Brain network disruption during aging.

Most work on brain changes with aging has focused on individual regions, especially those in the frontal lobe, which may shrink or lose activity even in the absence of disease. Andrews-Hanna et al. offer an important paper showing how long range interactions between brain regions are compromised with aging. The work looked at neural activity during a task in two large-scale networks that span the brain: the default network, used when we’re worrying, thinking of the past and future, or imagining people in our lives; and the attention network, used when we’re focusing on a specific task, such as word processing or math problems. The brain regions making up these systems were in sync in young people, but much less so, or not at all, in people over 60.

Figure - the younger brain, below, shows more synchronized activity than the older brain, above.

Brain imaging can predict the mistakes you are about to make.

From Fountain's review of work by Eichele et al.:

...brain patterns start to change about 30 seconds before an error is committed... changes were seen in two brain networks. One, called the default mode region, is normally active when a person is relaxed and at rest. When a person is doing something, like playing the game, this region becomes deactivated...researchers found that in the time leading up to an error, the region became active again — the subject was heading toward a relaxed state...Another network in the right frontal lobe gradually became less active, the researchers found. This is an area in the brain thought to be related to cognitive control, Dr. Eichele said, to keeping “on task.”

...it might be possible someday to develop a warning system — perhaps by monitoring the brain’s electrical activity, which is more practical — that could be used by people doing monotonous or repetitive tasks. Such a system would alert users when they are heading for a harmful or costly, not to mention mindless, mistake.

Positive psychology - a new organization

Some of you might wish to check out the website of the new International Positive Psychology Association (IPPA). It's board includes Martin Seligman, Mihaly Csikszentmihalyi, Tal Ben-Shahar, etc. The organization seeks to promote the science and practice of positive psychology and to facilitate communication and collaboration among researchers and practitioners around the world. A first world congress is planned for June 2009 in Philadelphia.

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.

Space versus body based number representation

Here is a fascinating bit of work from Brozzoli et al. showing how our touch perception can reveal the dominance of spatial over digital representation of numbers.

We learn counting on our fingers, and the digital representation of numbers we develop is still present in adulthood. Such an anatomy–magnitude association establishes tight functional correspondences between fingers and numbers. However, it has long been known that small-to-large magnitude information is arranged left-to-right along a mental number line. Here, we investigated touch perception to disambiguate whether number representation is embodied on the hand ("1" = thumb; "5" = little finger) or disembodied in the extrapersonal space ("1" = left; "5" = right). We directly contrasted these number representations in two experiments using a single centrally located effector (the foot) and a simple postural manipulation of the hand (palm-up vs. palm-down). We show that visual presentation of a number ("1" or "5") shifts attention cross-modally, modulating the detection of tactile stimuli delivered on the little finger or thumb. With the hand resting palm-down, subjects perform better when reporting tactile stimuli delivered to the little finger after presentation of number "5" than number "1." Crucially, this pattern reverses (better performance after number "1" than "5") when the hand is in a palm-up posture, in which the position of the fingers in external space, but not their relative anatomical position, is reversed. The human brain can thus use either space- or body-based representation of numbers, but in case of competition, the former dominates the latter, showing the stronger role played by the mental number line organization.

Testosterone predicts financial profitability

..at least on a stock trading floor in London. Dan Mitchell summarizes the work of Coats and Herbert, published in PNAS. Men with elevated levels of testosterone, the hormone associated with aggression, made more money. When the markets were more volatile, the men showed higher levels of the stress hormone cortisol. There is the minor question of which is cause and which is effect....

Mine is longer than yours....

The last game of the baby boomers: Who wins is not who has the most toys, but who lives longest. Check out this great New Yorker article by Michael Kinsley. And, by the way, you might refer back to my May 2, 2007 post on Gawande's excellent article on aging.

Stirring Dull roots with spring rain... at Twin Valley

I'm back in Madison, WI., at the old stone schoolhouse on Twin Valley road.

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.

8-month-old infants use intuitive statistics..

Here is a fascinating result from Xu and Garcia, a demonstration that our brains begin to employ statistics at a very young age. Here are some (slightly edited) clips from their paper:

One hallmark of human learning is that human learners are able to make inductive inferences given a small amount of data. Our hunter–gatherer ancestors may have tasted a few berries on a tree and then decided that all berries from the same kind of tree are edible. They may have encountered a few friendly people from a neighboring tribe and made the inference that people in that tribe are likely to be friendly in general. Once such generalizations are made, the inferences may go in the other direction as well. This type of statistical inference (going from samples to populations, and from populations to samples) is present in virtually every domain of learning, be it foraging, social interaction, visual perception, word learning, or causal reasoning . Inductive learning in general requires some understanding of intuitive statistics, perhaps a simpler version of what scientists do in laboratory experiments or field studies.

Xu and Garcia performed six experiments investigating whether 8-month-old infants are "intuitive statisticians." Their results show that, given a sample, the infants are able to make inferences about the population from which the sample had been drawn. Conversely, given information about the entire population of relatively small size, the infants are able to make predictions about the sample...This ability to make inferences based on samples or information about the population develops early and in the absence of schooling or explicit teaching. Human infants may be rational learners from very early in development.

Here is one of the experiments, which asked whether 8-month-old infants could use the information in a sample to make inferences about a larger population:

...8-month-old infants watched some events unfold on a puppet stage. Each infant was first given a set of six ping-pong balls in a small container to play with for a few seconds; half of the ping-pong balls were red, half were white. Then the infant was shown four familiarization trials. On each trial, a large box was brought onto the stage. The experimenter opened the front panel of the box and drew the infant's attention to the box. The box contained either mostly red ping-pong balls and a few white ping-pong balls or mostly white ping-pong balls and a few red ping-pong balls. The experimenter showed the infants these two displays alternately; thus the infants were equally familiarized with each display. Then the test trials began (see Fig. 1 for a schematic representation of the test events). On each test trial, the same box was brought onto the stage, its content not known to the infants. The experimenter shook the box for a few seconds, closed her eyes, reached into the top opening, and pulled out a ping-pong ball. She then placed it into a transparent sample display container next to the large box. A total of five ping-pong balls were drawn from the box, one at a time. In half of the test trials, a sample of four red and one white ping-pong balls were drawn. In the other half of the test trials, a sample of one red and four white ping-pong balls were drawn. After the five ping-pong balls were placed in the sample display container, the experimenter opened the front panel of the box to reveal its content. The infant's looking time was recorded. The experimenter then cleared the stage and started the next test trial until a total of eight test trials were completed. Only one outcome display was shown for each infant, either the mostly white or the mostly red one. On alternate test trials, the infants were shown the two samples (four red and one white or one red and four white). For an infant who saw the mostly red outcome display when the box was opened, the four red and one white sample was more probable and therefore expected, whereas the four white and one red ball sample was much less probable and therefore unexpected,{dagger} assuming each set was a random sample from the box. For an infant who saw the mostly white outcome display, the converse was true.


Figure - Schematic representation of the test events (Images 1, 3, and 5) The experimenter shook the box for a few seconds, closed her eyes, reached into the top opening, and pulled out a ping-pong ball. (Images 2, 4, and 6) She then placed the ball into a transparent sample display container next to the large box. Test outcomes are shown at the bottom.

The infants looked reliably longer at the unexpected outcome (M = 9.9s) than the expected outcome (M = 7.5 s). It appears that infants were able to predict the content of the box from which the samples had been drawn.

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).

What do you see and not see?

Here is an update of a well known demonstration that I have used in my lectures (and in my "I-Illusion" web-lecture at dericbownds.net) - on what happens when you focus your attention.

Money makes us happy...

In the Business section of the NY Times, Leonhardt points to a recent article by Betsey Stevenson and Justin Wolfers that disagrees with a classic paper published by Richard Easterlin in 1974, in which he argued that economic growth didn’t necessarily lead to more satisfaction. The prevailing idea as been that once a basic level of subsistence has been reached people care more about how much they make with respect to those around them than they do about their absolute level of income. An 'aspiration treadmill' makes people continuously dissatisfied (You own an iPod, now you want an iPod touch). Better public opinion data has been obtained over the past 34 years, and the bottom line is that income does matter, money indeed tends to bring happiness, even if it doesn’t guarantee it.

If anything...absolute income seems to matter more than relative income. In the United States, about 90 percent of people in households making at least $250,000 a year called themselves “very happy” in a recent Gallup Poll. In households with income below $30,000, only 42 percent of people gave that answer. But the international polling data suggests that the under-$30,000 crowd might not be happier if they lived in a poorer country.

Here is a summary graphic from Leonhardt's article (click to enlarge):

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.

Emotion enhancing learning and memory - a mechanism

Emotion enhances our ability to form vivid memories of even trivial events. Eric Nestler points to a study by Hu et al. that links this behavioral outcome to its molecular cause. They

...elucidated a molecular mechanism by which emotional stress and arousal promote long-term memory formation. In doing so, they brought together two well-characterized phenomena: that noradrenaline stimulates memory formation in the brain's hippocampus, and that the trPublish Postafficking of a type of glutamate receptor is important for a form of plasticity in the same brain region.

Malinow's team shows that, by stimulating noradrenaline release in the hippocampus, emotional stress leads to phosphorylation of glutamate receptors. This boosts the incorporation of these receptors at the synapse — the junction between nerve cells — which, in turn, enhances synaptic function and improves memory formation. Crucially, mice with a mutation that prevents phosphorylation of the relevant part of the glutamate receptor do not show noradrenaline-mediated memory enhancement.

Impressively, this study begins with a clinically important phenomenon — memory enhancement by emotional stress — and establishes a detailed biological pathway that underlies a behavioural endpoint in an animal model.

Negligent mouse moms - a model for humans?

From the laboratory of my Univ. of Wisconsin Zoology colleague Steve Gammie, along with Anthony Auger in the Psychology Department, an interesting account of a mouse model for human maternal neglect: a strain of mice that exhibit unusually high rates of maternal neglect, with approximately one out of every five females failing to care for her offspring. By comparing the good mothers to their less attentive relatives, this group has found that negligent parenting seems to have both genetic and non-genetic influences, and may be linked to dysregulation of the brain signaling chemical dopamine. In more detail, they:

...examined brain activity in neglectful and nurturing mice. c-Fos expression was significantly elevated in neglectful relative to nurturing mothers in the CNS, particularly within dopamine associated areas, such as the zona incerta (ZI), ventral tegmental area (VTA), and nucleus accumbens. Phosphorylated tyrosine hydroxylase (a marker for dopamine production) was significantly elevated in ZI and higher in VTA (although not significantly) in neglectful mice. Tyrosine hydroxylase levels were unaltered, suggesting a dysregulation of dopamine activity rather than cell number. Phosphorylation of DARPP-32, a marker for dopamine D1-like receptor activation, was elevated within nucleus accumbens and caudate-putamen in neglectful versus nurturing dams.

Enhancing our memories with brain implants.

Here are some interesting speculations by Gary Marcus on enhancing our memory - possibly through the use of computer chips as brain implants which combine cue-driven promptings similar to human memory with the location-addressability of computers. He does a nice job of distinguishing the differences in memory storage between our brains and computers.

Language evolution and the arcuate fasciculus

Did language evolve gradually via communication precursors in the primate lineage or did it arise spontaneously through a fortuitous confluence of neuroanatomical changes that are found only in humans? Rilling et al., reviewed by Ghazanfar, have used diffusion-tensor imaging to track putative differences in white matter connectivity between the frontal and temporal lobes, a pathway that is essential for language, by comparing humans, chimpanzees and macaque monkeys. They focused on the arcuate fasciculus,the fiber tract connecting the temporal to the frontal lobes in humans, which is essential for language in humans. Lesions to this pathway result in conduction aphasia, in which, among other deficits, patients can comprehend speech, but cannot repeat what was said. Rilling et al found that the organization of cortical terminations between the temporal and frontal lobes was strongly modified in the course of human evolution, and, crucially, this modification was gradual. They also noted a prominent temporal lobe projection of the human arcuate fasciculus that is much smaller or absent in nonhuman primates. This human specialization may be relevant to the evolution of language.


Figure from the News and Views summary by Ghazanfar (click to enlarge) - Chimpanzees are phylogenetically between macaques and humans in the primate lineage, and the similarly 'in between' pattern of their arcuate pathway terminations strongly suggest a gradual evolution of this pathway.(a) Changing patterns of connections between frontal cortical areas and the temporal lobe in humans, chimpanzees and macaque monkeys. AS, arcuate sulcus; CS, central sulcus; IFS, inferior frontal sulcus; IPS, intraparietal sulcus; PS, principal sulcus; PrCS, precentral sulcus; STS, superior temporal sulcus. (b) The voice area in the rhesus macaque relative to other auditory cortical areas and where the voice area would be if it were in a similar location as the human voice area. LS, lateral sulcus; IOS, inferior occipital sulcus; STS, superior temporal sulcus; other labels refer to cytoarchitectonic areal designations. The lateral sulcus is cut open to reveal the superior temporal plane. In this plane, the core region is thought to contain 'primary-like' areas, responding best to pure tones, whereas the surrounding belt areas are more responsive to complex sounds. The voice area in macaques is anterior to the core and belt regions. INS, insula; IT, inferotemporal cortex; Tpt, temporoparietal area.

Neuroenhancement - continued....

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