Politics on a weblog is like picking up a stick of old, wet dynamite.  You might grab it and absolutely nothing happens, or it might very well explode in your face.  It is for this reason that I try to avoid political discussion on prefrontal.org.  Every weblog must have a focus, and there are more than enough political blogs to go around.  Still, I am compelled to write just one post after the recent presidential election.  One post to say how much I have been desperately hoping for a new direction in our political system.  One post to tell you how much of that hope I have invested in one man.  One post to announce that I worked hard to help that man be successful.  One post, to tell you that he was in fact successful.

Congratulations, President-elect Barack Obama.

[Photo from Joe Raedle/Getty Images]

Reason #318 why Santa Barbara is such an awesome place to live is the fact that we are 90 minutes away from Vandenberg Air Force Base.  Vandenberg is a major spaceport in the United States for commercial and military space operations.  They don’t always post their launch schedule, but enthusiasts from around the world pool their collective knowledge to assemble a rough idea of when rockets will be blasting off. In my case I had luck on my side, as a local television station was covering the countdown of a target launch vehicle from Vandenberg last Tuesday. I hopped up off the couch and got in the car.

The mission was related to the NFIRE (Near Field InfraRed Experiment) satellite, which was designed to gather data on the orbital observation of rocket exhaust plumes. To calibrate the sensors on the satellite they needed a, well, rocket exhaust plume.  The target launch vehicle was a modified Minotaur ballistic missile, which was meant to simulate a ballistic missile launch for the NFIRE satellite.

My wife and I headed up into the hills of Santa Barbara to see if we could witness the launch.  Online Vandenberg observation FAQs indicated that it should definitely be visible. There was a two hour launch window that corresponded to two overhead passes of the NFIRE satellite (see above picture).  We barely made it in time - as the satellite made its first pass, but we saw nothing but a few shooting stars.  By looking at the orbital data for the NFIRE sat online (yea iPhone!) I knew the next satellite pass would begin at 11:57pm.  Sure enough, at 11:58 we saw a bright orange light coming up from the horizon and blazing up into the night.  Compared to your Fourth of July fireworks it wasn’t very special, but the knowledge that it was leaving the Earth’s atmosphere was about the coolest thing I have seen in a while.

Cheers to spaceflight everybody.

Endurance training has been shown to have a positive impact on affective state. Runners have known anecdotally about this effect for quite some time, but it is only in the last few decades that the neural underpinnings of this effect have been investigated. One mechanism that seems to be associated with increased positive mood is neurogenesis, or the creation of new neurons.

In a review of 14 studies examining the relationship between exercise and major depression Lawlor and Hopkor (2001) found that the magnitude of the antidepressant effect of exercise is generally equal to that of cognitive therapy. Strawbridge et al. (2002) further found that those who engage in exercise are less likely to develop a depressive disorder to begin with. These antidepressant effects have been shown to persist for over 21 months after exercise has stopped (Singh, Clements, and Singh, 2001). What causes this antidepressant effect?

The common belief used to be that the human brain did not form new neurons after early childhood, but recent evidence has accumulated that certain structures, such as the hippocampus, do create neurons as an adult (Lledo, Alonso and Grubb, 2006). The hippocampus is a structure in the brain known to be involved in memory and learning. In mice voluntary running has been shown to increase neurogenesis in the hippocampus (Naylor et al., 2008; van Praag, Kempermann, and Gage, 1999). The increase in neurogenesis has then been associated with reductions in depressive mood and depressive severity in rats (Bjørnebekk, Mathe, and Stefan Brene, 2005).

Running has also been associated with a reduced response to stress and anxiety. It can not only reduce the effects of a current stressful situation, but acts to guard against future stress (Greenwood and Fleshner, 2008). One source of this effect is a change of activity in the dorsal raphe nucleus (DRN), a center for serotonin in the brain. Hyperactivity in the DRN during stress has been shown to alter the behavior of an animal, often leading to a state of learned helplessness and avoidance (Maier and Watkins, 2005). In rats six weeks of wheel running was shown to significantly reduce DRN activity during uncontrollable stress (Greenwood and Fleshner, 2008). It also reduced the helpless behavior of the rats.

As a society the United States shells out over 25 billion dollars a year on antidepressants. The efficacy of these drugs is generally not as substantial as effects seen after exercise. Exercise also seems to impact a wider array of neural systems, positively affecting everything from single neurons to whole neural systems. Putting all of the above information into perspective, if I could create a pill that would increase positive mood in the same way that running does I would be a billionaire - seriously.

II. The impact on cognition

Exercise has been shown to provide cognitive improvements to both humans and animals. Researchers have observed benefits to long-term memory, learning, attention, executive control, and a host of other cognitive abilities. The brain as a whole seems to thrive on exercise.

One source of cognitive benefit is purely cardiovascular. Exercise increases cerebral blood flow and provides for more efficient glucose utilization (McCloskey et al., 2001). Let’s be clear, the brain lives on glucose. Over 25% of the energy you take in is going to fuel that little three-pound mass in your skull. When you are really working on a tough problem that percentage only goes up as energy usage increases. If you can more efficiently get energy where it needs to go that would represent a major benefit to cognitive processing.

Another source of cognitive benefit has to do with neurons and the environment they inhabit. The same mechanisms of neurogenesis described in section I are known to contribute to cognitive benefits as well (van Praag et al., 1999). Enhancement also is due to an increased level of brain-derived neurotrophic factor (BDNF) present after exercise. BDNF is a protein that helps existing neurons to survive and grow. Elevated corticosterone levels caused by acute stress tend to reduce levels of BDNF in the cortex and hippocampus, while exercise can raise levels significantly above baseline (Adlard and Cotman, 2004; Neeper et al., 1996).

Changes in the regional anatomy of the brain have also been observed after exercise. Grey matter differences in the frontal and temporal lobes were observed in association with individuals who exercise more frequently (Kemppainen et al., 2005). This may be related to the results of Colcombe et al (2004), who found that older adults with better fitness showed significantly higher activity in lateral frontal and superior parietal regions when engaged in an attention task.

Individuals suffering from cognitive deficits show benefits after beginning a new fitness regime. Exercise has been shown to improve the condition of Alzheimer’s patients (Teri et al., 2003) and stroke victims (Shepherd, 2001). While the effects are not gigantic, any improvement in the cognitive outcome of these disorders can greatly help a patient. Further, exercise reduces the risk of cognitive impariment, Alzheimer’s disease, and dementia to begin with (Lautenschlager, 2008; Friedland et al., 2001). This seems to be especially true if you have a genetic predisposition to these disorders.

As an aside, the PsyBlog has a great mini-review of typical cognitive enhancers and finds that between brain training, nutritional supplements, drugs, meditation and exercise that exercise is currently the best-bet for improving your cognitive ability. I tend to agree.

Much like the effect on mood, exercise affects a wide array of neural functions critical to cognition. Not only is there a boost in energy efficiency, but overall there is more energy available to burn. Further, the impact of events that seem to cause the most harm to our brain, such as acute stress, are marginalized and protected against. Together these factors help create a positive neural environment that supports cognitive improvement.

III. High as a kite

I would be remiss not to comment on the “runner’s high” that many people experience after extended exertion. This is often described as a state of euphoria or pleasure that occurs late into a long run. Recent evidence suggests that this state of euphoria is the direct result of engaging the brain’s endogenous opiate system. Boecker et al. (2008) found that strenuous running induced significant opiate binding in orbitofrontal, anterior cingulate, insula, and temporoparietal cortex in addition to multiple limbic and paralimbic subcortical areas. These are brain areas involved in the mapping of body state to emotional state. Their results are bolstered by other studies showing that naloxone, an opiate binding inhibitor, blocks the runner’s high from taking place (Janal et al, 1984).

It makes sense that our brain is providing this opiate system to us, otherwise running would be a pretty miserable experience. Still, opiates can be very addictive. Most of us might have already encountered opiates as medication in the form of morphine or codeine. Heroin is an illegal drug that is chemically similar to morphine and every bit as addictive. I have to wonder what role the opiate system plays in people getting addicted to running. We know that there are varying levels of susceptibility to drug addiction - two people can take the same amount of drug and only one will go on to become an addict. Is the same true of highly trained runners?

IV. Conclusions

This is perhaps less of a blog post and more a collection of interesting tidbits related to running that I have come across. Still, it helps that there is a big-picture view that goes along with all of the above. The view is this: exercise is nothing short of magic when it comes to your brain. The cognitive and emotional benefits you get from strenuous exercise are virtually unmatched when compared to prescription drugs or therapy. While this post has focused primarily on the neuroscience of exercise and running, you cannot ignore the other health benefits of exercise. Heart disease is the #1 killer of men and women in America. If you don’t get up and run for your brain, then (really) do it for your heart.

References

Adlard PA, Cotman CW. (2004). Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression. Neuroscience. 124(4):985-92.

Bjørnebekk A, Mathé AA, Brené S. (2005). The antidepressant effect of running is associated with increased hippocampal cell proliferation. Int J Neuropsychopharmacol. 8(3):357-68.

Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR. (2008). The Runner’s High: Opioidergic Mechanisms in the Human Brain. Cereb Cortex. Feb 21.

Colcombe SJ, Kramer AF, Erickson KI, Scalf P, McAuley E, Cohen NJ, Webb A, Jerome GJ, Marquez DX, Elavsky S. (2004). Cardiovascular fitness, cortical plasticity, and aging. PNAS. 101(9):3316-21.

Friedland RP, Fritsch T, Smyth KA, Koss E, Lerner AJ, Chen CH, Petot GJ, Debanne SM. (2001). Patients with Alzheimer’s disease have reduced activities in midlife compared with healthy control-group members. PNAS. 98(6):3440-5. Epub 2001 Mar 6.

Greenwood BN, Fleshner M. (2008). Exercise, learned helplessness, and the stress-resistant brain. Neuromolecular Med. 10(2):81-98.

Janal MN, Colt EW, Clark WC, Glusman M. (1984). Pain sensitivity, mood and plasma endocrine levels in man following long-distance running: effects of naloxone. Pain. 19(1), 13-25.

Kemppainen J, Aalto S, Fujimoto T, Kalliokoski KK, Långsjö J, Oikonen V, Rinne J, Nuutila P, Knuuti J. (2005). High intensity exercise decreases global brain glucose uptake in humans. J Physiol. 568(Pt 1):323-32.

Lautenschlager NT, Cox KL, Flicker L; et al. (2008). Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: a randomized trial. JAMA. 300(9):1027-1037.

Lawlor DA, Hopker SW. (2001). The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials. BMJ. 322(7289):763-7.

Lledo PM, Alonso M, Grubb MS. (2006). Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci. 7(3):179-93.

Maier SF, Watkins LR. (2005). Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neurosci Biobehav Rev 29(4-5):829-41.

McCloskey DP, Adamo DS, Anderson BJ. (2001). Exercise increases metabolic capacity in the motor cortex and striatum, but not in the hippocampus. Brain Res. 891(1-2):168-75.

Naylor AS, Bull C, Nilsson MK, Zhu C, Björk-Eriksson T, Eriksson PS, Blomgren K, Kuhn HG. (2008). Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. PNAS. 2008 Sep 2.

Neeper SA, Gómez-Pinilla F, Choi J, Cotman CW. (1996). Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 726(1-2):49-56.

Shepherd RB. (2001). Exercise and training to optimize functional motor performance in stroke: driving neural reorganization? Neural Plast. 8(1-2):121-9.

Singh NA, Clements KM, Singh MA. (2001). The efficacy of exercise as a long-term antidepressant in elderly subjects: a randomized, controlled trial. J Gerontol A Biol Sci Med Sci. 56(8):M497-504.

Strawbridge WJ, Deleger S, Roberts RE, Kaplan GA. (2003). Physical activity reduces the risk of subsequent depression for older adults. Am J Epidemiol. 156(4):328-34.

Teri L, Gibbons LE, McCurry SM; et al. (2003). Exercise plus behavioral management in patients with Alzheimer’s disease: a randomized controlled trial. JAMA. 290(15):2015-2022.

van Praag H, Kempermann G, Gage FH. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci. 2(3):203-5.

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Signs You Have Been Scanning Too Much

10. You wake up to the repeated beeping of your alarm clock, assume it’s just the scanner and go back to sleep.

9. While pouring syrup on your Eggo waffles, you note that you missed a few voxels.

8. Your knowledge of brain anatomy exceeds your knowledge of geography. As in, “The transverse occipital sulcus intersects the intraparietal sulcus near the level of the parieto-occipital fissure” and “The Sahara is in Afghanistan, I think.”

7. You have developed a rapid ritual for checking your body for metal that resembles the macarena.

6. When you seen drawings of brains in the popular media, you instantly decide whether or not they are anatomically correct.

5. Friends wonder how you can run a four million dollar scanner and still fail to program a VCR.

4. You suffer frequent left/right confusion and find yourself saying things like, “Make a left turn at the lights… No, I meant a *radiological* left!”

3. At parties, you scope out people’s subject-worthiness: “It was great talking to you. Say, what are you doing Friday night? … Do you have any metal in your body?…”

2. Not only can you recognize the brains of your frequently-scanned co-workers, but also their teeth from the bite bar impressions.

1. When reminded of a special occasion, you remember it fondly because the scanner was free all day long and you collected lots of good data.

HRFun is a small Cocoa application that allows a user to explore the construction of a canonical hemodynamic response from the summation of two gamma functions. This is the method used by the Statistical Parametric Mapping (SPM) folks to model what happens in the brain when a stimulus is applied. For instance, if I show a brief flashing checkerboard pattern to a subject while conducting functional MRI then areas of visual cortex would have signal changes similar to the canonical HRF. I was curious about how varying the parameters of the gamma functions would change the predicted hemodynamic response, so I created this application that lets me vary any parameter I want.

It’s not a terribly useful app, but for those who are curious to learn more about the SPM construction of a canonical HRF it can be a useful tool. HRFun is my first OS X application to be released, so there are probably some inefficiencies and bugs in the code. Still, I have been diligent to test the software out and smooth the rough edges. Also, the source code has been released under the GPL. So, if you need an Objective-C class to create a hemodynamic response you’re in luck!

Let me know what you think - positive or negative. This is a learning project, so any feedback is appreciated. My next goal is to figure out how to load an fMRI timeseries - then the real fun begins.

HRFun wiki page: http://prefrontal.org/wiki/index.php/HRFun

This is a piece we did as a cover illustration for the journal Human Brain Mapping. It depicts an axial slice of the brain composed of smaller images in the axial, sagittal, and coronal planes. To get the smaller images we used a simple Matlab script to go through each subject’s high-resolution 3D anatomical image and grab all possible 2D images in each plane. This resulted in 157 sagittal images, 189 coronal images, and 156 axial images for each subject. In total we ended up with about 10,000 smaller images to use. We then used the program MacOSaiX to take the thousands of small images and find the best fit for each hexagonal cell to represent the larger axial image. The blue and red coloring was added in Photoshop and represents the probabilistic values of white and gray matter in the current slice.

Click through to the larger image to really get a better feel for the photo. Cheers!

What is the goal for the second year? My primary goal is to post more often (2-3 times per week) and to aim for in-depth posts that take a bit more time to prepare. This will give the readers of this site additional material to peruse and gives me even more writing practice. The secondary goal is to continue filling in the quiet parts of the site, such as the ‘About’ and ‘Research’ pages. Who knows where this plan will take use 12 months from now, but if we can duplicate the success of the first year I will be more than happy.

Thanks for reading.

PCA is based on the idea that any group of variables will vary together to some degree. This covariance will be greater in variables that measure similar quantities. PCA capitalizes on the covariance of variables by using eigenvalue decomposition to extract components that can explain the greatest amount of variability in the data. A simple, two-dimensional example of this process is below.

The left figure above depicts the plot of two variables with high covariance. You can easily see that there is structure in the data, with levels of one variable highly related to levels of the other. PCA examines the cloud of data and asks, “along what dimension is the greatest amount of variability found?”. In the case of our plot, the greatest variability is found along the diagonal axis, which becomes the first component. After the variability of the first component is accounted for, a second orthogonal component will then be found. In this case the second component explains the spread of the data around the first component.

Combined the two components in the example explain 100% of the variability in the data. Still, they are not equal in their contribution. In this case the first component explains 97% of the variance, meaning that you could reduce your dataset by half using just the first component and you would lost only 3% of the variability.

We are trying to use PCA to examine individual differences between people in our fMRI study. By taking each person’s analysis results and running them through the PCA algorithm we are hoping to identify the underlying structure of variability between people. In conjunction with clustering algorithms, we can observe not only how people vary, but where in the brain the variability is strongest, and how people group together. Time will tell if this approach bears fruit, but it is a lot of fun to explore.

I used this device extensively when I was programming some Psychtoolbox scripts. By getting all the big bugs out of your experiment before ‘going live’ and testing on a MR phantom you can save a lot of time, energy, and frustration.

For most of July I have been in Lawrence, Kansas as an instructor for the KU Educational Talent Search summer camp ‘Discover Technology’. Talent Search is an educational opportunity program whose main goal is to shepherd students from underrepresented backgrounds though high school and encourage them to engage in post-secondary education. The Discover Technology summer camp is just one part of this year-round program.

I have been an instructor for Discover Technology for almost 10 years now. What brings me back year after year? Well, they pay me for my time, which is a plus. The biggest motivator though is that the course genuinely impacts the lives of the students. The graduation rate of most Kansas City, Kansas high schools is around 50% - Talent Search gets over 95% of their students through to their graduation. That is huge, and definitely worth a little time and effort on my part.