Re-localizing Broca

Nature is running a nice news article on the re-localization of Broca’s language area in the brain, and has as feature about it in their latest podcast.

Pierre Paul Broca originally described patient cases in which the patient suffered speech production deficits following injury to the left frontal hemisphere. However, a revisit to Broca’s original papers (see translations here and here), combined with a modern scanning of the preserved remains of Broca’s patients, has revealed that what has been called Broca’s area in modern times does not correspond to the areas implicated by Broca in his patient descriptions and neuroanatomical descriptions.

The story is interesting, but I’m amazed that the excitement is running so high. After all, lots of papers have already dethroned Broca’s (and Wernicke’s) area in the role of language processing. Take the example of the special issue of Cognition on language. Basically, what we know about language in the brain is beyond the talk (!) about Broca and Wernicke, and especially the models they suggested. Rather, both language comprehension and production require a larger neural symphony, and with substantial internal redundancy. IOW, Broca’s area can participate in comprehension, and Wernicke can play a part in production.

Nevertheless, the Nature news article is a good read, and I always recommend the Nature podcast.

-Thomas

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Brain reading conference

Back in February, BBC ran a story about fMRI researchers – shock, horror! – now being able to read people’s minds. In actual fact, the story was a bit more benign. Using a fairly new (and little used) type of fMRI analysis called “multivariate analysis” researchers such as Geraint Rees and John-Dylan Haynes are presently attempting to associate individual mental states with specific patterns of BOLD signal activity. If the mental states of interest can be precisely delineated it is possible to determine if a subject is “in” mental state A or B just from looking at the scanned fMRI data. For instance, in one experiment, described in the BBC story, subjects were asked to either subtract or add numbers shown on a screen without telling the experimenters which of the two potential choices they actually went with. Just by looking at the obtained scans Haynes and his colleagues were able to infer, in 70 % of the cases, whether the subject chose to add or substract – thus, to some degree, being able to “read” the subjects’ hidden intentions. Of course, in reality, the experimenters’ mind reading ability was extremely limited, being focused on only two, highly simple, forced choices. (If you want to read a good presentation of the mind reading possibilities offered by multivariate analysis, see this paper by Rees and Haynes.)

Yet, with all the recent talk about fMRI lie detection and what have you, work such as Haynes and Rees’ on multivariate analysis raises a number of interesting neuroethical questions. On May 9, Haynes is convening a bunch of top-notch speakers to discuss these questions, including Daniel Langleben (of fMRI lie detection fame), Adrian Owen, Henrik Walther, and Thomas Metzinger. He presents the colloquium with the following words:

Every thought is associated with a characteristic pattern of activation in the brain. By training a computer to recognize these patterns, it becomes possible to read a person’s thoughts from patterns of their cerebral activity. In this way a person’s brain activity can betray their thoughts and emotions, can gives clues whether they are lying, or can even predict what they are about to do.

This recent progress in brain science has made completely new insights into thought processes possible. We can now investigate how thoughts are stored in the brain, or how intentions unconsciously arise and affect our behavior. But these findings are not just of interest for the scientific disciplines involved. They have important implications for our understanding of human nature. Also, they lay foundations for important applications: For example, with the help of a “brain computer interfaces”, paralysed patients can control technical devices solely “with the power of their thoughts”.

In the 11th Berlin Colloquium, brain scientists from the USA, Canada and Europe will present this new field of “brain-reading”, while at the same time providing a forum for discussion on the future perspectives of these methods. In particular, the ethical question will be of interest, to which extent such “thought technology” is compatible with “mental privacy”.

It should be well worth your time going.

-Martin

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Want the job? Pass our OCD scan first, please

Is it possible to identify a psychiatric disorder using a structural brain scan? According to a team of researchers from Europe and Australia this can indeed be the case. In a recently published study in NeuroImage, researchers Carles Soriano-Mas et al. demonstrate that structural brain scans can identify subjects suffering from obsessive-compulsive disorder (OCD) with a 93.1% classification accuracy (for a whole-brain comparison). In addition, individual variance in OCD symptom severity was correlated with the measured neural differences. In other words, the more you suffer from OCD the more you are likely to stick out in the analysis as an oddball, compared to a healthy norm.

Here is an image showing the structural differences between OCD patiens (n=72) and healthy controls (n=72):

In the image, the heat scale indicates regions where OCD patients differ significantly from controls at the whole brain level. Interestingly, when the researchers focused on the most intense regions the predictive value of the brain scans dropped to 76.6% accuracy. This means that a whole-brain approach is the optimal for determining whether a subject is suffering from OCD.

The study clearly demonstrates that neuroscience is moving in the direction of single-subject analysis, and the application of advanced analysis methods to determine whether a given individual is structurally (or functionally) within the normal range. If the means are there, when will we see them being used — and misused? After all, if a brain scan has the close to 100% accuracy of telling whether a person is suffering from OCD, why not use it in the clinic right away? Or better, why not expect applicants to an important company position take such a scan? After all, if you suffer from OCD, you are less likely to be able to be in such a position, right? And while we’re at it, why not try for a similar approach for depression, anxiety, stress and introversion?

Are we right in being sceptical towards the application of such measures of psychic health? Methodological problems aside, should such a measure provide a robust assessment tool, why should we not use it? After all, psychological testing is really aimed at uncovering who people are. Apply for a top position and you are likely to be submitted to psychological and cognitive profiling. If scanners provide a better accuracy, would it not be preferable to use this method? Since society has decided to allow psychological and IQ testing, such measures should really be just another improved method. As a consequence, we should not be surprised to see them being used pretty soon — if they are not already in the stores.

The solutions are far from clear in the muddy waters following the blazing trail of neuroscience. As neuroscientific methods move along and create new opportunities, new problems arise, too. What is important is to bring these issues up front in the media and other forums of such debate. Neuroethics is as important as ever.

- Thomas

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Better lie detectors?

Is it really so that fMRI can enhance lie detection? This entirely depends upon your method of analysis, the experimental setup, and especially controlling for factors that influence the scanning results. Let’s take them one at a time

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Scroll through and look for fireworks

It’s a strange feeling. You scan what you think is a normal person, and have taken all precautions to make sure that there are no indications of medical complications. But once you look at the scans, there is something wrong with the brain you are looking at. As in this case, I scanned a person some while ago as part of my study of the brain in healthy ageing.

The finding is not as obvious as one should think. Why? Unless the lesions are so vivid that anybody can see it, training is required. Furthermore, research projects are not aimed at detecting or diagnosing pathology.

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Studying the brain-web pathways with MRI

It’s been a while, and whoah! have we been drowning in work or what? The media here in Denmark have caught on both our stories about teenage brains and stem cells in mother’s brains.

Here is a nice demo of how MRI can be used to study not only the brain per se, but also how mental functions work as different functional and physical networks. In a really neat study Takanashi et al. in NeuroImage combined fMRI and Diffusion Tensor Imaging, a scanning technique that basically makes it possible to calculate the brain fibers in the brain, i.e. their homogeneity, direction and so forth.

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Bowlby’s bulb

Can a brain scan reveal your relationship to your mother? According to a recent study, this may well be the case.

One of the theories in modern psychology is about the relationship between a child and her parent, especially the mother. Among such attachment theories is the original theory by John Bowlby. For a good description of attachment theory see Wikipedia. There’s also a good article (PDF) in Developmental Psychology on the history of attachment.
Basically, the theory of attachment demonstrated that the dyadic relationship between the infant and the mother can take the form of different styles — attachment styles. Such styles include secure attachment where the infant can use the mother as a secure base from which the immediate environment is explored. Insecure attachment, however, can come in different forms, including avoidant, ambivalent and disorganized (see also here). Studies have shown that the attachment style at birth is likely to influence the social functions in adulthood, and that the attachment style in one female is inherited by her offspring through a process called transmission (see also this excellent paper). Normally, this transmission is thought to be socially transmitted, although I think it’s a dubious conclusion since children are both genetically and socially related to their mother. However, a convincing study (PDF) in 2003 by Bokhorst showed that while genetic influence on temperament was relatively high, the influence on attatchment style was negligible.

But let’s get to the case: does attachment style demonstrate measurable effects on the brain? Indeed, this is what Erwin Lemche and colleagues found in a study using functional MRI. Based on previous findings that insecure attachment is related to heightened sympathetic nervous system activity (e.g. heart rate increase and cortisol secretion), Lemche et al. demonstrated that performance during a stress, relative to a neutral, prime stimulus condition involved bilateral amygdalae activation.

The subjects were shownn two series of 32 sentence statements describing self-centred or other-centred information. They had to report whether they agreed or disagreed with the statements by pressing a button. Before the presentation of the target sentences, subliminal messages with negative content were presented on some occasions (stress condition), or with nonsense sentence content (neutral condition). For example, the negative prime could be “My mom rejects me” presented for 30 milliseconds. In the neutral condition the prime could be “Ym umu jrecest em”, also presented for 30 milliseconds.

The activation of the amygdalae after negative primes was the same for all subjects. However, for those subjects who demonstrated an insecure attachment style (determined by the Adult Attachment Interview) the amygdalae activation levels was significantly higher when presented with the unconscious negative primes.

So having an insecure attachment style leads to higher activation to attachment-related primes. Taken together, this result demonstrates a role for amygdala in mediating attatchment relevant behaviour. Indeed, it is interesting to see how a phylogenetic “old” limbic structure is involved in an interpersonal psychological process, which is normally thought to involve more prefrontal cortical regions.

-Thomas

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A conscious veggie?

It should be mentioned that there is a highly controversial paper out in this week’s Science. Here, a study by Dr Adrian Owen shows that a patient that meets the criteria for vegetative state shows what can be thought of as signs of conscious life. You can see the MindHacks coverage of this story here. basically, the researchers asked their patient to imagine playing tennis or moving around her home and found that:

the patient activated predicted cortical areas in a manner indistinguishable from that of healthy volunteers

The researchers take this as a sign of the patient being conscious while still being unable to communicate, let alone perform any volutary behaviour. In this sense, it seems that the patient rather meets the criteria for locked-in syndrome. The study thus raises the question of whether this patient — indeed, any PVS patient — is conscious, and whether the diagnostic criteria are yet poorly defined and the symptoms similarly poorly understood.

Nevertheless, it should be considered an open question whether we should accept this finding as a true sign of consciousness in the patient. This is also covered nicely in a comment by Naccache in the same issue of Science. Pointing out some of the shortcomings of this study, as well as contrasting it to the many studies showing specific changes in PVS contrasted to normal consciousness, Naccache concludes:

Though not totally convincing on the issue of consciousness, the Owen et al. work paves the way for future functional brain-imaging studies on comatose and vegetative state patients. One can imagine probing each of the psychological properties of conscious processing listed above, and even trying to collect subjective reports by modifying the experimental paradigm.

As I have written earlier, this is indeed the case: we do not have a clear concept of the distinctions between coma, vegetative states, minimally conscious states or locked-in syndrome. Only during the past few years we have seen a dramatic increase in our understanding of these disorders. It is no doubt that our understanding will increase in the same manner during the next many years.

I have asked Dr. Owen and his co-author, Steven Laureys about this finding, and hope to get back to you with their replies shortly. In the meantime, you might be interested in this article (PDF) that Laureys and I co-authored with prof. Bernard Baars in TINS.

UPDATE: Nature has a podcast interview with Dr. Owen here.

-Thomas

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Aggressive brain tumor treatment via fMRI

Brain tumors are a huge problem in neurosurgery. Not only do you have to take into consideration the delicate network of blood supply to the brain that can ultimately lead to further damage to the brain. In addition, the tumor is placed with in a meshwork of cognitive functions. Cutting too much on one side of the tumor can lead to amnesia, too much of another part can lead to aphasia.

To alleviate this problem, MRI is currently being used to identify the tumor through conventional structural scans. In addition functional MRI can be used to identify vital functional nodes that borders to the tumor. In this way, neurosurgery can use a better estimate of the tumor’s position and extent, as well as avoid functional centres. In all, the precision of neurosurgery has improved dramatically with the use of MRI.

In an article in Radiology, a study now shows that the use of structural and functional MRI in preoperative surgical planning both leads to more precise and more efficient surgery. As a brief resume in Medscape.com reports:

In six cases, the neurosurgeon reported that functional MRI results led to a more complete resection, whereas two patients required a smaller craniotomy than had been planned. The surgeons also noted that surgical time was reduced by 15 to 60 minutes in 22 patients. Invasive imaging that would have been required for four patients was avoided.

In practice this has a tremendous impact for the livesof the patients. With the use of preoperative MRI brain tumors can now be more fully ablated, and at the same time patients will have a lower chance of suffering unwanted dysfunctions. From the Radiology paper, we can see this in one female patients. From the description of the patient:

Recurrent left parietal lobe anaplastic astrocytoma in 37-year-old right-handed woman. Surgery was not initially planned because of presumed involvement of receptive speech area. Left inferior and middle frontal gyral activation (yellow arrows) is consistent with dominant expressive speech area and is located at anterior border of more cephalad component of lesion. Left superior and middle temporal gyral activation (green arrows) is consistent with dominant receptive speech area and abuts inferior border of temporal component of lesion, with superior temporal gyral activation component lying anteroinferior to lesion. Biopsy was performed, and no postoperative neurologic deficits were documented.

-Thomas

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Next Im-Gen meeting

The next International Imaging Genetics Conference is opening its doors now for registration. The third year in a row, building on two successful conferences, this third meeting will also house two separate workshops: one on brain imaging for geneticists; and one on genetics for brain imagers. All in the spirit of crossing the bridge between genetics, brain imaging and statistics. As this course was brilliant last year, I’m hoping to attend in January 2007, too.

Here is the announcement:

The First and Second International Imaging Genetics Conferences were held to bring together national and international experts in neuroimaging, genetics, data-mining, visualization and statistics. Targeting physicians and scientific researchers, this annual conference features presentations from investigators world-wide and held in-depth discussions within the emerging field of Imaging Genetics. Given the known importance of both genetics and environment in brain function, and the role of neuroimaging in revealing brain dysfunction, the synergism of integrating genetics with brain imaging will fundamentally change our understanding of human brain function in disease. To fully realize the promise of this synergy, we must develop novel analytic, statistical, and visualization techniques for this new field.

This international symposium was held to initially assess the state of the art in the various established fields of genetics and imaging, and to facilitate the transdisciplinary fusion needed to optimize the development of the emerging field of Imaging Genetics. The Third Annual International Imaging Genetics Conference will be held on January 15^th and 16^th, 2007 at the Beckman Center of the National Academy of Sciences in Irvine, CA. We look forward to seeing you at this exciting upcoming event.

Monday January 15th:

• Nicholas Schork, UCSD “Multivariate Analysis of Combined Imaging and Genomic Data”
• Eleazer Eskin, UCSD “Analysis of Complex Traits Through Intermediate Phenotypes.”
• Tom Nichols, University of Michigan “Statistical Challenges & Opportunities in Imaging Genetics”
• Fabio Macciardi, University of Toronto “Integrating Imaging Genetics Methods in Schizophrenia.”
• David Goldman, NIAAA “Genes and Neurobiologies in the Addictions”
• David Goldstein, Duke Institute for Genome Sciences and Policy “Neuropsychiatric pharmacogenetics”
• Daniel Weinberger, NIMH/NIH: TBA

Tuesday January 16th:

• Joseph Callicott, NIMH “Does risk for schizophrenia arise from multiple genes in vulnerable pathways? Evidence from DISC1 and FEZ1″
• Lisa Eyler, UCSD “Genetics of Brain and Cognition: A Twin Study of Aging”
• Fei Wang, Peking University “Neuregulin 1 Genetic Variation and anterior cingulum integrity in schizophrenia and in health.”
• Andreas Meyer-Lindenberg, NIMH/NIH “Genetic characterization of prefrontal-subcortical interactions in humans.”

**New for 2007** Sunday January 14th:

*** Half-day Workshop tutorials will be offered the day before the conference at the Beckman Center- see website for details***

Workshop 1: What Geneticists need to know about Brain Imaging
Workshop 2: What Brain Imagers need to know about Genetics

Registration and conference information can be found at the conference website

-Thomas

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