Archive for July, 2006

drosophila.jpgWhat is the nature of instincts and inborn behaviour? The cover article of this week’s issue of Current Biology is an article by Kim et al. on how the central nervous system produces inborn behaviour. The researchers found that the innate behavior is initiated by a “command” hormone that orchestrates activities in discrete groups of peptide neurons in the brain (peptide neurons are brain cells that release small proteins to communicate with other brain cells and the body). The action of the hormonal influence, however, was not an all-at-once phenomenon. The ecdysis-triggering hormone or ETH, activated discrete groups of brain peptide neurons in a stepwise manner, making the fruit fly perform a well-defined sequence of behaviors.

Says Michael Adams, the research team leader:

Our results apply not only to insects; they also may provide insights into how, in general, the mammalian brain programs behavior, and how it and the body schedule events. By understanding how innate behavior is wired in the brain, it becomes possible to manipulate behavior — change its order, delay it or even eliminate it altogether — all of which opens up ethical questions as to whether scientists should, or would want to, engineer behavior in this way in the future”

An instinct is an inborn disposition for a specific kind of behaviour. Although we often regard instinctual behaviours to be in the domain of non-human animals, humans also have well-known instincts, the most known are found in infants. However, many researchers suggest that other behaviours — such as altruism, disgust, face perception, and language acquisitions are also instinctual, at least in part so.

Would the present result mean that behaviour — let’s start with instinctual behaviours — could be edited? Adams seems to think so, and in the Drosophila it certainly seems to be the case. Since the steps leading to the well-orchestrated instinctual behaviour were identified, and the neurochemical properties of these circuits are — or are soon — known, it should be a trivial thing to alter the behaviour at any stage during the process. What about human behaviour, then? In principle, the same idea should apply.

Complaints will certainly arise that “human behaviour is so much more complex than instincts”. Indeed it is. But recall studies of voluntary action, of subliminal perception and of automaticity (e.g. riding a bike). These behaviours resemble instinctual behaviour a lot. They are not under conscious control, or are at least not initiated by such. In this sense, it might be that even human behaviour can be edited in much the same way as the Drosophila.

Admitted, this study only focuses on the ecdysis sequence behaviour in an insect. So we need more advanced (still instinctual) behaviours to believe the story. Replications & variations as always… But hey, maybe this will end up as the next cure for odontophobia…?


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Avshalom Caspi and Terrie Moffitt [interview with Moffitt here on npr] made quite a splash in 2002 when they published the paper “Role of Genotype in the Cycle of Violence in Maltreated Children” in Science. They reported that maltreated children would differ in the development of antisocial personality and violent behaviour depending upon whether or not their genotype conferred high or low levels of MAOA expression, a neurotransmitter-metabolizing enzyme. Thus, Caspi and Moffitt showed that a genetic variation may moderate the influence of environmental factors on behaviour in a rather dramatic manner, fueling the growing suspicion that the old nature/nurture dichotomy is much too simplistic. Behaviour is most probably not determined by either an innate genetic Bauplan or the ever changing forces of our surroundings. In Caspi and Moffitt’s study, at least, children with a low-level MAOA genotype only developed an antisocial personality if maltreated (if you happen not to be maltreated, a low-level MAOA polymorphism will not cause you to develop an antisocial personality); but, at the same time, maltreatment doesn’t affect children with a high-level MAOA polymorphism, so the maltreatment is not a cause in itself either. Genes and environmental factors interact to produce behaviour, and the real question is how they do so.

In the July issue of Nature Reviews Neuroscience Caspi and Moffitt discuss some important implications of their research. First of all, if you wish to understand how external pathogens can influence the brain, as is all-important for psychiatric treatment, you have to factor in the individual person’s genetic make-up. The ability of environmental factors to alter the nervous system and generate a disordered mind variates with genetic differences at the DNA sequence level. Say Caspi and Moffitt:

Heterogeneity of response characterizes all known environmental risk factorsfor psychopathology, including even the most overwhelming of traumas. Such response heterogeneity is associated with pre-existing individual differences in temperament, personality, cognition and autonomic physiology, all of which are known to be under genetic influence16. The hypothesis of genetic moderation implies that differences between individuals, originating in the DNA sequence, bring about differences between individuals in their resilience or vulnerability to the environmental causes of many pathological conditions of the mind and body.

Secondly, to really understand this interaction of genes and environmental risk factors and pathogens, more epidemiological cohort studies must integrate neuroscience measurements. As Caspi and Moffitt observe:

First, evidence is needed about which neural substrate is involved in the disorder. Second, evidence is
needed that an environmental cause of the disorder has effects on variables indexing the same neural substrate. Third, evidence is needed that a candidate gene has functional effects on variables indexing that same neural substrate. It is this convergence of environmental and genotypic effects within the same neural substrate that allows for the possibility of gene–environment interactions. At present, such evidence concerning environmental and genotypic effects in relation to neural substrate measures is sparse, and therefore gene–environment interaction hypotheses are likely to be circumstantial at best, and flimsy at worst. But this situation is steadily improving. When we were constructing our hypothesis regarding the genetic moderation of the depressogenic effects of stressful life events, we were aided by direct evidence linking the 5-HTT candidate gene to individual differences in physiological responsiveness to stress conditions in three different experimental paradigms, including knockout mice, stress-reared rhesus macaques and human functional brain imaging.

Of course, imaging genomics studies, such as those by Hariri and Weinberger, or Meyer-Lindenberg, give a good idea of how genetics, brain activity and behaviour can be related to each other, using avant-garde research techniques.

Finally, both perhaps most intriguing, Caspi and Moffitt suggest that findings such as theirs indicate that genes react to environmental influences more than cause brain activity and behaviour. This stance is captured in a quote like this one:

[The] gene–environment interaction approach differs fundamentally from the ‘main-effect approaches’,
with regard to the assumptions about the causes of psychiatric disorders. Main effect approaches assume that genes cause disorder, an assumption carried forward from early work that identified single-gene causes of rare Mendelian conditions. By contrast, the gene–environment interaction approach assumes that environmental
pathogens cause disorder, and that genes influence susceptibility to pathogens. In contrast to main-effect studies, there is no necessary expectation of a direct gene-to-behaviour association in the absence of the environmental pathogen.

Clearly, as such experimental work in greater detail furnish us with a more precise view of genes build the molecular structure of the brain, and how these structures underlie behaviour, we will also become better suited to settle long standing philosophical issues, such as what innateness actually is.


Caspi, A. & Moffitt, T. (2006): Gene-environment interactions in psychiatry: joining forces with neuroscience. Nature Reviews Neuroscience 7: 583-590.


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News for the bookshelf

As we receive review copies of new books from different publishers, it’s a good idea to make you aware of the titles that are emerging these days. Although we’d like to, it won’t be possible to review all of those splendid books. Instead, we bring you here the latest new book titles. Indeed, besides being interesting to us as cognitive neuroscientists, we also find many titles relevant to discussions in neuroethics. Here are some titles that should be read by anyone interested in ethics, brain and humanity:

23prolems.jpg23 problems in system neuroscience, by van Hemmen & Sejnowski

About the book: The complexity of the brain and the protean nature of behavior remain the most elusive area of science, but also the most important. van Hemmen and Sejnowski invited 23 experts from the many areas–from evolution to qualia–of systems neuroscience to formulate one problem each. Although each chapter was written independently and can be read separately, together they provide a useful roadmap to the field of systems neuroscience and will serve as a source of inspirations for future explorers of the brain.

Note: Although stil reading the book, I there are a few chapters that are interesting to a neuroethics perspective, posing questions such as “what is the function of the thalamus?”; “shall we ever understand the fly’s brain?”; “what is the neural code?”; “how is time represented in the brain?”; and “what are the neural correlates of consciousness?”. The whole idea with this book is to pose problems that are still unanswered and that neuroscience should focus their effort on solving. The problem of what a neural code is, for example, is really one of the largest questions in modern neuroscience. Should we crack the code of the neural language, the expectation is that this will resolve our understanding of its workings and how it generates the mind.

Read more here

emotionreason.jpgEmotion and Reason, by Berthoz (translated from French)

About the book: ‘Emotion and Reason’ presents a groundbreaking new approach to understanding decision making processes and their neural bases. The book presents a sweeping survey of the science of decision making. It examines the brain mechanisms involved in making decisions, and controversially proposes that many of our perceptual actions are essentially decision making processes. Whether looking, listening, hearing, or moving, we choose to attend to certain stimuli, at the expense of others. In some psychiatric disorders the inability to respond selectively to certain stimuli can be harmful – such pathologies of decision making are additionally considered. Berthoz also considers how many decision making processes involve an internal dialogue with our other self, and how this dialogue with our “doppelganger” might be represented in the brain. He considers the important implications that a neuroscience of decision making can have for the judiciary – how we apportion blame and responsibility; for economics – with discussion of the growing field of neuroeconomics; and for theories of management. Lastly he examines decision making and creativity – if perception relies in part on decision making processes, how might this alter our view of the artistic process.
Note: “Believing as I do, that any simple look or action entails a choice, and that emotions are prepackaged decisions of great complexity, I welcome this text by Alain Berthoz and its thoughtful contributions”, Antonio Damasio

Read more here.

munakata.gifProcesses of change in brain and cognitive development, edited by Munakata and Johnson

About the book: This new volume in the highy cited and critically acclaimed Attention and Performance series is the first to provide a systematic investigation into the processes of change in mental development. It brings together world class scientists to address brain and cognitive development at several different levels, including phylogeny, genetics, neurophysiology, brain imaging, behavior, and computational modeling, across both typically and atypically developing populations. Presenting original new research from the frontiers of cognitive neuroscience, this book will have a substantial impact in this field, as well as on developmental psychology and developmental neuroscience.

Note: This book really is a mixture of developmental and general learning mechanisms in the brain. Topics range from the range of Hebbian learning; development of control of action; infants on continuity violations; the development of cognitive specialization; the infant as a synesthete; development of conceptual representations; and modules, genes and evolution. It is a truly fascinating ensemble of authors and topics that seek out to cover some of the most up-front issues not only in developmental issues, but something that should shed light on our “normal adult” cognitive operations as well.

Read more here


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There’s quite a nice little study by John O’Doherty and his group in the August issue of PLoS Biology pertaining to one of the most fascinating stuctures of the brain, the orbitofrontal cortex. They had subjects play a simple economic game with four different possible outcomes while being scanned in an MR-scanner: (1) receipt of a reward; (2) a missed reward; (3) avoidance of an aversive outcome (i.e., a monetary loss); and (4) receipt of an aversive outcome. The results showed that the medial part of the OFC exhibited increased activity not only when the subjects received a reward, but also when they avoided an aversive outcome. This indicates that to avoid an aversive outcome actually act as a reward, or as the authors write in the paper:

In avoidance learning, an animal or human learns to perform a response in order to avoid an aversive outcome. Here we provide evidence with fMRI that during such learning a part of the human brain previously implicated in responding to reward outcomes, the medial OFC, increases in activity following successful avoidance of the aversive outcome. These results are compatible with the possibility that activity in the medial OFC during avoidance reflects an intrinsic reward signal that serves to reinforce avoidance behavior.

Moreover, when the subjects, conversely, failed to obtain a reward or received an aversive outcome activity in the medial OFC decreased. O’Doherty and his colleagues suggest that this interesting finding can be explained by Solomon’s opponent-theory of motivation which hypothesizes that the termination of an affective process of some valence (positive or negative) is associated with the onset of a complimentary affective response of the opposite valence. In their discussion they offer the following interpretation of the medial OFC’s opponent response profile in regard to rewarding and aversive outcomes and their omission:

These OFC responses cannot be explained as PE [prediction error; MS], because activity does not decrease to rewarding outcomes
nor increase to aversive outcomes even as these outcomes become better predicted over the course of learning. Rather, responses to rewarding and aversive outcomes in this region likely reflect a positive affective state arising from the successful attainment of reward and a negative affective state from failing to avoid aversive outcome. Similarly, differential activity in this region to avoiding an aversive outcome and missing reward may reflect a positive affective response to successfully avoiding an aversive outcome and a negative affective state arising from failure to obtain a reward. Thus, our findings indicate that medial OFC activity at the time of outcome reflects the affective (or reinforcing) properties of goal attainment.

Furthermore, they relate their finding to the current on-going discussion of what possible functional roles the medial and lateral parts of the OFC play:

The findings reported here also help to address previous discrepancies in the reward neuroimaging literature as to thedifferential role of the medial versus lateral OFC in processing rewarding and aversive outcomes [29,44,45]. In the present study we show that the medial OFC responds to reward outcomes (as well as following successful avoidance of aversive outcomes), whereas both medial and lateral OFC responds during anticipation of reward. Indeed, when we tested for regions showing increases in activity to receipt of aversive outcome or omission of reward, we found a region of the lateral prefrontal cortex extending down to the lateral orbital surface with this response profile, implicating this region in responding to monetary an aversive outcomes [30]. These findings suggest the possibility that dissociable activity within the medial versus lateral OFC may be evident during receipt of rewarding and punishing events, but not during their anticipation.

I would like to see Paul Bloom replicate this result using just some reaction-time paradigm! (Sorry to all the non-fMRI hating psychologists about that last snide comment!)


Kim, H, Shimojo, S. & O’Doherty, J. (2006): Is avoding an aversive outcome rewarding? Neural substrates of avoidance learning in the human brain. PLoS Biology 4(8): e233.


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The New York Book Review has a great review by Edward Ziff and Israel Rosenfield of three forthcoming books on evolution. What makes the review so great also is that it describes the development of the idea of evolution, from the feeble beginnings of comparisons between dolphin fins and bird wings, through Darwin’s theory of evolution, to the modern synthesis of evolutionary theory and the linking of genes to evolution, variation and reproduction. It’s a highly recommendable read.


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motherbrain1.jpgHaving a baby has a large impact on how we live our lives (trust me). But whereas men may react with amazement, wonder, even jealousy of being left aside, little actually happens to our bodies after birth. The changes that happen in women are far more obvious, not only during pregnancy but after birth also. The production of milk, and the possibility of conditional learning of milk production to the child’s crying is just one example of how body, brain and mind get tuned into caretaking.

Furthermore, studies of oxytocin, a mammalian hormone that acts as a neurotransmitter in the brain, has been implicated in the bonding of the mother-infant attachment bond. Oxytocin is present in both sexes and is thought to be involved in social bonding, stress-reduction and orgasm, just to mention some. but the hormone seems to play a specific role in how mothers react to their newborns, and the establishment of a sound dyadic attachment. In this way, the brains of mothers change, both as a result of hormonal expression (loads of additional oxytocin) and the social interaction with the infant.

But did you know that some of the neurons in mothers’ brains actually stem from their babies? In other words: some of a mother’s brain cells are actually from the offspring.

This is just what a team of researchers from Singapore have found and published in the journal Stem Cells. It’s well known in this literature that fetal cells can enter the blood of circulation during pregnancy and remain there for many years after birth. These cells can, just as regular stem cells, develop into different kinds of tissue, including bone marrow, liver an spleen cells. But whether these cells can cross the blood-brain barrier has been less certain.


The expression of fetal stem cells in the mother’s cortex at 4 months after birth. Figure 1-H from the article.

This is exactly what the researchers found. By labelling fetal stem cells they discovered that these cells had indeed crossed the blood-brain barrier and moved into the brain. Furthermore, at measurement four days after pregnancy these cells had developed into neurons, astrocytes, oligodendrocytes or macrophage-like cells. In other words, they developed just as any other stem cell.

So babies gets into their mothers’ minds in more than through hormonal and psychological mechanisms.

However, what is actually the function of these neurons is more unclear. Does the workings of fetal neurons have any significance for their relationship, or any particular mental function in mothers? This is indeed an opening field, and an eye-opener to many people (including myself when I first read it). No results have been reported in either direction as of yet.

What has been studied, however, is how these fetal stem cells can actually play a supporting role in the mother’s brain in the case of pathology. In addition to documenting that fetal stem cells enter the mother’s brain, the researchers added a condition involving brain lesion of the mother’s brain. What they found was just as surprising: after a lesion to the brain, more fetal cells were found in the lesioned region. So the baby’s cells seem tuned into helping the mother regain herself in the case of injury.
Mind-blowing as this finding may be, little is still known about this phenomenon. The development, mechanism, function and evolution of this process is just beginning to be explored. But it already raises a whole range of questions: can we measure a difference between mother’s and “non-mother’s” brains, both structurally and functionally? Does this “fetomaternal microchimerism” lead to any advantages (i.e. survival) in mothers? What is the range of variation in this kind of expression: are there “good” and “bad” fetuses? Are mothers of many children better off in any respect of those with fewer children? Or is this process just a question of striking the energy balance, the child “paying back” what it deprived the mother of during pregnagcy?

So a portion of yourself resides somewhere in your mother’s brain (and body). Children are indeed the result of their parents, but now it seems that children pay back, too.


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save-brain2.jpgDoes talking in your mobile phone influence the workings of your brain? Yes, claims a new study in Neuropsychologia of healthy volunteers. But it’s not only bad, it seems; some cognitive functions become better during mobile phone radiation.

Mobile phone radiation and health concerns have been raised since the 1990s, especially following the enormous increase in the use of wireless mobile telephony throughout the world. This is because mobile phones use electromagnetic waves in the microwave range. These concerns have induced a large body of research (both epidemiological and experimental, in non-human animals as well as in humans). Concerns about effects on health have also been raised regarding other digital wireless systems, such as data communication networks.

Although previous studies have shown mixed and often conflicting results, these studies have been criticized for having a low statistical power. The current study included 120 subjects to improve the statistical power of the analyses; 58 males and 62 females from 18 to 70 years. Mind you, such a spread in age could actually be a confounding variable, and an age effect should have been included in the analysis. To that, the current study does not seem to have controlled for age and gender effects on the age sample.

The researchers gave the subjects a number of different cognitive tasks tapping into cognitive functions such as reaction time, encoding, verbal comprehension, and working memory. Radiofrequency radiation was induced through a regular Nokia mobile phone placed on a helmet that subjects wore during cognitive testing. The study was a double-blinded setup, so that neither researchers nor the subjects knew if the cellular phone was transmitting (or emitting radiofrequency radiation). Measures were taken to make sure that neither sound or heating would lead subjects to detect when the phone was transmitting. Subjects performed the tests (different versions of the test each time) during radiofrequency stimulation (both sham and real stimulation).
What was found was that the performance during radiofrequency exposure, compared to sham condition, changed theperformance on several tests. While the performance on reaction time decreased during exposure, performance on the Trail Making test B, which loads working memory, was increased during exposure. As the researchers write:

The results of this study provide statistical evidence of a cognitive difference in performance between the real and sham field [mobile phone] exposure conditions. The negative effects of [radiofrequency] exposure on [reaction time, RT] performance indicate that the more basic functions were adversely affected by exposure. In contrast, the improved RT for the working memory task suggests that [radiofrequency] exposure has a positive effect on tasks requiring higher level cortical functioning, such as working memory.

The results are also very interesting because several reports now support the view that using a cellular phone while driving leads to a reaction time comparable to that of having several alcoholic drinks. Through this study it seems that it’s not only the talking in the phone that pulls your reaction time down; it’s also the mere radiation itself.

But are the conclusions warranted? For one thing: the cognitive measures being made are rather crude. The reactions time measures should be less problematic, but as for concluding that working memory increases due to a Trail Making B test score only is really invalid. The Trail B is indeed a measure of how people can switch from one serial counting mode to another (numbers or alphabet). Working memory is really much more than keeping track of only one number or letter back. What should be applied is a so-called parametric n-back task (PDF). In addition, a better test battery should be applied. Although the current focus has been on reaction time, it now seems likely that effects on higher-order cognitive functions may take place, too. However, in order to make firm conclusions of such, we need better cognitive test batteries.

What, then, happens to our cognitive brains after prolonged exposure to radiofrequency waves? Here, we can only speculate, or as the authors point out:

The implications of this study can only be directed towards the effects of short-term exposure of [mobile phone radiofrequency radiation] on cognition. Further longitudinal research is required to determine the effects that long-term use of [mobile phones] (years) may have on health and cognition.

It’s still early days for studies on mobile phones, radiation and brain funcitoning. Many studies have used a less than optimal sample size and problematic experimental designs. Nevertheless these results seem to point out that just being exposed to radiofrequency radiation from a cellular phone induce changes in the brain’s workings. And now I start wondering whether my subjects in the MR scanner also change during scanning…


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icon_psychoanalysis.jpgToday we received this nice email from Paul Watson at Psychology Press. They are launching a new site for cognitive neuroscience news. I’ll let the email speak for itself:

Hi Martin & Thomas

Just a quick note to say we’ve recently launched a new Cognitive Neuroscience Arena which I think might be of interest to you two.

(We = Psychology Press, publishers of the journal Social Neuroscience, which you commented on in your blog post on July 4th)

We’ve included a link to the Brain Ethics blog on our blogs page.

As well as all our relevant books and journals, we’ve included a few other features that may be of interest to you and your readers:

1. The whole of the first chapter of our textbook “The Student’s Guide to Cognitive Neuroscience” is available to read free online (we think it’s a great introduction to the subject)

2. In a similar vein, we’ve also got the introductory article from our journal Social Neuroscience, also available to read free online (this is the same one which is on the Social Neuroscience journal website which you posted about).

3. There’s also a page of links to the latest Cognitive Neuroscience blog posts (courtesy of Technorati)

4. An a nifty GoogleMap showing forthcoming Cogntitive Neuroscience conferences (only 3 we know of at time of writing) at http://www.cognitiveneurosciencearena.com/resources/conferences.asp

And numerous other features including an RSS feed of our latest Cogntive Neuroscience books.

I’ve sent the link to your blog to Rose Allet who runs the marketing for the Social Neuroscience journal here at Psychology Press, so she may also email you and will probably send the URL of your blog to the editors of Social Neuroscience so they can see your comments).

If you’ve got any questions, feel free to drop me a line.


Paul Watson

Paul Watson, Senior E-Marketing Executive
Psychology Press



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violent-child.jpgViolence and criminal behaviour is today thought to involve a series of complex interactions between heritable and environmental factors. Centuries of debate of the relative contribution of nature and nurture have not reached anything resembling a solution, and even today we can find ardent proponents and defenders of each extreme view (see Steven Pinker on this, PDF).

While violence and crime has been part of all recorded history, the society’s understanding of the underlying causes of these acts and how they should be dealt with have changed over time. In modern times, we also see a wide variety of legal practices in dealing with criminals and violators: from the death penalties and multiple life sentences in the US, Russia and other countries, to briefer treatment sentences in Europe. These different societal solutions build – explicitly or implicitly – upon what causes violence and criminal acts, and how they should, if at all possible, be treated.

It would be no understatement to claim that the biological explanation of violence and crime has not been fully implemented (nor understood) by law makers or enforcers. Just as you could say about the society in general: aside from specific demonstrations of how violent offenders have larger or smaller neural damage, little is known about the biological properties of violence. Not that the literature has been flourishing with articles demonstrating such relationships. It hasn’t. Until now, where recent studies report detailed analyses of how genes and environments alter the brain’s workings to make people more or less prone to violence, impulsive acts and criminal behaviour.

In a most interesting paper (PDF) published in PNAS, a team of researchers from Austria, Italy and USA headed by Andreas Meyer-Lindenberg have uncovered neurobiological factors that contribute significantly to violence in humans. The team studied the normal allelic variation in the X-linked monoamine oxidase A (MAOA) gene, a gene that has also been shown to be associated with impulsive aggression in humans and animals.

In the study both structural and functional MRI methods were applied. First, the researchers asked whether the low expression variant of MAOA, known to be associated with increased risk of violent behaviour, would predict differences in the size of limbic structures such as the amygdala. Indeed, what they found was that the low expression MAOA predicted limic reductions, as can be shown from the figure article


Structural reductions in limbic and paralimbic regions due to genotype. The size of both the amygdala and cingulate cortex are predicted by benotype. The low expression MAOA have significantly reduced volumes of these structures, compared to the high expression MAOA group.

Second, the team studied how these structures worked using two fMRI paradigms. The first task was a facial expression matching task, a task known to involve the amygdalae. The amygdala activation was significantly influenced by genotype: the low MAOA group displayed higher amygdala activation and at the same time lower activation in cingulate cortex subregions, as well as left orbitofrontal cortex and left insular cortex – all brain regions implied in emotion processing.


Regions involved in facial expression matching (click image for larger version). As you can see from the graphs, there is a genotype-by-gender interaction.

The second task was an emotion memory task, where subjects were asked to encode and recall aversive (compared to neutral) valenced information. Here, the results pointed to a significant genotype-by-gender interaction effect, in that men with a low MAOA version showed increased reactivity of the left amygdala and hippocampus during recall. No such relationship was found for women.

Interestingly, the researchers also found a tight relationship between gender and genotype during the first volumetric study. Here, low-MAOA males showed increased orbitofrontal volume bilaterally, while no such relationship was found in females. In this sense, the MAOA allelic variances seem to influence males most.

Finally, Meyer-Lindenberg and his co-workers draw the lines to other studies relating MAOA variance to a highened sensitivity in low-MAOA males to aversive events (e.g. abuse) during childhood. The combination of a low-MAOA genotype with such events seem to produce abnormal regulation (through the cingulate) of the amygdala and an increased predisposition to impulsivity and violence. As the authors note:

Predisposition to impulsive violence by means of abnormal activation and regulation of emotion-related amygdala function might be further enhanced by deficient neural systems for cognitive control, especially over inhibition, the capacity to suppress prepotent but inappropriate behavior that might originate from a dysregulated affective response. Although the rostral cingulate is key to the regulation of acute affective arousal and emotional learning, inhibitory control of prepotent cognitive responses is thought to be critically dependent on caudal aspects of anterior cingulate. Our study of genetic influences on cognitive impulse control revealed a sex-dependent impairment in precisely this area of cingulate, affecting men only. Our finding of a genotype-by-sex interaction in this region therefore provides a plausible neural mechanism for reduced cognitive inhibitory control in risk allele-carrying males, suggesting synergistic impairment in cognitive and emotional neural regulatory mechanisms that might render MAOA-L men at especially high risk for a neural phenotype that plausibly relates to the slightly greater probability of impulsive violence.

Endnote: it might be useful to note that this study was conducted on healthy, non-criminal volunteers. The obvious step next is to study crime offenders (different types) and the complex interplay between genes, gender and childhood events.


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pvs.jpgIt’s all in the news these days. A man who has been in a coma (or is it “coma-like”, “almost coma” or what?) since a car accident in 1984 has now regained consciousness, and cognitive abilibties such as his speech. It’s already been written so much about this topic, but little is actually addressing the science. Often, the sensationalism is only covered. You can get them all by this simple google.

So why start writing about this here at BrainEthics? The story should have been covered by now? I think there are several reasons to address this story in a bit more detail, one of them being that the science, ethics and philosophical consequences are not – or very superfluously – noted. Another good reason is that the article describing this case has come out, and it’s available for free (PDF). Before we get to it, let me briefly let you know what I’d like to mention here:

  • the diagnosis – coma, vegetative state and related mental states are still very hard to tell apart, even to specialists
  • the development – much has happened to our knowledge about these states, but this knowledge has neither reached the general public, science writers nor always professionals dealing with these patients
  • the future – in addition to developments in traditional diagnosis, neuroimaging is already having a significant impact on our understanding on the relations and distinctions between these different states
  • the ethics – should we reach a scientifically valid model about states of consciousness the next step is to determine who is conscious and who is not – but still we are likely to ask “are our judgements correct?

The Diagnosis

If you are involved in a car accident and lose consciousness, the time from when you lose consciousness until you wake up is characterized by different stages where the brain’s level of functioning changes; from improved primitive reflexes to cognitive and mental restoration. A soon as you reach a state where you become aware of your surroundings, even the feeblest sensation, you have reach a state that is called post-traumatic amnesia (PTA). The person is conscious and appears responsive and they may even be able to talk to family members and medical staff, however after a short time, the person will forget all recollection of conversations and actions. The person will be disorientated and may not know the date, where they are, or why they are there.

The important discussion here is that we are discussing whether a person is conscious, or if he has any chance of becoming conscious again. A person in a coma is not conscious – he cannot be awakened, fails to respond normally to pain or light, does not have sleep-wake cycles, and does not take voluntary action. Coma is separate from vegetative state, in which the patient still has no cognitive neurological function or awareness of the environment. However, he has noncognitive function and a preserved sleep-wake cycle. Even more perplexing, the patient may exhibit spontaneous movements and he may open his eyes in response to external stimuli, and even track moving objects (or people) with his eyes. So why is this person not conscious? We know this from the fact that 1) he does not respond to verbal commands; 2) he shows no voluntary movements, only reflexes; 2) reports from people in this stage that have awakened show that they have had no experience. This, of course, is coupled to a variety of theory-bound measures of preserved vs. non-operative reflexes, and more recently neuroimaging.

What makes the diagnosis of coma and vegetative state so hard is that there are cases where patients show almost exactly the same symptoms as these conditions, only that they are aware. Patients in a minimally conscious state are indeed conscious, they may drift in and out of awareness, but they show signs of voluntary movement and communication. Terry Wallis is thought to be in this state, not coma, nor vegetative state. Another condition is locked-in syndrome, in which the patient is aware and awake, but cannot move or communicate due to complete paralysis of all voluntary muscles in the body.

The frequency of misdiagnosis of these patients has not been reviewed in full, but the fear is that it happens more often that we would like to. The misdiagnosis goes both ways: sometimes a patient is thought to be conscious while actually being in a persistent vegetative state. Other times – and this is the most problematic error – a patient that has some level of awareness (e.g. locked-in) is diagnosed with a coma or vegetative state.

The Development

How can we be so wrong about these patients? One reason is that we have just began to explore this field at the level of detail that we do today, incorporating better diagnostic tools and multi-modal assessment tools such as EEG, SPECT and MRI. A willingness to study consciousness, that mongrel concept that we still really don’t know what means, is another reason for the recent developments in this field. In all, our ability to distinguish between conscious and unconscious states has gone from a dichotomic distinction to a range of possibilities that are sometimes hard to distinguish.

This development is often the reason to the sensational awakenings that we can hear from time to time. News about a person regaining consciousness after 20 years from a coma (!) should be taken with a grain of salt. 20 years ago the diagnosis and distinctions to other (conscious) conditions was notas developed as today. So we should maybe think of this rather as a sensational awakening of the science surrounding these patients, not the patients themselves. That’s a bit harsh, but it is true that the conceptual and diagnostic improvements in this fueld has come through the past few years only.

The Future

What can we expect to happen in this field? First of all we can expect that neuroimaging tools will be used more. Today we can record EEG to exclude ideas about brain death; we use MRI images to see where in the brain we find lesions. But studies showing differences in the brain’s activity between these different patients have been emerging – see this article (PDF). The problem with these studies are that they are group studies. As I have argued previously, going from group study mean differences to the ability to identify individual differences – and diagnosing people on this ground – is not a straightforward thing. So tools needs to be developed that makes it possible to look at an individual scan to determine whether a person is conscious or not. As Steven Laureys from the University of Liège says:

Chronically unconscious or minimally conscious patients represent unique problems for diagnosis, prognosis, treatment, and everyday management. They are vulnerable to being denied potentially life-saving therapy….. This case shows that old dogmas need to be oppugned.

It should be noted that efforts are already being made for developing a “consciousness meter“. This stems from the finding of mid-operational awakenings; people undergoing surgery that are put into anaesthesia nevertheless wake up during surgery yet without the ability to notify others about their presence, often suffering pain as their sensations are restored. In other words; an induced locked-in syndrome. However, interesting as it has been it’s been hard to find any updates on the effectiveness of this apparatus. But we should probably think along these lines. Saying that, the consciousness meter suggested is based on EEG, and any measurement of a traumatised brain is bound to show different signals. That needs to be kept in mind.

What, then, about treatment? This is bound to follow the trace of our enhanced knowledge of these conditions. But what is interestig with the case of Terry Wallis is that he showed signes of rewiring of fibres in the brain. While these findings are in no way conclusive, they suggest that new intervention tools can be developed that focus on the regeneration of fibres in the brain. Not only general restitution, but maybe more focal, to the regions in which we have seen Wallis’ brain change (see changes in cerebellum, as indicated by white arrow below).


Diffusion tensor images of a brain at the first scan (left) and 18 months later (right). Color shows direction of white matter fibers, e.g., green for anterior-posterior fiber tracts. Large red area in second scan (arrow) shows what scientists think is growth of new neural processes in a part of the brain that controls movement. (Credit: Weill Cornell Citigroup Biomedical Imaging Center/Henning U. Voss.)

The Ethics

The growing knowledge about brain function and diagnosis of these cases should make us ask whether we are using the most up to date knowledge about these stages and states. Even more troublesome, spreading the knowledge to the entire world is a problematic affair, and even within the developed world. One thing is having an operational diagnostic system; an entirely different thing is seeing it implemented throughout the world. While the diagnosis of brain death is more or less universal across regions, cultures and religions, spreading the news about differential mental state diagnosis is only now beginning to spread. Hopefully, the use of evidence based medicine will provide the tools for such a knowledge dispersal.

Understanding that there is a tight relationship between the brain and the mind has a deep impact on our self-knowledge. Knowing how the brain works and breaks is a tale about yourself. It’s a direct relationship, not only a superficial association of flesh and mind. A loss of brain function is a loss of mental life (or part of it). All in all, the scientific study of unconscious states such as coma and persistent vegetative states are one part of the story that ties the brain and mind together tightly to a coherent picture of our minds as natural, biological phenomena.


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