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Showing posts with label behavioral neuroscience. Show all posts
Showing posts with label behavioral neuroscience. Show all posts

September 11, 2010

fMRI, BOLD and the Beautiful

ResearchBlogging.orgWhen 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) Effect of scopolamine and lorazepam on memory using fMRIon 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

April 02, 2009

An Anatomy of Noise And Its Implications

Noise is something we dislike, because by definition, noise means unwanted sound. But this definition is subjective, for what is music to my ears (say the heavy metal band Metallica) is noise to most people. In fact Iraqi prisoners were forced to listen to Metallica songs as a means of torture (culture shock and noise) by the American soldiers. Perhaps a better definition is, wrong sound at the wrong place at the wrong time.

Apart from acoustic noise; there is visual noise as found in television as ‘snow’, electronic noise (e.g. thermal noise or Johnson noise), cosmic noise and so on. Speaking of acoustic noise, one can’t help but think about the dreaded ‘noise pollution’ that seems to envelop us all. In addition to the nuisance it poses, it also causes anxiety, insomnia, increased blood pressure (hypertension), deafness and a hell lot of other bad things. So, it seems that noise is all bad. It’s not always so!

There is a disease called otosclerosis. In this disease, the footplate of stapes (a small bone in the middle ear) gets fixed to the oval window of the internal ear, producing conductive deafness. The patient can not hear normally as the ossicular (bony) conducting chain is at fault. But surprisingly, such persons hear well in noisy places (market, railway station). This phenomenon called Paracusis Willisii is said to occur due to the fact that one has to speak out real loud (over and above the background noise) in such places; thus making this loud voice cross the patients’ threshold of hearing. However, it may also be possible that the amplitude of the voice (in decibel) might ‘ride’ (summate) on the background noise amplitude, and this combined sound amplitude is heard by the ears. The brain then does some kind of fuzzy logic (or acts as a differential amplifier); and the ‘information’ is decoded. So, it seems that noise isn’t all that bad.

In ‘information theory’ even noise is said to contain information in it. One fine example that illustrates how visual noise might contain information is random dot stereography (and autostereogram). So, noise could be meaningful.

In diabetes mellitus, a very common disease across the globe, the blood glucose level rises. This and other metabolic products causes a condition called diabetic neuropathy, among other things. The person’s sense of touch is diminished and this results in inattention to sustained pressure(causes decreased circulation) or trauma to the affected area. This, along with the increased blood glucose and infection may then cause gangrene of the limb which might require an amputation of that limb. Cloutier et al have resorted to noise in an attempt to address the issue.

They applied mechanical noise directly over sensory neurons and have found that both vibration and tactile perception in these patients improved. This mechanical noise was christened as ‘stochastic resonance’ (stochastic means random or probabilistic; this particular term is coined since the frequencies are not tuned to match any particular frequency), and was applied at an imperceptible level. a biothesiometer, an instrument that checks vibration perception threshold or VPTThey applied this noise to the great toe of some of the affected individuals, while the controls received none (i.e. no SR). The effect was studied by measuring the vibration perception threshold (VPT). VPT was significantly lower in patients receiving SR compared to the controls (no SR). As the threshold was low, the patients’ sensitivity to detect vibration and tactile sensation improved. They hoped that a continually vibrating shoe insert could improve nerve function in these cases.

In another instance, Toshio Mori and Shoichi Kai of the University of Kyushu, Japan, showed that noise might improve brain function. They shone periodic signals (of 5 Hz flicker) onto the right eyelids and noisy signals onto the left eyelids of the subjects when they were at rest, and measured the intensity of their brain waves. Brain waves are electrical signals that occur in the brain due to the firing of neurons and are detected by electroencephalography (EEG). They found a sharp peak at 5 Hz, the frequency of the periodic varying signal. As they increased the strength of the noise signal relative to the periodic signal, a ‘harmonic’ peak emerged in the alpha wave band at 10 Hz. As the noise signal gained strength, this peak first increased and then diminished. The researchers believe that this harmonic peak is indicative of stochastic resonance in the cerebral visual cortex. Stochastic because of the non-linear way the brainwave behaves in response to the external stimulus. They argue that naturally occurring background electrical noise in the brain (from electron transport chains, neuronal activities) may play important roles in cognition and behavior.

However, not everything about noise is healthy as researchers from the University of California at San Francisco, USA suggest. They exposed healthy young rats to ‘white noise’, (random audio frequencies covering the full spectrum with randomly assigned amplitudes) and found that the development of their auditory cortex was delayed. They used electrophysiology tools to explore this. They also suspected that everyday environmental noise, also a type of white noise, could harm children by interfering with language acquisition and speech.

The story doesn't end here. Researchers have shown that noise has an important role in eukaryotic gene expression. When messenger RNAs (mRNA) are transcribed in the nucleus of a cell, they do so in a 'quantal' way; meaning that mRNAs are produced in spurt, in a stochastic (random) manner. The transcription process needs energy; as the promoter sequence have to be activated and for other biochemical reactions. This transcriptional noise may have implications in phenotypte diversity and cell differentiation process. Alternatively, bacterial pathogenicity may be increased by this 'noise' in gene expression.

The question is: should we scold our children when they continue with those awful noises? I am confused. But one more thing; it was this noise (in the microwave spectrum) that gave scientists the experimental proof that the Universe was expanding.

Last modified: never
Prolonged Mechanical Noise Restores Tactile Sense in Diabetic Neuropathic Patients.
Cloutier R, Horr S, Niemi JB, D' Andrea S, Lima C, Harry JD, Veves A.
Int J Low Extrem Wounds. 2009 Jan 6.

Noise in eukaryotic gene expression, doi:10.1038/nature01546

Noisy signals strengthen human brainwaves
T Mori and S Kai 2002 Phys. Rev. Lett. 88 218101

White Noise Delays Auditory Organization in the Brain

Noise, Wikipedia
Mori, T., & Kai, S. (2002). Noise-Induced Entrainment and Stochastic Resonance in Human Brain Waves Physical Review Letters, 88 (21) DOI: 10.1103/PhysRevLett.88.218101

November 08, 2008

Scientists Simulate Learning In Amoeba Using Memristor

It is surprising how small insects get energy from a wide range of food (not merely petrol or diesel), crawl, fly, reproduce and do so many maneuvers. Now it has been seen that amoeba, a unicellular organism, can learn and memorize too. We are far from creating devices of such versatility, let alone making them as compact as they are.

Amoebae can move, and they do this by changing the physical state they are made of: sol-gel state. The interior of amoebae contains endoplasm, which is in sol state; while the surrounding ectoplasm remains in gel state. The ectoplasm, being in gel state, is more viscous than it’s inside counterpart. When the organism moves, its contractile elements made of actin myofilaments contract, pulling the inside of the amoeba. This causes tension in the endoplasm, creating a change in the sol-gel state. If you squeezed a sponge ball that had been dipped in water, you would notice that water would spurt out from the pores of the sponge. Likewise, the increased tension inside, will create channels through the more viscous ectoplasm, courtesy some parts of ectoplasm (gel state) giving away (to sol state).

We know that reptiles hibernate in winter, when the humidity and temperature is low (we too are no exception). Amoebae too, slow their locomotion in response to these conditions. There are inherent oscillations within the amoeba (alternate sol gel transformation, changes in ionic flux etc) which are continuously adjusted with external signals like temperature and humidity. We, complex multicellular organisms, too have our own master oscillator (circadian clock) in the suprachiasmatic nucleus, which also continuously adjusts by lights falling on the retina.

Yoshiki Kuramoto of Kyoto University and colleagues subjected Physarum polycephalum, an amoeba, to three regularly-spaced dips in temperature and humidity, and found that its locomotive activity decreased. Thereafter, they noticed that a single dip was sufficient to elicit this response. It seems they adjusted their oscillations to the external cue and developed a conditioning later. The study implied that the amoeba anticipated that other such dips might be forthcoming, from the memory it learned. Such response did not occur when the temperature and humidity changes were irregular.

Memory in this case occurs due to the persistence of the channels etched by the organism in the ectoplasm. But this ‘memory’ did not persist for long, if we continued giving them a single dip instead of a regular triplet. This plasticity (change due to reorganization as a function of a stimulus) in amoeba has now been simulated with the aid of electronics by Massimiliano Di Ventra et al.

They used a capacitor, a resistor, an inductor in series and connected a ‘memristor’ in parallel with the capacitor. Memristors (for memory resistors)array of memristors are devices which consist of two layers of titanium dioxide (often present in medicine coatings and chewing gums). When current is applied to one layer, the resistance of the other changes. Leon Chua, of the University of California at Berkeley, predicted it long time ago; and now R. Stanley Williams and colleagues at Hewlett Packard have developed it. It can store memory like DRAM, but unlike DRAM it doesn’t forget when a current is no longer flowing. They hold promise as energy efficient chip for computers and we can also expect faster ‘booting’ of computers, since memory will already have been stored there. The adjoining figure shows ‘memristors’ in a row, as seen by atomic force microscopy (AFM).

Now when a current, fluctuating (AC) in a non periodical manner or a stable DC, was made to pass through the circuit, the memristor went to a low resistance state, virtually short circuiting and dampening the oscillation. However, with a regularly fluctuating current, whose frequency matched the resonant frequency of the circuit, the memristor went into a high resistance state, strengthening the oscillation. What connects electronics to amoeba is the memory that both the circuit retain. The memory of memristor, called memristance, is due to atomic rearrangement in the device. The high resistance state lingers for quite some time, so that next time one single pulse was necessary to put it into oscillation. This phenomenon is quite akin to the protozoal response.

It seems that those days are certainly not far when we will just need to jack-up a USB device in our head to boost up our memory.

Last modified: Nov 13, 2008
Reference: Tetsu Saigusa, Yoshiki Kuramoto (2008). Amoebae Anticipate Periodic Events Physical Review Letters, 100 (1) DOI: 10.1103/PhysRevLett.100.018101

October 28, 2008

Unlearning Memories: You Have Been Erased!

In the movie 'Eraser', John Kruger, played by Arnold Schwarzenegger, removed the identities and all relevant information of persons-at-risk and gave them brand new identities, to save their lives. The title of this topic derives its name from the famous dialog: "You have been erased!”.

In reality, memories can be erased too, even long term ones! In humans, diseases like Alzheimer’s dementia, cause defects in short term memory limiting further memory acquisition; which finally progresses to erasure of previously stored memories. In experimental animals, long term memories can be prevented if they are subjected to electrical shock, anesthetics (possibly work by disrupting London forces operating in hydrophobic pockets in dendrites thereby causing 'unbinding' of memory elements), hypothermia and other insults within 5 minutes of learning a specific task.

There are guardians of memories keeping a constant vigil so that ‘memories are forever’. For example, we have seen masons at work standing on those makeshift scaffolds. In our bodies too, a protein called PKM zeta constantly ferries across the synapse, to give its healing touch. A protein called PSD-95, when phosphorylated, takes the role of the scaffold, in this analogy. Inhibitors of PKM zeta cause loss of memory, as demonstrated in rats, when their memories for tastes vanished after a single ‘shot’ in their taste cortex. So, LTP is not the only mechanism that fosters memory and neural plasticity. Long term memory also uses gene activation and expression, and protein synthesis. Any interruption in either of these mechanisms will have its own deleterious effect.

Genes have been identified which produce proteins that are necessary for memory formation and their maintenance. These genes act fast in the central nervous system and are known as IEGs (Immediate Early Genes). IEG Arc, one such gene codes for Arc protein, which is abundant in the hippocampal neurons. Obviously, the mRNA (messengerRNA can be thought of as ‘command’ from a gene, while proteins are like the results of this command) for that gene is formed in the nucleus by transcription, but once transcribed, it goes to the dendritic spines (especially those which are active) along the cytoskeletal rail road formed by microtubules. In the dendritic spines they (mRNA) translate themselves into proteins, Arc proteins, in this example.

Guzowski et al did an interesting experiment. They infused antisense oligodeoxynucleotide (for the inhibition of Arc protein synthesis) straight into the hippocampus of rats. Antisense oligodeoxynucleotides (antisense ODN) are short sequences of deoxynucleic acids which block the translation of mRNA into protein. The rats forgot the tasks they learned, while they could still form new memories. Their spatial memory was badly damaged. They concluded that antisense oligodeoxynucleotides interfered with the maintenance phase of LTP.

rat negotiating Morris water mazeRats can be challenged spatially using the Morris water maze. As we see in the picture, the water pool has two raised platforms, which rats can locate (and remember) spatially after some training. Even the rats already trained successfully, lost this spatial (co-ordinates in space) memory and had severe difficulty floating, when they were challenged with these chemicals. Looks like, You Have Been Erased!

Contradictory (against the motion) Link: Memories like diamonds may be forver

ResearchBlogging.orgC. K. McIntyre (2005). Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus Proceedings of the National Academy of Sciences, 102 (30), 10718-10723 DOI: 10.1073/pnas.0504436102