Boundaries of Experience and Self

I've been slogging through journals that accumulated during my snow-bird phase last winter, and am going through a pile of back issues of the Journal of Consciousness Studies. I came across a review by Chris Nunn of a conference held by the consciousness and experiential psychology section of the British Psychological Association, St. Anne's College at Oxford in Sept. of 2006. on "Exploring the Boundaries of Experience and Self." Nunn notes that a more appropriate title for the conference might have been "Demonstrating Ambiguities of Language and Meaning Used in Relation to Experience and Self." I think his brief review (PDF here) is worth reading.

Spring at Twin Valley

This is a blog draft I saved to post while I'm away...these pictures around my Twin Valley Road home in Middleton, Wisconsin just before leaving for Mexico.
They show why I like to be in Wisconsin in the spring.

View from my window - Isla Mujeres

Turns out I can get wireless in the hotel lobby. I'm at the Playa Media Luna on Isla Mujeres, off of Cancun, the occasion being my 33 year old son's destination wedding (costs a lot less than the U.S.). I want to thank readers who sent annonymous or personal comments on this blog. If I needed any reinforcement to continue the effort, it certainly was there! Also, a number of people indicated they liked the personal material I put in the blog (music, personal attitudes and experience). This is why I'm inflicting the pictures in today's posts on you.

Schermer on happiness - science and history

An essay by Michael Schermer in the March 2007 issue of the Scientific American (PDF here), briefly notes several recent books on happiness research and emphasizes the point that assumptions about what constitutes happiness vary over time. Take sex:

"A century ago, an average man who had not had sex in three years might have felt proud of his health and forbearance, and a woman might have praised herself for the health and happiness benefits of ten years of abstinence."

Visual Illusions

Here are two sites of stimulating illusions that I return to when I need a moment of relief. One is by Michael Bach, the other is a part of the Scientific Psychic website.

Deric, a vacation, and thinking about MindBlog-opps!

(NOTE - somehow the comments got turned off for this post initially, I'm grateful to a reader for pointing this out to me.)
I will be in Mexico for a week, starting Wednesday May 23, to attend my son's wedding, and am uncertain whether it will be practical to continue doing blog postings. This potential hiatus makes me pause for a moment to mull over how this whole blog trip is going. I am a relative newbie to the business, having started this up in Febuary of 2006. On reading about the blog phenomenon in the New York Times, I thought to myself "Here I am doing all this reading and scanning about mind and brain stuff for my own pleasure, and also to prepare the occasional lecture...I might as well make the small extra effort of putting it online in case others are interested." I meant it to be an optional, casual activity. I also meant it to be fun, i.e. , not like work. For a retired academic type, with major obsessive compulsive tendencies, that is easier said than done. I've become addicted to the daily ritual, as well as paying the Feedburner.com site a few bucks a month to show me that by now that there are approximately 170 daily subscriptions to the site's RSS feed, and 350-400 views of individual postings (this is more people that I was reaching in my live university lectures). I have no idea how this compares with other sites out there that deal with similar stuff (and there are a lot of them - I don't look at them that much because I'm too busy reading the new material I find in the literature...).

I do get the occasional email and comment - there have been a few "thank you for doing this" emails that I really appreciated - but in general I'm surprised at how little feedback there is. I scratch my head and think, "I guess this thing is keeping me off the streets; yet, is it worth the energy I'm putting into it? Would getting out of the lockstep of two posts/day increase the perceived fun/work ratio and open up time for more thoughtful writing?" No resolution on any of this.... but, I thought I would put down these wandering thoughts. Comments welcomed.

Genetic basis for vulnerability to drug addiction.

Yacubian et al.(link to full text) demonstrate that human genetic variations that alter dopamine neurotransmission involved in reward pathways correlate with change in sensitivity to rewards and also with activity in the ventral striatum reward system. The data suggest a potential genetic basis for drug vulnerability. Here is their abstract:

Reward processing depends on dopaminergic neurotransmission and is modulated by factors affecting dopamine (DA) reuptake and degradation. We used fMRI and a guessing task sensitive to reward-related activation in the prefrontal cortex and ventral striatum to study how individual variation in genes contributing to DA reuptake [DA transporter (DAT)] and degradation [catechol-o-methyltransferase (COMT)] influences reward processing. Prefrontal activity, evoked by anticipation of reward irrespective of reward probability and magnitude, was COMT genotype-dependent. Volunteers homozygous for the Met allele, associated with lower enzyme activity and presumably greater DA availability, showed larger responses compared with volunteers homozygous for the Val allele. A similar COMT effect was observed in the ventral striatum. As reported previously, the ventral striatum was also found to code gain-related expected value, i.e., the product of reward magnitude and gain probability. Individual differences in ventral striatal sensitivity for value were in part explained by an epistatic gene–gene interaction between COMT and DAT. Although most genotype combinations exhibited the expected activity increase with more likely and larger rewards, two genotype combinations (COMT Met/Met DAT 10R and COMT Val/Val 9R) were associated with blunted ventral striatal responses. In view of a consistent relationship between reduced reward sensitivity and addiction, our findings point to a potential genetic basis for vulnerability to addiction.

Fantastic Dances...

Three of them, by Shostakovitch, which I recorded on my Steinway B at Twin Valley, Middleton Wisconsin.

Brain imaging that reflects moral responsibility.

In the common law tradition, criminal conviction depends on both actus reus (a harmful consequence and mens rea (the intent to harm). Young et al. (PDF here) set up an experimental test using different small stories to demonstrate that a subject's belief that he/she has caused intentional harm causes a larger increase in the activation of a region of the right temporal parietal junction (RTPJ in the figure.) than attempted harm, unknowing harm, and neutral effect.) The study suggests that moral judgments depend on the cognitive processes mediated by the RTPJ, previously associated with belief attribution, and, to a lesser extent, the PC, LTPJ, and MPFC, which compose a network of brain regions implicated in theory of mind.

The discussion of the paper is well worth reading. Here is one clip:

The current results also reveal an asymmetry between moral judgments of incompetent criminals (whose false beliefs prevent intended harm from occurring) and unlucky innocents (whose false beliefs lead them to cause unintended harms. Judgments of incompetent criminals were harsh, made on the basis of beliefs alone, and associated with enhanced recruitment of circuitry involved in belief attribution. By contrast, unlucky innocents were not entirely exculpated for causing harm on the basis of their false beliefs. Instead of showing an increased response in brain regions associated with belief attribution, whole-brain analyses revealed recruitment of brain regions associated with cognitive conflict: right inferior parietal cortex, PC, bilateral middle frontal gyrus, and bilateral anterior cingulate sulcus. All of these regions have been implicated in cognitive conflict associated with moral dilemmas, specifically where subjects endorse emotionally salient harmful acts to prevent greater harm. Here subjects had to override judgments against harm in favor of utilitarian considerations (e.g., the greatest good for the greatest number). Analogously, in the context of unknowing harm, subjects may partially override judgments against harm to exculpate agents on the basis of their false beliefs. Moral judgment may therefore represent the product of two distinct and at times competing processes, one responsible for representing harmful outcomes and another for representing beliefs and intentions.

Potential drug for chronic pain?

A new era in pain research may be coming. A particular class of sodium nerve channels (resistant to tetrodotoxin) are central in generating pain signals. Extensive screening for drugs that block this channel have yielded A-803467, a furan-amide. Jarvis et al. show that this drug attenuates neuropathic and inflammatory pain in a rat model. Chronic pain affects about 1.5 million people worldwide, and is currently treated with sodium channel blockers originally developed as anticonvulsants or antiarrhythmics. While beneficial for some patients, their clinical usefulness has been limited.

A magnet for your sleep?

Massimini et al. show that the deep sleep important in brain restoration and memory consolidation (associated with EEG slow-wave activity of 0.5–4.5 Hz) can be triggered and deepened by appropriate transcranial magnetic stimulation at less than 1 Hz. (PDF here.) How long will it be before we are being offered electromagnetic "sleep caps" to improve our memory and brain restoration during sleep?
Here is their abstract:

During much of sleep, cortical neurons undergo near-synchronous slow oscillation cycles in membrane potential, which give rise to the largest spontaneous waves observed in the normal electroencephalogram (EEG). Slow oscillations underlie characteristic features of the sleep EEG, such as slow waves and spindles. Here we show that, in sleeping subjects, slow waves and spindles can be triggered noninvasively and reliably by transcranial magnetic stimulation (TMS). With appropriate stimulation parameters, each TMS pulse at less than 1 Hz evokes an individual, high-amplitude slow wave that originates under the coil and spreads over the cortex. TMS triggering of slow waves reveals intrinsic bistability in thalamocortical networks during non-rapid eye movement sleep. Moreover, evoked slow waves lead to a deepening of sleep and to an increase in EEG slow-wave activity (0.5–4.5 Hz), which is thought to play a role in brain restoration and memory consolidation.

Videos on How the Mind Works.

Check out this link for interesting talks by Dennett, Gilbert, Schwartz, Savage-Rumbaugh, and others.

High speeding mapping of neural circuits with optical techniques.

Before I was seduced by studying how the brain works, I used to be a membrane biophysics, cellular, molecular biologist, and occasionally I come across a bit of work that is so neat and powerful that I want to mention it.

Wang et al. engineer the genetic delivery into neurons of a light sensitive rhodopsin membrane channel protein (ChR2), from an algae. Illumination of ChR2-positive neurons in cortical slices produces rapid photocurrents that can elicit action potentials. The timing, number, and spatial location of these action potentials can be controlled precisely by light, allowing functional mapping of cortical circuits. Here is their abstract:

To permit rapid optical control of brain activity, we have engineered multiple lines of transgenic mice that express the light-activated cation channel Channelrhodopsin-2 (ChR2) in subsets of neurons. Illumination of ChR2-positive neurons in brain slices produced photocurrents that generated action potentials within milliseconds and with precisely timed latencies. The number of light-evoked action potentials could be controlled by varying either the amplitude or duration of illumination. Furthermore, the frequency of light-evoked action potentials could be precisely controlled up to 30 Hz. Photostimulation also could evoke synaptic transmission between neurons, and, by scanning with a small laser light spot, we were able to map the spatial distribution of synaptic circuits connecting neurons within living cerebral cortex. We conclude that ChR2 is a genetically based photostimulation technology that permits analysis of neural circuits with high spatial and temporal resolution in transgenic mammals.

Fluorescence image of dye-filled layer VI pyramidal neuron; circles indicate locations where light-evoked synaptic responses were evoked.

A parietal EEG signal reflects social coordination

Tognoli et al. offer an interesting study (PDF here). They employed a rhythmic task in which pairs of subjects move their fingers at their own preferred frequency and amplitude with and without vision of the other's movements. Previous behavioral studies had shown that unintended spontaneous coupling may occur (transitions from independent to phase-locking behavior) when subjects see each other's hand movements. They were able to identify three distinct EEG rhythms [alpha - (mean frequency of 10.61 Hz); mu - (mean frequency of 9.63 Hz); and a lateralized centro-parietal component that they call phi (spanning the range 9.2–11.5 Hz; Fig. 2B)], one of which (phi, located over right centro-parietal cortex) "neuromarked" the presence or absence of social coordination. Here is their abstract:

Many social interactions rely upon mutual information exchange: one member of a pair changes in response to the other while at the same time producing actions that alter the behavior of the other. However, little is known about how such social processes are integrated in the brain. Here, we used a specially designed dual-electroencephalogram system and the conceptual framework of coordination dynamics to identify neural signatures of effective, real-time coordination between people and its breakdown or absence. High-resolution spectral analysis of electrical brain activity before and during visually mediated social coordination revealed a marked depression in occipital alpha and rolandic mu rhythms during social interaction that was independent of whether behavior was coordinated or not. In contrast, a pair of oscillatory components (phi1 and phi2) located above right centro-parietal cortex distinguished effective from ineffective coordination: increase of phi1 favored independent behavior and increase of phi2 favored coordinated behavior. The topography of the phi complex is consistent with neuroanatomical sources within the human mirror neuron system. A plausible mechanism is that the phi complex reflects the influence of the other on a person's ongoing behavior, with phi1 expressing the inhibition of the human mirror neuron system and phi2 its enhancement.

Identification of spectral components in the brain activity of participants. (A) The dual-EEG of pairs was recorded with two caps each containing 60 channels. The head schematic of the subject on the right shows the 60 electrodes color-coded to reflect their spatial location. Circled areas indicate regions of peak rhythmic activity: mu (electrodes colored brown situated above Rolandic fissure); phi (burgundy above right centro-parietal area); and alpha (blue above the occipital pole). Spectral plots were used to identify mu, phi, and alpha components during visual contact.

A Fantasia

This week's bit of relief...by Joseph Haydn, recorded on my Steinway B at Twin Valley, Middleton Wisconsin.

Neuroimaging of Subliminal Motivation

Pessiglione et al. (PDF here) do an interesting experiment in which they flash a picture of either a penny or a pound coin for 17, 50, 100 msec. followed by a masking picture. Subjects can report seeing the last, but not the first two images, so these first two are assumed to be subliminal. To characterize the effects of the monetary stakes, they recorded not only brain activity but also skin conductance and hand-grip force. Skin conductance response (SCR) is linked to autonomic sympathetic arousal and is interpreted as reflecting an affective evaluation of the monetary stake. Online visual feedback of the force exerted was displayed as a fluid level moving up and down within a thermometer depicted on the screen (see figure). Subjects were instructed that the higher the fluid level rose, the more of the monetary stake they would get to keep. At the end of the trial, subjects were given visual feedback of the amount of money that they had accumulated.

The incentive force task. Successive screens displayed in one trial are shown from left to right, with durations in ms. Coin images, either one pound (£1) or one penny (1p), indicate the monetary value attributed to the top of the thermometer image. The fluid level in the thermometer represents the online force exerted on the hand grip. The last screen indicates cumulative total of the money won so far...

The data show that the 50 msec stimulus of a pound coin image, which is not reported as seen, causes an increase in skin conductance and activity in the ventral pallidum that is almost as large as the increase caused by the 100 msec stimulus, which is seen. Both activities are much lower for the one penny stimulus. (Ventral pallidal neurons encode rewarding properties of environmental stimuli, and are thought to play a role in incentive motivation.)

Caudate, putamen, and accumbens are shown in green; external and internal pallidum are shown in blue, with limbic sectors in violet.

Cortical networks while the brain is at rest...

Pinsk and Kastner, review work (PDF here) of Vincent and colleagues (PDF here) on spontaneous fluctuations of neural activity in monkey brains during anaesthesia.

....studies have shown that the main human cortical networks exhibit correlated spontaneous activity while subjects are at rest. Vincent and colleagues provide the first evidence that such activity is neither restricted to the human brain nor tied to a conscious state. Their findings suggest that fluctuations of spontaneous activity across anatomically interconnected brain regions constitute a fundamental principle of brain organization. Such an interpretation is supported by the fact that organized patterns of brain activity are present in both humans and non-human primates.

As to the functional significance of correlated signal fluctuations, it may be that they maintain the integrity of the networks by reinforcing the synaptic connections between neurons that are essential for network operations in the awake state. Indeed, in stroke patients, the functional connectivity of a brain network has been found to break down when one of its parts is damaged. This loss of connectivity seemed to be correlated with the patients' behavioural impairments. Thus, the new findings may help in understanding both normal and pathological brain function.

Vincent et al. also investigated a possible monkey homologue of a cortical network that thus far has been studied only in humans. This human 'default' network exhibits BOLD activations when subjects are not performing any particular task, and is thought to support uniquely human functions — for example, thinking about ourselves and others, imagining the future, and daydreaming. The authors chose to study a seed region in the posterior cingulate cortex of the monkey brain; this brain region is anatomically similar in both species and is part of the human default network. They identified correlated activity in discrete regions of the frontal, parietal and temporal cortex, which may thus form an analogous default network in the monkey brain.

These findings challenge the view that the default network is uniquely human and is tied to human mental capabilities. But that challenge depends on the assumption that the posterior cingulate cortex is analogous in both species: despite the anatomical similarities, it is not known whether this area serves similar brain functions in the two species. Furthermore, the human default network has been defined in the awake state, whereas this possible monkey homologue was investigated under deep anaesthesia.

Do computer games keep you young?

Ichiko Fuyuno canvasses the opinion of neuroscientists on what brain training ploys can achieve. (PDF here).

A pill to boost or restore memory?

David Sweatt describes recent experiments by Fischer et al. on a compound that enhances memory performance in mice.

a, (click on figure to enlarge it.) Mouse models of age-dependent neurodegeneration exhibit poor learning and memory performance in spatially based learning tasks. However, when Fischer et al. administered HDAC inhibitors for 4 weeks before training, the performance of the mice was restored to essentially normal levels. b, After receiving HDAC inhibitors, the mice could even recall memories that had been formed and then apparently lost through neurodegeneration.

The authors provide a convincing proof-of-principle demonstrating that the inhibition of histone deacetylases can improve memory capabilities in a genetically engineered mouse model of neurodegeneration in the central nervous system (CNS).

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysine amino acids in proteins, including proteins in the nucleus called histones. Histones interact with DNA to form a complex known as chromatin and control the accessibility of DNA for gene transcription. Generally, acetylated histones form active chromatin complexes with DNA, which makes the DNA accessible to RNA polymerases, thereby regulating gene transcription. Inhibitors of HDACs block the ability of these enzymes to deacetylate histones, promoting histone acetylation in the nucleus and thus altering gene expression. Because altered transcription is known to be necessary for the formation of long-term memories, HDAC inhibitors have the potential to boost memory formation. This has been demonstrated in normal rats and mice; and the effectiveness of HDAC inhibitors in restoring memory function in mouse models of a human learning disability called Rubinstein–Taybi syndrome has also been documented.

Fischer and colleagues extend these findings through their studies of a genetically manipulated mouse model that they have generated. Such animals show age-dependent neurodegeneration in the hippocampus, a brain region that is essential for long-term spatial-memory formation in rodents. Indeed, using a variety of behavioural assays, the authors previously showed that these mice have pronounced deficits in recalling long-term spatial memories.

In their present work, Fischer et al. demonstrate that HDAC inhibitors restore the capacity for spatial memory. They also show that another known memory-boosting manipulation — environmental enrichment through exposing the animals to a variety of experiences over their lifetime — improves the memory of the genetically engineered mice by increasing the levels of histone acetylation in their hippocampi. Together, these findings provide compelling evidence that increased histone acetylation can overcome the diminution of memory function seen in this mouse model of age-dependent neurodegeneration.

Drink milk and live longer?

An interesting article is summarized in the Research Highlights section of the May 10 issue of Nature Magazine:

In yeast at least, the molecular pathway that extends an organism's life when it is put on a diet can be induced — without calorie restriction — by a vitamin found in milk. So says a team led by Charles Brenner from Dartmouth Medical School in Lebanon, New Hampshire, and Jeffrey Smith from the University of Virginia Health System in Charlottesville. (Cell, Volume 129, Issue 3, Pages 473-484)

The researchers showed that the vitamin, called nicotinamide riboside, raises in yeast the levels of a molecule known as NAD (nicotinamide adenine dinucleotide). This, in turn, activates the anti-ageing protein Sir2. Yeast make use of the vitamin through molecular pathways that have some genes in common with humans, raising the possibility that supplements could be designed to enhance humans' longevity.