chain occurs. Electrons are transported in the mitochondria along a series of electron acceptors to end up ultimately in cytochrome c, where they combine with oxygen, the ultimate electron acceptor, to form water. This chain is very important as it generates ATP, our own energy currency. Quantum entanglement may explain the subject in a new light.

Just a thought in passing, it is said that lightning follows the path of least resistance. I always wondered how it would know where to advance to next, since it had no prior information about what lied ahead. Now, this quantum computational algorithm may be the suitable one to address this issue.

Cerebellum-Part3

Just as a phosphorescent object is best seen in absence of light, the functions of some organs of our body is best revealed when they are removed or malfunctioning. The best known example is perhaps that of Best and Banting's discovery of insulin on their pancreatectomized dogs, (i.e. dogs whose pancreas was removed). Likewise, cerebellar diseases reveal many of its functions/things, the healthy cerebellum apparently didn't.

In about 1% of alcoholics, there is degeneration of the cerebellum, particularly the vermis, a midline cerebellar structure. The person develops nystagmus (jerky movement of eyeballs), an increasingly unsteady gait; superimposed on an unsteady stance. Vitamins and other medications are of little use. However, this instance clearly signifies the cerebellum's role in maintaining posture and movement.

Other posture and movement abnormalities like intention tremor occurs. Distance measuring and rapidly alternating tasks are also hampered. The cerebellum analyzes the 'error voltage' and stores the best response in its memory: all this data are destroyed in cerebellar disease. Thus when a patient reaches out for the tip of his nose, with his index finger, for example, the finger overshoots and gets past the target. This occurs as the relevant database as to how much force to be applied and for how long, before the brake (activation of antagonist muscles) is applied; are destroyed. This is known as past pointing. Now the patient understands it and tries to correct the error. He past points again, and this process goes on. Intention tremor results.

Related article: Cerebellum, electronically speaking
The Cerebellum- Part 2

Cerebellum: Electronically Speaking

Sometimes journeying into physiology textbooks can be a deja vu in electronics. The other day I was studying the way cerebellum learns from its past 'karma' and memorizes the best setting for an action. I was surprised to find that its learning resembled a lot with the op-amp (operational amplifier) ic's (LM741, for example) and its memorizing resembled to that of the EPROMs (erasable programmable read only memory, a picture of which is shown here on the left).

The cerebellum has one of the largest nerve cells of the body, the Purkinje cells, in addition to other types of cells. Purkinje cells have numerous tree-like branching dendritic processes. They receive two types of electrical connections; from the mossy fibers (about 250000 to 1 million fibers for each Purkinje cell) and climbing fibers (ONLY one for each cell).

The cerebellum fine tunes the movement that accompanies a certain task in the following way. The brain (lateral portions of the cerebellum and the basal ganglia) 'plans the action' even before we start an action. After the task has been executed, the cerebellum calculates the 'error', the difference between the planned trajectory and the achieved output in much the same way a does.

In the figure on the left, the op-amp is configured as a negative feedback, through resistance R2 which feeds a portion of output voltage back into its inverting input (since input is fed into its - terminal) amplifier. This way, the op-amp can have both a fraction of the output and input at the same pin, thereby the gain and other parameter remain 'stable'.


A still better analogy is that of the phase locked loop, the output phase of which 'locks' to the input frequency (diagram on the left). Likewise, the cerebellum too matches its expected action with that of the resulting action. The cerebellum is 'happy' with the performance when the error is minimum. At this moment of bliss, the climbing fibers fire for a long duration and with a characteristic waveform: a spike followed by a long trail. Now the information is written permanently.

Doesn't our experience of programming a 2716 (EPROM) tell a similar story; a peak programming voltage and a normal working voltage? When we wanted to program an EPROM, we needed to give it a high programming voltage in the beginning, followed by a steady 5 voltage thereafter till the EPROM 'learned'.

It doesn't end here. In the cerebral cortex, memory is consolidated in sleep, when it receives a spike voltage: the k-complex in the NREM stage of sleep. It seems that we have a micro, or may be a pico-controller in our brain.

To be contd.

Cell Voltage In Biology

The vibrations of the Big bang, which occurred billions of years ago, can still be found in the form of CBR (cosmic background radiation). They envelop the universe even today. Similarly, our cells continue to bathe in the salinity, as we are said to have evolved from our marine ancestors. Hence the concentration of Sodium and Chloride(ions, Na+, Cl-) in the outside of the cells are more than that of the interior. Naturally, Na+ would tend to diffuse to the interior, down the concentration gradient. Again, Na+ being a positively charged ion (cation), is also attracted by the negative charges in the inside of the cell. Thus there must be a mechanism to expel the intracelluar Sodium to the exterior. Here comes the enzyme Na+K+ATPase. It does its job at the expense of energy in the form of ATP (adenosine tri phosphate), a high energy phosphate compound. While it drives out 3 Na+, it lets 2 Potassium ions (K+) in, building up electronegativity in the process, as there is a 'net loss' of one positive charge from the interior of the cell. Thus the inside is negative with respect to the outside. Other factors like the negative charges of intracellular proteins also contribute to the intracellular negativity.

The electrical cells (dry cells, lead acid, nickel cadmium, lithium ion etc.), also produce/store electricity in the form of ions. But in addition to the above generalization, biological cell voltages may vary rhythmically (pacemaker cells), in response to a stimulus (action potential, generator potential) etc.. Not only that, the polarity of the cell (inside +ve; outside -ve), may even reverse (depolarization), which most commonly occurs due to influx of Na+ into the cell. Similarly, entry of chloride ions inside the cell or efflux of K+ (potassium ions) to the outside will lead to more negativity inside. This is called hyperpolarization.

Depolarized nerve fibers (depolarization occurs in other tissues too) carry spreading impulses along its axons just as electricity is carried by wires. Thus cells are not just batteries, they have wires fitted with them. The myelin sheath, its (axon's) covering, acts as the insulator while the interior (of axons, broadly speaking) acts as the ionic conductor.

When this insulation is breached, current leaks and demyelinating diseases like multiple sclerosis result.

Related Links: Cell voltage animation, shockwave flash
Pacemaker potential generation
Last updated: Aug 19, 2008
References: Hyperlinks provided

The Baffling Hairs

Scanning down the evolutionary tree, one can find semblances with our ancestors (naturally, as a part of the legacy). But there are instances when one can not explain certain things. For example, in humans we find hairs in the axillary areas (armpits), pubic areas which seem to defy logic, from an evolutionary perspective. Goats, lions or chimpanzees don't have them. Why in the first place did we need to have them or what is the purpose they serve, or couldn't have we done without them? We don't find any evolutionary parallel in the vertebrate kingdom (to the best of my knowledge).

One might say that the conversion of testosterone to dihydrotestoterone, in the said areas, by 5 alpha reductase, is the reason why they grow at those places. This DHT ( dihydrotestoterone) then combines with its receptor within the cytoplasm of the cells, and the receptor- ligand- combine translocate to the nucleus to exert their effects. My point is not that. I just want to know why, all of a sudden, humans needed to grow 'beard' at those odd places. I mean, what's so Darwinian about this?

One reason that seems to make sense is that those hairs at the intertriginous areas may help reduce friction while we move. But I am not sure, as it has not yet been documented. There are instances where there are excessive body hairs all over, hypertrichosis (a condition that could even be caused by the antihypertensive agent 'minoxidil') or hirsutism, where females produce excessive body or facial hairs. How heavily a woman is 'furred' could be determined by Ferriman Galway scale. Well these conditions do NOT have a predilection towards those key areas (that is, they are not axilla/pubis specific) and we can safely discard them as not being relevant here.

Body hairs may have some roles in heat regulation (erection of hair [known by various terms as: horripilation, goose-bumps, piloerection, cutis anserina etc. etc]---> increased depth of skin---> more insulation, provided by the subcutaneous tissue occupying this place). Body hairs could also provide superficial protection, or the maintenance of beneficial microbial flora, what purpose these intertriginous hairs serve is a mystery.

Another possible explanation is that, hairs being great thermal insulators (and electrical too), can prevent the heat of the adjacent thigh skin, to reach the testes. The testes are normally cooler than the core body temperature by about 2 degree centigrade. This way they may be doing great evolutionary service, by letting us procreate.
Can you shed some light on this thread?

Crazy Little Thing Called Life

Scientists have recently discovered a body of evidence regarding the existence of water on the red planet and has, for obvious reasons, gone gaga over it. They are conjuring up all the possibilities of existence of life on it.

Well, what are the basic ingredients of life? Are carbon, hydrogen, nitrogen and similar molecules extremely essential (mandatory) for life? What constitutes life and above all, how is life defined? If prions, (which are nothing but misfolded proteins, the cause of a myriad of illnesses like mad cow disease, kuru, scrapie and various other diseases) can be counted as living organisms, then perhaps any complex molecule or even radioactive elements like Polonium 210, which disintegrates on its own, to form many other elements, which in turn disintegrates (reminds me of Iron Maiden's 'Seventh son of a Seventh son' song), may be said to have life too, for they undergo an automatic activity. If you pore into the inside of an atom, you can see interactions in the nucleus: mesons; orbiting electrons around them, dutifully obeying Pauli's principle and many such activities that mimic life. Or are they living things themselves?

( En passant: Polonium 210 is found in tobacco in minute quantities; it was used to poison the famous Russian political dissident Alexander Litvinenko).

Life on earth perhaps needed the carbon skeleton, or it may even have been due to a chance occurrence. Microorganisms have been discovered in conditions in places, hitherto considered inviable for life (Bacillus stearothermophilus, B subtilis, Thermus aquaticus for example). The constituent of life could be molecules other than the conventional ones, even anti-matter! If we zoom in, we find tissues, cells, microtubules, mitrochondria, nucleus, the DNA and various other things which themselves are teeming with life. Zooming further still, we enter the constituent molecules to find the hadrons and the leptons, deeper still, quarks and gluons etc etc. They all seem full of life to me.

Look at the celestial objects. The sun is said to be a middle-aged star. So? Heavenly objects sometimes die a violent death: in supernova, or turn into neutron stars or black holes or some 'dwarf's. And the universe is said to have been born in the form of a major birth pang called the Big Bang. Are they living things then?

We know that there is a very small probability of finding two exactly similar humans, having all identical attributes. Likewise, no two electrons orbiting the nucleus can have the same quantum state, as per Pauli's exclusion principle (teleportation using entanglement/twiddling is an exception, for here two particles at a distance have the same properties) . This only shows that like unique human minds, the not-so-living things can also have their own uniqueness. Can they be said to have a life too, for they too move, have mass and energy. What about a cellphone or a computer or anything having AI(Artificial intelligence).

Let's be introspective. You are as much life as I am and we are made up of molecules arranged in a particular configuration: just matter; but where is the life? It may be here, in the entity called consciousness. Consciousness may be explained in terms of interactions among material elements. When we are dead, what exactly is missing? We may be brain dead, but the transplant surgeon may take out the kidney or cornea to transplant on others. Thus even after we die, we still continue to live in some of our tissues: they remain alive!

The question of life has to be addressed holistically, if we want to arrive at a sane and unanimous conclusion. Till then controversy will rage.

Women On Top

Today, the 8th of March, is the International Women's Day. Lets celebrate one more time to the health of the fairer sex. Though throughout the animal kingdom(almost), it is the male who looks better than the other of the species (take the case of a lion or a horse or a peacock, you will instantly realize who looks better), in the case of human beings, the situation is starkly the opposite. The females have a melodious voice, a glowing skin, a beautiful figure and what not.

They even have the genes on their side. When one considers the sex chromosomes, there are two X chromosomes in females vs one X and one Y chromosomes in the males. That way, they have less of many diseases including hemophilia. But they pass the bad genes onto the hapless male offspring, courtesy a poor Y chromosome. Their roles as mothers, daughters, girlfriends, or wives (bear in mind that not all wives are bad!), are irreplaceable in the society.

We must also be grateful to them that they don't eat us alive. Look at the sexual cannibalism that goes in the animal kingdom. Though the term is sexual cannibalism, actually it means devouring of the males by the females, always. It is practiced by the spiders, scorpions, mantids, and others. We are lucky, in that we are not bullied to that extent. We are a wee bit safer at the top ( of the pyramid) of the evolutionary tree.

So, next time don't grieve for the black widow spider, shed your tears for the male spider instead. God save the queen, and to hell with the king. Who bothers?

P.S. This article is dedicated to the most beautiful creatures on earth. Though some jokes have been cracked, it is really them who make us smile. Femme fatale, cherchez la femme, etc., are not only misleading but also misogynistic. I would rather say: 'No woman no smile' ( to rhyme like the Boney M).

Can't Spam The Ovum

Do you have the courage to ask your friends to spam your email inbox? I guess not. Though I will not be talking about e-mails in this post, I'll only compare the challenges a tiny ovum throws to a spam (flock) of sperms and wins the challenge too.

During procreation, sperms from the males are ejected (ejaculated) through the external urethral meatus. They get vigor (energized, by the action of fructose, a simple carbohydrate found in the vagina; a process called capacitation) in the female genital tract. Spirited and intoxicated, as they become, they (actually, millions of them) now charge towards the lonesome ovum like a raging bull (of Spain!). But this microscopic ovum is quite fussy in choosing just one (among say those 200-300 million!) .

Whether the ovum chooses the sperm or any random sperm or the fittest sperm chooses the ovum is something I do not know. Nobody knows for certain. But the accepted theory says it is the random sperm that hits the bull's eye. As it takes two to tango, the sperm and the ovum dance a jig and they drop their "veils" (polar bodies). They kind of, have a one to one talk, before they finally unite to achieve their goal (zygote).

Meanwhile the 'other' sperms continue their ova-ward journey, but now that the ovum has activated it's own firewall, it dodges them very efficiently. This firewall called zona pellucida is active once one sperm has unloaded its DNA in the ovum.

May be we can improve our own computer's firewall if we learn the ova's dialect. We have learned a few things like AI (artificial intelligence) from our knowledge of the brain and the plasticity of its synapses.

What happens next is very interesting. The 'ball of cells' (blastocyst) metamorphoses into the animal that are us. This is what Embryogenesis is about.