Attention Deficit Hyperactivity Disorder, how Ritalin might be working.

Ruth Williams, in Nature Reviews Neuroscience, points out an article by Drouin et al in The Journal of Neurophysiology that suggests a potential brain mechanism for the action of methylphenidate (Ritalin) in relieving attention deficit hyperactivity disorder (ADHD). ADHD sufferers essentially "pay attention to too many things." They find it difficult to filter out unwanted distractions and focus one issue at a time. Behavioral experiments with rats have shown that Ritalin improves behavior in a sustained attention task, just as it does in humans. Drouin et al found that administering Ritalin to rats (at a dose equivalent to that used in human therapy) caused an increase in the levels of the neurotransmitter noradrenaline in the rat's sensory cortex and reduced a long-latency phase of the brain's response to sensory stimuli. This latter effect may be important in filtering out sensory noise.

Free Will, Free Won't, or Neither? A refinement of Libet's work on the conscious control of spontaneous actions.

In a famous paper published in 1983, Libet et al. showed that the recordable cerebral activity (readiness-potential) that precedes a freely voluntary motor act occurs at least several hundred milliseconds before the reported time of conscious intention to act. The actual movement occurs 200-250 msec after the reported time of intention to act. The data are pretty spooky when you think about it. They say that your brain ("it") has started working on a action well before "you" think you are initiating it! This article has sparked a continuing debate on whether we actually have free will. Libet has suggested that the ~200-250 msec period between awareness of intention and the actual action was sufficient to permit a "veto" of the action if it was judged inappropriate. In this interpretation, we might be said to be "free won't" rather than "free will".

Lau et al. have now done a more nuanced version of LIbet's experiments. In a previous paper they showed that, when participants were required to estimate the onset of their intentions using Libet's procedure, the activity in the presupplementary motor area (pre-SMA) was enhanced ~228 msec before motor execution. In their most recent work they show that when participants were required to estimate the onset of their motor executions (instead of their intentions), the activity in the cingulate motor area was enhanced. This latter condition, judged to be more natural and have less task-demanding instructions. The perceived onset of intention could be as late as ~120 msec before the motor execution . "Together, these findings raise the question of whether the conscious control of spontaneous action can be done within a much shorter time window than we had expected, or whether, as suggested by Wegner (The illusion of conscious will Cambridge, MA: MIT Press, 2002), our impression of conscious control is simply illusory."

I think Wegner has it right. His book, and his interpretation of our sense of agency as an after the fact ' emotion of authorship' is a must-read for anyone interested in issues of conscious volition.

The Dali Lama and evolutionary science. He’s an awesome guy, but……

The Dali Lama deserves great credit for his efforts to integrate the insights of modern science and spiritual traditions, and he deals with this in his recent book, “The Universe in a Single Atom.” However, I really don’t think some of his critiques of the evolutionary theory and the limitations of science and materialism get it quite right....

Take for example, chapter 5, ''Evolution, Karma, and the world of sentience' While it is quite extraordinary that someone in his position has learned so much, it is also not surprising that he seems to be unaware of work that counters many of his perceived shortcomings of "Darwinian evolutionary theory."

pg 104 "that mutations..take place naturally is unproblematic..that they are purely random strikes me as unsatisfying. It leaves open the question of whether this randomness is best understood as an objective feature of reality or better understood as indicating some kind of hidden causality."

This doesn't compute for me. Ionizing cosmic radiation hitting a nucleotide and altering its replication is random, as are a number of low frequency errors made by enzymic processes involved in replication. We at least have a handle on what we mean by random. There are countless examples of how statistically small random changes can lead to complex results (like eyes, or different kinds of hormone and neurotransmitter receptors). "Hidden causality' , on the other hand, is a complete deus ex machina, or wild card, with no presently known means of evaluation within a materialistic scientific world view. If something pops up, great, but until then......

pg 104, "For modern science, at least from a philosophical point of view, the critical divide seems to be between inanimate matter and the origin of living organisms, while for Buddhism the critical divide is between non-sentient matter and the emergence of sentient beings." Aren't we talking about apples and oranges? I'm not understanding the usefulness of trying so hard to unify things, as (on pg. 111) "On the whole, I think the Darwinian theory...gives a fairly coherent account of the evolution of human life on earth. At the same time, I believe that karma can have a central role in understanding the origination of Buddhism calls "sentience", through the media of energy and consciousness."

pg. 115 "I find it [Darwinian account] leaves one crucial area unexamined, the origin of sentience." Virtually all descriptions of the evolution of the nervous system (Dennett's in "Consciousness Explained", for example) view the increasingly complexity of the nervous system - and the gradient of increasing sentience, consciousness, or whatever - as Darwinian adaptations that increase survival fitness of the organism.

pg. 114 "I feel that this inability or unwillingness fully to engage the question of altruism is perhaps the most important drawback of Darwinian...." There are now abundant models of how 'selfish' genes and organisms can generate altruistic behaviors. There is even a recent computer model of simple automata (agents with a limited set of receptors and elementary actions) that evolve various cooperative strategies. (Nature, 20:1041, 2006). See also my 5/26/06 post on "Cooperation, Punishment, and the Evolution of Human Institutions"

Anyway, enough. I won't ramble on. He really is an extraordinary guy. I totally support the idea that buddhist psychological insight offers some correlates with modern cognitive neuroscience, as between Buddha's foundations of mindfulness and steps in the evolution of the brain (mentioned in my "Beast Within" essay at dericbownds.net).

Genes, cognition, and dyslexia.

Learning to read and write places unusual demands on the brain: explicit awareness of the structural elements of language and their relation to arbitrary visual symbols, rapid temporal processing, fine motor control, and visual acuity. Because sophisticated reading and writing systems appeared only a few thousand years ago, it is very unlikely that reading skills were shaped directly by Darwinian selection. Spoken or sign language, on the other hand, is acquired virtually effortlessly during the first few years of life, and is supported by brain specializations that evolved over hundreds of thousands of years.

It is interesting that studies on several European, Canadian, and American families have found genetic changes that correlate with reading disorders, or dyslexia, independent of general cognitive performance. Fisher and Francks, in Trends in Cognitive Sciences, 10:250 (2006), provide an overview of four prominent examples (genes DYX1C1, KIAA0319, DCDC2, and ROBO1). These are not "genes for reading". None are specific to reading-related neuronal circuits, or even to the human brain. They do have intriguing roles in neuronal migration or connectivity. Individual genes do not specify behavioral outputs, cognitive skill, or even particular neural circuits. They "influence brain development and function interactively by affecting processes such as proliferation and migration of neurons, programmed cell-death, axonal pathfinding, connectivity, levels of neurotransmitters/receptors, and so on."

Future and previous goals represented by different neuronal population the prefrontal cortex.

Genovesio et al have measured the activities of a large number of individual prefrontal cortical neurons as monkeys selected a future goal on the basis of events from a previous trial involving visual cues. They found that prefrontal neurons had activity that reflected either previous goals or future goals, but only rarely did individual cells reflect both. Their comment: "This finding suggests that essentially separate neural networks encode these two aspects of spatial information processing. A failure to distinguish previous and future goals could lead to two kinds of maladaptive behavior. First, wrongly representing an accomplished goal as still pending could cause perseveration or compulsive checking, two disorders commonly attributed to dysfunction of the prefrontal cortex. Second, mistaking a pending goal as already accomplished could cause the failures of omission that occur commonly in dementia."

Stoking the Voters' Passions

This is the title of a review in Science Magazine by James Druckman of Ted Brader's recent book "Campaigning for Hearts and Minds - How Emotional Appeals in Political Ads Work." (Univ. of Chicago Press, 2006). The main focus is on television ads. Brader extends the work of others in experiments that show that ads that generate enthusiasm will increase political interest, participation, and confidence, whereas fear-provoking ads will cause people to reevaluate their preferences and potentially change their opinions. His experiments manipulated emotional stimulation entirely by including or excluding certain images and music, having nothing to do with the ads' contents.


CREDIT: COURTESY TED BRADER, graphic from Science Magazine. Cueing emotion: In Brader's enthusiasm experiment, one ad contained hopeful images and music while the other relied on the narration and less evocative imagery. (Both ads used the same positive script, here: "There's good news in your neighborhood. The future looks bright for a generation of young people.") The fear experiment compared the effects of the same unevocative imagery with those of threatening images and dissonant music. (In the negative narration for this pair, "It's happening right now in your neighborhood. A generation of young people is in danger.")

Fraternal birth-order effect on male sexual orientation.

For each additional brother that precedes him, a boy's chance of growing up to be gay increases by a third. A fascinating article and commentary in the current issue of Proc. Nat. Acad. Sci. now make the point "that the social influence of an older brother is irrelevant to whether his younger brother will develop a homosexual orientation. It is the number of older biological brothers the mother carried, not the presence of older brothers while growing up, that makes some boys grow up to be gay. Older stepbrothers in the home have no effect, although older biological brothers raised apart still exert their influence. These data, by elimination, strengthen the notion that the common denominator between biological brothers, the mother, provides a prenatal environment that fosters homosexuality in her younger sons."

One explanation that has been proposed is a maternal immunization hypothesis. "When a mother is carrying her first son, the placental barrier protects each from exposure to the other’s proteins. But inevitable mixing of blood upon delivery will expose the mother for the first time to male-specific proteins..., including those encoded on the Y chromosome. If her immune system produces antibodies to these proteins, then the placenta may actively transport those antibodies (indeed, all IgGs) to subsequent offspring in utero, potentially affecting development of later-born sons, but not later-born daughters."

Brain-machine interfaces

Check out this special WEB FOCUS presented by Nature Magazine. A new study in Nature demonstrates a human with spinal injury manipulating a computer, a television, a screen cursor, and robotic devices by thought alone. Implanted electrodes in his motor cortex recorded neural activity, and translated it into movement commands.

The Deepest Cut - removing one cerebral hemisphere

The right and left hemispheres of our brains have a long list of distinctive specializations, one example being the centering of linguistic functions in the left hemisphere and emotional processing in the right. It is an amazing testament to plasticity of our brains that an entire hemisphere can be removed in children (in a last-ditch effort to stop intractable epilepsy), with the remaining hemisphere learning to take on some functions (such as language) previously handled by the now-missing partner. Several such surgeries (one on an eight year old girl) are described in an interesting article, with the title of this post, by Christine Kenneally in the July 3 issue of The New Yorker magazine.

Mice feel each others' pain.

Recent experiments by Langford et al provide further evidence that simple mammals show 'emotional contagion', a simple precursor to human empathy. Such behavior had previously been clearly documented in more advanced mammals such as chimpanzees, dolphins, and elephants. The experiments demonstrated that a pair of mice injected in view of each other with a chemical solution (acetic acid) that caused a 30-minute stomach ache suffered significantly more distress when they saw a familiar mouse suffering than when they saw the same kind of pain in a stranger. The observer also became more sensitive to other kinds of pain. Thus social manipulation of pain sensitizes the whole pain system.

Credit: Science Magazine and Mona Lisa Chanda
When two mice had their paws injected with different amounts of formalin, which would induce different levels of licking behavior, the high formalin mouse licked less and the low formalin animal licked more, indicating that their behavior was influenced by their neighbor's status bidirectionally. Emotional contagion is an automatic primitive kind of empathy (human babies cry on hearing other babies cry, regardless of cause), it does not require understanding what others are experiencing, and is distinct from altruism. So far there is no evidence for these more advanced behaviors in mice.

Lapses in Attention.....

We frequently make errors during lapses in our attention, and Weissman et al have now looked at what is happening in the brain during this process. They determined that attentional lapses begin with reduced activity in anterior cingulate and right prefrontal regions that act in a top-down fashion to bias posterior sensory regions in favor of processing task relevant information. This reduced activation occurred before the stimuli used to test attention were presented, and was accompanied by decreasing sensory processing in the inferior occipital cortex. These prefrontal regions seem to modulate how well focused people are in the moment just before they have to perform. The same prefrontal areas implicated in focusing attention before stimulus presentation had greater activation during stimulation following a lapse.

Credit: Nature Neuroscience. The figure, from an accompanying review by Hedden and Gabrieli indicates some of the cortical regions associated with focused and lapsed attention. The arrows indicate reciprocal functional connections between prefrontal and parietal regions, and top-down modulation of occipital sensory regions by the prefrontal cortex. IFG, right inferior frontal gyrus; TPJ, temporal-parietal junction.

Lie Detection by MRI spooks ethicists

Helen Pearson writes a good summary of issues and current work on lie detection that catches brains in the act of deception, unlike conventional methods that rely on stress-induced changes in pulse rates or skin conductance. Particular areas of the prefrontal cortex thought to be involved in detecting errors and inhibiting responses become more active during lying. Several groups claim 90% certainty in detecting when individuals are lying in a laboratory setting. There is controversy over statistical methods used in the experiments, and there are no data about whether the technique can be beaten by countermeasures, as the more conventional measures can. Many people who do brain imaging think that claims for the technique may crash and burn as more work is done. There is sentiment for a regulatory scheme that would prevent the use of MRI for lie detection until there was sufficient evidence to conclude that it was proven safe and effective - much as the US Food and Drug Administration bars or approves a drug. There is something deeply unsettling and intrusive about peering into someone's brain, essentially 'mind reading' even before the subject can make a response.

Social Animals Prove their Smarts

This is the title of an interesting brief review of animal intelligence by Pennisi in the June 23 issue of Science Magazine. It points out the remarkable range of behaviors once thought unique to humans but now observed in social animals. The reigning paradigm now is that social living fostered the evolution of intelligence. Crows deceive each other, as do apes; hyenas keep track of social hierarchies. There is no doubt that animals can attribute intentions and motives to others. This ability can evolve quickly. Foxes bred to for 45 years to be comfortable with humans can understand human gestures (like pointing to food). Untamed foxes can not, even after extensive training efforts. What still has not been convincingly shown for any animal is the ability to understand that another individual is thinking something wrong. Human children develop this ability by the age of four.



The roots of social intelligence. Fellowship. Foxes bred to be tame are keenly tuned in to human behavior. From Science Magazine, Credit: Irene Plyusnia, Photo Courtesy Of Brian Hare.

Brain basis of risk-taking behavior in adolescents.

Mesolimbic regions of the brain, particularly the nucleus accumbens are involved in reward, risk taking, and addictive behaviors. Galvan et al have looked at the development of this system by making behavioral and fMRI brain imaging measurements in adults and children in response to tasks manipulating reward values. Accumbens activity in adolescents looked like that of adults in both extent of activity and sensitivity to reward values, although the magnitude of activity was exaggerated. In contrast, the extent of orbital frontal cortex activity in adolescents looked more like that of children than adults, with less focal patterns of activity. Their findings suggest that the accumbens becomes disproportionately activated relative to later maturing top–down control systems in the orbital frontal cortex, biasing the adolescent's action toward immediate over long-term gains.


Localization of nucleus accumbens (A) and orbital frontal cortex (C) activation to reward.
Credit: Journal of Neuroscience

Trust in Fish

A mutually beneficial interaction between two species of fish turns out to involve the careful appraisal of one by the other — and the appropriately virtuous behaviour by the former while being watched. This is yet another example of a complex social behavior once thought to be unique to mammals.


Credit: Nature Magazine

The small (wrasse) fish is a cleaner of its client (bream) fish. It removes parasites, but actually prefers eating the clients mucus, which is not in the client's best inrest (i.e. is non-cooperative). Bshary and Grutter found that eavesdropping clients (who observed cleaners working on other clients) spent more time next to 'cooperative' than 'unknown cooperative level' cleaners, which shows that clients engage in image-scoring behaviour. Furthermore, trained cleaners learned to feed more cooperatively when in an 'image-scoring' than in a 'non-image-scoring' situation.

The Mellow Years?: Neural Basis of Improving Emotional Stability over Age

Several studies have documented that older adults show a shift in the ratio of positive-to-negative emotion, with a reduction in the experience, memory, and recognition of negative emotion, but an increase for positive emotion. A recent article by Williams et al with the title of this post shows some of what is going on in in the brains of these older adults. They used fMRI (function Magnetic Resonance Imaging) or ERP (Event related potentials recorded on the surface of the scalp) to examine the activity of the medial prefrontal cortex (MPFC) that is central in inhibiting or enhancing emotional functions. Subject also rated their own reactions to photographs shown during the measurements of fearful, happy, or neural faces. A shift in responses to positive versus negative emotion over age was seen in both recognition and brain function. Recognition of negative emotion (fear, shown in red in right part of figure) showed a significant decline as a function of increasing age, whereas
recognition for positive emotion (happiness) increased.


Credit: J. Neuroscience

Changes in both ERP (over the time course 40–450 ms after stimulus) and fMRI measures over age. Happiness relative to neutral showed a decrease in activity over the medial prefrontal region (shown in blue), which was most apparent for neural activity elicited during the early phase of processing (40–150 ms after stimulus). In response to fear, in contrast, there was an increase in activity over the medial prefrontal cortex with age (shown in red), which ERPs showed was most apparent for neural activity occurring in the later phase of the time course (180–450 ms after stimulus).

Fear elicited corresponding increases in medial prefrontal activation, apparent during the later (180–450 ms) controlled phase of processing. In contrast, medial prefrontal activation to happiness attenuated over age, apparent in the early, automatic (within 150 ms) phase of the time course. These changes indicate that processing resources are shifted from the automatic phase of stimulus appraisal toward a greater allocation during the controlled phase of stimulus evaluation. The authors propose that this shift in resources supports better selective control of reactions to negative, particularly threat-related stimulation and allows positive responses to proceed without restraint. Their observation that this shift in processing of negative versus positive emotion predicted better emotional wellbeing with older age supports the view that it contributes to an increasingly adaptive regulation of emotion.

The authors propose that life experience and changing motivational goals may drive plasticity in the medial prefrontal brain systems to increase selective control over the balance of negative and positive emotion, with the consequence of improving emotional wellbeing.

"The motivation to achieve better emotional control in older adults may come from the increasing awareness of one’s mortality and the desire to maximize the meaningfulness of environmental events and input, over and above the need for acquisition. With repeated emotional experiences over the lifespan, humans may learn to be more selective about which input is likely to provide quality positive outcomes as opposed to cause distress. Consistent with this view, older adults are more selective about their social activities and tend to prioritize quality rather than quantity."

The mysteries of blog-land, Feedburner and Linkie Winkie

Having just put a feed for feed readers on this blog, I find myself totally out of my depth and would be most grateful if a techie happens to read this post and could enlighten me on what is going on. One of the icons at the lower right hand of this blog page directs you to FeedBurner, which offer to put the feed from this site onto MyYahoo, MyAol, MyGoogle or whatever feedreader you might be using. The guy helping me also put RSS and other icons on the page that let you place the feed directly on those readers without going through FeedBurner. Feedburner reports back that since I connected with it 5 days ago an average of 3 sites have subscribed to this blog's feed each day. One site, the Linkie Winkie web crawler, appears to sign up each day? It has minimum content, but a few links indicate that guys involved with SEO (search engine optimization) set it up as an altruistic gesture.....

I hope someone out there might explain this to me....

Oxytocin, Affiliative Neuroscience, make the NYTimes Op-Ed page!

The conservative columnist David Brooks has a Sunday Times (July 2) piece titled "Of Human Bonding," He suggests that some of Mr. Buffet's billions given to the Gates foundation could well be spent on research on affiliative neuroscience and hormones like oxytocin that promote bonding and nurturing behavior (see my Feb. 13 posting on oxytocin). Brooks notes that "Attachment theory has been thriving for decades, but it's had little impact on public policy. That's because the policy world is a supermagnet for people who are emotionally avoidant. If you go to a Congressional hearing and talk demography, you are treated like a serious policy wonk, but if you start talking about relationships, people look at you as if you're Oprah." ...."everything we're learning about the brain confirms the centrality of attachments to human development and the wisdom of Adam Smith's observation that the "chief part of human happiness arises from the consciousness of being beloved." (Brain research rarely reveals anything new about human nature; it just tells you which of the old verities are most important.)" Brooks points out that billions of dollars have been spent trying to improve math in reading scores in high schools, without engaging the core issue: the emotional disengagement caused by lack of caring and attachment.

Genes that regulate risk taking, addiction, obesity, sexual desire and orientation....

It is hard to ignore increasing evidence that significant personality variations can be inherited. We are not (to use the title of Steven Pinker's 2002 book) "blank slates."

An article by Amy Harmon in the June 15 N.Y.Times provides a nice table summary of a few of the genes known to influence behavior in humans and other animals:

INSIG2 - Obesity - A common gene variant that is associated with significantly increased risk of becoming fat among the more than 25 million Americans who carry it. Herbert et al. (2006) "A Common Genetic Variant Associated with Adult and Childhood Obesity". Science 312:279-283.

neuroD2 - Risk-taking - Mice lacking neuroD2 have a greatly reduced sense of fear. Variants of the human version of this gene may lead to risk-taking behaviors. Lin et al. "The dosage of neuroD2 transcription factor regulates amygdala development and emotional learning" Proceedings of the National Academy of Science 41:14877-14882

CYP2A6 - Nicotine Addiction - People with certain forms of this gene smoke more and are more likely to become addicted to cigarettes. Tailoring treatments based on which form of CYP2A6 a person has may help him or her quit. Minematsu et al. (2006) "Limitation of cigarette consumption by CYP2A6*4, *7 and *9 polymorphisms" European Respiratory Journal 27:289-292. Malaiyandi et al. (2006) "Impact of CYP2A6 genotype on pretreatment smoking behavioral and nicotine levels and usage of nicotine replacement therapy". Molecular Psychiatry (2006): 400–409.

AVPR1a and SLC6A4 - Dance talent - Variants of these genes are correlated with creative dance performance. Bachner-Melman et al. "AVPR1a and SLC6A4 Gene Polymorphisms Are Associated with Creative Dance Performance". PLoS Genetics 1(3): e42

DRD2 - Anorexia - Variants of this receptor for the neurotransmitter dopamine have been preliminarily linked to the risk of developing anorexia. Bergen et al. (2005) "Association of Multiple DRD2 Polymorphisms with Anorexia Nervosa" Neuropsychopharmacology 30, 1703-1710.

DRD4 - Sexual desire - Another dopamine receptor gene that is linked in this study with sexual desire and performance. Zion et al. (2006) "Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual differences in human sexual behavior: desire, arousal and sexual function". Molecular Psychiatry (published online ahead of print)

fruitless - Sexual orientation - Male and female fruit flies make different forms of this gene. Males carrying the female gene do not court females. Females carrying the male gene are attracted to other females. Demir and Dickson (2005). "fruitless Splicing Specifies Male Courtship Behavior in Drosophila" Cell 121:785-794.

Several Websites for Cognitive Neuroscience and Brain Information.

You might enjoy checking out The Neuroscience Gateway sponsored by the Allen Institute for Brain Science and Nature Magazine.

Also the Brain Connection aimed more at general public.

And, Brain explorer.

A site with many personal psychology and personality tests that you can take.

Links to a number of cognitive neuroscience sites.

Recent news in cognitive neuroscience.