I just got off the phone with my brother. He is a biology major at St. John’s so I trust him more or less on what he says. He was saying he just read a paper on nicotine. This is interesting in two ways; one the “Health Impact Fee” was just declared unconstitutional and more personally, I am a smoker. Before anyone jumps all over me, I know smoking is bad and it causes an enormous strain on the health care system. But is it all bad?
The paper my brother mentioned has to do with memory and cognition of smokers. It stated that after cessation the ability to recall information and to perform cognitive tasks was decreased. The use of nicotine replacement patches which deliver a constant dosage to the user is usually only recommended for no longer than six months. Well this paper showed that even after use of the patch, the subjects did not perform as well. This is over a half a year after the last cancerous inhalation. I have some papers on the genetics behind smoking and addictions in general. Basically some people are predisposed to certain addictions. I’m sure environment plays a role also. I didn’t start smoking until I was 22 and was living in Rome where everyone seems to smoke. But what really gets to me is that some people seem to think there is only one side to smoking, the bad side. So if anyone runs across this paper I would like to read it, my brother can’t remember where he read it. In the meantime I’m in the middle of finals and will probably go take a cigarette break now.

The finals are here and for some of us it is a time when we wish we could have done something different somewhere. We are not sure where but we still think that there was room for improvement and hope probably next semester will be it, this is a characteristic of the Type A person, who feels that the best is all that is desired no matter what. With the fear of finals, therefore comes the neurological question, 'where does fear originate from?’

Researchers began to find evidence that the amygdala was involved in the emotion of fear in the late 1930s. Then starting in the 1970s some scientists began using precisely controlled study designs to systematically map the brain's fear system. Research in rodents revealed brain pathways, centering on the amygdala, that were preprogrammed to respond to danger.

Accumulating revelations about this fear system led researchers recently to examine the human brain's response to fear with imaging studies. One study showed that pictures of frightening faces initiate a quick rise and fall of activity in the amygdala. In the future, scientists believe imaging techniques may help determine the course of treatment for disorders involving a malfunction in fear processing. For example, a person with an extreme fear of germs who continuously washes, known as an obsessive-compulsive disorder, often goes through months of behavioral therapy. The idea is to train the person to learn to overcome their fear.

Insight on the fear system also is motivating researchers to untangle the possible differences between fear and anxiety. Fear involves a quick hit-and-run process in the brain. Anxiety stirs a slower reaction that lasts a while. This suggests that the processing of the two emotions may be different. Indeed, early studies show that different parts of the amygdala may process anxiety versus fear. It also appears that some illnesses result from defects in these anxiety areas while others are more linked to fear paths.
Researchers also are examining the role of the amygdala in less distressing types of emotions, such as happiness. Whatever the case the use of the amygdala will be or has been more prevalent during the last few days, and hopefully will not be used till the next semester or for a while especially in conjunction to fear.

In the recent article of Nature(December, 2005) there was an interesting article called A painful factor which delves into the subject of allodynia or Neuropathic pain, which is pain that results from a non-injurious stimulus to the skin. The general known cause of this disorder is damage to the nerves that transmit sensory information (temperature, touch, etc.), and people with this condition experience crippling pain in response to a stimulus that is not painful normally. More, however is continually being learned about these mechanisms.
Recently it has been found, through research done by Coull et. al. (research which was also published in this issue) that injury to the nerves activates scavenger cells or microglia in the spinal cord which results in neuropathic pain. They have also shown that there is a critical link between the activation of microglia and altered sensory to neuronal processing. More specifically, a neuronal modulating protein called BDNF (brain-derived neurotrophic factor) was discovered to be the main mediator in signalling between microglia and neurons during neuropathic pain.
Experiments performed in the rat model proved that disrupting BDNF signalling was able to reverse allodynia which was already established. Many questions still have to be answered, including what signalling pathway eventually leads to the release of BDNF, but the outlook is optimistic for future treatments

I've reserved the 2530 computer lab (the one right next to the division office) for our final on Wednesday, at 4:00. You can type your essays, mail them to me, or print them out, or if you'd rather just do it long hand with pencil on paper, that's fine too. See you there!

International Business Machines Corp. (IBM) is teaming up with the Swiss Federal Institute of Technology to create a neural map of 60,000 cortical neurons. Through this study, they hope to further our understanding of the paths that neuronal communication takes, but I’m afraid that this study will not be as helpful as they expect. The area of the neocortical column being studied is 2 mm square, and comes from studies of multiple laboratory rats. Though this is a small area, the information needing to be processed in this study will be sufficient to fill 2,400 DVDs. This is a project of tremendous scope, but I feel that the information gained will only be applicable in very general senses. We are deriving all of our information from rats, and while mammalian nervous systems are very similar, neuronal positions might differ (within 2 mm) or neurons might be utilized in different ways. I think that the insight gained will most likely deal with the way that the layers of the neocortex communicate. Specifics involving precise cellular positions will not be of particular use, but building on the idea that different cell types are involved in different communication processes might be applicable to other nervous systems. The article describing this study was titled, “IBM: the computer brain,” and was found in Technology Review (Talbot, 2005). My biggest question about this project… What is involved in building a 5D model of circuitry?

Adrenoleukodystrophy, or ALD, is one rare genetic disorder among a group of disorders called leukodystrophies that affect the myelin sheath covering of nerve cells. In ALD high levels of saturated, very long chain fatty acids (VLCFA), accumulate in the brain and adrenal cortex. These VLCFAs are not broken down properly because the body does not properly produce the enzyme that is responsible for breaking down these fatty acid chains.

I was unable to find an exact mechanism behind why the presence of an excess of VFLAs acts to break down the myelin. One suggestion is that the accumulation of VFLAs may lead to an immune response that attacks the myelin. Another hypothesis is that VFLAs may act almost as soap does to dirt, allowing the myelin to become soluble, and in essence “washed away”. (http://carbon.cudenver.edu/~bstith/loren.htm)

As we know, many neurons rely on this insulating myelin sheath to function properly, loss of this myelin and the deterioration of function of the adrenal glands are the primary characteristics of ALD. There are two forms of ALD, X-linked ALD (X-ALD) and neonatal ALD.

X-ALD involves an abnormal gene located on the X chromosome. Research has identified a X-ALD gene on this chromosome that when mutated is responsible for X-ALD, and ruled out the idea that mutations on the VLCS gene being responsible for the disorder.

Because men lack the second X chromosome women carry, they are most affected by this disorder, and women are typically carries, with a few experiencing milder symptoms. Because the disorder affects the myelin sheath, which involves neurons in all areas of the brain, a wide variety and severity of symptoms may present themselves. Onset can occur in childhood or adulthood with the childhood onset form, beginning between the ages of 4 and 10 usually being most severe. Symptoms may include withdrawal, aggression, poor speech, seizures, and progressive dementia. The adult-onset form is usually milder and begins between the ages of 21 to 35 years. Symptoms often include stiffness, weakness and paralysis of lower limbs, and the disorder can also lead to a decline in brain function. Some female carriers of the disease may experience similar symptoms to a milder degree. Patients with ALD generally expect a poor prognosis after being diagnosed, with the disorder eventually leading to death within 1 to 10 years.

The following links may provide more information regarding ALD:

NINDS Adrenoleukodystrophy Information Page

History of adrenoleukodystrophy

The use of the movie "Lorenzo's Oil" as a Teaching Tool

The Human and Scientific Story of Adrenoleukodystrophy

Here’s a brief overview of what I discussed in regards to the hypothalamus and sleep from last week’s neuro slam.

There is an ascending arousal system that is active in the brain during wakefulness. This pathway activates the cerebral cortex and thalamus via monoaminergic neurons brainstem, hypothalamus, and basal forebrain. The waking pathway is mutually inhibited by the ventrolateral proptic nucleus (VLPO) of the hypothalamus. The VLPO promotes sleep and when damaged causes insomnia. Both noradrenaline and serotonin inhibit VLPO neurons as well as GABA and thus can be inhibited during wakefulness.

These to systems form a flip-flop switch, which ensure that sleeping and waking are discrete states. Another group of neurons in the hypothalamus, orexin neurons, regulate this circuit. These neurons are most active during wakefulness and are inhibited by neurons in the VLPO during sleep. People lacking orexin neurons will suffer from narcolepsy and will wake more often and fall asleep at inappropriate times–they are more likely to enter the transition state without this regulator.

The hypothalamus is also involved in homeostatic regulation of sleep. There is some evidence that there is some accumulating factor that is indicative of a need for sleep, though it’s not clear what this signal might be. Adenosine has been proposed as a homeostatic accumulator of the need to sleep, as it could be an indicator of depletion of ATP after prolonged wakefulness. This has been supported by experiments which show that injection of adenosine into the basil forebrain of cats or near the VLPO in rats causes sleep, and seems to indirectly activate VLPO neurons.

The dorsomedial nucleus of the hypothalamus (DMH) is important in circadian regulation of sleep. These neurons are a go-between for other groups of neurons and the suprachiasmatic nucleus (SCN), which acts as a biological clock. The DMH recieves signals from the SCN which then regulates circadian cycles of thermoregulation, sleep, corticosteriod release, and wakefulness and feeding. This three stage pathway is important for allowing circadian rhythms to adapt to environmental stimuli. The DMH integrates clock information from the SCN with feeding, temperature, social and other cues, providing animals with the flexibility to adapt their behavioral and physiological cycles to the environment.

During last weeks neuron-slam when sleeping disorders came up, I wondered more about narcolepsy. From a Jay-Z music video to the Deuce Bigalow: Male Gigolo movie, narcolepsy is seen as comical. I decided to dig a little deeper into this disorder. Narcolepsy is characterized by sleepiness and abnormal rapid eye movement (REM) sleep. This event is the form of cataplexy (sudden loss of muscle tone/strength), hypnagonic hallucinations (sleeping in a room in the presence of evil), and sleep paralysis. Frequency of those affected with this disorder is 0.02% to 0.05% (1:5000 to 1:2000) in of the population. Onset generally occurs in adolescence and is dominated by heredity (specifically associated with the gene HLA-DQB1*0602). The most commonly used diagnostic test is known as the multiple sleep latency test (MSLT), which is performed by nocturnal polysomnography (simultaneous and continuous monitoring of normal and abnormal physiological activity during sleep), followed by four to five daytime naps during which sleep latency is measured. Using polysomnography method, narcolepsy can be tested separate from idiopathic hypersomnia (another disorder characterized as sleeping for an excessive amount of time, but has normal waking intervals).
Mignot et al in 2002 published research using another diagnostic tool to measure narcolepsy in 250 patients. They found that narcolepsy-cataplexy patients commonly were hypocretin deficient. The idea here is that measuring CSF hypocretin-1 is a definite diagnostic test. Hypocretins, originally thought to be associated with appetite, are discretely located in the lateral and perifonical hypothalamus. However, hypocretin neurons project widely throughout the brain; including dense excitatory projections to monoaminergic (nerve cells or fibers that transmit nerve impulses by monoamine neurotransmitters like serotonin or norepinephrine) cell groups. Hypocretin neurons are suggested to be uniquely positioned to drive monoaminergic activity across the sleep cycle. Severing this excitatory input may cause the symptoms of narcolepsy.
This study can be found here:
The Role of CSF hypocretin...

Magic has amazed people for centuries however the age old saying “the hand is quicker than the eye” is slightly flawed. The saying should go “the hand is quicker than “the parietal cortex”. The parietal cortex is a small region of the brain located behind your ear and has to do with concentration. Psychologists at the University College of London found that this particular piece of gray matter holds the key to a phenomenon called “change blindness”. Often people overlook the obvious where their attention is challenged.

If subjects are shown pictures of two faces in quick succession on a computer screen then they are able to notice that the two are different. However, if the person is distracted by a menial task, like counting or even by a flicker on the screen, the subject frequently will not notice the change. Current research suggests that the parietal cortex might be involved in this ruse because functional-imaging studies link this region to visual awareness.

Researchers connected test subjects to a transcranial magnetic stimulator, which focuses a magnetic field on a selected area of the brain, and temporarily disrupts the neural circuitry there. Subjects were given the face test and with the machine turned (focused over the parietal cortex) on they usually failed to notice that the faces were different. Although it may seem surprising that the parietal cortex is involved, since it is not a traditional visual area, the cortex is critical to auditory, tactile awareness as well as visual concentration. This really makes you think about how awareness can be easily interrupted by simply concentrating on something else (like when drivers “zone out”). However this does yield new meaning that “magic occurs not in the magician’s hand but in the mind of the spectator.”

The subject of sleep really interests me and I wanted to read more so here is what I found...
The article was called The Science of Sleep and some of the facts in the article are similar to what we discussed during last weeks Neuro Slam, but there were some aspects I didn't know.
It is still unclear as to why we need sleep. Some researchers believe that sleep provides the body a chance to recuperate from the day, but in all actuality the amount of energy saved by sleeping 8 hours is only about 50 kCal...which is roughly the same amount of energy in a piece of toast. All that is known, is that sleep is essential to maintaining our cognitive abilities (memory, speech etc.) or important for development of the brain.
Experiencing a lack of sleep is a good way to feel and realize why we need sleep. After one night without sleep, concentration becomes more difficult, attention span shortens considerably, and memory is the first thing to fade. Also, research shows that sleep deprivation causes individuals to not be able to respond to changing situations. Judgement also lapses; sleep deprivation is thought to be a factor is such disasters as Chernobyl and the Challeneger shuttle explosion.
There are two types of sleep, non-REM (which has four stages) and REM. Here are the four stages of non-REM sleep:
Stage 1-(Light Sleep) In this stage we are half awake and half asleep and can easily be awakened.
Stage 2-(True Sleep) The longest stage. Within ten minutes of light sleep we enter this stage, and it lasts about 20 minutes. Breathing and heart rate slow down.
Stage 3&4-(Deep Sleep) Stage 3 the brain produces delta waves and breathing and heart rate are at their lowest. In Stage 4 there is limited muscle activity and rythmic breathing;this is the stage when children experience night terror.
REM sleep usually begins 70 to 90 after we fall asleep and we have 3 to 5 of these cycles per night. This is the period when dreams occur, our eyes move around and heart and breathing rate rise slightly.
As far as how much sleep we should get, it varies. Everybody is different, but the average is found to be aboue 7.75 hours.

Here is the link for the article: sleep and here is a link to a interesting sleep quiz: Quiz

The subject of sleep really interests me and I wanted to read more so here is what I found...
The article was called The Science of Sleep and some of the facts in the article are similar to what we discussed during last weeks Neuro Slam, but there were some aspects I didn't know.
It is still unclear as to why we need sleep. Some researchers believe that sleep provides the body a chance to recuperate from the day, but in all actuality the amount of energy saved by sleeping 8 hours is only about 50 kCal...which is roughly the same amount of energy in a piece of toast. All that is known, is that sleep is essential to maintaining our cognitive abilities (memory, speech etc.) or important for development of the brain.
Experiencing a lack of sleep is a good way to feel and realize why we need sleep. After one night without sleep, concentration becomes more difficult, attention span shortens considerably, and memory is the first thing to fade. Also, research shows that sleep deprivation causes individuals to not be able to respond to changing situations. Judgement also lapses; sleep deprivation is thought to be a factor is such disasters as Chernobyl and the Challeneger shuttle explosion.
There are two types of sleep, non-REM (which has four stages) and REM. Here are the four stages of non-REM sleep:
Stage 1-(Light Sleep) In this stage we are half awake and half asleep and can easily be awakened.
Stage 2-(True Sleep) The longest stage. Within ten minutes of light sleep we enter this stage, and it lasts about 20 minutes. Breathing and heart rate slow down.
Stage 3&4-(Deep Sleep) Stage 3 the brain produces delta waves and breathing and heart rate are at their lowest. In Stage 4 there is limited muscle activity and rythmic breathing;this is the stage when children experience night terror.
REM sleep usually begins 70 to 90 after we fall asleep and we have 3 to 5 of these cycles per night. This is the period when dreams occur, our eyes move around and heart and breathing rate rise slightly.
As far as how much sleep we should get, it varies. Everybody is different, but the average is found to be aboue 7.75 hours.

Here is the link for the article: sleep and here is a link to a interesting sleep quiz: Quiz

There were a couple of studies published in PNAS in November that used fMRI to compare different groups on their reaction to humor. Before I write about the studies I’d like to briefly explain how fMRI works. The most common fMRI technique, using BOLD (Blood Oxygenation Level Dependent) signal, measures neural activity by measuring changes in oxygen demand. As local activity increases, there is a local decrease in deoxyhemoglobin relative to oxygenated hemoglobin. Deoxyhemoglobin is paramagnetic and oxyghemoglobin is diamagnetic and so each produces a different magnetic resonance signal.

One of the studies in PNAS (Sex differences in brain activation elicited by humor) compared patterns of brain activation that humor appreciation caused in males and females. Both males and females had higher levels of activation while reading cartoons they rated as funny in the temporal-occipital junction and temporal pole, and the inferior frontal gyrus. These structures are involved in language processing and meaning. However, females activated additional structures more than males during the study including the left prefrontal cortex and specific structures within the mesolimbic area. The researchers suggest that the prefrontal cortex activation could be related to greater language processing and greater use of executive functions such as working memory by women. They related greater mesolimbic activation to more processing of humor through specific psychological reward networks associated with unpredictable stimuli.

The other study (Personality predicts activity in reward and emotional regions associated with humor) used the same methods to compare activation patterns elicited by humor of different personality groups using introversion-extroversion and stability-neuroticism measures. The researchers found that extroversion positively correlated with increased activation of the right orbital frontal cortex, ventrolateral prefrontal cortex, and bilateral temporal cortices. They explained that extroverts access heightened psychological rewards through the activation of these structures. Emotional stability positively correlated with the mesocortical and mesolimbic reward systems of the right orbital frontal cortex, caudate, and nucleus accumbens. Again this points to increased rewards in emotional stable individuals versus neurotic individuals.

From the Nature Journal, Cues to the Functions of Mammalian Sleep, by Jerome M. Siegel.

Sleep is a poorly definable term, the mechanisms and processes behind sleep are not completely clear, and even more vague is the function of sleep. Changes in brain metabolism and neuronal activity have lead to defining two different kinds of sleep, rapid eye movement (REM) and non-REM (NREM). Why these two kinds of sleep occur is still a mystery as well.

Generally, NREM sleep activity is found in neurons in the preoptic and basal forebrain regions. During NREM sleep, groups of sleep-active neurons in these regions are found to be highly active. If these neurons are stimulated NREM sleep can be induced, while damage to these neurons can greatly reduce sleep. Interestingly, because the preoptic and also anterior hypothalamic regions of the brain are also involved in controlling body temperature, NREM sleep can be increased when the preoptic regions are heated.

REM activity can be located in the pons and adjacent midbrain regions. These areas contain REM sleep on cells, neurons that are most active during REM sleep. These cells are responsible for triggering inhibition and withdrawl of excitation to motoneurons, thus causing the loss of muscle tone that is seen during REM sleep. Artificial activation of these neurons can create REM sleep, while damage to these neurons can diminish and even prevent REM. Simlar to NREM sleep, temperate can have an effect on REM sleep activity. Cooling the regions associated with REM sleep can increase REM sleep amount.
Aside from the specialized REM and NREM sleep on neurons, general neuronal activity shows patterns of being most active during waking hours and REM sleep,and least active during NREM sleep.

A few people were interested in the ambiguous picture test and “bizarreness scale” that were briefly mentioned in the commentary I read for neuroslam. The author of the commentary did a study in which a group of psychotic schizophrenic patients and an age & sex matched group of otherwise normal people were given TAT tests and were asked to report their dreams which were judged for bizarreness. That study has not yet been published. However, I did find some general information that might help clarify what the intentions of the study seemed to be.

TAT (thematic apperception test) is a widely used projective personality test. It consists of a series of ambiguous pictures of social situations. The subject must generate a story about the picture. Their responses are supposed to be indicative of underlying personality dynamics, conflicts, motives, etc. but are normally judged by psychologists in a very subjective way. As anticipated, psychotic patients responded to the TAT test differently than the control group. But, the psychotic patients and control group had similar scores for dream bizareness. As for the bizarreness scale, I haven’t found any useful information on that. So, we’ll have to wait until Hobson & Scarone & Co. publish their data.

With finals week looming and a lack of sleep almost certain, it is important to point out the fact that there are risks associated with driving while sleeping. I know that I have driven long distances only surviving because of the miracle drink known as coffee. This week’s NeuroSlam topic is sleep, and since I was given free rein on what topic I chose, I decided to go with paper that we could all relate to – The Hazards and Prevention of Driving While Sleepy.

While driving, there are two basic requirements: keep the vehicle within the lane while maintaining an appropriate speed. However, beneath this seemingly simple task, is the complex sequence of functional requirements needed in order to safely operate a motor vehicle. This includes perception of relevant cues, making appropriate decision, performance of necessary control movements, and the maintenance of a level of attention that allows the driver to respond to normal driving situations, but also to deal with emergences.

According to this study, approximately 20% of all car crashes could have been caused by sleepiness. Although sleepiness is a generally hard term to clearly define, this study has broken it down into two major areas. The first is the subjective experiences which are used as a synonym for a variety of terms such as drowsiness, languor, inertness, sluggishness, tiredness, exhaustion, weariness, boredom, fatigue, and the list goes on. The other general description of sleepiness is used to explain the behavioral and physiological changes due. Sleepiness is also hard to quantify, with its effects only being inferred from manipulations through sleep deprivation or prolonged wakefulness.

One of the biggest changes in behavior during driving is during the occurrence of lapses, or blocks, known as microsleeps. These microsleeps cause a progressively unevenness in performance and resulted in a decline of optimal levels of response times, cognitive slowing, memory problems, and time-on-task decrement. Specific behaviors included an increase of lane position variability (weaving between lanes), increase in speech variation, and increase in off-road events. It has also been shown that higher cognitive processes are affected, which result in adaptation of a higher risk strategy.

Some of the factors known to increase the risk of sleepiness-related crashes include: increasing time on the road, having experienced reduced sleep in the period before driving, driving on a highway, being a young male, and sleep disorders, such as insomnia or obstructive sleep apnea. Shockingly, studies have found that after only 17 hours of sustained wakefulness, driving behavior has deteriorated to the equivalent to a driver with a blood alcohol level of 0.05%!

The ultimate goal of studies of sleepiness and driving is to develop on-board technology that continuously monitors the driver’s status and can signal either the driver or the vehicle during a period of increased risk of a crash. Although sleep and the complete effects it has on driving, some researchers are predicting that within 5-10 years the technology will exist that will be able to help prevent sleepiness-related crashes.

This paper also explored what can do in order to help with sleepiness while driving. They found that 150 mg of caffeine (equivalent to two cups of coffee) and a nap of no longer than 15 minutes was effective in reducing driving incidents for up to 2 hours with approximately 5 hours of sleep the previous night. However, a combination of both of those actions was better then doing only one. A 500mL “energy drink” (one which contained 160mg caffeine, glucose flavoring, vitamin B complex, glucuronolactone, and taurine) was found to be at least as effective as caffeine alone. Slow-release caffeine (300mg) was shown to improve driving behavior for 5 hours. Interesting enough, frequently used countermeasures for sleepiness, such as listening to loud music, short burst of cold air, where less effective and appear to have only transient effects in reducing sleepiness.

So has your finals finish and you start to head home, please be alert to the sleepiness level of both yourself and those around you. Drive safe!!

Maclean, A.W., D.R.T.Davies, and K. Thiele. 2003. The hazards and prevention of driving while sleepy. Sleep Medicine Reviews. 7(6):507-521.