Brain Foods...

Gómez-Pinilla contributes a review article to the latest issue of Nature Reviews Neuroscience on how various dietary factors, in addition to some gut and brain hormones, increase the resistance of neurons to insults and promote mental fitness. I pass on one figure dealing with dietary omega-3 fatty acids, followed by a summary table.

The omega-3 fatty acid docosahexaenoic acid (DHA), which humans mostly attain from dietary fish, can affect synaptic function and cognitive abilities by providing plasma membrane fluidity at synaptic regions. DHA constitutes more than 30% of the total phospholipid composition of plasma membranes in the brain, and thus it is crucial for maintaining membrane integrity and, consequently, neuronal excitability and synaptic function. Dietary DHA is indispensable for maintaining membrane ionic permeability and the function of transmembrane receptors that support synaptic transmission and cognitive abilities. Omega-3 fatty acids also activate energy-generating metabolic pathways that subsequently affect molecules such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF1). IGF1 can be produced in the liver and in skeletal muscle, as well as in the brain, and so it can convey peripheral messages to the brain in the context of diet and exercise. BDNF and IGF1 acting at presynaptic and postsynaptic receptors can activate signalling systems, such as the mitogen-activated protein kinase (MAPK) and calcium/calmodulin-dependent protein kinase II (CaMKII) systems, which facilitate synaptic transmission and support long-term potentiation that is associated with learning and memory.

(Click to enlarge table.)

Brain exercise/fitness links...

Tom Hanson, the Editor of OpenEducation.net, asks me to pass on these two separate posts on brain exercise/fitness, noting some firms that I have mentioned previously, and so I do this as a professional courtesy.

Evaluating mental exercises

This article on pumping up your little grey cells in the Times of London is worth reading, also this New Scientist article.

Schizophrenia and the Brain

Here is a very nice instructional video from Thompson at UCLA, whose images I have shown in previous posts, showing brain developmental differences in normal and schizophrenic children between the ages of 4 and 21. It also shows how recently developed drugs inhibit the degenerative changes.

Growing new brain cells enhanced by social contact

From the editor's choice section of the May 30 issue of Science, a suggestion that increased social input from a larger number of other animals enhances the survival of new brain cells in brain areas involved in communication:

Out With the Old, In With the New

Might this adage, which some pundits have claimed as the basis for the vernal electoral calamities that have befallen the Labour Party in the United Kingdom, apply equally forcefully to the turnover of neurons in the brain? Adar et al. have performed a painstaking histological and immunofluorescence accounting of the survival likelihoods of newly born neurons in the brain of the zebra finch, a songbird that serves as an animal model for studying innate and learned influences on vocal communication. They focused on the nidopallium caudale (NC) region because it participates in auditory processing and is activated by social stimuli (other songbirds in this notably social species). By varying the complexity of the social environment, they found that the youngest cells--which had recently migrated from the site of their birth and were still becoming integrated, quite literally, as they established syn-aptic connections with existing NC neurons--were more likely to have survived if the bird had been exposed to a large group of male and female birds; conversely, in birds housed with only one other individual, the survival of older (though still relatively young) cells was enhanced. One interpretation of these data is that an increase in demand--in the form of an upturn in auditory/social inputs needing to be processed--acts as a selective pressure favoring the survival of new recruits.

Spatial memory requires new nerve cells.

At least this appears to be the case in mice. Here is the abstract from Dupre et al.

The dentate gyrus of the hippocampus is one of the few regions of the mammalian brain where new neurons are generated throughout adulthood. This adult neurogenesis has been proposed as a novel mechanism that mediates spatial memory. However, data showing a causal relationship between neurogenesis and spatial memory are controversial. Here, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. These findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning.

(More specifically, the experiments involved generating transgenic mice that selectively overexpressed the pro-apoptotic protein Bax in neural precursor cells in an inducible manner. Overexpression of Bax removed newly born cells in the adult dentate gyrus and caused a strong deterioration in the relational processing of spatial information in the Morris water maze. Animals were unaffected when tested on simpler forms of spatial knowledge; nor were they affected in tasks where memory could be acquired without the hippocampus.)

Brain imaging of belief, disbelief, and uncertainty

A fascinating fMRI study by Sam Harris and colleagues has used functional magnetic resonance imaging (fMRI) to study the brains of 14 adults while they judged written statements to be true (belief), false (disbelief), or undecidable (uncertainty). (Yes, this is the same Sam Harris who wrote "The End of Faith" and "Letter to a Christian Nation."). To characterize belief, disbelief, and uncertainty in a content-independent manner, they included statements from a wide range of categories: autobiographical, mathematical, geographical, religious, ethical, semantic, and factual. They show that belief, disbelief, and uncertainty are mediated primarily by regions in the medial PFC, the anterior insula, the superior parietal lobule, and the caudate. The acceptance and rejection of propositional truth-claims appear to be governed, in part, by the same regions that judge the pleasantness of tastes and odors.

...the final acceptance of a statement as true or its rejection as false appears to rely on more primitive, hedonic processing in the medial prefrontal cortex and the anterior insula. Truth may be beauty, and beauty truth, in more than a metaphorical sense, and false propositions may actually disgust us.
...When compared with both belief and uncertainty, disbelief was associated in our study with bilateral activation of the anterior insula..., a primary region for the sensation of taste. The anterior insula has been regularly linked to pain perception and even to the perception of pain in others. This region, together with left frontal operculum (also active in the contrast disbelief - belief), appears to mediate negatively valenced feelings such as disgust. Studies of olfaction have shown that the left frontal operculum is engaged when subjects are required to make active judgments about the unpleasantness of odors. Thus, regions that have been regularly implicated in the hedonic appraisal of stimuli, often negative, appeared in our study to respond preferentially when subjects rejected written statements as false. Our results appear to make sense of the emotional tone of disbelief, placing it on a continuum with other modes of stimulus appraisal and rejection.
...Several psychological studies appear to support Spinoza’s conjecture that the mere comprehension of a statement entails the tacit acceptance of its being true, whereas disbelief requires a subsequent process of rejection...Understanding a proposition may be analogous to perceiving an object in physical space: We seem to accept appearances as reality until they prove otherwise...subjects assessed true statements as believable faster than they judged them as unbelievable or undecidable. Further, because the brain appears to process false or uncertain statements in regions linked to pain and disgust, especially in judging tastes and odors, this study gives new meaning to a claim passing the “taste test” or the “smell test.”

MindBlog becomes a drop-out student at a brain enhancement site

When the folks at happy-neuron.com offered me a free log in to check out their brain enhancement/preservation exercises I said "Sure, I'll try it out and do a review." The site offers a brief discussion of the science of brain fitness is offered, and the scientific contributors have reasonable credentials. Several have associations with gerontology and aging programs, as is the case with other brain enhancements sites. The single study I was pointed to testing the effects of the happy-neuron exercises was a pilot effort carried out by Robert Bender, a geriatrics and family practice physician in Des Moines, Iowa. He did not respond to my email requesting information on the study.

Well.... to do a proper review one really has to get into it, and I tried, but simply was unable to do this. One could just pick directly from ~ 35 classic style tests (of memory, attention, language, executive function, and visual spatial skills) with a thin video game veneer, or let a "coach" present you with 20 minutes worth of exercises. I chose the "coach" option which chooses exercises for you, monitors your progress, strengths and weaknesses, etc. (It didn't tell me what my strengths and weaknesses were, but perhaps I didn't stick with it long enough for it to get back to me...) The exercises were mildly engaging and indeed left me feeling 'brain tired' after 20 minutes. I did get a bit tired of variations on the towers of Hanoi game (classic form, then basket balls in hoops, then bells in cathedral towers, etc.) I found the 'exit' or 'next' buttons sometimes blanked out or froze the browser window.

I found it difficult to get hooked on the system in a daily basis (I came along before the video game revolution on which my kids were raised). The exercises soon took on an "eat your spinach" aspect. I suspect my motivation might have been greater to pursue them if had been accumulating more striking evidence of my own impending cognitive decline.

I did find it very interesting to pursue the exercises to the point of brain fatigue, which my brain was clearly saying "enough of this, dammit, I'm tired." However, I have not found exercise to the point of fatigue useful or relevant in the daily gym routine to which I am addicted (varying combinations of running, swimming, weights at the Univ. of Wisconsin gym). I feel it would take a similar sort of addiction process to bind me to the routine performance of games like these, and I did not get reinforcement from the "coach" that might have nudged me in that direction ("Hey, you're doing great on executive function and rotating visual images, but your short term memory sucks...")

I may continue to putter with this as well as other brain exercise sites, and if lightning strikes and I get enthusiastic, I'll report back to you.

Lacking power diminishes cognitive function

An implication of meritocracies is that individuals who lack power are low achievers because they are less capable or less motivated than those who acquire power. Smith et al. propose, alternatively, that powerless people often achieve less than powerful people because lacking power itself fundamentally alters cognitive functioning and increases vulnerability to performance decrements during complex executive tasks.

In a experiment carried out on 101 Dutch university students, simply assigning each participant to be either a superior or a subordinate in a computer-based task altered their performance on tests of executive function. (Participants were told that the superior would direct and evaluate the subordinate. This evaluation would purportedly determine the subordinate's payment for the experiment, whereas the superior would be paid a fixed amount.) Smith et al. found that the powerless were less effective than the powerful at standard tests evaluating ability to update, inhibition, and planning. Because existing research suggests that the powerless have difficulty distinguishing between what is goal relevant and what is goal irrelevant in the environment, a further experiment was carried out to establish that the executive-function impairment associated with low power is driven by goal neglect.

This work consistent with the idea that the cognitive alterations arising from powerlessness may help foster stable social hierarchies. The results also have implications for management and organizations. In many industries (e.g., health care, electric power), errors can be costly. Increasing employees' sense of power could lead to improved executive functioning, decreasing the likelihood of catastrophic errors.

Brain exercises

A few moments with google, using search items like "brain exercises" will immediately bring you to a large number of web sites that offer to improve your mental function, combat the decay of mental performance with aging, etc. Some of these have appeared since my previous posting which listed several. A recent NYTimes article (from which the graphic on the left is taken) points to a number of these sites and offers an interesting discussion.

I have held back from taking the plunge into brain exercises, partly because I'm afraid of what I might find find out about how far gone I already am, and partly because some which appear to be most thoroughly researched and academically respectable want your money. But, now happy-neuron.com has offered me a free login to try out their regime, and so I have taken the bait. I will be offering my opinion of this site after immersing in their 20 min exercise sessions for a few weeks, and if I have the stamina or remaining self-esteem (and get offered a free login), will review some of the other sites in subsequent posts.

The Posterior–Anterior Shift in Aging

Here is some more interesting information on brain changes with aging (material I almost don't want to know about, knowing that I'm surely well along with the 'compensations for neural decline' being described.... ):

Older adults reallocate neural resources, increasing activity in prefrontal cortex to perform cognitive tasks, presumably to compensate for declining neural processing in posterior brain regions. Davis et al. show: 1). that this reflects the effects of aging rather than differences in task difficulty (i.e. not due to the same cognitive tasks tending to be more demanding for older adults than for younger adults); 2). that the shift in fact reflects compensation (the age-related increase in PFC activation is positively correlated with cognitive performance and negatively correlated with the age-related decrease in occipitotemporal activity.); and 3). that the deactivation of the midline "default network" associated with conscious rest processes, which must be suppressed for successful cognitive performance, is reduced in posterior midline cortex but increased in medial frontal cortex.

The experiments were performed on 12 younger (mean age = 22.2 years) and 12 older adults (mean age = 69.2 years), presumably referenced by the Y and O prefixes in this figure from the paper (I'm not clear from the text on what distinguishes YM and YP, but I think they refer to the two different tasks, episodic retrieval and visual discrimination).

Figure (click to enlarge) - The posterio-anterior shift pattern for activations: across 2 different tasks and 2 levels of confidence, the occipital cortex showed greater activity in younger than in older adults A, whereas PFC showed the opposite pattern (B). The PASA pattern for deactivations: across 2 different tasks and 2 levels of confidence, posterior midline cortex (precuneus, C) showed greater deactivations in younger than older adults, whereas the anterior midline cortex (medial PFC, D) showed the opposite pattern. Notes: Activation bars represent effect size for each modeled effect, and error bars represent standard error for peak activity across participants.

Enhance your working intelligence with simple exercises...

Bakalar points to an interesting study by Jaeggi et al. showing that fluid intelligence (the kind of mental ability that allows us to solve new problems without having any relevant previous experience) can be enhanced by simple working memory training. It turns out that carefully structured training of the kind of memory that allows memorization of a telephone number just long enough to dial it enhances performance on standard tests of fluid intelligence. This suggests that fluid intelligence and working memory depend on the same brain circuitry.

An antidepressant enhances brain plasticity

The title of the article by Vetencourt et al. is "The Antidepressant Fluoxetine Restores Plasticity in the Adult Visual Cortex. " [Fluoxetine hydrochloride, i.e. Prozac, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.] Here is their abstract:

We investigated whether fluoxetine, a widely prescribed medication for treatment of depression, restores neuronal plasticity in the adult visual system of the rat. We found that chronic administration of fluoxetine reinstates ocular dominance plasticity in adulthood and promotes the recovery of visual functions in adult amblyopic animals, as tested electrophysiologically and behaviorally. These effects were accompanied by reduced intracortical inhibition and increased expression of brain-derived neurotrophic factor in the visual cortex. Cortical administration of diazepam prevented the effects induced by fluoxetine, indicating that the reduction of intracortical inhibition promotes visual cortical plasticity in the adult. Our results suggest a potential clinical application for fluoxetine in amblyopia as well as new mechanisms for the therapeutic effects of antidepressants and for the pathophysiology of mood disorders.

A mouse model for PTSD suggests a therapy

Pibiri et al. have performed experiments on mice that model the emotional hyper-reactivity (including enhanced contextual fear and impaired contextual fear extinction) that is observed in human post traumatic stress disorder (PTSD) patients. They suggest that activation of neuronal steroid synthesis might be useful in PTSD therapy. The edited abstract:

Mice subjected to social isolation (3–4 weeks) exhibit enhanced contextual fear responses and impaired fear extinction. These responses are time-related to a decrease of ... allopregnanolone (Allo) levels in selected neurons of the medial prefrontal cortex, hippocampus, and basolateral amygdala...In socially isolated mice, S-norfluoxetine, in doses that increase brain Allo levels but fail to inhibit serotonin reuptake, greatly attenuates enhanced contextual fear response. The drug SKF decreases corticolimbic Allo levels and enhances the contextual fear response in group housed mice... A recent clinical study reported that cerebrospinal fluid Allo levels also are down-regulated in human PTSD patients and correlate negatively with PTSD symptoms and negative mood. Thus, protracted social isolation of mice combined with tests of fear conditioning may be a suitable model to study emotional behavioral components associated with neurochemical alterations relating to PTSD. Importantly, selective brain steroidogenic stimulants such as S-norfluoxetine, which rapidly increase corticolimbic Allo levels, normalize the exaggerated contextual fear responses resulting from social isolation, suggesting that selective activation of neurosteroidogenesis may be useful in PTSD therapy.

Even brief stress can zap your brain...

Well...to be sure, we're talking about rat brains, but the message is probably there for us as well. An interesting (and sobering) piece of work from Sapolsky's laboratory shows that a single dose of corticosterone, i.e. an increase in its levels of the sort that would be induced by temporary stress, is sufficient to induce the hyper-growth of nerve cell dendrites in the basolateral amygdala and heighten anxiety behaviors. Here is the complete abstract, followed by a figure from the paper:

Stress is known to induce dendritic hypertrophy in the basolateral amygdala (BLA) and to enhance anxiety. Stress also leads to secretion of glucocorticoids (GC), and the BLA has a high concentration of glucocorticoid receptors. This raises the possibility that stress-induced elevation in GC secretion might directly affect amygdaloid neurons. To address the possible effects of GC on neurons of amygdala and on anxiety, we used rats treated either acutely with a single dose or chronically with 10 daily doses of high physiological levels of corticosterone (the rat-specific glucocorticoid). Behavior and morphological changes in neurons of BLA were measured 12 days after the initiation of treatment in both groups. A single acute dose of corticosterone was sufficient to induce dendritic hypertrophy in the BLA and heightened anxiety, as measured on an elevated plus maze. Moreover, this form of dendritic hypertrophy after acute treatment was of a magnitude similar to that caused by chronic treatment. Thus, plasticity of BLA neurons is sufficiently sensitive so as to be saturated by a single day of stress. The effects of corticosterone were specific to anxiety, as neither acute nor chronic treatment caused any change in conditioned fear or in general locomotor activity in these animals.

Figure - Representative camera lucida drawing of neurons from animals treated either acutely (A) or chronically (B) with CORT (Right) compared with their respective vehicle-treated controls (i.e. injection without the hormone) (Left).

Brain changes in dyslexia - different in Hong Kong and Chicago

Siok et al show that the brain changes associated with dyslexia in an alphabetic versus an ideographic language can be different. In alphabetic language, a reader sees a letter and associates it with a sound. Chinese characters correspond to syllables and require much more memorization. Both Chinese and English dyslexics find it harder to make their way through even fairly simple written material. This study suggests that their brain mechanics as they try to read may be as different as Chinese is from English. Here is their abstract:

Developmental dyslexia is a neurobiologically based disorder that affects approximately 5–17% of school children and is characterized by a severe impairment in reading skill acquisition. For readers of alphabetic (e.g., English) languages, recent neuroimaging studies have demonstrated that dyslexia is associated with weak reading-related activity in left temporoparietal and occipitotemporal regions, and this activity difference may reflect reductions in gray matter volume in these areas. Here, we find different structural and functional abnormalities in dyslexic readers of Chinese, a nonalphabetic language. Compared with normally developing controls, children with impaired reading in logographic Chinese exhibited reduced gray matter volume in a left middle frontal gyrus region previously shown to be important for Chinese reading and writing. Using functional MRI to study language-related activation of cortical regions in dyslexics, we found reduced activation in this same left middle frontal gyrus region in Chinese dyslexics versus controls, and there was a significant correlation between gray matter volume and activation in the language task in this same area. By contrast, Chinese dyslexics did not show functional or structural (i.e., volumetric gray matter) differences from normal subjects in the more posterior brain systems that have been shown to be abnormal in alphabetic-language dyslexics. The results suggest that the structural and functional basis for dyslexia varies between alphabetic and nonalphabetic languages.

Release of creativity by frontotemporal dementia

An article by Sandra Blakeslee describes FTD, or frontotemporal dementia, through which some patients have become gifted in landscape design, piano playing, painting and other creative arts as their disease progressed. The composer Ravel composed “Bolero” in 1928, when he was 53 and began showing signs of this illness with spelling errors in musical scores and letters. The structure and repetition of this musical piece is mirrored by the graphic shown here, an image of a migraine by Anne Adams,a bench scientist with FTD who became drawn to structure and repetition. Enhanced artistic abilities arise when frontal brain areas decline and posterior regions take over. Injury or disintegration of dominant inhibitory frontal cricuits appears to release or disinhibit activity in other areas. The result of compromising one part of the brain can be to induce other parts to remodel and become stronger.

Neuroenhancement - continued....

Nature magazine continues its coverage of reactions to an December article on cognitive-enhancing drugs. Here is the PDF of a summary.

The Amazing Aging Brain

Check out this interesting site, illustrating how the brain changes on aging.

The World in the Brain

Here are a few excerpts from a brief essay by Steve Kosslyn in the Edge.org series "What have you changed your mind about?

There is a really elegant solution to the problem that the genes can't know in advance how far apart the eyes will be. To cope with this problem, the genes overpopulate the brain, giving us options for different environments (where the distance between eyes and length of the arms are part of the brain's "environment," in this sense), and then the environment selects which connections are appropriate, and the useless connections are pruned away. In other words, the genes take advantage of the environment to configure the brain.

This overpopulate-and-select mechanism is not limited to stereovision. In general, the environment sets up the brain (above and beyond any role it may have had in the evolution of the species), configuring it to work well in the world a person inhabits. And by environment I'm including everything outside the brain — including the social environment. For example, it's well known that children can learn multiple languages without an accent and with good grammar, if they are exposed to the language before puberty. But after puberty, it's very difficult to learn a second language so well.

This perspective leads me to wonder whether we can assume that the brains of people living in different cultures process information in precisely the same ways. Yes, people the world over have much in common (we are members of the same species, after all), but even small changes in the wiring may lead us to use the common machinery in different ways. If so, then people from different cultures may have unique perspectives on common problems, and be poised to make unique contributions toward solving such problems... to understand how any specific brain functions, we need to understand how that person was raised, and currently functions, in the surrounding culture.

A similar, more brief, response to the edge.org question was offered by Jeffrey Epstein, A science Philanthropist:

The question presupposes a well defined "you", and an implied ability that is under "your" control to change your "mind". The "you" I now believe is distributed amongst others (family friends , in hierarchal structures,) i.e. suicide bombers, believe their sacrifice is for the other parts of their "you". The question carries with it an intention that I believe is out of one's control. My mind changed as a result of its interaction with its environment. Why? because it is a part of it.