Thursday, March 29, 2007

Yellow - Off, Blue - On: A new neural code that could help epileptics

While there has been some work on a light therapy for Bipolar disorder, and specifically limiting exposure to blue light to keep the circadian clock in check; this time the effects of blue and yellow pulses of light , deep inside the brain, as investigated by an MIT team, have resulted in a promising treatment for epilepsy.

Epilepsy, as we all know , is caused by excitation of neurons at a focal point and the subsequent spreading of that activation, so that all or a majority of neurons get excited at the same time. The normal treatment , in case the epileptic fits become life threatening, is neurosurgery, or removing the brain area around the focal point.

This research has focused on the effects of yellow pulses of light, inside the brain , on neurons engineered to express the halorhodopsin gene, a gene that responds to yellow light by opening the chloride ion channels. This results in a hyperpolarisation of the cell and thus ensures that the neuron doesn't fire easily. I believe they have performed the experiments in laboratory cultures (in vitro) and plan to replicate on transgenic mice containing this gene, so it is a long haul from here to some actual treatment options for epileptics. Still the possible applications are fascinating:

Many epilepsy patients have implanted electrodes that periodically give their brains an electric jolt, acting as a defibrillator to shut down overactive neurons. This new research opens up the possibility of an optical implant that could do the same thing, using light instead of electricity. The Media Lab neuroengineering group plans to start studying such devices in transgenic mice this year.


Thus we have a radically new treatment option for epilepsy. It is also pertinent to note that the same group had earlier identified a mechanism whereby blue pulses of light could lead to excitation of the brain. thus, with appropriate implants in the brain, one can , using light, control the excitation and inhibition of neuronal circuits. What advantages these offer over traditional electrode implants needs to be seen.

The group also plans to use the new method to study neural circuits. Last year, Boyden devised a technique to stimulate neurons by shining blue light on them, so with blue and yellow light the researchers can now exert exquisite control over the stimulation and inhibition of individual neurons.


Lets hope they succeed in their efforts, not only to help epileptics with non-surgical treatments, but also to more deeply 'see' the neural circuits and the neural codes.


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Beware of the mouse who knows when it is in a trap (or den or nest or bed)

We all know that even a mouse is a tiger in its own den. But for that mouse to become a tiger it must have an awareness of when it is in a den and when it is'nt. Till now, knowledge of abstract concepts like a den or a nest or a bed or a mouse-trap were limited to humans and higher primates. Mice, being such lowly creatures, were not supposed to have abstract concepts and though they may remember a particular den or nest as their own, when placed in a new nest they would supposedly be not aware that the enclosure/ furniture can serve as a nest. To put things simply, they were not supposed to identify objects based on their functionality. If one changed the shape or size of the nest, or the construction material, then they were supposed to get confused and would have not able to still identify the object as a nest or a bed.

All that has become history now, with a new study (pdf) that clearly demonstrates that the mice have abstract concepts in their mind and that specific neurons in the hippocampal area fire when the mouse is in a bed or is entering / exploring one. We already know that we have place cells in hippocampus that fire when a mouse is in a particular location in space and that these are tied to episodic memory. Hippocampus has also been involved in learning mechanisms and it is only appropriate that we discover concept cells in hippocampus that fire when different concepts like bed/ nest/ trap are encountered. And of course we also know of Halle Barre neurons in fusiform gyrus that fire when viewing a particular face.

In this study,the authors found that there were three kind of cells in the CA1 region of the hippocampus, that had distinct firing patterns related to the concept of nests. Whenever a mouse encountered a nest , the transient-on class would increase their rate of firing. If the mouse was not facing the nest, then these cells would not fire; only when the mouse was facing and about to enter the nest were these neurons firing. The second group of neurons were the persistent-on ones, which would fire at a very high rate once the mouse was in the nest and would continue to do so till the time the mouse left the nest. The third type were juts the opposite of these - the persistent- off ones that ceased their normal firing rate, once the mouse entered the nest. Perhaps the rat have not only a concept of nest , but also of not-nest. The base firing of the persistent-off neurons may be a signaling mechanism within the mice brains to indicate that the mice is not in a potentially homely place.

You can read more about the study at the Neurophilosopher (and there you'll also find a great video of a mouse in the study exploring the nest, along with firing neurons) , but what I am amazed is that inst it logical then that the mice also have a concept of a trap - a potentially dangerous enclosure. And whatever variations we may make, isn't it evident that just like we can recognize a trap in its various guises, the mice too can. Making them of wood or metal or of different sizes should not matter. Thus, if the mouse has been exposed to a trap once, there is no use trying to lure it in trap of different type? But maybe I'm just being pessimistic; maybe the lesson we can draw from this study is to make the traps similar to their 'nests', so that they are comfortable and eager to enter in the trap. At long last a study that leads to better mouse traps!


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Wednesday, March 28, 2007

Depression, Neurogenesis and Spatial navigation

We all know that hippocampus is the seat of both memory as well as spatial abilities (cognitive map theory). We also know that most of the neurogeneisis in adult humans happens in hippocmapus. We also know that depression is caused by stress and both stress and depression lead to or are correlated with reduced neurogeneisis in the hippocmapus (my learning helplessness theory of depression) .

Now a new study has found that depressed people have impaired spatial navigation abilities. Putting 2 and 2 together it is highly plausible that this relationship between depression and impaired spatial navigation is mediated by the reduced neurogeneies or atrophy in hippocampus.

Relatedly, a good article (pdf) regarding how new anti-depressants are targeting neurogenesis in hippocampus as a mechanism to alleviate depression.

Three cheers to the cognitive map theory- the focus with which this blog started!!

Hat Tip: BPS Research Digest

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Simulating the future and remebering the past: Are we prediction machines?

This post is about an article by Schacter et al (pdf) regarding how the constructiveness of memories may crucially be due to the need to simulate future scenarios. But before I go to the main course, I would like to touch upon a starter: Jeff Hawkins Heirarchical Temporla Memory (HTM) hypothesis. I would recommend that you watch this excellent video.

As per Jeff Hawkins, we humans are basically prediction machines, constantly predicting the external causes and our responses to them. Traditionally, the behaviorist account has been that we are nothing but a bundle of associations- either conditioned pavlovian associations between stimuli and stimulus-response or a skinerrian association between our operant actions and environmental rewards. Thus every behavior we indulge in is guided by our memory of past associations and the impending stimulus. Jeff Hawkins refines this by postulating that we are not passive responders to environmental stimuli, but actively predict what future causes (stimuli) are expected and what our response to those stimuli may be. Thus in his HTM model, the memory of past events not only exerts influence via a bottom up process of responding to impending stimulus; but it is also used for a top-down expectation or prediction of incoming stimulus and our responses to it. Thus, we are also prediction machines constantly using our memory to predict future outcomes and our possible responses.

Now lets get back to the original Schacter article. Here is the abstract:

Episodic memory is widely conceived as a fundamentally constructive, rather than reproductive, process that is prone to various kinds of errors and illusions. With a view toward examining the functions served by a constructive episodic memory system, we consider recent neuropsychological and neuroimaging studies indicating that some types of memory distortions reflect the operation of adaptive processes. An important function of a constructive episodic memory is to allow individuals to simulate or imagine future episodes, happenings, and scenarios. Because the future is not an exact repetition of the past, simulation of future episodes requires a system that can draw on the past in a manner that flexibly extracts and re-combines elements of previous experiences. Consistent with this constructive episodic simulation hypothesis, we consider cognitive, neuropsychological, and neuroimaging evidence showing that there is considerable overlap in the psychological and neural processes involved in remembering the past and imagining the future.


As per the paper the same brain areas and mechanisms are involved in both remembering a past event and imagining a future one - and the regions involved include the hippocampus. These findings in itself are not so fascinating, but the argument that Schacter et al give for , as to why, the same regions are involved in both memory retrieval and future imaginings, and how this leads to confabulations and false recognitions is very fascinating. As per them , because we need to simulate the future events, and as the future events are never an exact replica of past events, hence we do not store the past events verbatim, but store a gist of the event, so that we can recombine the nebulous gist to create different possible future scenarios. Due to this fact (the need for simulation of future events), the memory is not perfect, and in normal individuals it is possible that they confabulate (attribute the source of their memory erroneously) or make false recognitions on memory tests like the DRM.

Fisrt a bit of background on DRM paradigm. In this test, a list of related words are presented to a subject: eg yawn, bed, night, pillow, dream, rest etc. All of these relate to the theme of sleep. Later in a recall test, when this thematically related word is presented to normal subjects, they most often say that they had encountered the word sleep earlier. However given an unrelated word like hunger, most are liable to recognize that the word was not encountered previously. What Schachter et al found was , that in those subjects that had damage to hippocampus/ other memory areas and were amnesics, this effect of confabulating the gist word was reduced. In other words, those with brain damage to memory areas were less likely to say that they had encountered the related word sleep during the original trial. this, despite their poor performance in overall remembering of old list items as compared to controls. This clearly indicates that remembering the gist vis-a-vis details is very important memory mechanism.

I believe that we should also take into account the prototype versus exemplar differences in categorization between the males and females into account here. I would be very interested to know whether the data collected showed the expected differences between males and females and hopefully the results are not confounded due to not taking this gender difference into account.

Anyway , returning to the experimental methodology, another sticking point seems to be the extending of results obtained with semantic memory (like that for word lists) to episodic memory.

Keeping that aside, the gist and false recognition data results clearly indicate that the constructive nature of memory is an adaptation (it is present in normal subjects) and is disrupted in amnesics/ people with dementia.

Thus, now that it is established that memory is reconstructive and that this reconstruction is adaptive, the question arises why it is reconstructive and not reproductive. To this Schacter answers that it is because the same brain mechanism used for reconstructing memory from gist are also used for imagining or simulating future scenario. They present ample neuropsychological, neuroimaging and cognitive evidence on this and I find that totally convincing.

The foregoing research not only provides insights into the constructive nature of episodic memory, but also provides some clues regarding the functional basis of constructive memory processes. Although memory errors such as false recognition may at first seem highly dysfunctional, especially given the havoc that memory distortions can wreak in real-world contexts (Loftus 1993; Schacter 2001), we have seen that they sometimes reflect the ability of a normally functioning memory system to store and retrieve general similarity or gist information, and that false recognition errors often recruit some of the same processes that support accurate memory decisions. Indeed, several researchers have argued that the memory errors involving forgetting or distortion serve an adaptive role.

However, future events are rarely, if ever, exact replicas of past events. Thus, a memory system that simply stored rote records of what happened in the past would not be well-suited to simulating future events, which will likely share some similarities with past events while differing in other respects. We think that a system built along the lines of the constructive principles that we and other have attributed to episodic memory is better suited to the job of simulating future happenings. Such a system can draw on elements of the past and retain the general sense or gist of what has happened. Critically, it can flexibly extract, recombine, and reassemble these elements in a way that allows us to simulate, imagine, or ‘pre-experience’ (Atance & O’Neill 2001) events that have never occurred previously in the exact form in which we imagine them. We will refer to this idea as the constructive episodic simulation hypothesis: the constructive nature of episodic memory is attributable, at least in part, to the role of the episodic system in allowing us to mentally simulate our personal futures.


I'll finally like to end with the conclusions the author drew:

In a thoughtful review that elucidates the relation between, and neural basis of, remembering the past and thinking about the future, Buckner and Carroll (2007) point out that neural regions that show common activation for past and future tasks closely resemble those that are activated during “theory of mind” tasks, where individuals simulate the mental states of other people (e.g., Saxe & Kanwisher 2003). Buckner and Carroll note that such findings suggest that the commonly activated regions may be specialized for, and engaged by, mental acts that require the projection of oneself in another time, place, or perspective”, resembling what Tulving (1985) referred to as autonoetic consciousness.


This Seems to be a very promising direction. The 'another time and place' can normally be simulated withing hippocampus that also specializes in cognitive maps. We may use the cognitive maps to not only remember past events, but also simulate new events. In this respect the importance of dreams may be paramount. Dreams (and asleep) may be the mechanism whose primary purpose is not memory consolidation; rather I suspect that the primary function of dreams is to work on the gist of the memory from the previous day, simulate possible future scenarios, and then keep in store those memories that would help and are likely to be encountered in future. Thus, while dreaming we are basically predicting future scenarios and sorting information as per their future relevance. Not a particularly path-breaking hypothesis, but I'm not aware of any thinking is this direction. Do let me know of any other similar hypothesis regarding the function of dream as predictors and not merely as consolidators.


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Body Posture affecting memory recall

First Mixing Memory wrote about it; and now Dave at Cognitive Daily was enchanted with this study that shows that if one assumes a body posture during memory retrieval, which is the same as the body posture at the time of memory formation, then the recall is better. I do like this study, and I think it is important, but am hardly surprised or overwhelmed by the results.

To explain the study in a nutshell (you are encouraged to read about the study at Mixing Memory or Cognitive Daily), the authors found that juts like some smells, sights or sounds can trigger associated memories, so too can the body posture. Now, to m this doesn't come a s a surprise because I have always been fascinated by the three other senses that are normally ignored by those who claim we have juts five senses: sight, sound, touch (includes all somato-sensory senses like pain , temperature etc), smell and taste. The three other senses that are normally ignored are Vestibular sense (or the sense of balance), kinesthetic sense (or the sense of self movement) and the proprioception sense (the sense of body position and posture).

Evidently if memory encoding uses some sort of sensory inputs to encode a particular memory, it is clear that memories would be assorted with all of the sense modalities and a trigger in any of them that is strong enough, can trigger that memory recall.

One can test this for the other sense too - the vestibular and kinesthetic - and one would find that one can recall memories better if the same vestibular or kinesthetic conditions are invoked. Experimentally one can have people dance, put them in merry-go-rounds, put them atop an elephant, let them drive, let them go up and down in the lift and ask for congruent or incongruent memory recall. I wont be surprised if the same effects are observed with the kinesthetic sense too. Maybe one of you can make this your thesis and tell me the results, so I can blog about it later!

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Tuesday, March 27, 2007

Get onboard The Tech Link Train

I was tagged on the Tech Link Train by Alvaro at the SharpBrains blog- many thanks! This is a "link train" of science and technology blogs, so lets get straight down to business.

If you are "tagged":

1. Write a short paragraph at the beginning of your post and link back to the blog that put you on the list in the paragraph. This isn’t a suggestion. You need to break up the duplicate content string. Someone took the time to add you so the least you can do is give them an extra linkback.
2. Copy the list of originals below completely and add it to your blog. If you would like a different keyword for your blog then change it when you do your post and it should pass to most blogs with that keyword.
3. Take the additions from the blog that added you and place them in the “Originals” list.
4. Add no more than 5 new technology, science, or consumer electronics blogs to the list in the “My Additions” section.

My additions:

Mind Hacks

The Thinking Meat Project

BrainEthics

Cognitive Daily

Mixing Memory


The originals:
Intelligence Theories and Tests
The Mouse Trap
Brain-based Business
Future-making Serious Games
The Thinking Blog
SharpBrains Brain Fitness
Developing Intelligence
Brain Hammer
SCLin's Neuroscience blog
Pure Pedantry
The Corpus Callosum
Madam Fathom
Memoirs of a Postgrad
Peripersonal Space
The Phineas Gage Fan Club
Neurophilosophy
Healthoma
Neural Gourmet
bio::blogs
Dr.Katte’s Blog
Brain Blogger
DigitalPhocus
Alpesh Nakar
OneTipADay
The How To Geek
The TechZone
Mega TechNews
Tech Buzz
Techzi
Connected Internet
John Chow dot Com
Ted Leung on the Air
Geek is a chic
you’ve been HACKED
IDIOT TOYS
JMH Techtronics
Web Services
UtterlyGeek
Tech It Like A Man!
Ugh!!’s Greymatter Honeypot
techboyardee
The Tech Inspector
Smart Machines
Kuiper Cliff
businessbytesgenesmolecules
MindBlog

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Encephalon #19 is online now!

Encephalon #19 is now online at the Peripersonal Space. This time it is themed around the misperceived dichotomy between reason and emotion and is served with a handsome and generous dressing of quotes. Rush over and fulfill your appetite.

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Thursday, March 22, 2007

Brave Heart: does will power reside in heart?

I have written earlier regarding the Heart Rate Variability, that is primarily caused by the Autonomous Nervous System (the opposite effects of PNS and SNS), and how a flexible HRV is related to better response to stress and reduced anxiety in face of external stressors. While looking at the evidence and linkages between HRV and emotional regulation, I had also speculated in it that a lower baseline or resting HRV may be reflective of depression and low regulation/motivation; while a high resting or baseline HRV reflective of Mania and high regulation/ motivation.

A recent study has looked into the issue of whether cognitive self -regulation (will power / motivation) is also associated with HRV. The study reported that higher baseline HRV was associated with more will-power and ability to resist temptation. Also, as they had surmised that will-power is a limited resource and hence the ability to resist temptation must exhaust the will- power ability, hence if the subjects showed higher HRV during the resisting temptation phase, then they would have exhausted their will-power reserves and would not persist in subsequent demanding tasks and this is exactly what they found.

The study consisted of measuring HRV, while the subjects were given a choice of eating cookies/candies or carrots. those who chose carrots over candies (thus exhibiting more will-power to resist the temptation of candies) also showed higher HRV.

In the second experiment, after the subjects chose candy or carrot , and hence supposedly exhausted their limited will-power cognitive reserves, they were asked to do a tough anagram exercise. Those who had chosen carrots were more likely to give up the task earlier. Yet those with higher baseline HRV showed high motivation and will -power regardless of whether they chose candies or not.

This I believe is a good corroborator of Higher resting HRV to be related to better self-regulation and mania , while lower baseline HRV to be related with depression and poor self-regulation. So maybe our hearts do tell us a lot about ourselves, our abilities to resist temptations and our will -powers.

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