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Oh no, I'm going to get in trouble!

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.

Hariri review in TICS

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.

Genes, brain/mind and behaviour

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]

Normative brains and group studies

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:

• The downside of spatial normalisation in fMRI of medial temporal lobe structures
• Effects of spatial normalization on detection of perirhinal cortex activation in individual subjects using fMRI
  

How genes make up your mind

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."

Im-Gen videos now up

As I mentioned in this post, the videos from this year's International Imaging Genetics Conference would be just around the corner. Turns out that was a precise prediction. The videos for all speakers are now online. Buy some chips and a cola and put yourself in front of a double-screen projector (one with the video and one with the PDF) and enjoy!

CIMBI alive

The Center for Integrated Molecular Brain Imaging (CIMBI) is now officially opened. The overall idea behind this massive project is to study cognitive, psychological and biological phenomena with a multi-modal approach, combining data from genotyping, PET scanning and MRI scanning. The main project of CIMBI is to study "the neural bases of personality dimensions that predispose individuals to affective and substance use disorders, with special emphasis on the serotonergic neurotransmitter system". In other words: to study the biological mechanisms behind personality formation. They are currently recruiting (and looking for) the best-qualified personnel for the new available positions.

One part of the CIMBI project involves looking at how genes coding for seretonin affect the seretonin transport function, and furthermore how the function of seretonergic areas of the brain operate depending on the genetic makeup of a subject. In this latter part, I am involved in doing the MRI study, including three fMRI protocols:

1. Processing of facial affect - how genes affect the processing of facial expression, especially the difference between aversive and neutral faces.
   
2. Memory processing in the medial temporal lobe (MTL) - how different parts of the MTL make different contribution to specific phases in memory processing: preparation, encoding, rehearsal and retrieval.
3. Categorization task - the difference between choosing between high-specificity options (within-category choices, e.g. "donkey or zebra") or low-specificity options (between-category choices, e.g. "living or non-living")
   

Data will be combined between fMRI (BOLD and perfusion), genotype and seretonine function as measured with PET. In addition we are looking at the relative contribution of changes in volume and form of MTL areas to the overall signal differences found in other modalities.

Imaging Genetics stuff

The slides of most of the presentation from this year's International Imaging Genetics Conference are now available through their website. I surely hope they'll add the videos soon. There are a few that I'd like to have a second (third...n'th...) look at.

I have a few comments to some of the presentations, and to keep in mind:

• Nik Schork presented and discussed ways to visualize the imaging/genetics data (especially the latter. Unfortunately, these slides are still missing from the list
• Tom Nichols gave a good talk that to me helped binding the fields of genetics, neuroimaging and statistics a bit more together. Again, these slides are also missing
  
• Bernie Devlin is worth having in mind when thinking critically about the projects done in this field.
  
• Andreas Meyer-Lindenberg gave a really cool talk about his work on Williams-Beuren syndrome, and how genes play a role in the brain in social cognition.
• Ahmad Hariri gave an equally neat talk about individual differences in appetitive drive.
• Dan Weinberger has this extra way of grabbing his audience's attention and make them forget all about jet lag and coffee thirst. His talk about the lessons from the study of COMT were most interesting.
  

Admitted, it is far from sufficient to see some slides. You can only get the ghist of what you're missing. So let's hope that the Irvine people will add the videos soon. Stay tuned.