Looking for hidden signs of consciousness

In the 22 March issue of Nature, Kerri Smith discusses the debate over a 'brain-activity' test for patients in a vegetative state (PDF download HERE).

A team, led by Adrian Owen of the MRC Cognition and Brain Sciences Unit in Cambridge, UK, used functional magnetic resonance imaging (fMRI) to show that a woman left in a vegetative state after a car accident could respond to requests to imagine playing tennis or navigate around her house (A. Owen et al. Science 313, 1402; 2006)... Laureys, a member of this team, has now tested this technique on 24 healthy volunteers, who were similarly instructed to imagine either walking around their house or playing tennis. The tasks activate separate networks in the brain, and the scans proved able to tell correctly which task was being performed (M. Boly et al. NeuroImage doi:10.1016/j.neuroimage.2007.02.047; 2007)...showing that the method works reliably in healthy brains proves its robustness. "Our challenge is to find markers that tell us 'this is a hopeless case' or 'this is a case where we should increase our therapeutic efforts'," says Laureys.

Imagining spatial navigation (left) and playing tennis.

Fractal Animation

From Jock Cooper:

A primer on, and reservations about, TMS - transcranial magnetic stimulation

O'Shea and Walsh offer a brief introduction to TMS, and its use in cognitive neuroscience:

As any schoolboy with a toolkit or a broken toy soon appreciates, to find out how a machine works you need to take it apart, and to put it back together again, you need to know how it works. The next lesson is that, no matter how hard you try, you always end up with a handful of leftover nuts and bolts. These remaining components can be informative: will your machine still work without them? The same logic applies to one approach to understanding human brain function: by investigating the effects of lesions in animals and accidental brain damage in humans we can ask which parts are necessary for specific functions. Over the past twenty years, it has become possible to interfere with human brain functions safely and reversibly, and to control when and where the interference is induced. The technique, known as transcranial magnetic stimulation (TMS), has become a mainstay of cognitive neuroscience.

A PDF verion can be downloaded HERE.

There is controversy over the ethics of using this techniques on humans, it can cause seizures or psychosis in some subjects. This is the subject of a letter to the editor in the March 23 issue of Science from Leslie Sargent Jones of the Univ. of S. Carolina:

When Science publishes research using healthy human subjects, one assumes there was minimal risk and/or vital clinical value. This does not appear to be the case for the work by D. Knoch and colleagues ("Diminishing reciprocal fairness by disrupting the right prefrontal cortex," Reports, 3 Nov. 2006, p. 829). Their results on the dorsolateral prefrontal cortex's role in judgments of fairness and self-interest are interesting, but they largely validated what was already suspected.

Experimental subjects received repetitive transcranial magnetic stimulation (rTMS) for 15 min to produce "suppression of activity in the stimulated brain region." The rTMS generated an electric maelstrom powerful enough to disrupt all activity for 7 min. Animal rTMS research (with overexposure as in LD50 drug toxicity studies) shows that anything studied (e.g., receptor levels) is modified. For rTMS in humans, known risks range from headaches to, more rarely, seizures or psychosis (1). Long-term occult changes and self-reported symptoms in healthy subjects have not been studied, and rTMS continues to be used for studies both fascinating and frivolous (just check the literature).

The use of rTMS on healthy subjects does not meet the definition of "minimal risk" (45 CFR section 46.102: risks… "not greater … than those … encountered in daily life"). We know that healthy subjects don't risk seizures or psychosis in their "daily life." What we don't know is what the residual effects of this activity-swamping tsunami of electrical current are. The Report demonstrates a naiveté about the possibility of rTMS having long-term or negative consequences. Oddly, some of these authors have used rTMS to treat neuropsychiatric disorders on the basis of its long-lasting effects (2). Roentgen's technology was also once thought harmless, and x-rays were used to check shoe sizes (3). We know better now.

1. K. Machii, D. Cohen, C. Ramos-Estebanez, A. Pascual-Leone, Clin. Neurophysiol. 117, 455 (2006).
2. C. M. Miller, Newsweek, "Minds and magnets," 11 Dec. 2006 (http://www.msnbc.msn.com/id/16008890/site/newsweek/).
3. J. Duffin, C. R. R. Hayter, Isis 91, 260 (2000).

Your Brain on Music

I have finally finished reading, and would like to strongly recommend, Daniel J. Levitin's book "This Is Your Brain on Music." The website for this book has fascinating musical examples. The beginning chapters of the book offer the most entertaining, efficient, and engaging explanations of music's essential elements (such as pitch, timbre, rhythym, loudness, anticipation, etc.) that I have ever seen. I also particularly liked chapters 6 and 9, on emotion and instinct.

Levitin's research has studied the involvement of more 'primitive' parts of the brain, like the cerebellum, in music comprehension and generation. In this vein the recent report by Wong et al. in Nature Neuroscience, showing that musical training can change brainstem encoding of linguistic pitch, is of interest. Here is their abstract:

Music and speech are very cognitively demanding auditory phenomena generally attributed to cortical rather than subcortical circuitry. We examined brainstem encoding of linguistic pitch and found that musicians show more robust and faithful encoding compared with nonmusicians. These results not only implicate a common subcortical manifestation for two presumed cortical functions, but also a possible reciprocity of corticofugal speech and music tuning, providing neurophysiological explanations for musicians' higher language-learning ability.

Interlude: some Franz Liszt

Since I am doing an adjacent post on music and the brain, I thought I would post a bit more of my playing: Les Cloches de Genève, from Années de Plèrinage, recorded last year on my Steinway B at Twin Valley, Middleton, Wisconsin.

The Inner Life of a Cell - another audio-visual interlude

Correlation of conscious perception with synchronization of neural activity across cortical areas.

Melloni et al. offer interesting measurements that correlate electrical activity with stimuli that are consciously versus unconsciously perceived. Their abstract:

Subliminal stimuli can be deeply processed and activate similar brain areas as consciously perceived stimuli. This raises the question which signatures of neural activity critically differentiate conscious from unconscious processing. Transient synchronization of neural activity has been proposed as a neural correlate of conscious perception. Here we test this proposal by comparing the electrophysiological responses related to the processing of visible and invisible words in a delayed matching to sample task. Both perceived and nonperceived words caused a similar increase of local (gamma) oscillations in the EEG, but only perceived words induced a transient long-distance synchronization of gamma oscillations across widely separated regions of the brain. After this transient period of temporal coordination, the electrographic signatures of conscious and unconscious processes continue to diverge. Only words reported as perceived induced (1) enhanced theta oscillations over frontal regions during the maintenance interval, (2) an increase of the P300 component of the event-related potential, and (3) an increase in power and phase synchrony of gamma oscillations before the anticipated presentation of the test word. We propose that the critical process mediating the access to conscious perception is the early transient global increase of phase synchrony of oscillatory activity in the gamma frequency range.

(click on image to make it larger). Scalp topography of induced gamma power and phase synchrony for the visible and invisible condition. Top row, Visible condition. Bottom row, Invisible condition. The background color indicates induced gamma power averaged in a 50–57 Hz frequency range. Each head represents the average of a 150 ms time window. Time 0 indicates the onset of the sample word. Lines connect pairs of electrodes displaying significant synchronization. The full article, which contains further color illustrations, can be downloaded HERE.

The structure of consciousness

This is the title of an essay by Buzsaki in the March 15 issue of Nature. It has the following summary of three basic architectural schemes that are present in mammalian brains:

The simplest uses strictly local wiring. In this kind of circuit, typified by the cerebellum, a few neuronal types form individual 'modules' that may be repeated as necessary. Because interaction between modules is restricted to neighbours, it is massively parallel in nature. In different species, the size of locally organized brain structures — including the basal ganglia, thalamus and cerebellum — roughly scales with the number of modules they contain.

An entirely different type of network uses random connections, with a more or less equal probability of connecting local, intermediate or distant neurons. A unique example of such a random connectionist scheme is the recurrent excitatory circuit of the hippocampal CA3 region.

The third architectural scheme, exemplified by the neocortex, combines local modularity with more random, long-range connectivity. This complex wiring scheme shares many properties with 'small-world' or 'scale-free' networks. The advantage of this arrangement is that the number of intermediate steps between any two neurons — the synaptic path length — can remain relatively constant when network size is scaled up, because even a small fraction of long-range connections can dramatically reduce the average path length. Although intermediate and long-range interconnections demand resources and space, they are critical for globally distributing the results of local computations throughout the entire cerebral cortex.

He suggests a view of subjective consciousness (that has been proposed also by several other researchers):

.... that the local–global wiring of the cerebral cortex and the perpetual, self-organized complex dynamics it supports are necessary ingredients for subjective experiences. Environmental inputs can be seen as perturbations of the ongoing spontaneous activity. If they manage to perturb ongoing activity for a sufficiently long time in a big enough population of neurons, their effect will be noticed; that is, we will become conscious of them. In contrast, the locally organized cerebellar cortex, used largely for sensorimotor integration, does not give rise to self-generated or spontaneous activity, and its response to input remains local and non-persistent. Importantly, we generate no subjective record of such local computations.

The complete essay can be downloaded HERE.

Damage to the prefrontal cortex increases utilitarian moral judgements

In other words, people with a rare injury - damage to the ventromedial prefrontal cortex - expressed increased willingness to kill or harm another person if doing so would save others’ lives. Benedict Carey's review (March 22 NY Times) of the paper by Koenigs et al. (PDF download HERE) notes that:

The findings are the most direct evidence that humans’ native revulsion to hurting others relies on a part of neural anatomy, one that evolved before the higher brain regions responsible for analysis and planning.

Koenigs et al:

...show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions, produce an abnormally 'utilitarian' pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person's life to save a number of other lives). In contrast, the VMPC patients' judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements.

Lesions of the six VMPC patients displayed in mesial views and coronal slices. The colour bar indicates the number of overlapping lesions at each voxel. (Click on the figure to enlarge).

Innateness and culture in language evolution - a bit of heresy.

Kirby et al ask:

Although languages vary, they share many universal structural properties. Where do these universals come from? A great deal of research has proceeded under the assumption that this is essentially a biological question: that languages have the structure they do because of our innate faculty for acquiring and processing language.

They suggest:

...that there are serious problems with this orthodox evolutionary/biolinguistic approach. It treats language as arising from two adaptive systems, individual learning and biological evolution, but in doing so misses a third: cultural transmission. The surprising consequences of taking all three adaptive systems into account are that strong universals need not arise from strong innate biases, that adaptation does not necessarily imply natural selection, and that cultural transmission may reduce the selection pressure on innate learning mechanisms. Our conclusions call into question the existence of strongly constraining biological predispositions for language, and the prominence of adaptationist explanations for the structural properties of languages.

Here are two useful figures from the paper, and the details of the Bayesian model they use you can find in the PDF of the article.


Fig. 1. (Click to enlarge) The structure of language arises from the interactions between three complex adaptive systems. As individuals, we acquire language using learning mechanisms that are part of our biological endowment (characterized in this paper in terms of prior bias). This learning machinery acts as the mechanism by which language is transmitted culturally through a population of individuals over time. Ultimately, this process of cultural transmission leads to a set of language universals (which can be expressed as a distribution over types of languages). The relationship between learning machinery and consequent universals is nontrivial but can be uncovered using the framework developed here. Finally, the structure of languages that emerge from this process will affect the fitness of individuals using those languages, which in turn will lead to the biological evolution of language learners, closing the loop of interactions.


Fig. 2. (Click to enlarge). The link between biological predispositions and language structure. Genes (in combination with the nonlinguistic environment) give rise to mechanisms for learning and processing language. These determine our innate predispositions with respect to language (our prior linguistic bias). Bias is a property of an individual, but the (universal) structure of human language emerges from the interaction of many individuals over time. Therefore, cultural transmission bridges the link between bias and universals. Although genes code for bias, biological fitness will in part be governed by the extended phenotype (i.e., language structure). To understand language evolution, we must understand this linking mechanism.

Brain imaging can infer your hidden intentions....

As a followup to the 3/14 posting on NeuroLaw, this report from Haynes et al. seems relevant. Here is their abstract, along with a figure from their paper:

When humans are engaged in goal-related processing, activity in prefrontal cortex is increased. However, it has remained unclear whether this prefrontal activity encodes a subject's current intention. Instead, increased levels of activity could reflect preparation of motor responses, holding in mind a set of potential choices, tracking the memory of previous responses, or general processes related to establishing a new task set. Here we study subjects who freely decided which of two tasks to perform and covertly held onto an intention during a variable delay. Only after this delay did they perform the chosen task and indicate which task they had prepared. We demonstrate that during the delay, it is possible to decode from activity in medial and lateral regions of prefrontal cortex which of two tasks the subjects were covertly intending to perform. This suggests that covert goals can be represented by distributed patterns of activity in the prefrontal cortex, thereby providing a potential neural substrate for prospective memory. During task execution, most information could be decoded from a more posterior region of prefrontal cortex, suggesting that different brain regions encode goals during task preparation and task execution. Decoding of intentions was most robust from the medial prefrontal cortex, which is consistent with a specific role of this region when subjects reflect on their own mental states.

Left: A spherical searchlight centered on one voxel (vi) was used to define a local neighborhood. For each scanning run, the spatial response pattern in this local spherical cluster was extracted during preparation of either subtraction or addition. We then trained a pattern classifier with a subset of the data to recognize the typical response patterns associated with covert preparation of the two mathematical operations (see Experimental Procedures) and measured the local decoding accuracy. Then, the searchlight was shifted to the next spatial location.

Middle: Highlighted in green are medial brain regions (superimposed on a saggital slice of an anatomical template image) where this local classifier was able to decode significantly above chance which intention the subjects were covertly holding in an independent test data set. Highlighted in red are regions where it was possible to decode the intention during the execution of the task.

'Thinking about thinking' shown in Rats...

A simple experiment can be used to demonstrate 'thinking about thinking', or metacognition in humans, monkeys, and bottlenose dolphins. In dealing with uncertain situations, we more likely to decline a visual, auditory or memory discrimination task that can involve reward or punishment if we are uncertain of the discrimination (more/less, same/different) being requested. Thus we are testing possible future outcomes. This behavior has not been seen in pigeons and rats.

In a recent issue of Current Biology Foote and Crystal now:

demonstrate for the first time that rats are capable of metacognition—i.e., they know when they do not know the answer in a duration-discrimination test. Before taking the duration test, rats were given the opportunity to decline the test. On other trials, they were not given the option to decline the test. Accurate performance on the duration test yielded a large reward, whereas inaccurate performance resulted in no reward. Declining a test yielded a small but guaranteed reward. If rats possess knowledge regarding whether they know the answer to the test, they would be expected to decline most frequently on difficult tests and show lowest accuracy on difficult tests that cannot be declined. Our data provide evidence for both predictions and suggest that a nonprimate has knowledge of its own cognitive state.

PDE of article HERE.

Why antipsychotics lose their effectiveness...

Antipsychotics often lose efficacy in patients despite chronic continuous treatment. Why this occurs is not known. It is known, however, that withdrawal from chronic antipsychotic treatment induces behavioral dopaminergic supersensitivity in animals. Samaha et al. show in experiments with a rat model system using clinically relevant does of haloperidol and olanzapine that loss of antipsychotic efficacy is linked to an increase in dopamine D2 receptor number and sensitivity. This data suggests that dopamine supersensitivity overcomes the behavioral and neurochemical effects of antipsychotics while they are still in use.

Karate Chimp

As a followup to my 3/22/07 post on primate origins of morality, I thought I would pass on two entertaining videos of the chimp repertoire. The Karate Chimp is just for fun, the spearing chimp in the accompanying post is a new discovery.

KARATE CHIMP

Spearing Chimp

Chimps fashion sharp pointed spears they use to stab prey (in this case a Bush Baby. The actual thrusting of the spear was not caught on camera. The chimp then proceeds to break the tree open in order to get to the bush baby that it had speared inside. It's been heavily reported.

Exploiting the moral impulse

Daniel Gilbert writes a nice OpEd piece in today's NY Times, titled "Compassionalte Commercialism" (He is the psychology professor at Harvard whose book "Stumbling on Happiness" I abstracted in a series of posts 6/29/2006.)

In an advertising campaign that began last week, Nissan left 20,000 sets of keys in bars, stadiums, concert halls and other public venues. Each key ring has a tag that says: “If found, please do not return. My next generation Nissan Altima has Intelligent Key with push-button ignition, and I no longer need these.”

This campaign is clever, but not particularly original.

It was 1997, and the man who was crouched on the sidewalk at 68th and Broadway in New York City was one of the most pathetic souls I’d ever seen. His limbs were twisted in what appeared to be arthritic agony and tears were streaming down his face. “Please,” he whimpered. “Please, somebody help me.”

Most passers-by did what they were named for, but my wife and I stopped. The man looked up. “Please,” he sobbed. “I just want to go home.” My hand needed no guidance from my brain as it reached into my wallet and extracted $10. “Thank you,” he said as I handed him the money. “Thank you so much.” My wife and I mumbled some embarrassed words and walked on.

We hadn’t gone a block when she tugged my sleeve. “Maybe we should have gotten him into a cab,” she said. “He could barely stand up. He might need help. We should go back to see.” My wife is the patron saint of lost kittens and there is no arguing, so we went back to see. And what we saw was our horribly crippled friend walking briskly and happily up 68th Street, opening the door to a late-model car, getting in and driving away after what was apparently a short day of theatrical work.

I know two things now that I didn’t know then.

First, I now know that my hand did what human hands were designed to do. Research suggests that we are hard-wired with a strong and intuitive moral impulse — an urge to help others that is every bit as basic as the selfish urges that get all the press. Infants as young as 18 months will spontaneously comfort those who appear distressed and help those who are having difficulty retrieving or balancing objects. Chimpanzees will do the same, though not so reliably, which has led scientists to speculate about the precise point in our evolutionary history at which we became the “hypercooperative” species that out-nices the rest.

The second thing I know now that I didn’t know then is that this was the most damaging crime I had ever experienced. Like most residents of large cities, I’d been a victim before — of burglary once, of vandalism several times. But this was different. The burglars and vandals had taken advantage of my forgetfulness (“Why didn’t I double lock the door?”) and taught me to be better.

But the actor on 68th Street had taken advantage of my helpfulness and taught me to be worse. The hand that had automatically reached for my wallet had been slapped, and once slapped was twice shy. I’ve never again given money to a stranger without scrutinizing him for the signs that distinguish suffering from its imitation. And because I don’t know what those signs are, I typically just walk by.

Now corporate America has taken a lesson from the guild of shameless grifters. Nissan’s plan to leave those 20,000 sets of keys in public venues is every bit as crafty as the fraudulent performance that a decade ago left me with holes in both my pocketbook and soul. There is no selfish reason to bend down and pick up a key ring, but Nissan knows that we will bend without thinking because the impulse to help is bred into our marrow. Our best instinct will be awakened by a key ring and then punished by a commercial. Like rubes throughout the ages, we will be lured by a false cry of distress and quickly cured of our innocence and compassion.

We are used to commercial tricks that play on our fears. The official-looking letter marked “Verification Audit” is actually a magazine subscription renewal form; the credit card company’s ominous call to “discuss your account” is actually an attempt to sell new services.

Should we now get used to commercial tricks that play on our humanity? How would we feel about a device planted in trash bins that screams “I’m stuck!” until the lid is opened, at which point it continues, “Stuck in a dead end job, that is — and if you are too, then let us show you how to make millions in real estate with no money down”? Is it O.K. to send a thousand doleful puppies into the streets with tags that say: “Thanks for checking. And speaking of checking, our bank charges no monthly fees”?

What happens to us when greed masquerades as need, when cries for help become casting calls for chumps, when our most noble actions make us patsies? “You put an idea out there and seed it,” said the president of the advertising agency that came up with Nissan’s key ring ploy. “And people carry it for you.” Indeed they do. The idea being seeded and carried in this case is that the world cries wolf, that our moral impulse betrays us and that smart people should keep on walking.

Brain movies...

Great images, even if the verbal narrative is a bit vacuous. The time lapse photos of neurons growing in cell culture are nice, as they fade into a cartoon version....

New brain cell synthesis supports new memories? It isn't that simple.

Several laboratories have performed experiments suggesting that our ability to store new memories might be related to the generation of new nerve cells in the hippocampus, which is essential to forming episodic memories. Now Kandel's laboratory now offers the contrary finding that reducing new nerve cell synthesis can enhance working memory. Their abstract:

To explore the function of adult hippocampal neurogenesis, we ablated cell proliferation by using two independent and complementary methods: (i) a focal hippocampal irradiation and (ii) an inducible and reversible genetic elimination of neural progenitor cells. Previous studies using these methods found a weakening of contextual fear conditioning but no change in spatial reference memory, suggesting a supportive role for neurogenesis in some, but not all, hippocampal-dependent memory tasks. In the present study, we examined hippocampal-dependent and -independent working memory using different radial maze tasks. Surprisingly, ablating neurogenesis caused an improvement of hippocampal-dependent working memory when repetitive information was presented in a single day. These findings suggest that adult-born cells in the dentate gyrus have different, and in some cases, opposite roles in distinct types of memory.

Their full paper (PDF download HERE) has a nice illustration of the techniques used.

Reduce social recognition in mice by reducing amygdala oxytocin receptors.

From Choleris et al. :

Social recognition constitutes the basis of social life. In male mice and rats, social recognition is known to be governed by the neuropeptide oxytocin (OT) through its action on OT receptors (OTRs) in the medial amygdala. In female rats and mice, which have sociosexual behaviors controlling substantial investment in reproduction, an important role for OT in sociosexual behaviors has also been shown. However, the site in the female brain for OT action on social recognition is still unknown. Here we used a customized, controlled release system of biodegradable polymeric microparticles to deliver, in the medial amygdala of female mice, "locked nucleic acid" antisense (AS) oligonucleotides with sequences specific for the mRNA of the OTR gene. We found that single bilateral intraamygdala injections of OTR AS locked nucleic acid oligonucleotides several days before behavioral testing reduced social recognition. Thus, we showed that gene expression for OTR specifically in the amygdala is required for normal social recognition in female mice. Importantly, during the same experiment, we performed a detailed ethological analysis of mouse behavior revealing that OTR AS-treated mice underwent an initial increase in ambivalent risk-assessment behavior. Other behaviors were not affected, thus revealing specific roles for amygdala OTR in female social recognition potentially mediated by anxiety in a social context. Understanding the functional genomics of OT and OTR in social recognition should help elucidate the neurobiological bases of human disorders of social behavior (e.g., autism).

The whole article can be downloaded HERE.

Take a whiff of Oxytocin and become a better mind-reader!

Domes et al. show that a single oxytocin dose from a nasal inhaler (Syntocinon spray, Novartis, Basel, Switzerland) improves the ability of 21-30 year old men to infer the mental state of others from social cues triggered by small muscle movements in the eye region. Here is a PDF of the article. Previous work has shown that oxytocin, in addition to its familiar roles in labor and lactation, reduces responses to social stress and increases trust in social interactions.