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Archive for March, 2006

Traumatic brain injury distorts the brainFrom time to time I receive emails from people who have relatives or other loved ones that suffer from a neurological or psychiatric condition. I respond to these the best that I can. Today, I'd like to share with you one such response. This is why neuroscience is important; it opens up a better understanding of diseases and treatments. Is your loved one suffering from a vegetative state – is he unconscious all the time, even though being awake – or is he in a minimally conscious state – actually emerging into awareness? Even worse: is he in a locked-in state – being fully aware but unable to communicate, and treated as unconscious?

The email below is anonymized in order to avoid identification. The text is otherwise unedited.

Hello, my name is RD. My 27 year old son, P was in a car accident 3 years ago. He was age 23 at the time of the accident. P suffered a traumatic brain injury. He now lives in a nursing home. In his medical records he is diagnosed as persistent vegetative state. I would call it minimally conscious state, especially these past several months.

We, his family have been very active in his life. I have searched everywhere I can think of for help, in-depth information, clinical trials, anything that may help him. He is aware of his surroundings. He is using his arms now, where 6 months ago he couldn't. He plays ball with his little girl. She was 5 months old when he had his accident. She plays pic-a boo with him. He smiles…especially when someone who he hasn't seen for a while comes to see him, his uncles for instance.

I am looking for someone to take interest in his condition, to see if he can be help. I just pray that someone will give him a chance. I know he has the potential to improve. We just need to be pointed in the right direction. Can you help or do you know who someone who can?

And here is my response:

Dear RD,

Thank you for your email and please excuse my much belated reply.

I am deeply sympathetic to your son's condition and your problem. We are all moved by these tragic accidents. Through my previous work as a clinical neuropsychologist, I have seen people suffering from the same condition that your son is now.

My own shortcomings to be of any serious help to you is that I am living in Copenhagen, Denmark. Although you do not mention explicitly, I think you are living in the US. The medical treatment of post-traumatic amnesia, ranging from coma through vegetative state and to minimally conscious states, is still being improved from day to day. In countries such as the US and Denmark the treatment should be similar, on average. However, there may be places that are more focused and knowledgeable on these cases.

On your feelings that your son is actually better than vegetative state, I would suggest trying to find professionals that deal with the diagnosis of these problems daily. You should always bear in mind four (opposing) facts:

  • Vegetative state patients display signs and behaviours that makes us think that they are aware, conscious and responding. However, if a patient is truly in a vegetative state these signs are automatic responses, and not signs of conscious mental life
  • Vegetative state is often misdiagnosed (publications by e.g. Steven Laureys in Belgium). Many patients are at a higher level of function, such as minimally conscious or locked-in
  • Although a diagnosis is set at vegetative state, the condition of a patient might still improve. The rule is often that that the longer a person stays in a coma or vegetative state the worse the diagnosis. Saying that, one should never lose hope. We do not fully understand the mechanisms behind loss of consciousness, and even less about the awakening from such states.
  • Should a person regain consciousness after a vegetative state, one should always remember that the loss of consciousness had a specific and dramatic cause. Although consciousness may be restored (even as episodes) the brain is often significantly damaged. The person might still be unable to speak, attend, see etc. Many psychological and cognitive functions may be severely distorted or non-functioning

You do not mention where your son's diagnosis has been set, or where in the US you live, but I will suggest some names below. Unfortunately, I have no personal correspondence with Fins or Schiff, but know them through the scientific literature I read. Steven Laureys I know a bit, but I would suggest going to Schiff or Fins first, or the place (university / hospital) they are situated.

Joseph Fins at the Center for Bioethics, Colombia University (homepage)
Nicholas D. Schiff at the Department of Neurology and Neuroscience, Weill Medical College of Cornell University (E-mail)

Steven Laureys (Belgium, for further US directions) at the Cyclotron Research Centre (E-mail)

I hope this could be of any help to you and your family.

Sincerely,
Thomas

References

Laureys S. (2005). Science and society: death, unconsciousness and the brain. Nat Rev Neurosci, 6(11), 899-909

Laureys S. (2005). The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci

Laureys S, Pellas F, Van Eeckhout P, Ghorbel S, Schnakers C, Perrin F, Berre J, Faymonville Me, Pantke Kh, Damas F, Lamy M, Moonen G, and Goldman S. (2005). The locked-in syndrome : what is it like to be conscious but paralyzed and voiceless? Prog Brain Res, 150, 495-511

Laureys S, Perrin F, Schnakers C, Boly M, and Majerus S. (2005). Residual cognitive function in comatose, vegetative and minimally conscious states. Curr Opin Neurol, 18(6), 726-733

– Thomas

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Synaesthesia is a rare condition where people experience some percepts as a different sensory modality than the one they normally belong to – e.g., numbers as colours, or tones as shapes. It is, thus, a positive (and rather bizarre!) syndrome, where an abnormal trait is present, not absent, in the affected person.

Synaesthetes clearly posses brains that are differently wired up than non-synaesthetes. It has been speculated by some neuropsychologists, such as V.S. Ramachandran, that the sensory areas of the synaesthetes' brains are connected in an abonormal fashion, such that, for example, signals normally destined for their number areas end up in the colour area.

Experimental work casting light on such hypotheses is finally forthcoming, and a lot of what is presently known has now been collected in the new issue (February 2006) of the journal Cortex. Edited by Jamie Ward and Jason Mattingley, it contains contributions by just about every researcher currently working on synaesthesia. And remember: Cortex doesn't require a subscription to access!

Reference

Ward, J. & Mattingley, J., eds. (2006): "Cognitive neuroscience perspectives on synaesthesia. Cortex, vol. 42, issue 2.

– Martin

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Neuroscience affects the way we think about ourselves. It affects how we think of normal and abnormal minds. It has influence on how people are judged according to law, whether they have been acting willfully or under the effect of psychoactive drugs, sleep disturbance, brain injury or psychiatric disease. But how do our scientific models relate to the way neuroscience is used in the courts?

In a new article in Nature Reviews Neuroscience, Nigel Eastman and Colin Campbell are giving a critical remark on how the law system is making use of neuroscience. They claim that:

(…) there is a profound mismatch of legal and scientific constructs, as well as methods, arising from their expression of different social purposes. More specifically, in terms of the stage that brain science is currently at, the law is unlikely, at least if it fully understands the science it is being offered, to prefer population based evidence of association of violence with biological variables, be they genetic or neuroimaging in nature, to psychological evidence that can suggest, even if not prove, mental mechanisms underlying commission of a particular offence.

Law and science are not using the same language. More to the point, judging a person on the basis of evidence that has been done on groups, is highly problematic, to put it mildly. This points to the very basis of one of my earlier blog remarks that doing group studies says little about our ability to put a single subject’s scan in one group or another.

So far so good. I completely agree. But at the very end, Eastman and Campbell make a strange conclusion:

Only if science were to achieve a very high level explanation of offending in terms of genetics or brain function might the position be altered. Perhaps fortunately, it seems likely that such explanation is a long way off. Indeed, some might say that, were we to achieve such a level of biological understanding of ourselves, we would have ‘biologically explained away personhood’, and have subsumed both legal and moral responsibility into biology.

Why would an explanation of the bio-basis of personality make us have less personality? Would a biological explanation of consciousness take our feelings away? I think this is a most strange assumption and it is academic BS! Let’s put it this simple: did the explanation of stars make them in any way less star-like? No.

So what are they really claiming? If you are a naturalist, like me, you actually do think that the mind is a direct result of what happens in the brain. And nothing else. By this view, the current science of the brain is incpmplete because we have not fully understood how this works. So if we find the biological solution to personhood, we have been able to describe what happens in the brain when we are conscious, acting individuals. And it will give us the means to explain what goes wrong when someone kills another person “unmotivated”, rapes a woman, steals and lies. We already know a bit about how this works and how it can go wrong. But this knowledge makes us not one single grain less human, does it? Actually, I’d say that the insights provides us the tools to intervene when something goes wrong, and to give the best possible treatment. In that sense, neuroscience is actually humanizing.

See also this transcript from “All in the mind” at Radio National.

-TZR-

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Becoming conscious of a visual input

Click on the image to see full size

What happens in the brain when we become conscious of something? What processes and structures are responsible for becoming aware? Is consciousness an either-or process or can we have in-between forms of perception?

We have recently attempted to put those questions into empirical terms. In a study that is now in press in NeuroImage, we asked subjects to report how clearly they saw visual stimuli. The stimuli were simple geometrical shapes (circle, square, triangle) that were presented at different durations, from approximately 16 msec to about 150 msec.

From a previous behavioural study, we have concluded that conscious perception is not an either-or, and that there are instances where subjects report having “vague” percepts. That is, some stimuli are experienced as “something being presented” withouth being able to determine what was presented. Detection without identification.

Question is, how does the brain work under these conditions? In this study we have showed that vague perception shares much of the same network of fronto-parieto-temporal and cortico-thalamo-cortical network as seen during conscious perception. However, we also identify some unique activity in the brain during vague perception, especially in the prefrontal cortex.

I’ll leave this news hanging in the air/ear (…) just for now. When the article is published, I will link to the PDF. I’ll leave it to Mark Christensen, the PI of this project, to put it in his own words. Take also time to look at the image below.

NOTE: Why is this research important to neuroethical consideations? First of all, it demonstrates that specific types of experience are closely related to what happens in the brain. It shows that questions about the mind can be asked — and answered — by neuroscience. And it strengthens our view that conscious vs. unconscious perception is not a clear dichomotic distinction. Rather, we need to make use of more elaborate ways to study reports of conscious perception. Finally, this finding strengthens models suggesting the necessity of a widespread brain network to support consciousness (see also this article, PDF). Knowing what it means to be conscious tells a lot about what it means to be human.

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Subjective reports of graded perception
by Mark S. Christensen
In an fMRI, which is to be published in NeuroImage, we have shown that subjective reports of perceptual clarity correlates with graded neural activation within a parietal, premotor, basal ganglia and frontal operculum network.

In a simple visual masking experiment, we asked subjects to report their subjective experience of perceptual clarity of masked visual stimuli on a graded scale ranging from no perceptual experience, over a vague/glimpse like experience, to a clear perceptual experience. This was done during an event-related fMRI experiment.
Within fronto-parietal-thalamic areas where the activity was increased for clear perceptual experiences compared to no perceptual experience, we found a network, where the activation varied in a gradual way, following the subjective report. Furthermore, we found areas in insula and frontal cortex outside the fronto-parietal-thalamic network, where the intermediate, fringe-state showed unique activation.
The results provide the first evidence of sensory fringe states, and that the subjective experience of conscious perception has a counterpart in graded neural activation. Furthermore, they strengthen the scientific value of subjective reports. Finally, we show that within a network for conscious perception that includes the parietal and premotor cortices, the subjective experience resides.

Reference:

Christensen MS, Ramsøy TZ, Lund TE, Madsen KH, Rowe JB (in press). An fMRI study of the neural correlates of graded visual perception. Neuroimage

The neural correlates of clearly perceived visual stimuli have been reported previously in contrast to unperceived stimuli, but it is uncertain whether intermediate or graded perceptual experiences
correlate with different patterns of neural activity. In this study, the subjective appearance of briefly presented visual stimuli was rated individually by subjects with respect to perceptual clarity: clear, vague
or no experience of a stimulus. Reports of clear experiences correlated with activation in a widespread network of brain areas, including parietal cortex, prefrontal cortex, premotor cortex, supplementary
motor areas, insula and thalamus. The reports of graded perceptual clarity were reflected in graded neural activity in a network comprising the precentral gyrus, intraparietal sulcus, basal ganglia and the insula. In addition, the reports of vague experiences demonstrated unique patterns of activation. Different degrees of perceptual clarity were reflected both in the degree to which activation was found within parts of the network serving a clear conscious percept, and additional unique activation patterns for different degrees of perceptual clarity. Our findings support theories proposing the involvement of a widespread network of brain areas during conscious perception.

-TZR-

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I thought it would be a good thing as a host to welcome you to this new blog. We discovered it while travelling through the blogosphere. So why take the chance and change the host now? Well, why not? Any time would be a bad time, so the sooner the better. But given the better features provided by WordPress we think that it provides us the tools to create an even better blog.

Let me walk you through the new and fancy things you can with this new site:

  • Categorized items: we now sort all our entries by category, so they may be easier for you (and especially us) to find later on. Please note that we can use multiple categorizations for one item (it may be e.g. free will and law).
  • Separate pages: we have made separate pages for each of the contributors to this blog (Martin Skov and Thomas Z. Ramsøy), as well as one about the blog. More specific pages are bound to follow.
  • Search function: now what item contained that story about evolving brains again? If you don’t seem to find it through our categories, try our search function
  • Calendar: you can even see when we added items (hurrah)
  • Better RSS feed: hopefully, you’ll find the RSS feature here even better than the previous one. Note that you can go for either the full rss or the comments

We hope that you find this blog better and maybe even more attractive than our previous site. Stay tuned for more neuroethics items.

-TZR-

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As discussed before here on the blog, imaging studies by Josh Greene, Jorge Moll and others have demonstrated that emotional responses play a pivotal role in forming moral judgments. A new study by Sylvie Berthoz adds further information to this growing story.

Berthoz and her colleagues had subjects read short stories describing transgressions of social rules. The stories either described situations where (1) the subject was the agent of transgression, and the violations was accidental, or situations where (2) the protagonist was another person than the subject, and the violations was accidental, or situations where (3) the subject was the agent of transgression, and the violations was intentional, or situations where (4) the protagonist was another person than the subject, and the violation was intentional. Thus, Berthoz et al. were able to contrast intentional moral transgressions performed by one self from transgressions performed by others, or from accidental transgressions.

This contrast showed significant bilateral amygdala activation, and Berthoz et al. speculate that such activation may be related to one’s anticipation of possible punishment as a consequence of one’s own immoral behaviour. This suggestion, of course, squares well with ideas from the emerging field of social neuroscience – especially the hypothesis that social cooperation rests upon a tit-for-tat regime: If I share my ressources with you, I expect something in return. If I don’t get anything back, I will punish you. It is pretty clear, as well, that the back-bone of the success of such social behaviour is the brain’s reward and punishment system: The expectancy of a return is modulated by the reward system, and the anticipation of a punishment – which works to keep you from cheating the other members of your social group – is modulated by the punishment system, including the amygdala.

Now, it would be very interesting to apply a genetic analysis to this result. Maybe we would then find a similar variance as reported by Hariri with regard to serotonin re-uptake and mood? That is, some people may be more afraid of transgressing moral rules than others due to a difference in amygdala activity. It is rather obvious, after all, that some people won’t loose any sleep over sticking it to you!

Reference

Berthoz, S. et al. (2006): Affective response to one’s own moral violations. To appear in NeuroImage.

-MS-

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If you have read Thomas’ fine introduction to Ahmad Hariri’s work on the link between gene expression, serotonin re-uptake and emotion, you may be interested in hearing more about the story from the horse’s own mouth. If so, check out this new review, in press for publication in the April issue of Trends in Cognitive Science.

Reference

Hariri, A. & Holmes, A. (2006): Genetics of emotional regulation: the role of the serotonin transporter in neural function. To appear in Trends in Cognitive Science.

-MS-

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This is a new conference on combining the knowledge from genetics, neuroimaging and behavioural science. A brief look at the program is enough: I’m going!

7th EMBL/EMBO Joint Conference 2006
3-4 November 2006, EMBL Heidelberg, Germany

Genes, brain/mind and behaviour

Research in the life sciences is revealing how genes are differentially expressed in the brain and how types of behavior reflect the functioning of different neural networks. Scientists are also exploring the relationship between the neurophysiology of the brain and the nature of consciousness.

Science and technology always work in tandem. Neurotechnology refers to the set of tools that have been developed to analyze and influence the human nervous system, especially the brain. We would like to assess the uses that are – or could in the future be – made of new neurological knowledge and technologies. What are the consequences when biochemical solutions to behavioral problems such as depression, addiction, or eating disorders take precedence over attempts to repair the social environment, or defective inter-personal relations? How do we avert the risk of psychopharmacology being abused for neurochemical enhancement?

While new knowledge coming out of the neurosciences has an enormous potential for beneficial applications in diverse fields, treating or manipulating the mind will also have important social, legal and bioethical implications. These are some of the main issues that will be the focus of the next inter-disciplinary EMBL/EMBO Science and Society conference in 2006 in Heidelberg, Germany.

Programme

Poster [2MB]

-TZR-

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In a NeuroImage article this February, Krishnan et al. demonstrate how poor spatial normalization can be for the hippocampus. Spatial normalization is an image processing step applied in neuroimaging when typically you are doing group studies. As it says on Wikipedia.com:

Human brains differ in size and shape, and one goal of spatial normalization is to deform human brain scans so one location in one subject’s brain scan corresponds to the same location in another subject’s brain scan.

Human brains are like fingerprints. On a general level they are alike, but they differ significantly when we look at the details. There are large individual differences if we look at where sulci and gyri appear and disappear in the brain; even whether you have one or two sulci.

Krishnan et al. have looked at the hippocampus, and found large variations in the position and extent of spatial normalization, not only due to sample size (i.e. how many subjects were included), but also when comparing the operation in patients with Mild Cognitive Impairment and healthy subjects. Put another way, if you do spatial normalization — which you do if you want to compare groups at the brain level — the operation may induce a bias in your results. For example, it may lead you to think that the loss of hippocampal gray matter is larger than it actually is.

To open up the lid slightly to one of my forthcoming publications, we have looked at more structures of the medial temporal lobe, including the temporopolar, entorhinal, perirhinal and parahippocampal cortex, as well as the amygdala and hippocampus. We have found that spatial normalization of these areas leads to significant dicplacement of the different structures. It’s sometimes so bad that what is identified as the perirhinal cortex in the original brain (native space) is partly displaced into the hippocampus.

Here is an image of the coregistration pandemonium in the medial temporal lobe. It shows the coregistration of the left perirhinal cortex in six subjects. The structure was drawn as a region of interest and then normalized according to standard SPM warping:

Quite a mess, right? An optimal normalization would give no variation, just one colour, and one neat structure. But this looks nothing of that. A bit of explanation might be in its place: the walls of the figure show coronal (left), sagittal (right) and axial (bottom) slices; the middle part displays the region of interest in 3D

This has a tremendous impact both theoretically and clinically. There is currently a huge interest in this region and whether it is specifically operation in memory (the Squire-Zola model), or whether it has additional roles in visual perception, novelty processing and cross-modal perception (see latest article by Buckley & Gaffan).

Think of it: if you go through all papers reporting hippocampal activation in an fMRI paradigm, but if you re-do the analysis properly, or look at the individual scans, you see that most of the hippocampal activation is actually perirhinal. I’ll never trust a spatially normalized image again.

OK, to some people this is old news, but let’s face it: most of us eat the results from group studies raw, without chewing too much about how these images were made, i.e. normalized. Well, now I hope you do.

If you want to read more I have two relevant abstracts:

-TZR-

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I have written a small piece about imaging genetics (IG) in Science & Consciousness Review. IG is IMHO really going to revolutionize cognitive science, hopefully even philosophy of mind. The findings made here point altogether to how tightly coupled the mind is to its physical brain, and how our minds are made by our brains.

Just a small passage from my piece:
“Genes control the development of neurons to make up brains, but they also govern neuronal gene expression during our daily lives. (…) Genes work at every level of the neural process. They are the fundamental building blocks for both the structure and the functioning of the brain. They set the stage for how neurons and functional groups of neurons act in response to different inputs. Genes are therefore fundamental for the way we experience, think and behave.”

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