A gene for each thought

As the community — and thought — about imaging genetics grows, new studies are emerging. These studies focus on the way that genes are found to play a role in different cognitive functions. In a recent special issue of Behavior Genetics, the focus is on the progress in the linkage between the genetic map and behavioural traits. There are a lot of interesting articles in this special issue, altough I find a few especially intriguing.

In a nice review, Steven Buyske reviews different findings that map cognitive functions and the gene map. Here's the abstract:

Cognitive Traits Link to Human Chromosomal Regions

Human cognition in normal and disease states is both environmentally and genetically mediated. Except for measures of language-specific abilities, however, few cognitive measures have been associated with specific genes or chromosomal regions. We performed genome-wide linkage analysis of five neuropsychological tests in the Collaborative Study on Genetics of Alcoholism sample. The sample included 1579 individuals (53% female, 76% White Non-Hispanic) in 217 families. There were 390 markers with mean intermarker distance of 9.6 cM. Performance on the Digit Symbol Substitution Test, a component of the Wechsler Adult Intelligence Scale-R, showed significant linkage to 14q11.2 and suggestive linkage to 14q24.2. This test of sustained visual attention also involves visual-motor coordination and executive functions. Performance on the WAIS-R Digit Span Test of immediate memory and mental flexibility showed suggestive linkage to 11q25. Although the validity of these results beyond populations with a susceptibility for alcohol dependence is unclear, these results are among the first linkage results for non-language components of cognition.

But hey, there's more. There are studies on the association of genes and anxiety and neuroticism; gene association of feelings of loneliness; gene association to age at first cigarette; genes on academic skills; and genes on IQ (of course).

The question is: where will it end? Of course, genes are abundantly represented in the body. They are, after all, the receipt to every cell and how they should work. But what level of description and explanation should we apply in this gene-to-cognition mapping? I fear that at least in some studies, old "folk-psychological" concepts about cognitive traits are compared to high-detailed analysis and knowledge about the genes. In order to understand how genes get expressed in a way that they shape behaviour, we need to work out the intermediate stages. We need to know how genes influence neurons, transmitters, plasticity on one level; how they shape interacting neurons and neural assemblies; and finally how this cumulates into one or the other kinds of behaviour. The leap from gene to behaviour is, IMHO, too wide. The solution is in the nitty-gritty details.

Way to go CIMBI!

-Thomas

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Refreshing Quotes from Neuroscience

Here's another new feature here at BrainEthics. Some quotes from neuroscience and related fields are so provocatively refreshing that they deserve a place of their own. Why not highlight them here, as we fall upon them. Quotes are great, since they seem to grasp the ghist of a whole idea, in one or a few sentences it captures the meaning of an entire book, a whole research trend, a misconjecture in the literature.

I'll start off with this great quote from Gilles Laurent, who writes in a chapter in a recently published, interesting book (worth mentioning in a post of its own) called "23 problems in system neuroscience". Here, Laurent opposes what he sees as a cortico-centrism; an unwarranted fascination with the cerebral cortex at the expense of subcortical (and other) structures:

"Why this obsession with cortex? (…) most scientists act as if King Cortex appeared one bright morning out of nowhere, leaving in the mud a zoo of robotic critters, prisoners of their flawed designs and obviously incapable of perception, feeling, pain, sleep, or emotions, to name but a few of their deficiencies. How nineteenth century!"

-Thomas

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Logothetis doesn’t like to be BOLD … alone

Yesterday, Nikos Logothetis gave a great talk at the annual keynote lecture for the Copenhagen University Research Priority Area "Body and Mind". In the lecture, Logothetis touched upon several issues on the workings of the brain – from his perspective. But at the later Master-class where it was possible to have a one-to-one discussion with him, there was little doubt about Logothetis' view about how to understand the workings of the brain and mind. And especially how to study it with neuroimaging techniques.

BOLD fMRI, he claims, can tell us something about where in the brain something is happening. But other than that, it can tell us very little about what happens in that region. In other words, Logothetis is not fascinated by the current "blobology" (AKA neo-phrenology) that is seen in much of today's neuroimaging research papers. Logothetis argues that in order to say anything intelligible about brain function, we need to go beyond the current focus on where in the brain something is happening. We need to move towards integrating multiple imaging modalities in order to get a better picture of neural processes. Logothetis himself suggested and talked mostly about EEG and deep electrodes, and MEG, in combination with BOLD fMRI. But at the master class Logothetis also discussed the use of multiple MRI modalities such as the combination of perfusion MRI (Arterial Spin Labeing) and BOLD fMRI. But BOLD alone? No way!

To the right you can see the key slide from my talk at the Master class, positing the problem of combining measurements of perfusion and atrophy to BOLD fMRI measures, as co-variates. In ageing studies, we can see BOLD fMRI changes, but there is a question whether the well-known changes in brain perfusion and atrophy plays a role in chaning the BOLD signal. That was my question to Logothetis. Click on the image to see the full details.

Oh, and did I mention that Logothetis gives little for the current neo-phrenological thoughts about a 1:1 match between a cognitive function and a brain area? The brain doesn't work that way…

-Thomas

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Genetics and the evolution of language

Let me point you to a nice article, by Simon Fisher and Gary Marcus, in the January issue of Nature Reviews Genetics. Fisher was one of the co-discovers of the link between a verbal dyspraxia disorder in an English family and a point mutation on the FOXP2 gene. Marcus, a former student of Steven Pinker, is well-known for his critique of connectionist models of language-aquisition. Although I personally think it overstates the case for innate modules, I wholeheartedly recommend Marcus' book The Birth of the Mind which is, as far as I know, the first, and still only, popular account of what is known today about the genetic basis of brain development. Together, they have earlier written a review of the FOXP2 story in Trends in Cognitive Science. The present paper aims to show how genetical studies can aid our understading of the evolution of language.

In recent years interest in this topic has been booming. A large number of possible adaptative causes have been proposed by a range of researchers. [Language Evolution, edited by Morten Christiansen and Simon Kirby, will give you a short overview of most of these hypotheses.] There is a problem with this approach, though, in that it tends to focus on just one magical change in hominid behaviour, with the accompaying change to the brain being passed on to following generations. To take one prominent example, Robin Dunbar, for instance, sees the decisive moment in the evolution of language to be the expansion of hominid social groups, some time around the appearance of homo erectus, making it advantageous to be able to keep account of the larger number of conspecifics through communication. Dunbar speculates that a change in our ability to mentalize – sometimes also referred to as Theory of Mind – could be the new cognitive function to have facilitated this improved capacity for social communication. Another, more simpleminded hypothesis, is the still widespread idea that neuronal changes to Broca's area brought about a novel ability to string together words into syntactical phrases.

But, as more and more becomes known about the brain processes underlying language, it appears increasingly unrealistic that any such single-stroke wave of the magic wand will suffice to explain the emergence of language. The neural language system is enormously complex and encompasses, to just name a few things, auditory analysis, conceptual knowledge and memory, semantic selection processes, motor control, and a great number of other functions. It stands to reason that all these processes must have evolved on an individual basis. It is therefore much more probable that the evolution of language has gone through several different adaptive events since the last common forefather of homo and pan.

This is exactly the approach taken by Fisher and Marcus. They call it "descent with modification", and write that "[in this paper] we argue that language should be viewed not as a wholesale innovation, but as a complex reconfiguration of ancestral system that have been adapted in evolutionarily novel ways". The offshot of this approach is that the evolution of language can be studied by comparing human genetics and neurobiology to other species. Write Fisher and Marcus:

(…) although non-human primate communication shows qualitative differences from human language, studies have established that most components of language how some degree of continuity with other species. For example, the human vocal tract supports a wider epertoire of speech sounds than could be produced by other primates, but the capacity to create richly modulated formants is not unique to humans. Likewise, many animals and birds can distinguish different human speech sounds, and adult tamarin monkeys can discriminate between the distinctive rhythmic properties of different languages. Debate continues about exactly how much of the machinery of language is species – or language – specific; for example, opinion is divided over whether recursion represents the only component that is genuinely new to the human species. Nevertheless, views that consider language to be fully independent of ancestral systems are no longer tenable, and there is a growing recognition that cognitive, physiological, neuroanatomical and genetic data from non-speaking species can greatly inform our understanding of the nature and evolution of language.

The bulk of Fisher and Marcus' paper is dedicated to a review of methods for such genetical comparisons of humans to other species. But its true importance lies in the way it dismantles the adaptionist programme in evolutionary psychology. Like language, social cognition, reasoning, and other forms of cognition, are in most cases complex amalgams of a range of neurobiological processes, and therefore very unlikely the product of "wholesale innovation". A more precise picture of the evolution of human cognition is to be found through an detailed understanding of how the human brain differs from other species, and through a comparison of the genes and gene-expression systems characterising these species.
Reference

Fiser, S. & Marcus, G. (2006): The eloquent ape: genes, brains and the evolution of language. Nature Reviews Genetics 7: 9-20. [The paper can be downloaded from Marcus's homepage.]

-Martin

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Proof of a visual word form area?

The visual word form area (VWFA) is one of the most contested concepts of modern neuroscience. Its proponents claim that a dedicated slice of cortex in the occipitotemporal region of the brain – probably centered on the fusiform gyrus – underlie the ability to read. The most radical version of this hypothesis states that the VWFA is a specialized module – an idea that implicates some sort of genetical determinism. Since writing only has been around for some 6000 years many researchers doubt that there have been enough time for such a module to evolve. Instead, they expect reading to piggybackride on other, perhaps more general, visual processes.

The April 20 issue of Neuron contains a case study of man surgically treated for epilepsy that bears on these questions. As a consequence of excision of cortical tissue posterior to the putative VWFA this patient developed a case of pure alexia where, whereas before surgery he took ~600 ms to read a word, regardless of word lenght, after surgery his reading slowed to ~1000 ms for three-letter words and increased by ~100 ms per additional letter.

Crucially, postsurgical fMRI tests showed that the VWFA no longer responded more to words than to other objects, even when words were contrasted with viewing a simple fixation point. The authors suggest that this lack of activation is explained by the fact that postsurgically the VWFA is no longer receiving its normal input. Instead, a more widespread activation pattern, including frontal, parietal, and temporal sites, appear to "take over", resulting in a letter-by-letter reading strategy.

While the study clearly demonstrates that the VWFA plays some kind of (important) role in reading, it doesn't really illuminate what type of function the VWFA performs. And, at the same time, it cannot be said to settle the question of modularity, since the patient was a 46-old man who, of course, has had amble time to develop a reading skill from learning. As Alex Martin notes in a great accompanying resumé, the study do, however, leaves unresolved "the vexing problem of how to account for the intersubject consistency in the general location of the VWFA and other category-related regions in ventral occipitotemporal cortex. One possibility is that the VWFA performs a visual processing function that predisposed it to being co-opted for reading." But there may also be other reasons. In any case, it is a very nice study that will prove important for further debates on both reading and modularity.

Reference

Gaillard, R. et al. (2006): Direct intracranial, fMRI, and lesion evidence for the causal role of left inferotemporal cortex in reding. Neuron 50: 191-204.

Martin, A. (2006): Shades of Déjerine – forging a causal link between the visual word form area and reading. Neuron 50: 173-175.

-Martin

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Special issue on synaesthesia

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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Unravelling the evolution of language?

There is now an online-only published paper in PNAS from the Max Planck Institute on the evolution of language. What is surprising is that the researchers have used functional MRI to infer the evolutionary lineage from their results. Basically, what Angela Friederici and her colleagues have done is to compare language processing that is “simple” to processing that is “complex”. While simple processing activated left frontal operculum, a phylogenetically older region of the brain, more complex language processing also activated Broca’s area, which is thought to be a more recent development specific to humans. in addition, the researchers also studied the white matter connectivity of the two brain regions by using MR tractography. Here, they found that the two regions showed different structural connectivity signatures, further supporting the functional segregation of these two areas.

This makes the researchers conclude:
“Here we report findings pointing toward an evolutionary trajectory with respect to the computation of sequences, from processing simple probabilities to computing hierarchical structures, with the latter recruiting Broca’s area, a cortical region that is phylogenetically younger than the frontal operculum, the brain region dealing with the processing of transitional probabilities”I first found this through the Max Planck Society press release page. Just reflecting briefly on this, I think that despite the study is interesting itself in terms of functional segregation of language processes, I am not convinced about the argument about the phylogeny of the two regions. As we know from research on subcortical structures such as the “limbic system“, we cannot divide between the phylogenetic “old” and limbic brain and the “newer” cortical brain. It is today considered total gibberis, because evolution of “higher” areas in the cortical surface has had a dynamic and synergetic co-evolution of cortical and subcortical areas. In similar vein, I suspect that the evolutionary trajectories of the frontal operculum and Broca’s area share a lot, and that a clear-cut division between the two areas will prove hard to make.

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Fusiform — not alone

One of the important basic discussions in congitive neuroscience is that of the fusiform face area (FFA). The FFA has been suggested as a part of the fusiform gyrus that is solely dedicated to face perception. The rationale is that faces have been evolutionary special and selected for, and that the FFA is an evolved module specifically dealing with faces.

As the story goes, researchers such as Isabel Gauthier and her colleagues have demonstrated that the FFA is also active when study participants are asked to discriminate between different types of birds and cars and even when participants become expert at distinguishing computer generated nonsense shapes known as greebles. These activations were not as profound as those seen when subjects perceived faces, but they still demonstrate a less clear-cut role of the FFA. At the Human Brain Mapping 2005 in Toronto , Canada, we saw Gauthier and Nancy Kanwisher battle it out, and it is clear that this is by no means a settled issue. The selectivity and encapsulation of neuro-cognitive modules is one of the hot topics in modern cognitive neuroscience, though even in its infancy it was a much debated issue. Just take John Hughlings Jackson’s (1882/1932) famous and excellent quote:

“I am neither a universalizer nor a localizer…In consequence I have been attacked as a universalizer and also as a localizer. But I do not remember that the view I really hold as to localization has ever been referred to. If it is, it will very likely be supposed to be a fusion of, or a compromise of recent doctrines”

In a recent study reported in Neuropsychologia by Steeves et al., the FFA does not seem to be sufficient to produce face recognition. Well, that does not come as such a surprise maybe, since we do know that face perception is the result of processes starting in the retina. But the whole idea is that the FFA is something special for face processing. But Steeves et al.s study show that the FFA is part of a larger network, and that face processing consists of many different steps and subprocesses. Their patient study of D.F., combined with fMRI studies demonstrate that

1. For gross detection of face-nonface decitions, the FFA does not seem necessary although it can be activated. For this, the occipital face area (OFA) seems to do the work.
2. For face identification — i.e. recognising a familiar face — the FFA is involved, but still involves a network of different modules (including the OFA)

In short, Oma und Opa get your OFA going, too. Here is the article’s abstract, but you can get the article here (PDF):

The fusiform face area is not sufficient for face recognition: Evidence from a patient with dense prosopagnosia and no occipital face area

Steeves et al.

We tested functional activation for faces in patient D.F., who following acquired brain damage has a profound deficit in object recognition based on form (visual form agnosia) and also prosopagnosia that is undocumented to date. Functional imaging demonstrated that like our control observers, D.F. shows significantly more activation when passively viewing face compared to scene images in an area that is consistent with the fusiform face area (FFA) (p

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