The varied causes of depression

There is a new review article in CMAJ about the neurobiology of depression. And then there is the multi-part series on depression over at Neurotopia by the excellent Sci.

So I thought I'll link these for the benefit of my readers. While it may sound an oxymoron to do a review of a review, let me briefly summarize the review article.

The article lists three important contributing factors for depression. The first is genetics; the second childhood stress and the third ongoing or recent psychosocial stress. And of course different neurobiological mechanisms underlie all three factors.

To take by way of example, we have the famed monoamine theory of depression whereby low baseline serotonin (and norepenipherine) levels in the brain are held responsible for depressive symptoms. This hypothesis derives most evidence from the effects of anti-depressants on the brain. Now depression also has a genetic heritable component (this is apparent from twin studies); some of the heritability of depression can be explained by polymorphisms of various genes affecting the serotonin system, primary among them being the gene affecting Serotonin Transporter or SERT. thus, the underlying serotonin system can be treated as one biological system that has a strong genetic component.

To take by way of second example, consider the hypothalamic-pituitary-adrenal axis that is involved in response to stress. This system is abnormally developed if the child is exposed to stress in a critical developmental window. Experiments with rats and monkeys confirm that abnormal and stressful environment during early childhood, leads to abnormal functioning of this axis, that later pre-disposes to depression. thus, this HPA axis may be taken as a proxy for the component that is due to development and epigenetics.

To take by way of third example, consider the Brain Derived Neurotropic factor in the brain. This BDNF is responsible for survival of new neurons and for new synapse formation (synaptic plasticity) during adulthood; new neurons and new synapses help us to learn (by neurogenisis in the hippocampus), especially when the environment is stressful; now there are two polymorphisms of the gene coding for BDNF; the 'MET' allele cause reduced hippocampal volume at birth, hypoactivity in resting state in hippocampus, increased metabolism in hippocampus while learning and relatively poor hiipocampal dependent memory-function. From all this it is apparent that MET allele somehow leads to less synthesis of BDNF and thus low learning in hippocampus as a result of reduced neurogenesis / synaptogenesis. Now, the same MET allele also raises the risk of depressionand the mediating factor is the stress responsivity of the individual. Thus, the BDNF may mediate the sensitivity of a person to the same external psychosocial stress and might be very crucial via the gene-environment interaction effects. Also prolonged stress, which may result in prolonged BDNF secretions and thus lead to toxicity and opposite paradoxical effects may be another putative mechanism linkibng stress exposure in adulthood to underlying pathophysiology of reduced neurogenesis.

The above may seem too simplistic but it points us in the right direction- some neurobiological systems like the serotonin system may be largely genetic in nature and our treatment approaches based around this fact. Others like the HPA axis malfunctioning may be entirely environmental in their origin, and maybe preventive interventions like ensuring stress free childhood for all, should be the policy focus here. Depending on the plasticity of later HPA axis, therapy or medications may be the treatment options. Finally, other neurobiological systems involved, like the BDNF and stress sensitivity/over-exposure, may display complex gene-environment interactions and again knowing the nature of these systems will help us counter the symptoms using a combination of CBT/ medication.

Depression is definitely a much complex disorder to be completely understood on the basis of a single review article, or even a series of blog posts, , but the underlying neurobiological mechanisms and systems clearly indicate how genetics, environment (especially during critical developmental window) and and epigenetics (gene-environment interactions) are involved in its etiology and how different interventions and treatments taking these into account have to be developed.


aan het Rot, M., Mathew, S., & Charney, D. (2009). Neurobiological mechanisms in major depressive disorder Canadian Medical Association Journal, 180 (3), 305-313 DOI: 10.1503/cmaj.080697

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Self relevance and the reality-fictional blur

There is a new study in PLOS One that argues that we make reality-fictional distinction on the basis of how personally relevant the event in question is. To be fair, the study focuses on fictional, famous or familiar (friends and family) entities like Cinderella, Obama or our mother and based on the fact that these are arranged in increasing order of personal relevance, as well as represent fictional and real characters, tries to show that one of the means by which we try to distinguish fictional from real characters is by the degree of personal relevance these characters are able to invoke in us.

The authors build upon their previous work that showed that amPFC(anterior medial prefrontal cortex) and PCC (Posterior Cingulate cortex), which are part of the default brain network, are differentially recruited when people are exposed to contexts involving real as opposed to fictional entities. From this neural correlate of the regions involved in distinguishing fiction from reality, and from the known functions of these brain regions in self-referential thinking and autobiographical memory retrieval, the authors hypothesized that the reality-fictional distinction may be mediated by the relevance to self and this difference in self-relevance leads to differential engagement of these brain areas. I quote form the paper:

In the first attempt to tackle this issue using functional magnetic resonance imaging (fMRI), we aimed to uncover which brain regions were preferentially engaged when processing either real or fictional scenarios . The findings demonstrated that processing contexts containing real people (e.g., George Bush) compared to contexts containing fictional characters (e.g., Cinderella) led to activations in the anterior medial prefrontal cortex (amPFC) and the posterior cingulate cortex (PCC).

These findings were intriguing for two reasons. First, the identified brain areas have been previously implicated in self-referential thinking and autobiographical memory retrieval. This suggested that information about real people, in contrast to fictional characters, may be coded in a manner that leads to the triggering of automatic self-referential and autobiographical processing. This led to the hypothesis that information about real people may be coded in more personally relevant terms than that of fictional characters. We do, after all, occupy a common social world and have a wider range of associations in relation to famous people. These may be spontaneously triggered and processed further when reading about them. A logical extension of this premise would be that explicitly self-relevant information should therefore elicit such processing to an even greater extent.

To study the above hypothesis they used an experimental study that used behavioral measures like reaction time, correctness and perceived difficulty of judging propositions involving fictional, famous and close entities. Meanwhile they also measured , using fMRI, the differential recruitment of brain areas as the subjects performed under the different entity conditions. The experimental design is best summarized by having a look at the below figure.

What they found was that for the control condition and the fictional condition the reaction time , correctness and perceived difficulty associated with the proposition was signifciantkly different (lower RT, lower correctness and more perceived difficulty) than for the famous and friend entities condition. Thus, from the behavioral data is was apparent that real characters were judged faster , accurately and more easily than fictional characters. The FMRI data showed that , as hypothesiszed, amPFC and PCC were recruited significantly more in personal relevance contexts and showed a gradient in the expected direction. The below figure should summariz the findings:

In particular, in line with our predictions, regions in and near the amPFC (including the ventral mPFC) and PCC (including the retrosplenial cortex) were modulated by the degree of personal relevance associated with the presented entities. These regions were most strongly engaged when processing high personal relevance contexts (friend-real), secondarily for medium relevance contexts (famous-real) and least of all in the low personal relevance contexts (fiction) (high relevance>medium relevance>low relevance).

The amPFC and PCC regions are known to be commonly engaged during autobiographical and episodic memory retrieval as well as during self-referential processing. Regarding their specific roles, there is evidence indicating that amPFC is comparatively more selective for self-referential processing whereas the PCC/RSC is more selective for episodic memory retrieval . The results of the present study contribute to the understanding of processes implemented in these regions by showing that the demands on autobiographical retrieval processes and self-referential mentation are affected by the degree of personal relevance associated with a processed scenario. It should additionally be noted that the extension of the activations in anterior and ventral PFC regions into subgenual cingulate areas indicates that the degree of personal relevance also modulated responsiveness in affective or emotional regions of the brain .

Here is what the authors have to say about the wider ramifications:

That core regions of the brain's default network are spontaneously modulated by the degree of stimulus-associated personal relevance is a consequential finding for two reasons. Firstly, the findings suggest that one of the factors that guide our implicit knowledge of what is real and unreal is the degree of coded personal relevance associated with a particular entity/character representation.

....

What this might translate to at a phenomenological level is that a real person feels more “real” to us than a fictional character because we automatically have access to far more comprehensive and multi-flavored conceptual knowledge in relation to the real people than fictional characters. This would also explain why a real person we know personally (a friend) feels more real to us than a real person who we do not know personally (George Bush).

I would say that there are other broader implications. First it is important to note that phenomenologically, Schizophrenia/psychosis is charachterized by an inability to distinguish reality from fiction. What is fictious also starts seeming real. A putative mechanism of why even fictional things start assuming 'real' dimensions may be the attribution of personal relevance or significance to those fictional entities. If something, even though fictional in nature, become highly personally relevant, then it would be easier to treat it as real. What ties things together is the fact that the default brain network is indeed overactive in the schizophrenics. If the PCC and amPFC are hyperactive, no wonder even fictional entities would be attributed personal relevance and incorporated into reality. I had earlier too discussed the delusions of reference with respect to default network hyperactivity in shizophrenics and this can be easily extended to now account for the loss of contact with reality , with the relevance and reality linkage in place. when everything is self relevant everything is real.

As always I am excited and would like some experiments done with schizophrnics/scizotypals using the same experimental paradigm and finding whether there is significant differences in the behavioral measures between controls and subjects and whether that is mediated by differential engagement of the default brain network. In autistics of course I hypothesize the opposite effects.

Needless to say I am grateful to Neuronarrative for reporting on this and helping me make one more puzzle piece fit in place.



Abraham, A., & von Cramon, D. (2009). Reality = Relevance? Insights from Spontaneous Modulations of the Brain's Default Network when Telling Apart Reality from Fiction PLoS ONE, 4 (3) DOI: 10.1371/journal.pone.0004741

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SES and the developing brain

I have written about poverty/SES and its effects on brain development/IQ earlier too,and this new review article by Farah and Hackman in TICS is a very good introduction to anyone interested in the issue.

The article reviews the behavioral studies that show that SES is correlated with at least the two brain systems of executive function and language abilities.It also review physiological data that shows that even when behavioral outcomes do not differ ERP can show differential activation in the brains of people with low and middle SES , thus suggesting that differences that may not be detected on behavioral measures may still exist. They also review (f)MRI data that shows no structural differences in the brains of low and middle SES children, but definite functional differences.they also review experimental manipulation of social status in labarotaories, and show how those studies also indicate that SES and executive function are correlated.

They then turn to the million dollar question of the direction of causality and for this infer indirectly based on the SES-IQ causal linkages.

What is the cause of SES differences in brain function? Is it contextual priming? Is it social causation, reflecting the influence of SES on brain development? Alternatively, is it social selection, in which abilities inherited from parents lead to lower SES? Current research on SES and brain development is not designed to answer this question. However, research on SES and IQ is relevant and supports a substantial role of SES and its correlated experience as causal factors.

Slightly less than half of the SES-related IQ variability in adopted children is attributable to the SES of the adoptive family rather than the biological. This might underestimate environmental influences because the effects of prenatal and early postnatal environment are included in the estimates of genetic influence. Additional evidence comes from studies of when poverty was experienced in a child's life. Early poverty is a better predictor of later cognitive achievement than poverty in middle- or late-childhood, an effect that is difficult to explain by genetics. SES modifies the heritability of IQ, such that in the highest SES families, genes account for most of the variance in IQ because environmental influences are in effect at ceiling in this group, whereas in the lowest SES families, variance in IQ is overwhelmingly dominated by environmental influences because these are in effect the limiting factor in this group. In addition, a growing body of research indicates that cognitive performance is modified by epigenetic mechanisms, indicating that experience has a strong influence on gene expression and resultant phenotypic cognitive traits . Lastly, considerable evidence of brain plasticity in response to experience throughout development indicates that SES influences on brain development are plausible.

Differences in the quality and quantity of schooling is one plausible mechanism that has been proposed. However, many of the SES differences summarized in this article are present in young children with little or no experience of school , so differences in formal education cannot, on their own, account for all of the variance in cognition and brain development attributable to SES. The situation is analogous to that of SES disparities in health, which are only partly explained by differential access to medical services and for which other psychosocial mechanisms are important causal factors .

The last point is really important and can be extended. Access to health services for low SES people may be a reason why , for eg, more schizophrenia incidence is found in low SES neighbourhoods. which brings us to the same chicken-and-egg question of the drift theory of schizophrenia- whether people with schizophrenia drift into low SES or low SES is a risk factor in itself. Exactly this point was brought to my attention when I was interacting with a few budding psychiatrists recently, this Martha Farah theory about the SES leading to lower IQ/ cognitive abilities. It is important to acknowledge that low SES not only leads to left hypo-frontality (another symptom of schizophrenia), schizophrenia is supposed to be due to lessened mylienation and again nutritional factors may have a role to play; also access to health care, exposure to chronic stress and lesser subjective feelings of control may all be mediating afctors that lead low SS to lead to schizophrenia/ psychosis.Also remember that schizophrenia is sort of a devlopmenetal disorder.

Well, I digressed a bit, but the idea is that not only does low SES affect 'normal' cognitive abilities, it may even increase the risk for 'abnormal' cognitive abilities that may lead to psychosis, and his effect of SES on IQ/cognitive abilities/ risk of mental diseases is mediated by the effect of SES on the developing brain. I have already covered the putative mechanisms by which SES may affect brain development, but just to recap, here I quote from the paper:

Candidate causal pathways from environmental differences to differences in brain development include lead exposure, cognitive stimulation, nutrition, parenting styles and transient or chronic hierarchy effects. One particularly promising area for investigation is the effect of chronic stress. Lower-SES is associated with higher levels of stress in addition to changes in the function of physiological stress response systems in children and adults. Changes in such systems are likely candidates to mediate SES effects as they impact both cognitive performance and brain regions, such as the prefrontal cortex and hippocampus, in which there are SES differences.

We can only hope that the evil of low SES is recognized as soon as possible and if for nothing else, than for advancing science, some intervention studies are done that manipulate the SES variables in the right direction and thus ensure that the full cognitive potential of the children flowers.



HACKMAN, D., & FARAH, M. (2009). Socioeconomic status and the developing brain Trends in Cognitive Sciences, 13 (2), 65-73 DOI: 10.1016/j.tics.2008.11.003

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Encephalon #66 is now out!

Encepahlon #66 is now out at the Ionian enchantment and is an official no-frills no-fuss edition; It contains a motley collection of articles and some of the ones that caught my fancy were a Effortless Incitement commentary on a Daniel Neetle paper related to how likely it is that you know about your sibling's death, based on whether you are fully related or step-siblings or maternally/paternally related half-siblings. Another good article is on the spatial memory encoding by Neurophilosophy.

An unusual article worth checking out is Podblack cat's article exploring whether poetry is inspirational in nature and dependent on one-shot creative process (maybe having a long previous gestation period, but resulting in a dramatic giving-to-birth moment)or can be perfected with practice and hard work. Although I am a pretty hardliner adherent to practice as being superior to inborn talent/giftedness theory, I would still maintain that poetry is more of a un/subconscious skill and is not easily broken into explicit steps that can be first verbalized, practiced and then later gained expertise in- it is more like learning to ride a bicycle- you have to learn it and become good with practice, but you cannot really teach much there. I respect Stephen Fry a lot, and would definitely read the Ode Less Traveled, but I'm not sure I completely buy the theory that you can really teach poetry! I write poetry myself and so am entitled to my own opionion on that front!

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Why is Science Important: the Film

As many of you might know, I had contributed to the web based project 'Why is science important' run by Alom Shaha. You can read my contributions here.The web site was a vehicle to the final target of filming the myriad reasons why people involved with science find it interesting/ important. The film has now been completed and is available in its entirety at the why is science important website. It has been beautifully made and deserves wide circulation.

I am also trying to embed the video here, but beware that you need to turn HD off if you are on a slow connection, else the download rate would be pathetic.


Why is Science Important? from Alom Shaha on Vimeo.

I would also like to add a small note that while I wholeheartedly agree with Alom that creativity and curiosity are what make Science interesting and important, I would still like to stress the 'truth' factor on which I dwelt in my original posting. In my view, a delusional person also very creatively constructs an elaborate delusional framework to make sense of his experiences, and he is indeed very curious to find out and explain things, but lacking any insight/ grounding in reality can't be deemed to be scientific. Science has to be seen from the prism of the most approximate construal of reality that we have, to distinguish it from other similarly creative and curiosity guided phenomenon like the pseudosciences of astrology, religion (which satisfy existential curiosity and are very creative at times in their tenets, beliefs etc) etc. To me, science still stands for the only method that can bring me closer to the 'truth' and thus help me deal most pragmatically with the external reality.

But do read the different views that are presenetd excellently and deftly by Alom. Kudos to him for taking such an initiative. If it were to me, I would mandate that this film be shown to all school children and teachers who are interested in Science to give them a broader perspective. Please do link from your blogs or circulate otherwise.

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The factor structure of Religiosity and its neural substrates

A new article in PNAS by Grafman et al, argues that Religiosity can be broken down into three factors and the underlying machinery that these factors use are basic Theory Of Mind (ToM) circuitry, thus substantiating the claim that religion occurred as a byproduct of basic ToM related adaptations, although not ruling out that once established Religion may have provided adaptive advantage.

First a detour. I am more interested in this study as I had once claimed that Schizophrenics were more religious than Autistics and I have been maintaining that Religion is just one aspect of an underlying hyper-mentalizing to hyper-physicalism continuum on which these two spectrum disorders lie on opposite ends. The case for less ToM abilities in ASD seems to be fairly settled; its also becoming apparent that in Schizophrenia spectrum disorders you have excess of ToM abilities; This study by showing the ToM to Religion linkage, fills in the gaps and another puzzle piece falls in place.

On to the study. The authors first show that Religious Belief can be split into three factors. they use a novel (to me) technique of Multi Dimensional Scaling (MDS) to tease out the factors associated with religious belief. I have not checked how MDS works, but I assume it is similar to Factor analysis and can give us reliable factor structure underlying the data. They build on previous research and discovered the following three factors:

1. God’s perceived level of involvement,
2. God’s perceived emotion, and
3. religious knowledge source. 

The first factor refers to endowing intentionality to superantural agents like God; the second factor refers to endowing emotions to God an dthe thierd factor refers to the source of the religious beliefs- whether it is doctrinal or derived from experience. Thus the trinity of intention, emotion and belief - alos the trinity involved in ToM tasks. The authors do a good job of describing the factors, so I'll let them do it.

Dimension 1 (D1) correlated negatively with God’s perceived level of involvement (–0.994), Dimension 2 (D2) correlated negatively with God’s perceived anger (–0.953) and positively with God’s perceived love (0.953), and Dimension 3 (D3) correlated positively with doctrinal (0.993) and negatively with experiential (–0.993) religious content. D1 represents a quantitative gradient of a single concept and we will be referring to it as ‘‘God’s perceived level of involvement.’’ D2 and D3 represent gradients of contrasting concepts; we will be referring to them as ‘‘God’s perceived emotion’’ (D2) and ‘‘religious knowledge source’’ (D3).

God’s perceived level of involvement (D1) organizes statements so that ‘‘God is removed from the world’’ or ‘‘Life has no higher purpose’’ have high positive coordinate values, while ‘‘God’s will guides my acts,’’ ‘‘God protects one’s life,’’ or ‘‘God is punishing’’ have high negative values. Generally speaking, on the positive end of the gradient lie statements implying the existence of uninvolved supernatural agents, and on the negative end lie statements implying involved supernatural agents.

God’s perceived emotion (D2) ranges from love to anger and organizes statements so that ‘‘God is forgiving’’ and ‘‘God protects all people’’ have high positive-coordinate values, while ‘‘God is wrathful’’ and ‘‘The afterlife will be punishing’’ have high negative values. Generally speaking, on the positive end of the gradient lie statements implying the existence of a loving (and potentially rewarding) supernatural agent, and on the negative end lie statements suggestive of wrathful (and potentially punishing) supernatural agent.

Religious knowledge (D3) ranges from doctrinal to experiential and organizes statements so that ‘‘God is ever-present’’ and ‘‘A source of creation exists’’ have high positive-coordinate values, while ‘‘Religion is directly involved in worldly affairs’’ and ‘‘Religion provides moral guiding’’ have high negative values. Generally speaking, on the positive end of the gradient lies theological content referring to abstract religious concepts, and on the negative end lies theological content with moral, social, or practical implications.

This breakup of religiosity into three factors is itself commendable, but then they go on to show, using fMRI data that these factors activate areas of brain associated with ToM abilities. I don't really understand all their fMRI data, but the results seem interesting. Here is what they conclude:

The MDS results confirmed the validity of the proposed psychological structure of religious belief. The 2 psychological processes previously implicated in religious belief, assessment of God’s level of involvement and God’s level of anger (11), as well as the hypothesized doctrinal to experiential continuum for religious nowledge, were identifiable dimensions in our MDS analysis. In addition, the neural correlates of these psychological dimensions were revealed to be well-known brain networks, mediating evolutionary adaptive cognitive functions.

This study defines a psychological and neuroanatomical framework for the (predominately explicit) processing of religious belief. Within this framework, religious belief engages well-known brain networks performing abstract semantic processing, imagery, and intent-related and emotional ToM, processes known to occur at both implicit and explicit levels (36, 39, 50). Moreover, the process of adopting religious beliefs depends on cognitive-emotional interactions within the anterior insulae, particularly among religious subjects. The findings support the view that religiosity is integrated in cognitive processes and brain networks used in social cognition, rather than being sui generis (2–4). The evolution of these networks was likely driven by their primary roles in social cognition, language, and logical reasoning (1, 3, 4, 51). Religious cognition likely emerged as a unique combination of these several evolutionarily important cognitive processes (52). Measurable individual differences in these core competencies (ToM, imagination, and so forth) may predict specific patterns of brain activation in response to religious stimuli.

As always I am excited and would like to see some field work being carried out to determine religiosity in ASD and Schizophrenia spectrum groups and see if we get the same results (less religiosity in autism and more religiosity in schizophrenics) as predicted, based on their baseline ToM abilities.

PS: I was not able to use the DOI lookup fetaure of Research Blogging, but the DOI of article is  10.1073/pnas.0811717106



* Dimitrios Kapogiannis,, * Aron K. Barbey,, * Michael Su,, * Giovanna Zamboni,, * Frank Krueger,, * and Jordan Grafman (2009). Cognitive and neural foundations of religious belief PNAS

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Evidence for heightened Agency in Schizophrenia

I have been maintaining that Autism and Schizophrenia are opposites on a continuum and one dimension on which they differ is Agency , with autistics attributing too less agency to themselves (and others), while schizophrenics attributing too much agency to themselves (and others).

The case for people with ASD is fairly settled. They have deficits in theory Of Mind (ToM) and one mechanism by which this deficit seems to arise is via their attributing less agency to themselves as well as others.

For Schizophrenics too, it was speculated that they have problems with agency , but a clear illustration that they have an enhanced agency attribution device was not firmly established. This study, which dates back to 2003, in my opinion, establishes the fact that their is hyper-agency attribution (or hyper-self-menatlizing) in schizophrenics.

The study in question is one by Haggard et al , and it uses an experimental paradigm to illustrate that schizophrenics indeed have problems with self- agency attribution, and that too in the hypothesized direction.

Here is the abstract:

An abnormal sense of agency is among the most characteristic yet perplexing positive symptoms of schizophrenia. Schizophrenics may either attribute the consequences of their own actions to the intentions of others (delusions of influence), or may perceive themselves as causing events which they do not in fact control (megalomania).Previous reports have often described inaccurate agency judgments in schizophrenia, but have not identified the disordered neural mechanisms or psychological processes underlying these judgments.We report the perceived time of a voluntary action and its consequence in eight schizophrenic patients and matched controls.The patients showed an unusually strong binding effect between actions and consequences. Specifically, the temporal interval between action and consequence appeared shorter for patients than for controls. Patients may overassociate their actions with subsequent events, experiencing their actions as having unusual causal efficacy.Disorders of agency may reflect an underlying abnormality in the experience of voluntary action.

Now, let us pause and recollect that Chris Frith had postulated that the voluntary action mechanism in Scizophrenics is somewhat malformed and specifically there is a disconnect between intention attribution and voluntary action manifestation. He however had not clearly stated that there would be over-attribution of intention to voluntary actions. We all know that dopamine is associated with voluntary action (voluntary movements) and that baseline dopamine is in excess in schizophrenics. This paper ties things in together showing that excess dopamine secretion in basal ganglia and cortical areas may lead to greater biding between intentions and subsequent actions (consequences) and by this mechanism may lead to over-attribution of agency. Of course the paper doe snot establish this mechanism but just speculates on it as one of the possible mechanisms. It is also important to pause and note that schizophrenics have a jumping-to-conclusions bias and thus if an intention and action were more tightly bound (occurred in time in close proximity)_, then they are more likely to judge the two events to be related and the intention to cause the action.

Now let me get to the actual experiment. Haggard et al asked schizophrenics as well as matched controls to note subjective time (using Libets approach) when they decided to voluntarily press a computer key, and also subjective time when they first heard an auditory tone . The tone was presented 250 ms after their voluntary key press. As has been established earlier, and using controls in this experiment, people advance the key press in future (shift it towards future time from the exact time they actually pressed the key) so that subjectively the key press happens after some time form the objective key press and in the direction of the tone presentation. Thus, the effective subjective time between the key press and the tone is reduced. This binding between a voluntary action and its consequence , happens in normal individuals too, but in schizophrenics this happened significantly more in magnitude ans was dependent on two factors. first, like in normals , the voluntary key press was advanced in time towards the tone presentation, but this advance was significantly greater than in the case of controls. Secondly, the subjective auditory tone was sort of anticipated and shifted back in time towards the voluntary key press in schizophrenics. Thus, in schizophrenics, it seemed to them that the auditory tone had occurred prior to when it was actually presented. This lead to overall very significant reduction in subjective time experienced between the voluntary key press and the tone hearing, thus binding the two events strongly and leading to stronger agency inferred. to quantize the things a bit, in normal controls the voluntary key press was on the average occurring 26 ms from the actual key press, the auditory tone was heard 5 ms from the actual presentation and thus the subjective difference between the key press (intention) and tone (consequence) was 250-(26+5)= 239 ms. In schizophrenics, the key press was deemed to occur 60 ms after the actual key press, however most importantly the tone was not heard subjectively after its presentation, but was heard anticipatory 139 ms before its actual presentation, thus the actual perceived subjective time between the key press (intention) and the tone (consequence) was 250-60-139 = 51 ms only. Now , one can easily see, that if perceived subjective time between tow events is shortened in schizophrenia, then wont they end up falsely clubbing many coincidental things too together, because they seem to follow each other in close temporal proximity.

To appreciate the results, one needs to put these results in the broader context of what we know about agency in schizophrenics:

Previous laboratory studies have investigated agency using action attribution tasks. In these tasks, the patient is asked to perform an action, and is shown a visual image corresponding to that action, for example, a line drawn with a pen , a video of a hand making a manual posture , or a computerised image of a joystick moving. By introducing a mismatch between the performed action and the visual feedback, experimenters investigate the accuracy of attribution judgments. The subject has to attribute the viewed image either to an action he has just been instructed to make or to some other source. Interestingly, all these studies have found schizophrenics abnormally willing to attribute to themselves actions which in fact differ from the ones they performed. Thus, they are less sensitive than control subjects to spatial, temporal or kinematic mismatches between actions and visual feedback. The direction of these results points towards an excessive, rather than a reduced, sense of agency. Such results have been interpreted in the context of an internal forward model. Schizophrenic patients’ errors involve mostly over-attribution, implying a forward model with an unusually tolerant comparator.

Impaired judgement of agency can also be linked to the brain abnormalities underlying the disease. Agency involves forming a conscious mental association between one’s own intentional actions, and their consequences in the outside world. Thus, agency may be a conscious aspect of a more general system for instrumental or operant learning about environmental contingencies and rewards. Animal learning studies show that dopaminergic circuits, including the basal ganglia and medial forebrain are essential for associating actions with their effects, and for motivating behaviours. Brain imaging studies in man show that these same areas are active when a voluntary action produces a reward or other salient consequence . Moreover, these dopaminergic circuits are overactive in schizophrenia . Excessive dopaminergic activity might therefore explain abnormalities of conscious agency in schizophrenia, such as over-association between intentions and external events.

This is how they interpret their results:

More importantly, our schizophrenic patients seem to show an exaggerated version of the normal binding effect, or hyperbinding. These results could account for the findings of some action attribution experiments. Franck et al. asked patients and controls to move a joystick and then to observe their movements on a computer screen after a delay. The experimenters systematically varied the delay to investigate at what point the two groups ceased to accept the observed action as their own. Control subjects detected the temporal discrepancy between their action and the image with delays of around 100–150 ms. Schizophrenic subjects were much more tolerant, and accepted the viewed action as their own even for delays of 300 ms. Overall, the detection threshold for the relevant action was increased by about 150–200 ms for the patients compared to the controls. This value can be compared to the 180 ms difference between our patients and controls in the implied perceptual duration of the interval between action and tone.

The direction of the attribution effect is important: schizophrenics over-attributed events to their own agency. Our data suggests that schizophrenic patients have unusually strong associations between conscious representations of action and consequence. Thus, they might bind action and viewed image across the substantial delay periods imposed in the Franck et al. experiment, and be unaware of the artificially-induced lag between these events. There may be a critical period in which to perceive the consequence of an action. Actions and events falling in this period may be perceptually bound. A deficit in setting the duration of this critical period in schizophrenics could contribute to the shifts we found in their subjective temporal experience. This view would interpret abnormal conscious experience in schizophrenia as a problem in predicting the consequences of one’s own actions. Further work could investigate whether temporal analysis in schizophrenic patients is defective only when concerning their own actions, or also when observing actions made by others.

I am thrilled as usual and predict that if the same experimental paradigm is used with Autistic, then they will show very little or no forward movement of subjective time between their actual voluntary key-press and the subjective feel of when they decided to press the key. Also, there would be no anticipatory backwards movement of subjective time for when the tone was heard. Thus, Autistic would perceive the time gap as 250 ms only, or may even perceive the time to be more than 250 ms depending ion whether they move the voluntary key press subjective time back in time. No matter what they should show lesser binding between the intention (if they can form one) and consequence.

Haggard P, Martin F, Taylor-Clarke M, Jeannerod M, Franck N. (2003). Awareness of action in schizophrenia Neuroreport, 14 (7), 1081-1085

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Brain Awareness Week: March 16-22, 2009

Dana foundation organises International Brain Awareness Week (BWA) each year and this year I have partenered with them and wish to do something online during that week to raise brain awareness. I would request all my blog friends to do atleast a blog swarm related to brain awareness during that time. Meanwhile I'll keep it a surprise as to what I plan to do in that week!

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