NRSC 2110 Blog

Last week I returned home from running some errands to find my husband on his laptop playing an action packed video game while the kids are sitting on the floor playing games on the Wii. I want to let them relax but I'm worried they are all killing brain cells with these mindless games.

Maybe, I worry too much? The article Children Wired: For Better or Worse found in the September 9, 2010 issue of Neuron magazine describes some benefits to playing action-packed video games. This is good because in this highly technological world we live in I'd be fighting a losing battle in my home.

Games that showed the highest benefits were full of action and were multidimensional. These games also pull the player in emotionally. It is important to note that studies were conducted with a young adults and not children because of the violence in some of the video games. Some enhancements have been found in vision, attention, cognition, and motor control. The medical community and healthcare professionals are seeing benefits in gaming for patients also. Some research being done shows people with amblyopia (a developmental deficit of vision) and those with attention issues are benefitting from playing video games.

For the younger kids, preschool programming showed some cognitive benefits, in particular an increase in the vocabulary of preschoolers when they view shows like Dora the Explorer. For obvious reasons shows like Teletubies actually prove to reduce language skills. Preschool programs that elicit responses, labels objects, and models proper language in addition to modeling social skills benefit children. However, the new baby/infant videos do not seem to have the same types of benefits. Babies benefit from watching their parents interact in the world. This is not something that can be gained from a video or TV show.

It may be that there is a link in the social skills being taught in preschool programming and the high intensity emotional component of action packed video games that leads to the cognitive benefits that are being observed in these studies. Educational computer games incorporate repetition and interaction as a way of teaching "educational" information but do not have an emotional component. Therefore educational computer programs do not seem to have the same benefits as the emotionally charged video games.

Until now the world of education and the world of behavioral science has studied technology. PET scans and fMRI are allowing neuroscience to share in this new area of research. These new brain-imaging techniques are allowing for real time studies of the brain. This is beneficial to studying the effects gaming has on the brain. Studies are finding that video games are affecting reward pathways. Neuroscience will be able to shed light on the effects these games are having on executive function and control of attention, as well as, reward pathways. Hopefully new studies will emerge that will incorporate neuroscience and technology so educational programs can be developed that will illicit the same learning benefits as action packed video. Wouldn't it be cool if learning history and math on the computer were just as fun (and beneficial) as playing one of those action packed video games?!

Each year, over half a million Americans die from drug use. In a recent study published in Nature Neuroscience, addiction was defined as "a chronically relapsing disorder characterized by a compulsion to seek and take drugs, a loss of control over intake, and the emergence of a negative emotional state during abstinence." But that's not what addiction is, not really. Addiction is a high-speed chase into the depths of human despair. It's no man's land- black, and empty, and unbearable. And relapse is worse. Relapse is the shadows in the darkest corners of human existence. So wouldn't it be great if there were a cure for this relapse monster? Researchers may have found just that.

In a study published in January (http://www.nature.com/neuro/journal/v14/n4/full/nn.2758.html), researchers studied an area of the brain called the ventromedial prefrontal cortex (vmPFC) and its role in reducing context-induced heroin seeking (because we all know that being in a place where you used to shoot up is just as risky as having the needle poised in your veins). In previous studies on cocaine addiction in rodents, activation of the vmPFC inhibited drug relapse. Bossert et al. challenged this idea by identifying a subpopulation of neurons in the vmPFC that increases context-induced heroin-seeking behavior upon activation.

To identify this population of neurons in the vmPFC, scientists used Fos immunohistochemistry to show that reexposure to an environment associated with heroin consumption activated these neurons. The rats were exposed to two contexts: in context 1, rats were trained to self-administer heroin 3 hours per day for 12 days by pressing on a lever. In context 2 (which differed from context 1 in tactile, visual, auditory, and circadian components), rats could still press a lever, but did not receive heroin. Consequently, they eventually stopped pressing the lever. Following the extinction training, rats were reintroduced to either context 1 or 2 and given lever access, although no heroin was supplied.

The most significant finding was that 71% of the neurons recruited by reexposure to context 1 were excitatory glutamatergic neurons (13% were inhibitory GABA neurons). Thus, reexposure to an environment associated with heroin recruits excitatory pyramidal neurons. Most importantly, these neurons are responsible for the learned association between environmental factors and the effects of heroin.

Bossert et al. then used an innovative method to selectively inactivate vmPFC neurons that were activated in the heroin context. A prodrug called Daun02, which decreases cell excitability for several days, was injected into the vmPFC after reexposure to the heroin context. When exposed to context 1 a second time, rats that received the prodrug immediately following reexposure to the context 1 the first time showed a decrease in context-induced activation of vmPFC neurons, AND diminished heroin-seeking behavior.

So why is this important? Researchers have found a neuron population involved in environmentally triggered relapse, and we now know that this population reacts differently for heroin than it does for cocaine. But how promising is this study in the future of addiction? It's quite obvious that just quitting a drug will never keep you safe from the drug itself. But at least we know which neuron population is responsible for the horrific heroin relapse. So instead of going to the methadone clinic, junkies can just get parts of their ventromedial prefrontal cortex lesioned. And if they're addicted to heroin AND cocaine, well then they're really screwed.

That's what bothers me about addiction studies like these: rather than feeling enlightened and hopeful, I feel discouraged and even more in the dark than I was before I read the study. While it's great that 'our knowledge is expanding in the field of addiction,' the plausibility of expanding this study to humans (which are different from genetically engineered rodents), is slim to none. For all their scientific wisdom, researchers could never accurately convey what addiction is. Relapse can't be scientifically treated, because no matter how many neurons you activate or inactivate, the house on the corner can still kill you. Relapse is the razor's edge between life and death, not the number of lever presses inside a cage.

We've all been there. You're standing across from someone animatedly relating a crucial piece of their day to you and five minutes later when you zone back in you realize you haven't heard a word they said. Do you fake it, politely nodding, and hope you won't be asked for your opinion? Do you apologize and ask them to repeat themselves? In school you might have been known as "that kid", always day dreaming and becoming preoccupied with everything other than the lesson at hand. Maybe the last time you were reading a book you couldn't get through a page without watching your neighbor water their lawn or taking an enthusiastic interest in the fly buzzing around the window. You may have been diagnosed with ADD or simply adopted the diagnosis on your own with the rest of our culture as a buzz word for excusing our collective distractibility. Laptops, smart phones, and constant stimulation could make anyone a little scattered. Now, thanks to Neuroscience, you can blame it, along with a host of other things, on your biology. Research published in the Journal of Neuroscience in May of 2011 could even be used to support blaming it on your parents.

People involved in the study were asked to score themselves on their attention spans and ability to focus on their daily tasks. They used a test that has been used to measure distractibility many times before. The density of gray matter in the left superior parietal lobe of those in the study correlated directly with their reports of distractibility. The researchers were able to disrupt activity in the implicated area of the brain using transcranial magnetic stimulation to further test their theory that there is a biological basis for distraction and the ability to ignore it. During the disruption, the people involved in the study became more susceptible to distraction as was expected. By using TMS while subjects were performing a task researchers were able to observe how susceptible the subjects were to outside stimuli while messing with this area of the brain. Researchers were pleased to make a connection between reports of low attention span, biology, and measurable laboratory tests.

Next time you zone out, offer an apology that you can't focus on the conversation at hand because your parietal lobe is giving you trouble and simply won?t filter out the pretty girl who just walked by, the construction in the street, or the smell of coffee wafting it's way through the office, or you could just spring for lunch.

Our society has become a sleep deprived one which has lead researchers to study the effects of it. It has now been accepted that sleep is needed for memory consolidation. Does sleep improve all types of memory? People generally think so but what if a study found that to not be true?

Researchers at Georgetown University and Catholic University have apparently found an exception to this idea of memory consolidation during sleep for motor sequence learning. I found this article to catch my eyes easily as having taken a class on the neurobiology of learning and memory; the researchers were definitely daring to challenge this already accepted idea. They focused their study on implicit consolidation which I found interesting because it seems that dreaming of performing a patterned motor sequence and remembering would help the most.

In their study,(http://www.jneurosci.org/content/27/46/12475.full.pdf+html) the researchers studied 36 right-handed college students at 3 different visits with half of the participants tested in the morning (8am) and half in the evening (8 pm). The morning group had 12 hours of awake-rest between their 1st and 2nd visits and 12 hours of sleep between their 2nd and 3rd visits. The evening group had the opposite, with the sleep full rest first. Also half of the participants were given instructions with mention of the patterned sequences and half were just given minor instructions. In addition, 18 right handed subjects were used as controls and were allowed to sleep in between the 3 testing?s.

For each visit the subjects were given the alternating serial response time task which involved the subjects responding to pushing a button to a target (a filled in circle) that appeared in one of 4 circles that were aligned in a row. The circle stayed filled in until the correct key was pressed. Then another circle filled in and the experiment with 8 warm-up trials and then 80 experimental ones consisting of patterns which alternated with random trials. The researchers also performed cued and probed time trials to differentiate between pattern and random trials. (Note: my explanation of their study might be a bit confusing but that?s because I found theirs not as well explained as it could have been. Unless, of course I went to another study which they directed me to a study with a better description of the methods)

The researchers found that daytime enhancement occurred for overall reaction time but not for pattern specific learning. Speed only improved if the rest period was over the day and not when it was overnight. This seemed very odd to me (which they kind of admitted to) and makes me believe it was poorly constructed. It seems obvious that college kids are going get better after 8 am as most college kids are still asleep at 8. Maybe if they did it at 10 am and 10 pm or if they had to be awake for, say, 2 hours before the test. The results might have been different then.

In the end, I found the title very interesting and it made me want to read the article but I was disappointed. The article wasn?t written as clearly as it should have been and I had a hard time following it. It referred to other papers so many times that I found it distracting. With that fact and the fact that the experiment was poorly conceived, it seemed to me that their experiment didn?t test anything new and that they were just testing what others already have. They also had so many different discussions that that also made the paper rather confusing.

I would have liked to have seen something more than just behavioral testing. For example, it would have been more interesting if they measured the subject?s brain activity during the tasks. More neuroscience testing would have helped make their research stronger. Also, while reading the article, I found myself wondering why studying sleep-dependent consolidation of implicit patterned motor learning is even important. How would that be beneficial to us? I can definitely see the use in researching sleep-dependent consolidation for motor learning in general but why would learning about sleep-dependent consolidation and patterned motor learning exactly help us with our lives? I?m all ears if someone could give me an example to change my mind. Again, I definitely believe research should continue on consolidation and motor learning and I find that fascinating.

The last thing I?m going to note involves their last sentence which they mentioned interpreting implicit consolidation features saying, ?deciphering each component will make it possible to better understand and use off-line (implicit) performance enhancements?. The performance enhancements part slightly bothered me because that brings up a whole can of ethical issues but I?ll save that for another time.

I?m sure most of us can remember reaching a certain age in high school and having our parents wish we spent more time learning our school material than learning bad habits (such as smoking) from our peers. The irony? The same potentiation that seems to be responsible for the learning and memory that allows us to master our scholastic material may be responsible for our ?learned? addictions. (And our parents thought they could blame the bad kid down the street).

A study (http://www.cell.com/neuron/abstract/S0896-6273%2809%2900580-7) published in the September 2009 issue of Neuron indicates that Dopamine (DA) may be what helps enable our synapses to undergo the types of synaptic plasticity that underlies our addictions and appears to have many similarities to the plasticity underlying our learning and memory including a strong involvement of the hippocampus.

It has been established that both DA signaling and the hippocampal circuitry have a major role in drug addiction. The researchers in this study aimed to study the in vivo synaptic potentiation underlying addiction in awake freely moving animals. Nicotine had already been shown to alter synaptic plasticity, however it had been done in animals that were either anesthetized using an agent that is known to alter the functionality of ligand-gated channels, or given enough nicotine to give an awake mouse a seizure. The researchers here introduce a more physiologically relevant measurement.

In their study, the researchers used the amplitude of the pop spike (PS) (the spike that is produced when a population of cells all fire together) to measure potentiation of synaptic transmission. With the recording electrode placed in the dentate gyrus, they found that when they injected nicotine into mice the PS amplitude showed a significant increase over the baseline animals that were not given nicotine; this indicates that significant synaptic potentiation was induced by nicotine exposure.

Having first established that the nicotine was acting through nicotinic acetylcholine receptors, they injected nicotine directly into the hippocampus. Finding that the nicotine now did not induce a significant change in synaptic potentiation, their results suggest that nicotine must exert its effects in a way that extends beyond the hippocampal circuitry alone.

So where does dopamine fit in to our learned addiction? Well without dopamine our potentiation disappears. When researchers injected a D1-type DA receptor antagonist (both systemically and locally into the hippocampus) the potentiation induced in the hippocampal circuitry by nicotine is inhibited. This strongly suggests that the D1 DA receptors enable the nicotine induced synaptic potentiation. Also of interest, using an agonist of the D2-type DA receptors (these are autoreceptors that will inhibit the firing of midbrain DA delivering neurons when activated) inhibits the nicotine-induced potentiation. However, when an antagonist of the D2-type receptors is used, allowing an even larger DA signal to be delivered from the midbrain, we see enhanced potentiation even beyond the before seen nicotine-induced potentiation. This suggests the magnitude of the DA signal influences the strength of the nicotine-induced potentiation.

How does this translate into memory based behavioral observations? The conditioned place preference (CPP) test was used to find out. When nicotine was administered significant CPP was observed. So it appears they are learning an addiction.

So the next time you see all the college undergrads smoking on their breaks between courses you can appreciate the irony in that the very same synaptic mechanisms allowing them to master their studies allowed them to learn their addiction that interferes with said studies. With the help of DA of course.

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With the stress of finals just around the corner, I find myself desiring some sort of remedy to help me with all the studying that needs to done. I often wonder how my brain is able to remember the immense amount of material for all of my classes, and retrieve it when it comes to exam time. Moreover, I want to be able to use that mechanism for remembering and somehow enhance it. What I desire is a way for me to enhance the ability of my brain to form declarative memories that will last on a long term basis.

A study (http://www.jneurosci.org/content/30/39/13066.full) published in the Journal of Neuroscience on September 29, 2010 indicated that CREB might play a key role in the regulation of long term memory formation. CREB (cAMP responsive element binding protein) is a transcription factor that binds to the CREB binding protein. It was found that absence of presenilins (genes thought to play important roles in synaptic functioning as well as memory) correlated to reduced CREB binding protein. Thus, these investigators believe that the CREB binding protein is crucial to the formation of short and long term memories.

Different experiments on mice were conducted throughout the study to test for the degree of influence that CREB binding protein may play in the formation of memories. It was previously thought that CREB binding protein was not required for the formation of short term memories. Yet, the scientists were still curious to see if a complete loss of the binding protein would affect short term memory.

Behavioral analysis using long term and short term memory formation was performed. The experimenters used spatial learning and memory tests, fear associative memory tests and object-recognition tests. In CREB binding protein mutants, impairment in the formation of long term memories was evident. Furthermore, these mutants failed short term memory tests indicating that CREB binding protein is necessary for the formation of both types of memory formation.

CREB binding protein has also been implicated in a lot of neurodegenerative diseases such as Alzheimer?s disease and Huntington?s disease. The formulation of a drug to enhance memory storage could be life changing for individuals who suffer from loss of memories as a result of neurodegenerative disease. However, this type of drug could also be useful to the everyday population of people that just want help remembering (whether for educational purposes or due to loss of memory ability resulting from aging).

A memory drug would cause extreme ethical debates. Additionally, if it were to be found unethical and illegal for someone to take these types of memory enhancing drugs, it could lead to random or mandatory drug testing for our future students. Much like drug testing is done for athletes; it could be that drug testing is done on students before exams to ensure their integrity. However, as we approach this new realm of scientific and medical advancements we must ask ourselves how far is too far? And ultimately what is a little memory enhancement going to hurt? If anything, it just might could improve our society and make us better learners.

Those of us in dating in high school in the late 80′s can attest to the stinging truth revealed in Def Leppard's song, "Love Bites" shortly after a nasty break-up. But it was only recently that scientists employing state-of-the-art brain imaging fMRI technology have been able to view the similarities between the biting pain of rejection from a lover and physical pain.

A study (http://www.pnas.org/content/108/15/6270) published in the April 12 issue of Proceedings of the National Academy of Science (PNAS) has provided the most direct evidence showing a common brain circuit underlying the pain of rejection and physical pain.

In their study, the researchers at Columbia University, University of Michigan and University of Colorado, Boulder studied 40 subjects who had experienced rejection and break-up with a lover within the past six months. They tested each subject on two tasks, a social rejection task and a physical pain task, while imaging their brains.

In the scanner, subjects looked at the faces of their ex and thought about how it felt during their split and a snapshot of their brain was taken. Next they were shown a headshot of a friend of the same sex as their former partner and thought about a recent positive experience they shared. This provided the social rejection condition.

To compare the social rejection experience to the experience of "physical pain" they attached a thermal device to the volunteers' forearms and set it to produced a "painful", but not harmful level.

In both men and women, rejection and painful heat activated brain circuits underlying distress (e.g. Anterior Cingulate cortex) and the sensation of pain e.g. somatosensory cortex).

Although this seems seems intuitive from centuries of poetry, tragic plays and lyrics, knowledge at a mechanistic level showing the same circuits are activated gives scientists new ways to deal with both. It makes one wonder if taking pain-killers shortly after a break-up might be a treatment option.

The common mechanism between social rejection and physical pain may be one reason why heroin and alcohol, both analgesics for pain, are irresistible amongst country and grunge musicians whose melodic ruminations center on tragedy, angst and painful relationships. Kurt Cobain comes to mind when he said, "Thank you for the tragedy. I need it for my art."

Last year the British pop group ironically named, "The Wanted", brilliantly connected the idea that pain from being unwanted/rejected and searing physical pain were one and the same in their popular song "Lose My Mind". Here are the lyrics and the video (http://youtu.be/lv2CDjyPRkg)

They say that time
Heals everything
But they don't know you
And the scars you bring

'Cos you left a jagged hole
And I can't stand it anymore

If heartache was a physical pain
I could face it I could face it
But you're hurting me
From inside of my head
I can't take it I can't take it

I'm gonna lose my mind
I'm gonna lose my mind

I'd erase my thoughts
If only I knew how
Fill my head with white noise
If it would drown you out
Kill the sound

If heartache was a physical pain
I could face it I could face it

But you're hurting me
From inside of my head
I can't take it I can't take it

I'm gonna lose my mind
I'm gonna lose my mind

And I'd rather be crazy
I'd rather go insane
Than having you stalk
My every thought
Then having you here inside my heart

If heartache was a physical pain
I could face it I could face it
But you're hurting me
From inside of my head
I can't take it I can?t take it

I'm gonna lose my mind
I'm gonna lose my mind