House of Mind

World Science Festival | May 29 - June 2, 2013

Tue, 21 May 2013 09:56:00 -0400

World Science Festival | May 29 - June 2, 2013:

Minds Expanded. 5 Days. 50 Events. Infinite Ideas.

The World Science Festival (WSF) is back in NYC and kicking off next week :) The festival is not specific to neuroscience but there will be a lot of neuroscience related events. This year, scientists from NYU/Columbia/Sinai will man a brain table on Brain Boulevard at the Ultimate Science Street Fair in Washington Square Park on Sunday, June 2, 2013. We will have a brain bank, C. elegans specimens, and a spiker box for recording electrical signals from your muscles! Yours truly will also be there from 3PM-6PM if you want to drop by and say hi. In addition, there will be other interactive exhibits like the Space Place, Climate Corner and Innovation Alley.

Hope some of you can make it!

Hello, I have a Bachelors in Psychology and am currently applying for a Masters in Cognitive neuroscience at UCL. In my application i've been asked to submit what type of research i'm interested in. Do you have any tips with regards to latest research in this field or what you would write about so that I have more chance of my application being accepted? Kind regards Nicole Caruana Malta. Love your blog btw !! xx

Tue, 21 May 2013 09:37:00 -0400

Hi,

I am not in the area of cognitive neuroscience so it is hard to say. I would suggest doing some research and finding an area/topic of special interest to you because by the time you get in/conduct your research projects/graduate there will probably be a new direction/finding in the field. Basically, what is relevant and new now will probably be a little older and perhaps less exciting down the line. I think you should go into something you’re intellectually invested in so that you can come across as passionate. That’s just my two cents. And thanks!

Good luck!

NIH Details Impact of 2013 Sequester Cuts

Wed, 15 May 2013 10:47:30 -0400

NIH Details Impact of 2013 Sequester Cuts:

After weeks of worrying about how the mandatory across-the-board 2013 budget cuts known as the sequester would play out at the National Institutes of Health (NIH), the biomedical research community now has final figures. The bottom line is as grim as expected: The agency’s overall budget will fall by $1.55 billion compared to 2012, to $29.15 billion, a cut of about 5%, according to an NIH notice today. That is essentially what NIH predicted as part of the 5.1% sequestration.

As a result, NIH expects to fund 8283 new and competing research grants this year, a drop of 703, according to this table. That number firms up the “hundreds fewer” awards that NIH officials warned of earlier this year. Including ongoing (already awarded) grants that are ending, the total number of research grants will drop by 1357 to 34,902 awards. The decline “reflects the fact that NIH’s budget is being shrunk due to the new budget and political reality, which is bad news for researchers and the patients they are trying to help,” says Tony Mazzaschi of the Association of American Medical Colleges in Washington, D.C.

NIH will try to keep the size of the average award consistent with 2012; it will not award inflationary increases for future years. The agency also expects to trim continuing grants. Grants that were cut up to 10% earlier this year because of budget uncertainty “may be partially restored,” but probably not to the original commitment level, NIH’s notice says.

To be honest, when I read this article my heart dropped a little because it highlights one of the harsh realities that people in science would rather not think/talk about. I’ve always felt it was a privilege to be able to do science with federal funds but this is still disappointing. I can’t help but think how much harder getting a PhD and a postdoc is going to be :( However, I understand that sometimes you just gotta do what you gotta do and cut corners when and where you have to.

Science is not for the faint of heart. You’ve been warned.

Oh, and I too find your blog extremely interesting and enjoyable. Keep it up.

Tue, 14 May 2013 15:21:06 -0400

Thanks =]

Though I can understand the principle of this ask, IQ has been historically criticized and recently officially debunked, and as such giving specific stats is kind of anti-progressionist because it simply gives you an arbitrary figure of a test score commonly misconceived to be an even remotely accurate measure of intelligence. It appears to be more beneficial, when in fact it is the opposite.

Tue, 14 May 2013 15:20:49 -0400

Agreed :)

For that last study you presented you might want to put the average declines they reported in your account of it. I'd say it makes it a bit more accessible and clear when you can say "an average decline of 6 IQ points" rather than just the more vague 'loss of IQ'. I dunno if you'd want to talk about p values as well bearing in mind how much they varied, I guess that's gonna exclude people without stats knowledge though. Great blog btw :)

Tue, 14 May 2013 15:00:27 -0400

Hi,

That’s a good point. I guess I didn’t go into specifics about IQ decline because I don’t think IQ is as reliable of a measure of cognitive capacity and/or intelligence. I assumed that whoever read this and wanted to know specifics would go to the original article or one of the multiple write-ups it has received. I would talk about p values as you suggested, which may help, but in the interest of making the blog oriented towards a layperson I tend to to generalize/summarize. All in all, I don’t think that the work in the previous article is great (I have problems with the neuropsychological function measures), but it’s the most recent longitudinal study that I know of on the topic.

Thanks for reading my post so thoughtfully :) I love reading comments because it gives me an idea of how my audience thinks and what they understand. I’d also like to add that I welcome questions relating to my posts and the original articles :)

Long-term Effects of Cannabis Use on Memory and Executive Function

Tue, 14 May 2013 14:24:07 -0400

Cannabis is easily the most widely used illegal substance in the world. Although it still illegal at federal level, Washington and Colorado have legalized recreational cannabis use. Studies examining the relationship between marijuana use and neuropsychological function should be taken into consideration when making/reforming laws and health policies. I have received multiple questions regarding the effects of marijuana on memory and health and recently found a longitudinal study on this matter.

Prior evidence suggests that long-term, heavy cannabis use may cause enduring neuropsychological impairment beyond the period of acute intoxication (i.e. being high). Moreover, the magnitude and persistence of impairment depends on several factors including: quantity, frequency, duration and age of onset. Greater quantities, more frequent and earlier onset of use are associated with a poorer neuropsychological outcome. However, studies that compare pre-initiation neuropsychological functioning with longitudinal data on post-initiation functioning are scarce.

Meier et. al investigated the association between persistent cannabis use and neuropsychological functioning (assessed over a 20 year period) in over 1,000 individuals. Subjects received neuropsychological testing prior to onset of use (childhood; 1985-1986) and after some had developed a persistent pattern of use (~38 years old; 2010-2012).

Important findings included:

Subjects with more persistence cannabis dependence showed greater IQ decline. Those who never experienced cannabis experienced a slight increase in IQ.
Subjects with more persistent cannabis dependence generally showed greater neuropsychological impairment across different areas of mental function: executive function, memory, processing speed, perceptual reasoning and verbal comprehension. The greatest impairments were in the domains of executive function and processing speed.
Neuropsychological deficits induced by cannabis use were still significant even when the researchers controlled for: past 24 hour cannabis use, past-week cannabis use, persistent tobacco, alcohol and/or hard drug dependence, and schizophrenia (all of which alternative explanations for poorer neuropsychological function).
The effect of cannabis dependence on cognitive decline remained significant even after controlling for years of education. Persistent cannabis users with a high school education or less experienced greater IQ decline.
Subjects who had an adolescent onset of use and were diagnosed with dependence prior to 18 years of age tended to become more persistent users. Importantly, adult-onset cannabis users did not appear to experience IQ decline as a function of cannabis use.
Within-person IQ decline was apparent regardless of whether cannabis was used frequently or infrequently a year before testing. Thus, cessation of cannabis use did not restore neuropsychological functioning among adolescent-onset former persistent cannabis users.

So it looks like persistent use of cannabis is particularly detrimental with adolescent onset. Some have speculated that this may be due to puberty, a critical period of brain development in which circuits related to decision-making, executive-function, and reward are undergoing reorganization/rewiring. Neurotransmitter systems like dopamine are also vulnerable during this period as they have not fully matured yet. Thus, the authors suggest that cannabis use exerts neurotoxic effects during this developmental period.

However, one must remember that although the authors show compelling data, their data correlational and is not sufficient to establish causation. Furthermore, there is no mechanism underlying the negative impact of cannabis use on neuropsychological function- merely speculations (see above). It is also possible that there is another variable related to cannabis use and neuropsychological decline that the authors did not rule out. Another limitation of the study was the heavy reliance on self-reporting measures like self-reported frequency of use. Finally, it is hard to estimate dosages due to the variety of strains and potency of cannabis.

I would personally suggest taking this information for what it’s worth. Neuroimaging studies in adolescents (humans) reveal structural and functional brain differences associated with cannabis use so we know that cannabis use changes the brain. I personally believe that cannabis use has negative effects on memory and general health, but I do not think that it’s as simple as the “Weed will make you stupid.” notion that some adults try to instill in adolescents. After all, we already KNOW about the dangers and costs of alcohol/tobacco use and people still use them. For me, the key is to delay onset of use (if you must use) and to prevent adolescent use of cannabis. If you are a teenager with cannabis dependence, it is never to late to quit and try to remedy the effects.

Source: (Click on the link for abstract)

Meier et. al. (2012). Persistent cannabis users show neuropsychological decline from childhood to midlife. Proceedings of the National Academy of Science (PNAS). 109 (40): 2657-64.

Terminal Lucidity

Sun, 05 May 2013 23:08:45 -0400

I was introduced to this concept last week while I was attending the funeral of someone who was thought to have experienced this during his last day alive. I visited the home where he passed away and was told that the nurses and family members were in awe of his passing because he had become “another person” during his last days of life. Some aspects of his memory seemed to have come back and he was more lively that he had been in awhile. I had never heard of such phenomena and decided to look into it. Below are some of the things I found.

Terminal lucidity refers to the unexpected return of mental clarity and memory shortly before death in patients suffering from severe psychiatric and neurological disorders. This return of mental clarity usually occurs in the last minutes, hours of days before the patient’s death. Examples include case reports of patients suffering from tumors, strokes, meningitis, dementia or Alzeheimer’s disease, schizophrenia, and affective disorders. This is particularly striking considering that many of these disorders are caused by degeneration and degradation of the cerebral cortex, hippocampus, and other brain areas that are involved in memory and cognition processes.

Several accounts suggest that during terminal lucidity, memory and cognitive abilities may function by neurologic processes that differ from those of the normal brain. So far the assumption is that the improvement of brain disorders or dysfunctions is caused by the altered brain physiology of the dying. There are two ways in which terminal lucidity is thought to exist: the severity of mental disturbance can improve slowly in conjuction with the decline of body vitality (typically schizophrenia cases) or full mental clarity may appear abruptly and unexpectedly shortly before death (more common in dementia cases). Although terminal lucidity has not been attributed to a specific medical cause, some authors have suggested that a high fever prior to dying might induce terminal lucidity.

Although terminal lucidity has been reported for around 250 years, it has received little medical attention because of its complexity and transience. Not to mention the ethical guidelines for the responsible conduct of research and the fact that these patients are already mentally ill, making it even more difficult to include them in empirical studies. Academic interest in terminal lucidity declined after the mid-19th century. However, in 1975, Turetskaia and Romanenko published a detailed article concerning 3 cases of schizophrenic patients in a medical journal. According to Nahm and Greyson, this article is the only publication on terminal lucidity and mental disorders in medical journals throughout the 20th century. However, within the last few years interest in terminal lucidity in mental disorders has increased again due to recent case reports published by Brayne et. al (2008) and Grosso (2004) (see reviews below).

The authors’ goal is to stimulate research on the pathophysiology of terminal states. For example, research on terminal lucidity could help elucidate the factors influencing the relationship between the mind and the brain, particularly as the brain deteriorates. Moreover, it could further understanding of memory and cognition processes and facilitate the development of new therapies aimed towards reversing the loss of memory and cognitive function in these patients.

Sources:

Nahm, M., Greyson, B., Kelly, EW., & Haraldsson, E. (2012). Terminal Lucidity: A review and case collection. Archives of Gerontology and Geriatrics, 55:138–142.

Nahm, M., and Greyson, B. (2009). Terminal Lucidity in Patients With Chronic Schizophrenia and Dementia: A survey of the literature. Journal of Nervous and Mental Disease, 197 (12): 942-4.

Hi, just curious, what made you want to study neuroscience? Was it like an extremely influential person, or did you come by it yourself?

Wed, 01 May 2013 12:15:10 -0400

Hi!

Thanks for this question. I sort of fell into neuroscience by accident. I was a bio major who was interested in behavior. I used to write off human behavior as being the object of study of psychology and related disciplines until I took a neuropsychology course that exposed me to the biological processes underlying different behaviors and the methodology researchers used to study what used to be intangible phenomena like perception, emotion, etc… I did extremely well (I obtained near perfect scores without really trying very hard and was the top of the class). At this point, I realized that thinking this way came naturally to me and that I could mix biology with psychology through behavioral neuroscience. I spoke about my career plans with my professor, who was very encouraging and supportive (Thanks Dr. Clinton!). I sought out a summer undergraduate research fellowship in which I worked at a Psychiatric Department, but on the basic research side of things, and thought: I can do this! And just like that, I applied to grad school on a whim the following semester and got in :)

Originally, I thought I wanted to be a psychiatrist until I volunteered at an interdisciplinary psychiatric research center and saw what everyday is like for psychiatrists. Dealing with people’s mental state/health seemed like too much for me :X

"There are, of course, inherent tendencies to repetition in music itself. Our poetry, our ballads,..."

Sun, 31 Mar 2013 17:37:12 -0400

““There are, of course, inherent tendencies to repetition in music itself. Our poetry, our ballads, our songs are full of repetition; nursery rhymes and the little chants and songs we use to teach young children have choruses and refrains. We are attracted to repetition, even as adults; we want the stimulus and the reward again and again, and in music we get it. Perhaps, therefore, we should not be surprised, should not complain if the balance sometimes shifts too far and our musical sensitivity becomes a vulnerability.””

- Oliver Sacks, Musicophilia: Tales of Music and the Brain

Aloha! We loved your article & have also found in counseling hundreds of people and exploring gut instincts that the gut has much more to tell us about ourselves than when we need food and when we do not. We hope you will look at our work and research on this subject in our book "What's Behind Your Belly Button? A Psychological Perspective of the intelligence of Human Nature and Gut Instinct" on Amazon. Yours, Martha Love and Robert Sterling

Thu, 28 Mar 2013 04:52:51 -0400

Hi! Thanks for your feedback :) Indeed! I personally learned about the enteric nervous system around 3 years ago and am still surprised about how little we know about this system in comparison to other CNS systems. Our lab has recently become interested in the gut for similar reasons. Specifically, the gut is rich in serotonin, which my PI is fascinated with so now we are looking for ways to maybe incorporate the gut into our early life experience/neurodevelopmental studies. Thanks for the heads up!

Scenes from NYU’s Brain Fair as part of BraiNY on March...

Mon, 25 Mar 2013 11:59:00 -0400

Scenes from NYU’s Brain Fair as part of BraiNY on March 13, 2013.

Inside the NYU Community Brain Fair

Wed, 13 Mar 2013 17:43:00 -0400

Hi guys!

Just wanted to give you an update regarding the NYU Community Brain Fair and NYC Brain Awareness Week… In regards to the Brain Fair, we’re still here! So feel free to drop by and visit one of our many exhibits. Topics covered include : History of Neuroscience, Top 10 Brain Myths, Famous Brains (think H.M., Oliver Sacks, and Chuck Close), Chemical Senses, Alzheimer’s Disease, Parkinson’s Disease, Addiction Pathways, Caloric Sensing in Flies, Neuroeconomics and Neuropsychology. The Neuroanatomy table even has real human brains on display for the oddly curious :)

Other hands-on exhibits include risk discounting games, optical illusions the jelly bean flavor experiment, observing C. elegans mutants under the microscope, and playing a reward related game that resembles beer pong!

Also, we tried to have something for everyone and we even have a Kids table with (anatomically correct) brain hats, arts and crafts, brain mazes, etc…

If you can’t make it, that’s ok! Click here for other braiNY events you can make it to.

Pictures coming later!

Hi There! My name is Kathryn and I just recently came across your blog. In May I graduated from NYU's Applied Psychology program and am currently taking a gap year (or two or three) to figure out where to go from here. I was excited to see that your interests are very similar to mine and even more excited to see that you also go to NYU. I'm thinking about pursing neurology and would like to ask you a few things if you get the time. Please email me at kcv213@nyu. Thanks! Have a great day :)

Mon, 11 Mar 2013 17:25:05 -0400

Hi,

Sorry for the super late reply but my NYU e-mail account has been hacked forever so it is hard for me to access it. I would suggest not taking more 2 leap years because after that it is hard to get back into science. I guess what I am saying is that it’s good to take a break to make yourself a stronger candidate, but if you take off the time and don’t become a better candidate, you’ll have to do some explaining. Are you referring to neurology as a medical specialization or neuroscience? This is important as they are two different academic trajectories that may require different things.

Feel free to ask any more questions through here.

Hope this helps!

The "Cinderella Effect"

Mon, 11 Mar 2013 13:07:00 -0400

The "Cinderella Effect":

The Cinderella Effect is a term in evolutionary psychology that refers to higher incidence of maltreatment and/or abuse in children by step-parents compared to biological parents.

From an evolutionary perspective, natural selection has favored intensive parental care in humans. Thus, parents have to commit a lot of time and resources to raise children. Moreover, parents also have to be able to protect and defend their investment.

According to Daly and Wilson (click title for full article), if the psychological underpinnings of parental care have evolved by natural selection, care-providing animals may be expected to direct their care selectively towards young that are a) their own genetic offspring and b) able to convert parental investment into increased prospects for survival and reproduction. This notion is known as the theory of discriminative parental solicitude and has been described and verified in a broad range of care-giving species. From this perspective, adoption of unrelated young has been interpreted as a failure of discrimination. In humans, adoption by unrelated caretakers is a recent cultural invention than repeated aspect of ancestral environments, meaning that it could not have been a feature of parental psychology as it evolved.

However, step-parental care is ubiquitous across cultures and species, while also being present throughout history. The main explanation as to why this occurs is thought to be that investing pseudoparental care in a new mate’s offspring is adaptive and favored by natural selection. In humans, for example, suitable mates are scarce may be scarce and established couples usually stay together for longer than one breeding season.

On these grounds, Daly and Wilson hypothesized that any and all sorts of child abuse and exploitation would occur at elevated rates in steprelationships than in genetic parent-child relationships. This differential mistreatment is what the authors refer to as the “Cinderella Effect.”

Considerable support has been found for the Cinderella Effect, but the theory does not come without controversy. Confounds such as socieconomic status and personality differences between parents that live with their own children and parents who become parents have been brought up although studies in Canada and the US have assessed these factors and found them to be non-plausible.

Findings supporting the Cinderella Effect include: Stepparents beat very young children to death at per capita rates over 100 times higher than the corresponding rates for genetic parents. Stepparents also perpetrate both nonlethal physical assaults and sexual abuse at much higher rates than genetic parents. Abused stepchildren were almost always the eldest in the home. Cinderella effects are large regardless of marital registration (abuse can happen by unrelated live-in boyfriends, not necessarily a spouse).

Sources:

Daly and Wilson. The Cinderella effect is not fairy tale. TRENDS in Cognitive Sciences (2005). 9 (11): 507-8.

Daly and Wilson. (2008). Is the “Cinderella Effect Controversial? A Case Study of Evolution-Minded Research and Critiques Thereof. Foundations of Evolutionary Psychology (pp. 383-400). Psychology Press.

neuromorphogenesis: Mapping brain activity is neuroscience’s...

Sat, 09 Mar 2013 18:55:19 -0500

neuromorphogenesis:

Mapping brain activity is neuroscience’s lofty new goal

Now that we have the human genome pinned down, understanding the brain should be biology’s next great, bold challenge. So say a group of leading scientists who propose to track the activity of the entire brain, neuron by neuron, millisecond by millisecond.

The Brain Activity Map (BAM) project, first floated in June last year, was also hinted at by US president Barack Obama in his State of the Union Address in February. The fact that it has not yet been formally announced or funded has not stopped researchers expanding their proposal. Writing in Science, they now predict that in 15 years’ time it should be possible for non-invasive technology to observe 1 million neurons in real time. That’s enough coverage to analyse the function of several regions of a mouse’s cerebral cortex. The ultimate goal will be to extend this to the human brain.

Along the way, the hope is that the project will transform the technology of neuroscience – in the same way that the Human Genome Project (HGP) helped take genome-sequencing from pipe dream to everyday reality – and ultimately revolutionise our understanding of brain function. It is the right thing to do at this time, says Paul Alivisatos, director of Lawrence Berkeley National Laboratory in California, the lead author of the proposals.

But just how do you go about mapping a brain? This is a question that two projects with similar lofty goals are already grappling with. The Human Brain Project, which won a billion-euro research prize earlier this year, aims to do it by creating a computer simulation of the entire brain. The Human Connectome Project is using magnetic resonance imaging to track the fibres that connect different regions of the brain on the millimetre scale, giving a rough-grained roadmap of the brain. In contrast, BAM aims to generate the traffic report by getting down to the neuronal level, mapping which neurons fire at which time and how they are synchronised.

Brain invaders

To do so, researchers will need to find non-invasive ways to record the firing of individual neurons, because all current methods involve opening the skull and, often, sticking electrodes into brain tissue. “Right now, you’re literally driving posts into the brain. It’s not very sophisticated,” says neurobiologist John Ngai of the University of California, Berkeley.

A few groups have already started working on new approaches. For example, the MindScope project at the Allen Institute in Seattle aims to map the mouse visual cortex. The team identifies where neurons are firing by injecting the brain with dyes or using genetically engineered proteins that bind to calcium molecules. When a neuron fires, calcium flows into the cell and activates the dye or protein.

While powerful and widely used, calcium imaging alone is too slow to generate the kind of real-time map that the BAM project requires, saysMichael Roukes of the California Institute of Technology in Pasadena. A faster alternative would be to record the electrical activity of neurons, but the wires required to do this are invasive and tend to be relatively large. To get around the size issue, Roukes’s lab is creating tiny silicon-based nanowires that are connected to an array of electrodes, recording from multiple neurons at once. This allows the researchers to triangulate the position of any given neuron. Their tiny size means that they are less disruptive than other wires would be but you would still need to undergo an invasive procedure to implant them. Roukes’s team has tested the technology in insects and are now moving on to rats. Eventually, he says, they should be able to locate and record the activity from a million neurons at once.

Decoding the brain

But such an activity map is meaningless if it only shows connections and firing patterns without giving any clue why a circuit fires, says Karl Deisseroth of Stanford University in California. One way to image these cause-and-effect relationships is through optogenetics, which involves genetically engineering mice so that their neurons fire when hit with a beam of light shone through the skull. The firing neurons leave a protein trail, allowing researchers to see which circuits responded to the light or other stimuli.

Other promising technologies come from beyond the realm of biology. Alivisatos’s nanotechnology lab is engineering quantum dots that could be embedded in the cell membranes of neurons. When a neuron grows a new connection, it would stretch the quantum dot particle, causing it to emit light. Similar particles could respond in the same way to changes in the membrane’s voltage. In the lab, the dots are extremely fast and their light does not fade over time, but more work needs to be done to see whether having these dots implanted disrupts the function of the neurons.

The problem plaguing all of these light-based techniques is the brain’s density. It is no good having a technology that tells you that a neuron has fired by giving off a flash of light, if you cannot detect that light. The best microscopes currently available can detect light from 3 to 4 millimetres into the brain, enough to see light signals coming from the cortex of a small animal, but not enough to see deep-seated structures such as the hippocampus. “For this, we will need to redesign the basic concept of the microscope,” says Rafael Yuste of Columbia University in New York.

Despite the many technologies on the horizon, the BAM team is not worried about betting on the wrong one. “The thing right now is to get several ideas tried,” says Alivisatos. Once promising contenders emerge, then the simultaneous mapping of millions of neurons can begin in earnest.

Number crunching

The next issue will then be how to deal with the terabytes of data generated every day. Researchers already have their hands full sorting out the behaviour of just a few hundred neurons at a time – the current state of play. Expanding this to millions will demand the development of better computational and statistical techniques, says Konrad Körding of Northwestern University in Evanston, Illinois.

Moreover, to make sense of these activity records neuroscientists will also need to confront the fact that every brain is different, and changes over time. “If I have your brain and my brain at the level of individual neurons, it would be very difficult to line these brains up and compare them. That is a big challenge,” says Olaf Sporns of Indiana University in Bloomington.

Fortunately, that challenge is likely to diminish over time, as neuroscientists begin to recognise general patterns that emerge as they collect more data. General patterns that represent memories of faces or motor decisions, for example.

Artificial brains

Once these patterns begin to emerge, the research possibilities are endless. The HGP bore an entire new field of science in the form of genomics. At this stage it is impossible to predict what “connectomics” will unveil.

Yaser Abu-Mostafa of Caltech expects it will eventually lead to advances in artificial intelligence systems that mimic the brain. “I don’t want to say there will be an artificial brain on your desk in three years, but it will happen,” he says. “This project is the real catalyst.”

Another obvious application is medical: comparing the differences in activity between neurotypical brains and those with conditions such as schizophrenia, clinical depression or autism. Clay Reid of the Allen Institute hopes BAM will develop a technology that can be used to screen for brain differences that may indicate these conditions early. The map could also help researchers understand how they arise and manifest themselves, leading to better treatment.

Bone to pick

Not all neuroscientists are banging the drum for BAM, however. Partha Mitra at Cold Spring Harbor Laboratory in New York says that the technologies currently being discussed are still too far in the realm of imagination and still too invasive to start to think about applying them to humans. You cannot open a human brain to test an invasive technology, he says. “Everyone should be reminded that we have skulls.”

Others worry that despite the project’s far-reaching goals and methods, its approach is too narrow. “The best research combines and looks at multiple levels of detail,” rather than just focusing on the connections between neurons and fibres, says Susan Bookheimer of the University of California, Los Angeles. She says that BAM’s map, while useful, may still not explain phenomena like consciousness and cognitive function, which probably emerge at a broader scale.

If BAM does get the go-ahead – and this is a big if, given the US government’s imminent spending cuts – it will remain to be seen whether the technology will advance as quickly as it did during the HGP. But its proponents are necessarily optimistic. One lesson that we learned from the HGP’s achievements, says Yuste, is “that the predictions were too conservative”.

Journal reference: Science, DOI: 10.1126/science.1236939; Neuron, DOI: 10.1016/j.neuron.2012.06.006

Brain Awareness Week in NYC (March 9-17, 2013) Starts tomorrow...

Fri, 08 Mar 2013 13:37:43 -0500

Brain Awareness Week in NYC (March 9-17, 2013)

Starts tomorrow at the AMNH with the Food and the Brain exhibit :) Throughout next week, multiple institutions and research groups have joined forces in promoting outreach efforts and making our field more accessible (and fun) to the general public. Chances are, whatever your interest may be, somebody will be able to talk to you about it. So get out there and start learning! In addition, think of it as a networking opportunity; especially if you are interested in applying to grad school.

Also, NYU’s Neuroscience department will be hosting a special brain fair in which all are welcome. Stop by and you might even meet me in person. I’ll be at the Chemical Senses table :)

neuromorphogenesis: Gut instincts: The secrets of your second...

Thu, 31 Jan 2013 20:40:33 -0500

neuromorphogenesis:

Gut instincts: The secrets of your second brain

When it comes to your moods, decisions and behaviour, the brain in your head is not the only one doing the thinking

Embedded in the wall of the gut, the enteric nervous system (ENS) has long been known to control digestion. Now it seems it also plays an important role in our physical and mental well-being. It can work both independently of and in conjunction with the brain in your head and, although you are not conscious of your gut “thinking”, the ENS helps you sense environmental threats, and then influences your response. “A lot of the information that the gut sends to the brain affects well-being, and doesn’t even come to consciousness,” says Michael Gershon at Columbia-Presbyterian Medical Center, New York.

If you look inside the human body, you can’t fail to notice the brain and its offshoots of nerve cells running along the spinal cord. The ENS, a widely distributed network of neurons spread throughout two layers of gut tissue, is far less obvious, which is why it wasn’t discovered until the mid-19th century. It is part of the autonomic nervous system, the network of peripheral nerves that control visceral functions. It is also the original nervous system, emerging in the first vertebrates over 500 million years ago and becoming more complex as vertebrates evolved - possibly even giving rise to the brain itself.

Digestion is a complicated business, so it makes sense to have a dedicated network of nerves to oversee it. As well as controlling the mechanical mixing of food in the stomach and coordinating muscle contractions to move it through the gut, the ENS also maintains the biochemical environment within different sections of the gut, keeping them at the correct pH and chemical composition needed for digestive enzymes to do their job.

But there is another reason the ENS needs so many neurons: eating is fraught with danger. Like the skin, the gut must stop potentially dangerous invaders, such as bacteria and viruses, from getting inside the body. If a pathogen should cross the gut lining, immune cells in the gut wall secrete inflammatory substances including histamine, which are detected by neurons in the ENS. The gut brain then either triggers diarrhoea or alerts the brain in the head, which may decide to initiate vomiting, or both.

You needn’t be a gastroenterologist to be aware of these gut reactions - or indeed the more subtle feelings in your stomach that accompany emotions such as excitement, fear and stress. For hundreds of years, people have believed that the gut interacts with the brain to influence health and disease. Yet this connection has only been studied over the last century. Two pioneers in this field were American physician Byron Robinson, who in 1907 published The Abdominal and Pelvic Brain, and his contemporary, British physiologist Johannis Langley, who coined the term “enteric nervous system”. Around this time, it also became clear that the ENS can act autonomously, with the discovery that if the main connection with the brain - the vagus nerve - is severed the ENS remains capable of coordinating digestion. Despite these discoveries, interest in the gut brain fell until the 1990s when the field of neurogastroenterology was born.

We now know that the ENS is not just capable of autonomy but also influences the brain. In fact, about 90 per cent of the signals passing along the vagus nerve come not from above, but from the ENS (American Journal of Physiology - Gastrointestinal and Liver Physiology, vol 283, p G1217).

The feel-good factor

The second brain also shares many features with the first. It is made up of various types of neuron, with glial support cells. It has its own version of a blood-brain barrier to keep its physiological environment stable. And it produces a wide range of hormones and around 40 neurotransmitters of the same classes as those found in the brain. In fact, neurons in the gut are thought to generate as much dopamine as those in the head. Intriguingly, about 95 per cent of the serotonin present in the body at any time is in the ENS.

What are these neurotransmitters doing in the gut? In the brain, dopamine is a signalling molecule associated with pleasure and the reward system. It acts as a signalling molecule in the gut too, transmitting messages between neurons that coordinate the contraction of muscles in the colon, for example. Also transmitting signals in the ENS is serotonin - best known as the “feel-good” molecule involved in preventing depression and regulating sleep, appetite and body temperature. But its influence stretches far beyond that. Serotonin produced in the gut gets into the blood, where it is involved in repairing damaged cells in the liver and lungs. It is also important for normal development of the heart, as well as regulating bone density by inhibiting bone formation (Cell, vol 135, p 825).

But what about mood? Obviously the gut brain doesn’t have emotions, but can it influence those that arise in your head? The general consensus is that neurotransmitters produced in the gut cannot get into the brain - although, theoretically, they could enter small regions that lack a blood-brain barrier, including the hypothalamus. Nevertheless, nerve signals sent from the gut to the brain do appear to affect mood. Indeed, research published in 2006 indicates that stimulation of the vagus nerve can be an effective treatment for chronic depression that has failed to respond to other treatments (The British Journal of Psychiatry, vol 189, p 282).

Such gut to brain signals may also explain why fatty foods make us feel good. When ingested, fatty acids are detected by cell receptors in the lining of the gut, which send nerve signals to the brain. This may not be simply to keep it informed of what you have eaten. Brain scans of volunteers given a dose of fatty acids directly into the gut show they had a lower response to pictures and music designed to make them feel sad than those given saline. They also reported feeling only about half as sad as the other group (The Journal of Clinical Investigation, vol 121, p 3094).

There is further evidence of links between the two brains in our response to stress. The feeling of “butterflies” in your stomach is the result of blood being diverted away from it to your muscles as part of the fight or flight response instigated by the brain. However, stress also leads the gut to increase its production of ghrelin, a hormone that, as well as making you feel more hungry, reduces anxiety and depression. Ghrelin stimulates the release of dopamine in the brain both directly, by triggering neurons involved in pleasure and reward pathways, and indirectly by signals transmitted via the vagus nerve.

In our evolutionary past, the stress-busting effect of ghrelin may have been useful, as we would have needed to be calm when we ventured out in search of food, says Jeffrey Zigman at UT Southwestern Medical Center in Dallas, Texas. In 2011, his team reported that mice exposed to chronic stress sought out fatty food, but those that were genetically engineered to be unable to respond to ghrelin did not (The Journal of Clinical Investigation, vol 121, p 2684). Zigman notes that in our modern world, with freely available high-fat food, the result of chronic stress or depression can be chronically elevated ghrelin - and obesity.

Gershon suggests that strong links between our gut and our mental state evolved because a lot of information about our environment comes from our gut. “Remember the inside of your gut is really the outside of your body,” he says. So we can see danger with our eyes, hear it with our ears and detect it in our gut. Pankaj Pasricha, director of the Johns Hopkins Center for Neurogastroenterology in Baltimore, Maryland, points out that without the gut there would be no energy to sustain life. “Its vitality and healthy functioning is so critical that the brain needs to have a direct and intimate connection with the gut,” he says.

But how far can comparisons between the two brains be taken? Most researchers draw the line at memory - Gershon is not one of them. He tells the story of a US army hospital nurse who administered enemas to the paraplegic patients on his ward at 10 o’clock every morning. When he left, his replacement dropped the practice. Nevertheless, at 10 the next morning, everyone on the ward had a bowel movement. This anecdote dates from the 1960s and while Gershon admits that there have been no other reports of gut memory since, he says he remains open to the idea.

Gut instincts

Then there’s decision-making. The concept of a “gut instinct” or “gut reaction” is well established, but in fact those fluttery sensations start with signals coming from the brain - the fight or flight response again. The resulting feeling of anxiety or excitement may affect your decision about whether to do that bungee jump or arrange a second date, but the idea that your second brain has directed the choice is not warranted. The subconscious “gut instinct” does involve the ENS but it is the brain in your head that actually perceives the threat. And as for conscious, logical reasoning, even Gershon accepts that the second brain doesn’t do that. “Religion, poetry, philosophy, politics - that’s all the business of the brain in the head,” he says.

Still, it is becoming apparent that without a healthy, well-developed ENS we face problems far wider than mere indigestion. Pasricha has found that newborn rats whose stomachs are exposed to a mild chemical irritant are more depressed and anxious than other rats, with the symptoms continuing long after the physical damage has healed. This doesn’t happen after other sorts of damage, like skin irritation, he says.

It has also emerged that various constituents of breast milk, including oxytocin, support the development of neurons in the gut (Molecular Nutrition and Food Research, vol 55, p 1592). This might explain why premature babies who are not breastfed are at higher risk of developing diarrhoea and necrotising enterocolitis, in which portions of the bowel become inflamed and die.

Serotonin is also crucial for the proper development of the ENS where, among its many roles, it acts as a growth factor. Serotonin-producing cells develop early on in the ENS, and if this development is affected, the second brain cannot form properly, as Gershon has shown in mutated mice. He believes that a gut infection or extreme stress in a child’s earliest years may have the same effect, and that later in life this could lead to irritable bowel syndrome, a condition characterised by chronic abdominal pain with frequent diarrhoea or constipation that is often accompanied by depression. The idea that irritable bowel syndrome can be caused by the degeneration of neurons in the ENS is lent weight by recent research revealing that 87 out of 100 people with the condition had antibodies in their circulation that were attacking and killing neurons in the gut (Journal of Neurogastroenterology and Motility, vol 18, p 78).

If nothing else, the discovery that problems with the ENS are implicated in all sorts of conditions means the second brain deserves a lot more recognition than it has had in the past. “Its aberrations are responsible for a lot of suffering,” says Pasricha. He believes that a better understanding of the second brain could pay huge dividends in our efforts to control all sorts of conditions, from obesity and diabetes to problems normally associated with the brain such as Alzheimer’s and Parkinson’s (see “Mental illnesses of the gut” below). Yet the number of researchers investigating the second brain remains small. “Given it’s potential, it’s astonishing how little attention has been paid to it,” says Pasricha.

Mental illnesses of the gut

A growing realisation that the nervous system in our gut is not just responsible for digestion (see main story) is partly fuelled by discoveries that this “second brain” is implicated in a wide variety of brain disorders. In Parkinson’s disease, for example, the problems with movement and muscle control are caused by a loss of dopamine-producing cells in the brain. However, Heiko Braak at the University of Frankfurt, Germany, has found that the protein clumps that do the damage, called Lewy bodies, also show up in dopamine-producing neurons in the gut. In fact, judging by the distribution of Lewy bodies in people who died of Parkinson’s, Braak thinks it actually starts in the gut, as the result of an environmental trigger such as a virus, and then spreads to the brain via the vagus nerve.

Likewise, the characteristic plaques or tangles found in the brains of people with Alzheimer’s are present in neurons in their guts too. And people with autism are prone to gastrointestinal problems, which are thought to be caused by the same genetic mutation that affects neurons in the brain.

Although we are only just beginning to understand the interactions between the two brains, already the gut offers a window into the pathology of the brain, says Pankaj Pasricha at Johns Hopkins University in Baltimore, Maryland. “We can theoretically use gut biopsies to make early diagnoses, as well as to monitor response to treatments.”

Cells in the second brain could even be used as a treatment themselves. One experimental intervention for neurodegenerative diseases involves transplanting neural stem cells into the brain to replenish lost neurons. Harvesting these cells from the brain or spinal cord is not easy, but now neural stem cells have been found in the gut of human adults (Cell Tissue Research, vol 344, p 217). These could, in theory, be harvested using a simple endoscopic gut biopsy, providing a ready source of neural stem cells. Indeed, Pasricha’s team is now planning to use them to treat diseases including Parkinson’s.

Emma Young from Sheffield, UK

Hey! What do you know about the resulting effects of abuse and neglect on brain development? I know about Perry's work with Romanian orphans. Anything else? Also, why are Romanian orphans so widely cited in psychology work? Or am I just noticing something that isn't there?

Sat, 26 Jan 2013 15:38:00 -0500

Funny you should ask because that’s actually what our lab studies. We use naturalistic and experimental animal models of early life abuse in rodents and study the later life neurobehavioral outcomes. I was lucky enough to get to present some of our data in the Early Life Stress and Behavioral Development nanosymposium at the annual Society for Neuroscience (SfN) meeting. In rodents, early life abuse engages the amygdala, alters the development of the HPA-axis (stress system), disrupts social behavior and results in a depressive-like behavior during adolescence and adulthood. This area of research is very popular and prominent figures/labs include:

Martin Teicher (studies effects of childhood maltreatment via human neuroimaging)
Nim Tottenham (studies how early life experiences shape brain development and responses to social stimuli in childhood and adolescence in humans)
Mar Sanchez (studies how early life abuse changes brain structure and function as well as neuroendocrine development in primates; she is particularly cool because she does longitudinal studies)
Regina Sullivan (employs paradigms of early life abuse and studies the infant response to abuse as well programming effects of maternal care related to social behavior and depressive-like behavior)
Michael Meaney (king of maternal care and epigenetic programing related to stress responses and hippocampal development)

Click here for a review that includes work from Perry as well as some of the people mentioned above. If you are more interested in additional reviews, I would check out some by Heim and/or Nemeroff!

Considering I usually do not read papers published in psychology journals, I’m not sure :X

I've been looking for scholarly articles on neurotransmitters and their relations to learning, and memory. Would you be able to recommend any? Greatly appreciated.

Sat, 26 Jan 2013 00:32:00 -0500

Mol Neurobiol. 2011 Dec;44(3):449-64. doi: 10.1007/s12035-011-8214-0. Epub 2011 Nov 11.

Serotonin and prefrontal cortex function: neurons, networks, and circuits.

Puig MV, Gulledge AT.

Source

The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. mvpuig@mit.edu

Abstract

Higher-order executive tasks such as learning, working memory, and behavioral flexibility depend on the prefrontal cortex (PFC), the brain region most elaborated in primates. The prominent innervation by serotonin neurons and the dense expression of serotonergic receptors in the PFC suggest that serotonin is a major modulator of its function. The most abundant serotonin receptors in the PFC, 5-HT1A, 5-HT2A and 5-HT3A receptors, are selectively expressed in distinct populations of pyramidal neurons and inhibitory interneurons, and play a critical role in modulating cortical activity and neural oscillations (brain waves). Serotonergic signaling is altered in many psychiatric disorders such as schizophrenia and depression, where parallel changes in receptor expression and brain waves have been observed. Furthermore, many psychiatric drug treatments target serotonergic receptors in the PFC. Thus, understanding the role of serotonergic neurotransmission in PFC function is of major clinical importance. Here, we review recent findings concerning the powerful influences of serotonin on single neurons, neural networks, and cortical circuits in the PFC of the rat, where the effects of serotonin have been most thoroughly studied.

Mol Brain. 2010 May 13;3:15. doi: 10.1186/1756-6606-3-15.

Emotional enhancement of memory: how norepinephrine enables synaptic plasticity.

Tully K, Bolshakov VY.

Source

Department of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA. ktully@mclean.harvard.edu

Abstract

Changes in synaptic strength are believed to underlie learning and memory. We explore the idea that norepinephrine is an essential modulator of memory through its ability to regulate synaptic mechanisms. Emotional arousal leads to activation of the locus coeruleus with the subsequent release of norepineprine in the brain, resulting in the enhancement of memory. Norepinephrine activates both pre- and post-synaptic adrenergic receptors at central synapses with different functional outcomes, depending on the expression pattern of these receptors in specific neural circuitries underlying distinct behavioral processes. We review the evidence for noradrenergic modulation of synaptic plasticity with consideration of how this may contribute to the mechanisms of learning and memory.

Neuropharmacology. 2010 Jun;58(7):951-61. doi: 10.1016/j.neuropharm.2010.01.008. Epub 2010 Jan 21.

Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum.

Lovinger DM.

Source

Laboratory for Integrative Neuroscience, NIAAA/NIH, 5625 Fishers Lane, Rockville, MD 20852, USA. lovindav@mail.nih.gov

Abstract

The dorsal striatum is a large forebrain region involved in action initiation, timing, control, learning and memory. Learning and remembering skilled movement sequences requires the dorsal striatum, and striatal subregions participate in both goal-directed (action-outcome) and habitual (stimulus-response) learning. Modulation of synaptic transmission plays a large part in controlling input to as well as the output from striatal medium spiny projection neurons (MSNs). Synapses in this brain region are subject to short-term modulation, including allosteric alterations in ion channel function and prominent presynaptic inhibition. Two forms of long-term synaptic plasticity have also been observed in striatum, long-term potentiation (LTP) and long-term depression (LTD). LTP at glutamatergic synapses onto MSNs involves activation of NMDA-type glutamate receptors and D1 dopamine or A2A adenosine receptors. Expression of LTP appears to involve postsynaptic mechanisms. LTD at glutamatergic synapses involves retrograde endocannabinoid signaling stimulated by activation of metabotropic glutamate receptors (mGluRs) and D2 dopamine receptors. While postsynaptic mechanisms participate in LTD induction, maintained expression involves presynaptic mechanisms. A similar form of LTD has also been observed at GABAergic synapses onto MSNs. Studies have just begun to examine the roles of synaptic plasticity in striatal-based learning. Findings to date indicate that molecules implicated in induction of plasticity participate in these forms of learning. Neurotransmitter receptors involved in LTP induction are necessary for proper skill and goal-directed instrumental learning. Interestingly, receptors involved in LTP and LTD at glutamatergic synapses onto MSNs of the “indirect pathway” appear to have important roles in habit learning. More work is needed to reveal if and when synaptic plasticity occurs during learning and if so what molecules and cellular processes, both short- and long-term, contribute to this plasticity.

Curr Med Chem. 2009;16(7):796-840.

Neuro-transmitters in the central nervous system & their implication in learning and memory processes.

Reis HJ, Guatimosim C, Paquet M, Santos M, Ribeiro FM, Kummer A, Schenatto G, Salgado JV, Vieira LB, Teixeira AL, Palotás A.

Abstract

This review article gives an overview of a number of central neuro-transmitters, which are essential for integrating many functions in the central nervous system (CNS), such as learning, memory, sleep cycle, body movement, hormone regulation and many others. Neurons use neuro-transmitters to communicate, and a great variety of molecules are known to fit the criteria to be classified as such. A process shared by all neuro-transmitters is their release by excocytosis, and we give an outline of the molecular events and protein complexes involved in this mechanism. Synthesis, transport, inactivation, and cellular signaling can be very diverse when different neuro-transmitters are compared, and these processes are described separately for each neuro-transmitter system. Here we focus on the most well known neuro-transmitters: acetyl-choline, catechol-amines (dopamine and nor-adrenalin), indole-amine (serotonin), glutamate, and gamma-amino-butyric acid (GABA). Glutamate is the major excitatory neuro-transmitter in the brain and its actions are counter-balanced by GABA, which is the major inhibitory substance in the CNS. A balance of neuronal transmission between these two neuro-transmitters is essential to normal brain function. Acetyl-choline, serotonin and catechol-amines have a more modulatory function in the brain, being involved in many neuronal circuits. Apart from summarizing the current knowledge about the synthesis, release and receptor signaling of these transmitters, some disease states due to alteration of their normal neuro-transmission are also described.

Prog Brain Res. 2008;172:567-602. doi: 10.1016/S0079-6123(08)00927-8.

Serotonin/dopamine interaction in learning.

Olvera-Cortés ME, Anguiano-Rodríguez P, López-Vázquez MA, Alfaro JM.

Source

Laboratorio de Neurofisiología Experimental, Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, Morelia, México. maesolco@yahoo.com

Abstract

Dopamine (DA)-serotonin interactions dealing with learning and memory functions have been apparent from experimental approaches over the past decade. However, since the former evidence showing that these cerebral neurotransmitter systems are involved in the regulation of the same cognitive processes, few experimental studies have been done to further clarify the nature of DA-serotonin interactions for cognitive processes sharing common brain structures. Nevertheless, a regulatory role of 5-HT/DA interactions in cognition and the prefrontal cortex (PFC) and the striatum as a neuroanatomical substrate for these DA/5-HT interactions, are now recognized. Experimental evidence indicates that pharmacological disruption of serotonin neurotransmission results in a facilitative effect on the processing of mnemonic information by cerebral regions under strong, functional DA modulation, such as the striatum and the PFC; on the other hand, increased serotonin neurotransmission appears to have a detrimental effect on cognitive functions integrated in these structures. These effects seem to occur through the interaction of different pre- and postsynaptic DA and serotonin receptor subtypes acting as opposite systems underlying cognitive abilities. Some studies, focused on DA-serotonin interactions underlying the pathophysiology of neurological and psychiatric diseases, which evolve with cognitive dysfunctions in human beings, have shown that drugs that are able to modify DA or serotonin neurotransmission may exert beneficial effects on cognitive functions, even though improvement of motor, mood and behavioural disturbances are the main objectives of pharmacological treatment of these diseases. The complete significance of DA-serotonin interactions in cognitive functions could be addressed by future experimental and clinical studies.

Hi!

I searched and found these on PubMed. The first 3 are available as free downloads. Enjoy!