Week 6 - Neurobiology and Behavior

I am currently taking a Visual Neuroscience class at UPenn and it has really opened my eyes (no pun intended) to the complexities of the nervous system, especially the visual system. There are so many intricacies to the vision that after 3 weeks of class, I couldn't even imagine how much more we were going to learn about vision because we had already covered so many things!

Anyway, to the point of this posting, I read a study that discussed the importance of corollary discharge signals in saccadic eye movement, which are the rapid, voluntary shifts in eye position between steady fixations. In this study, they recorded from certain corollary discharge signal neurons in a primate model. The recorded from neurons that were known to relay between the superior colliculus (an important visual center in the brain) to the frontal eye field. They then injected a certain chemical to inhibit the relay system and in turn found that the primates were no longer able to make saccadic movments between two fixed points and that the second saccade was completely off from the first saccade. So, what this demonstrates is that corollary discharge signals are important in mainting a steady visual precept despite sudden retinal shifts caused by saccades.

I just read an article in the science section of the NTY that I found very provocative and disturbing- "Scientists Try to Predict Intentions".

The story is this: scientists at Berlin's Bernstein Center for Computational Neuroscience have been studying the MRIs of people engaged in making decisions- at this stage of research the decisions are simple ones- whether to add or subtract two numbers, or which of two buttons to push. These neuroscientists were able to determine that the brain activity associated with decision-making is mostly localized to the prefrontal cortex region; further, by studying the MRI images associated with different intentions ("I will subtract" or "I will push the red button" they were able to identify what they called "thought signatures", patterns associated with addition, subtraction, etc. They claim to have "identified people's decisions about how they would later do a high-level mental activity".

At this point, their predictive accuracy rate is 71%, which is only 20% better than pure chance, but still, what astounding consequences this could have on our somewhat fragile civil liberties. Are the "thought police" far behind? In Britain, the article said, the powers-that-be are already keeping track of  known malcontents (who have not yet committed any crime)as potential future criminals. Throw in some really invasive technology that can identify intentions and you've got a sci-fi situation on your hands. Or a situation from our collective past- the witch trials of Europe or the McCarthy hearings in the US. Just add MRIs! Frightening stuff.

But, to be fair, the article also points out the fact that such resesearch and the technologies it may engender could proved enormpusly helpful for paralyzed people.

After reading numerous postings on motion sickness I began to wonder how we prevent it. Dramamine (dimenhydrinate) an oral medication and Transderm Scop (scopolamine) a patch you place behind your ear are perhaps the two most widely prescribed treatments. Having previous experience with both drugs I never realized they actually worked by crossing the blood brain barrier and acted in the central nervous system. After last weeks lecture it seems incredibly obvious now that the most logical place to send inhibitors would be the brain. Scopolamine (in Transderm Scop) works by inhibiting the secretion of saliva and sweat and decreasing gastrointestinal secretions and motility. More directly- the medicine works by reducing the activity of nerve fibers in our inner ear- which is as we discussed in class what brings about the discrepancy between the sensory discharge and the corollary discharge. Unfortunately from reading through the pharmacology of this medication I couldn’t distinguish between whether or not the drug is acting on one particular system-such as the sensory discharge- because it is directly reducing the movement in our ear, or if it is working on both sensory and corollary because it is effecting the entire system? Regardless, it is amazing that chemical inhibitors are able to have what seems to be pretty direct control over various inputs and expectations. With that in mind, perhaps I am missing something in the complete understanding of how the drug is working, but if we are able to develop a drug that is inhibiting one type of mismatch between sensory discharge and corollary discharge, then why can’t something similar be developed to control the sensations of phantom limb?Drug Info: http://www.rxlist.com/cgi/generic/transscop_cp.htm

When we discussed why we throw up when we feel a non-localized interruption of our corollary discharge, I started thinking about how ridiculous it is. I mean, the notion that our body's raction to unknown stress is sleep made me laugh. I had never thought about it like that before. I wonder, though, if it is the same with depression. One of the main symptoms of depression is an increase or disruption of sleep activities. Is it possible that the stress of the chemical imbalance or situation that provokes depressive episodes interferes with our corollary discharge in a way that parallels non-localized stress such as motion sickness? Do mental inputs have the same kind of painful effect on the body as physical ones?

Before taking this class, I was a strong advocate of taking responsibility for one’s actions. I believed humans were ultimately in control of their behavior (excluding patients who are mentally ill due to chemical imbalances, etc). Now, I’m starting to think differently, especially after learning about corollary discharge signals and central pattern generators. Our perceptions of our inputs are now jaded by corollary discharge signals and our movements can be performed without conscious thinking due to central pattern generators. I’m starting to think that after taking this course, I’m going to ultimately come to the conclusion that our own conscious thinking has very little to do with our behavior.

I also started wondering how these corollary discharge signals and central pattern generators are important in terms of evolution and life. I remember watching this discovery channel episode about the brain, where there was this study done to test participants ability to walk over hurdles (somewhat like an easy obstacle course) while listening to random words. At the end of the obstacle course, they were asked to recite the words said to them. Older patients remembered few to no words while younger patients remembered most of the words. The scientist concluded that older patients needed more of their brain to concentrate on walking and therefore could not concentrate on remembering the words. Younger patients were better at multitasking. That’s scary to think that as people age, their central pattern generators don’t function as well, and therefore repetitive tasks like walking require conscious thinking in order to perform.

This study exemplified how essential it is to be able to perform more than one task at a time as well as how important it is for our corollary discharge signals to monitor our inputs. Without such devices, we wouldn’t be able to sip coffee while reading, read while on the elliptical, see an unshaken world, etc. The benefits definitely outweigh the trivial costs of motion sickness.

After reading the post on autogenic feedback training, I began to think how dangerous such device could be. Maybe we are not in control of such autonomous nervous system functions for a reason. Maybe our nervous system knows what’s best for us. Tampering with the way our body is supposed to function always seems wrong to me because the body is so perfectly designed for a reason. That’s why I hate taking drugs (even Advil), because I believe that most of the time, our bodies are perfectly capable of dealing with its own problems. And most of the problems we face with our bodies are due to us not taking care of our bodies. I don’t’ know…. Just some thoughts.

  I was online looking for example of disorders associated with corollary discharge other than just car sickness and.  I actually found a couple of article and a student web paper from 2003 (/bb/neuro/neuro03/web2/mcoleman.html) that were on corollary discharge and schizophrenia.  From what I have been able to gather corollary discharge comes into play with individuals who have positive schizophrenic symptoms particularly auditory hallucinations.  Apparently for individuals with schizophrenia their corollary discharge does not work properly and they have trouble distinguishing covert speech, thoughts, from overt speech, things that are actually said.  I have never really though about it until this point but it would be really difficult and scary if you could not determine your thoughts from what you were actually saying!  Imagine thinking something terrible about a friend’s new hair cut and not realizing whether you were thinking it or actually saying it!

I think, further, this may have implications (as posted earlier) for perception.  If your corollary discharge is not working property there are huge implications on many levels.  Also, humans are all very different so I wonder if there are minute differences in our corollary discharge that actually cause us to experiences things different, not having as large an implication as in schizophrenia but still having an effect….just more to ponder…and to be thankful that as far as I know my corollary discharge is just fine, thank god!

So I was thinking about what we were discussing in class; that we can walk without thinking about it, type on a computer without consciously sending a signal to each finger at each moment, etc. I thought this was very interesting, and I happily continued to peruse the issue in my head. I thought about motion sickness and mixed signals, and about the blood vessels in your eyes that you don’t “see” even though they are there… I was merrily meditating on all these ideas, when suddenly I looked down and realized I had been taking notes on organic chemistry the entire time. I didn’t remember a lick of the stuff I was writing, but there it was, on the page. It was even legible and coherent. I found this rather amusing and startlingly appropriate.

Someone mentioned in one of their posts how they sometimes correlated personality with how the aforementioned phenomena might affect different people. Now, to be honest, I kinda feel that with all this talk about everything being “a product of the brain” and i-boxes within boxes and whatnot, our definition of personality has probs been mangled beyond recognition at this point, however, if I were able to send myself back to the time before I was enrolled in this class, back when things were simple, I would have said to you that I have a very “scatter-brained” personality. I am the queen of tangents. I am the empress of non sequiturs. I think nine things at once, and when I try to say them all they get garbled together and it comes out all wrong and is therefore usually interpreted as dirty(as most things are). A former boyfriend of mine was always complaining that I would be in the middle of a conversation with him and suddenly I would run away and start talking to someone else. When he would confront me about it later, I’d just get confused because I couldn’t remember that I hadn’t finished our conversation before I ran off and started the next one. My point is, I always wondered what the heck was wrong with me that new thoughts were always flooding into my head and I couldn’t freaking concentrate on one thing, that I could move on to something new without even realizing it. I guess what I am trying to say is that like walking, or typing, or taking notes while thinking about something else, the human brain seems to apply this concept of ignoring certain signals and focusing on others to everything, not just physical stimuli but “I-function” type (self perpetuated) stimuli too. I think that’s pretty sweet.

That being said, I think my “I-function” regulator is broken.

Maybe that’s what I’ll use as my excuse next time my friend yells at me because my room is a mess. I mean seriously, do you know how hard it is to clean your room with a busted corollary discharge monitor? Not easy my friends, not easy.

I read the short paper linked to the outline of our lecture which basically says that even people born without limbs--not just amputees--have phantom limb syndrome. This implies that we are born with an internal neural map.  So the neurons in the central nervous system that lead out to a hand that was either amputated or never there to begin with 'expect to see' a hand, but they just end at the stump of the limb, which causes the discordance and discomfort.  The important part is that the neurons have this expectation even without amputation. Think about the theory of tabula rasa--when we are born our minds are a clean slate. We know our brains are made out of neurons, like the neurons that go from our central nervous systems out to our hands.  If there is a map for the patterning of neurons from the central nervous system to the hand, wouldn't it follow that there is a map for the neurons in our brains?  Not really a clean slate, is it? There would have to be, considering we are born knowing how to breath, knowing when we're hungry--both processes are mediated by the brain.  But how far does this map extend into the brain? How much is there a map for? If there's a map for a hand that doesn't even exist, is there a map in the brain for connections that still are to be made? These might be questions more appropriate for a developmental biologist, but it's still interesting to consider the extent of our internal neural map.

According to a new study conducted by German scientists at the University of Bonn and published in the online edition of the Nature Neuroscience journal, the brain appears to function and process data more chaotically than previously believed. These researchers claim that the standard model in which information is received and transferred from neuron to neuron does not only occur at the synapses. This study suggests that neurons release chemical messengers along the full length of the extensions, thereby stimulating the neighboring cells.

More specifically, the researchers studied the "white matter" in rats' brains. This part of the brain holds the linkages between the left and right halves. These links are comprised of axons and ancillary cells, however notably lack dendrites and synapses. This implies that one would not expect to witness the release of messengers in this area of the brain. However, the scientists were capable of showing that certain cells in the white matter react to glutamate, a key neurotransmitter which is released when signals are found at synapses.

If correct, this groundbreaking discovery not only shatters widely validated findings about the brain and its fundamental mechanisms, but could also potentially lead to the development of new drug therapies.

I found the concept of central pattern generators (CPG) and corollary discharge sequences intriguing. They offer a means of understanding the nervous system in intriguing ways that reflect both the complexity of interactions associated with specific types of response, and the simplicity inherent in the physical manifestation of these responses. Yet I wonder how easily specific patterns can be fully identified and sequenced. In class we considered how such systems might operate within simple sea creatures. Using such methods to understand behaviors in humans however, is (and will be) exceedingly more difficult. (We are unlikely to remove body parts of people in order to identify patterns within the CPG.)

Artificial life, however, offers a means by which we can learn and speculate about CPG in different life forms. Researchers at the University of Hawaii, for example, are working on developing robots and other forms of artificial intelligence by modeling the neuromorphic pattern generator of their robots after the CPG in humans. Indeed, they have implemented the use of what they call a “very large scale integrated (VLSI) chip” containing oscillator circuits designed to mimic the output of motor neurons in a way that parallels the actions of the CPG with its inherent simplicity in the physical manifestation of the response. The result is that the robots designed by these researchers walk more “smoothly” with less of the ungainly awkwardness associated with the walking gait control of robots.

Link to NIH

I think one of the dangers of study in any field is becoming too narrowly focused on any one idea, and losing the grand integrative scope of things. This is not a critique, but a reminder I guess, something that we should always keep in mind. Neural control of body and brain is a huge part of the picture, but cannot be the whole picture. A central pattern generator may seemingly give us the ability to walk without thinking about it, but if our muscles did not have acetylcholine receptors we would not be able to move at all.

The mechanism of a central pattern generator is great for explaining how we can do things like walk without thinking about it, or (if we were birds) fly without learning how to. The mechanism of a CPG is not responsible for all the aspects of motor control though. Located along our muscles there are nerves with special receptors called stretch receptors, they respond to the stretching of one muscle that occurs when its antagonistic muscle contracts. The impulse elicited is neurally transmitted in a big circle (bypassing "conscious" control) and returns to the muscle in which it originated, and it causes the muscle to contract. This explains why we can spontaneously contract our knee and instead of getting stuck that way, it bounces out again. Because the muscle is contracted with a force proportional to the force with which it was stretched it also accounts for why we dont kick our doctor in the stomache when he does the pataellar tendon reflex test.

I think it would be inefficent of the brain to generate two patterns for each action, one for muscle (a) and one for muscle (b) the antagonistic muscle, or for it to generate a pattern that is twice as long because it specifies all contractions of muscles (a) and (b). It seems most efficent for our brain to take advantage of the role of reflexive motor mechanisms. Also if it does the latter it can utilize the contribution of gravity to the movement in order to expend less energy. So, for our brain to get its job done most efficently, it may utilize mechanisms and forces not under its direct control.

I came across an article in the New York Times, “Panel Finds Flawed Data in a Major Stem Cell Report”, that could possibly change the way people feel about stem cell research. In the past few years, there has been much arguing back and forth between people in the scientific, political, and religious worlds about research on stem cells, which were believed to be able to mature into any cell that a body needed. The problem that they could mainly come from aborted fetuses, but the benefit was that diseases such as Parkinson’s and Alzheimer’s would become things of the past. However, this article states that there are problems in the data that presented that stem cells could become any other cell in the body; those who have done the same experiments have come up with entirely different data, and the information is being reviewed by other scientists to see if it is still credible. While it is still uncertain whether or not the information is still viable, there is now a possibility that the high expectations that the both the scientific society and society as a whole had are incapable of being met.

http://www.nytimes.com/2007/02/28/science/28stem.html?em&ex=1173243600&en=229cb1df636c14d2&ei=5087%0A

In my intro bio class this year we had a bolg on muscle memory. When we had that blog I never really though about what was behind muscle memory, I was just trying to finish my post so I would credit. Now that I'm in neurobio, though, I find myself thinking about what is behind muscle memory. I think that it is very clear that we use muscle memory every single day. We don't think about how to walk, talk, or write. Does msucle memory completely cut out the brain and just rely on the motor neurons connected to the muscles in question or is it happening so fast that we just do not realize that our brain is being used?

I have read stories when a man with complete amnesia can still "remember" how to play the piano as well as he could before. This man can also still walk and talk. If this man can't remember anything else and has brain damage, why can he do these things? Is that part of his brain working fine or is it just not a part of these activities?

Another issue this brings up in my mind is when people totally forget how to do something. When I was young I forget how to talk. I couldnt form words anymore. Was my brain taking over and trying to control my muscles? Or were my muscles just not reacting to stimuli in the correct way? I'm sure every single person has tripped while walking. Maybe nothing at all was in your way, but suddenly your leg didnt move in the right way and you stumbled. This could be a momentary laspse in your muscles memory or could your brain just be handling too much and just forgets to tell your leg to move. I think that muscle memory is a very interesting topic that contains many questions, at least for me.

A central pattern generator is network of neurons found in the nervous system which is responsible for the generation of rhythmic behaviors such as walking, swimming, and breathing. This “motor symphony” of movement is not orchestrated by one unit, or conductor, but is the result of interaction between many semi-autonomous parts. Therefore, with CPG, an organism is able to exhibit rhythmic activity in the absence of sensory inputs. In class we discussed the development of CPGs as being genetic and/or the result of experience. CPGs are formed during early embryonic development where neuronal circuits are organized to enable spinal cord and brain stem circuits to generate efficient motor patterns, such as breathing. An illustration of the genetic origin of CPGs comes from the experiment discussed in class where new born birds where placed in straight jackets. After the period where a bird would normally ‘learn’ to fly had passed, the jackets where removed and the young birds were still able to fly.  This study indicates that the motor patterns necessary for flight are not learned. In order to further prove the genetic origin theory of CPGs it would be necessary to locate and change the specific gene and observe if the pattern changes (the motor patterns in flight, for example).  

What intrigues me is the idea that CPGs may be a result of experience and that these systems are modulated by sensory feedback. If CPGs induce natural rhythmic behaviors can the frequency and phases of a CPG be selectively modified to increase the accuracy and efficiency of a particular behavior? In searching for the answer to this question I came across an article by Paul S. Katz, David J. Fickbohm and Christina P. Lynn-Bullock. The article physiologically and morphologically identified specific neurons in opisthobranch mollusks shown to be part of the central pattern generator underlying dorsal swimming. They refer to these neurons as the dorsal swim interneurons, or DSIs.

The motor pattern for swimming is generated as a result of the properties of CPG neurons and their synaptic interconnections. Sensory neurons, which are located in the fused cerebropleural ganglion, synapse directly and indirectly on the dorsal ramp interneuron which monosynaptically excites the CPG dorsal swim interneurons. The DSIs synapse onto two other CPG interneuron types: cerebral neuron 2 (C2) and the ventral swim interneurons (VSIs).

The DISs are immunoreactive for the neurotransmitter serotonin. “Physiological evidence strongly suggests that the DSIs release serotonin and that it is used both as a classical neurotransmitter, evoking fast and slow synaptic actions, and as a neuromodulator, altering the cellular and synaptic properties of other neurons”. The effects of this modulation include the enhancement of synaptic strength and increased excitability of CPG cerebral interneuron 2.

When the DISs are active they evoke neuromodulatory actions on other CPG neurons modulating their cellular and synaptic properties. It would then be logical to assume that by naturally or artificially modifying DISs activity the resulting behavioral pattern of swimming can be changed, or enhanced.

What are some natural neuromodulators that affect central pattern generated behaviors in humans and can these be artificially modified in order to enhance behaviors? I’ll keep looking.

http://icb.oxfordjournals.org/cgi/content/full/41/4/962

Class discussion this week peaked my interest in motion sickness. Although I myself generally do not experience any type of motion sickness, I have family and friends who do. I have watched curiously as they have needed to sit in the front of a bus, open a window, or get out of a moving vehicle completely.

This week I read an article about Dr. Stephen Hawking, who has studied gravity and plans to experience a world without it in the near future. Dr. Hawking had plans to go into space. However, first, he has plans to participate in a space flight simulation of sorts.

The company that provides these simulation experiences is called Zero Gravity Corporation and has been taking “thrill seekers” on this specific ride since 2004 for $3,500 a trip. However, the company was founded in 1993 and since then has entertained about 2,500 customers. What interested me about the Zero Gravity Corporation, and about their trips, is the fact that since their first trip only 1 or 2 percent of their clients have become “spacesick.” This means that despite being nicknamed the “vomit comet,” relatively few people experience motion sickness on these flight simulations.

Although I can understand motion sickness on land and on the sea, I am confused by motion sickness and space travel. In class we discussed the fact that astronauts usually feel extreme motion sickness within the first few hours after take off. After those first few hours the motion sickness generally subsides and the astronauts are able to comfortably work, explore, and relax. When in this simulator, and when in a spaceship, individuals are obviously unable to view any movement. However, are they able to sense movement in any other way? Does gravity affect the way in which human beings sense movement, or do not sense movement? Does a lack of gravity eventually eliminate any disagreement between the sensory input and the corollary discharge signals sent to an individual’s brain that could cause motion sickness? Why are astronauts only get “spacesick” during the first few hours of flight?

This week’s discussion about corollary discharge was very intriguing to me. From what I understand, corollary discharge signaling is the phenomenon of the brain sending a signal to various muscles to create an output and a copy of the signal getting sent to the auditory system, desensitizing it so it doesn’t get overloaded. I read a very interesting article in the New York Times called “Block that Chirp: Volume Control in Crickets”. (http://www.nytimes.com/2006/01/31/science/31obox.html?ex=1173157200&en=d1f5c958d1946aec&ei=5070) In crickets, it has been determined that at the precise moment a cricket moves its forewing muscles to create a chirp, its auditory neurons become inhibited. However, no corollary signal is created when the cricket moves the same muscles- albeit in a different pattern- while flying. It can therefore be assumed that at the same time that the central nervous system sends a signal to the motor nerves, it also produces a corollary discharge that inhibits the response of the auditory neurons. This is of course the response in someone or something that has proper functioning of all of their body parts. But what happens when you have corollary discharge in a person who does not have this proper functioning? If you are mute, and you pretend to scream, will there be a signal that gets sent to your auditory neurons? Will they desensitize themselves even though you are not capable of making any noise? Is this like phantom limb, where an expectation signal is being sent out to the limb, even though the input signal is not present? Do mutes experience discomfort in the part of their body that expects to receive a signal but doesn’t in the same way that an armless person will experience discomfort in the area where their limb should be?

     Things like watching my finger move, and expecting images in the background to remain still are things I have always taken for granted. It's absolutely amazing how our brain can provide the complex function of keeping an image still as it moves across the retina through the interaction of corollary discharge signals.  But also, this brings up the point that the reality we perceive depends on if our corollary discharge signal are in effect, or how they are interacting. Corollary discharge signals might be interacting differently in different people and thus different people might interpret the same reality in different ways. Thus, a stampede of questions comes into mind.

 Is this part of  the explanation for individuality? Does this contribute to why we are all different from each other? Is it possible that we each may have different central pattern generators that generate patterns for the interaction of corollary discharge signals? Could this explain why people have different unique walks, different enough from another person to verify your identity?

http://news.bbc.co.uk/1/hi/technology/2712995.stm

Could this explain why our enjoyment of types of music varies from person to person? Why some have more rhythym than others? Does trying to explain these individual differences with central pattern generators and patterns of corollary discharge signals seem too farfetched?

We are all equipped with  generally the same brains, with the same parts and connections, capable of the same functions yet we are all so different with regard to personalities, skills and talents, and preferences. I personally think the variability of central pattern generators and how corollary discharge signals interact in each person might explain this.