psychosis
Cognitive control: when less is more!
Jul 20th
Yesterday I wrote a post about ADHD and creativity and how the frontal lobes hypo-function and dopamine may be the mediating factors involved. Today I serendipitously came across this article by Thomson-Schill et al in which they posit that frontal cortex hypofunction during childhood is beneficial, on average, as it enables convention learning and thus linguistic acquisition.
What they basically mean is that frontal cortex has been found to be involved in cognitive control i.e. in higher cognitive functions like planning, flexible thinking etc ; and the frontal cortex does this by biasing the competitive responses elicited by a stimuli by goals /existing beliefs / other task related information that is maintained in the working memory. To take an example, cognitive control is often measured by tasks such as the stroop task. the strrop task measures how well you are able to suppress the prepotent response tendency of naming the color-term itself by the task-relevant constraint that you name the color of the term instead. when a color term like ‘green’ is presented in Red color, then the green as well as red linguistic response compete with each other. In the absence of frontal biasing in teh direction of color ie.e red, we are apt to name the color-term itself i.e green by default which is the habitual response. Children , who have less well-developed frontal cortices generally perform poorer at the stroop task than adults as their frontal cortex does not bias or tilt the scales in favor of the color used rather than the color-term presented.
The authors claim that this inability to bias results on the basis of pre-existing knowledge/beliefs leads to a greater ability to learn. They posit that learning conditions (that maximize competition ) are different from performance conditions (where one response needs to be selected or competition minimized) and the child’s brain is optimized for learning by not having frontal inhibition and control. An example they give is filtering noise form signal which the child are able to do, but adults can’t. for eg. if a new language has a phrase ‘et tu brute’ and 75 % of times it is in this form and 25% of times it is of the form ‘et tu vous Brute’, then adults will tend to probability match and select the utterance/ utter themselves phrase ‘et tu brute’ 75% of times and ‘et tu vous Brute’ 25 % of times. This is because when they want to utter the phrase their existing knowledge that sometimes the other phrase is also used, makes them sensitive to variations. In child’s brain on the other hand a competition between the two phrases takes place and as there is no moderating influence involved, the outcome hundred percent of the time is ‘et tu brute’. Thus, they are able to learn conventional meaning of a phrase/word etc more easily than an adult who gets bogged down by variations. Thus sometimes, less is more!
However the reason I got hooked to this study is the implications they draw for ADHD/Autism and creativity. I’ll quote them verbatim on the issue:
Central to our proposal is the claim that the timing of PFC development has been the target of selection and, therefore, that variations in timing are functionally meaningful. Recent neuroimaging studies have revealed potentially important differences in the timing of PFC development across typical and atypical individuals. Variations in the trajectory of PFC maturation (based on repeated measures of cortical thickness) have been associated with cognitive measures in typically developing children (Shaw et al., 2006). Children with attention-deficit hyperactivity disorder (ADHD) exhibit a delay in cortical maturation that is most prominent in the PFC (Shaw et al., 2007). In contrast, children with autism spectrum disorders (ASD) undergo early maturation of the PFC (Carper, Moses, Tigue, & Courchesne, 2002). A better understanding of the implications of these timing changes for both learning and performance may illuminate some of the behavioral and cognitive patterns associated with these diagnoses (e.g., impaired acquisition of social conventions in ASD), as well as offer a fertile ground for testing the validity of our hypothesis that typical PFC development involves a trade-off in favor of learning to the detriment of performance in infancy and early childhood.
This gels quite nicely with what I have been speculating for some time, that ADHD and Autism are opposed and that ADHD is childhood equivalent of psychosis. ADHD kids are bound to be good learners, more divergent creative and have better social and linguistic skills. Autistic kids on the other hand would be better performers (say child prodigies in memory etc) , more convergent thinkers, and have less social and linguistic skills- one mechanism of which may be lesser ability to learn social and linguistic conventions- like the usage of metaphorical terms.
On creativity this is what the authors say:
Creativity—the ability to approach an object or a situation from an alternative perspective—may benefit from the unsupervised competition that occurs in the absence of prefrontal control. Consider one common assessment of creative thinking, the Alternative Uses Task: When attempting to think of ways to use an object in some atypical way, adults struggle. In this case, an active PFC might, paradoxically, hinder flexible thinking, because the representation of the object is sculpted by prior experience and expectations. Interestingly, young children are immune to this kind of functional fixedness (German&Defeyter, 2000). Successful performance in similar tasks of ideational fluency has been associated with EEG changes in prefrontal regions (e.g., Mo¨lle, Marshall, Wolf, Fehm, & Born, 1999). Furthermore, patients with PFC damage solve insight-problemsolving tasks better than do their healthy counterparts (Reverberi, Toraldo, D’Agostini, & Skrap, 2005). This apparent flexibility of behavior can be interpreted as a stimulus-driven response: A mind that is at the mercy of its environment is not shaped by expectations or beliefs. This interpretation highlights a parallel between functional fixedness and probability matching, in that both of these ‘‘adult’’ phenomena involve biasing stimulus–response associations based on expectations. This proposal suggests new avenues of investigation into the processes that support creative thought and into putative relations between creativity and psychological disorders associated with hypometabolic prefrontal function (i.e., a state of lower energy consumption in the PFC, as in bipolar disorder, for example).
The above analysis of creativity in terms of hypofunction of frontal cortex bodes well for my theories of creativity-ADHD relationships as well as creativity-psychosis (bipolar etc) relationship, both of which involve developmental or functional hypofucnction of frontal cortex.
Thompson-Schill, S., Ramscar, M., & Chrysikou, E. (2009). Cognition Without Control: When a Little Frontal Lobe Goes a Long Way Current Directions in Psychological Science, 18 (5), 259-263 DOI: 10.1111/j.1467-8721.2009.01648.x
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Autism, Psychosis and circadian clock
Jun 1st

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I recently came across this post by Michelle Dawson that states the thesis that one of the abnormalities in Autism spectrum disorders is due to abnormal circadian clock functioning. More specifically, the clock is internally driven and has a greeter ‘free running’ period and does not entrain readily to environmental and social clues.
Autistics whose sleep-wake cycles carry on independently from environmental and social cues are said to be “freerunning.”
The usual response to freerunning in autism is to see this as an autism-related sleep disorder. There is very preliminary evidence that freerunning autistics can be successfully treated with melatonin. Bourgeron (2007) refers to a short case study about an autistic whose free-running was remediated by melatonin treatment.
If you feel a bit overwhelmed by all the circadian clock related terminologies, I wholeheartedly recommend BoraZ’s clock tutorial series , especially this one.
Dawson further says:
Glickman (2010) speculates that some autistics’ failure to chain our sleep-wake cycles to environmental cues may arise from our atypical perception. My totally wild guess might be that an extreme freerunning phenotype in autism may be contributed to in part by cognitive versatility in autism, which would result in perceived environmental cues affecting sleep-wake cycles in an optional rather than mandatory way.
I wont speculate about the reasons behind why autistics have a greater free-running period and less entrainment to social and environmental clue, but I woudl say that instead of giving them flexibility, I would presume that this locks them into their internal rhythms, while others are more responsive to environment and better adapted. That brings me to the opposite phenotype of ASD…the psychotic phenotype shown by Schizophrenics, depressives and Bipolars.
As per this PLOS Genetics article:
The contribution of the circadian regulatory system, arising from conflicts between internal biological clocks and environmental (solar) and social clocks, is evident in affective disorders. All major affective disorders (such as unipolar depression, OMIM #608516; bipolar disorder, and schizophrenia, OMIM #181500) include circadian phase disturbances in sleep, activity, temperature, and hormone levels (for reviews see [84]–[86]). Moreover, there is evidence that if rhythms can be altered/stabilised using relevant therapies, improvements in the primary symptoms can occur. For example, in some instances sleep deprivation has an antidepressant effect in patients [87]. Conversely, many disorders with a primary anomaly in the circadian system are associated with depressed mood. Seasonal affective disorder (SAD; OMIM #608516) is a common condition where depressive symptoms occur during shorter winter days [88]–[90]. Two inherited sleep phase disorders, familial advanced sleep phase syndrome (FASPS; OMIM #604348) and delayed sleep phase syndrome (DSPS), are both associated with abnormal affective states [91],[92]. Furthermore, individuals with a behavioural preference for “eveningness” have a greater tendency to develop depression [93].
The above to me seems hypersensitivity to social and environmental cues in affective/psychotic disorders. contrast this with ASD description by the same authors:
Other behavioural disorders with circadian and sleep-related disturbances include autism spectrum disorders (ASD) (OMIM %209850) [81]). Behavioural disturbances in ASD may arise in part from an inability of an individual’s circadian oscillator to entrain to environmental and social cues. One specific correlate of ASD is a low level of melatonin, and one of the enzymes critical in the synthesis of melatonin, acetylserotonin-O-methyltransferase (ASMT, OMIM *300015), is implicated as a susceptibility gene for ASD [82].
The role of melatonin seems to provide a clue. In autism, there seems to be low levels of melatonin and perhaps hypo-sensitivity to melatonin changes. In contrast Bipolar is marked by hypersensitivity of Melatonin receptors:
It has been suggested that a hypersensitivity of the melatonin receptors in the eye could be a reliable indicator of bipolar disorder, in studies called a trait marker, as it is not dependent on state (mood, time, etc.). In small studies, patients diagnosed as bipolar reliably showed a melatonin-receptor hypersensitivity to light during sleep, causing a rapid drop in sleeptime melatonin levels compared to controls.[58] Another study showed that drug-free, recovered, bipolar patients exhibited no hypersensitivity to light.[59] It has also been shown in humans that valproic acid, a mood stabilizer, increases transcription of melatonin receptors[60] and decreases eye melatonin-receptor sensitivity in healthy volunteers[61] while low-dose lithium, another mood stabilizer, in healthy volunteers, decreases sensitivity to light when sleeping, but doesn’t alter melatonin synthesis.[62] The extent to which melatonin alterations may be a cause or effect of bipolar disorder are not fully known.
The above is not the only source implicating Bipolar disorder and circadian clock dysfunction., See more here and here. The big question is not whether ASD and Affective disorders are both circadian rhythm disorders, but the big question is whether they show opposite phenotypes with respect to circadian clocks- one showing too little entrainment while the other too much?
Barnard, A., & Nolan, P. (2008). When Clocks Go Bad: Neurobehavioural Consequences of Disrupted Circadian Timing PLoS Genetics, 4 (5) DOI: 10.1371/journal.pgen.1000040
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Autism and white Matter/Myelination: the opposite of creativty/psychosis phenotype?
May 26th

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A new paper by Ben Bashat et al extends their earlier findings that had found that there was accelerated maturation of white matter in children with Autism. In this new paper they use Tract Based Spatial statistics (TBSS) to determine the white matter integrity of children (age around 3 years) with Autism as compared to normal controls. Of course they used Diffusion tensor Imaging to find out Fractional anisotropy and other measures of white matter integrity.
Essentially they found that in some regions/tracts there was greater Fractional Anisotropy (FA) as compared to controls. These regions/tracts were genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). They also found that in areas of high FA there was corresponding decrease in Radial diffusivity (Dr). What this essentially means, to my naive mind, is that greater conductance or speed of action potential in axons would primarily be due to enhanced myelination which reduces leakage or lateral flow of AP.
I’ll like to contrast the results with an earlier study I had blogged about regarding creativity, psychopathology and white matter mylienation connection. As per that study an inverse relation was found between people high on creativity (divergent type) and Fractional anisotropy in frontal regions, i’e there was low FA. Also importantly there was increased Dr (radial diffusivity) in the same regions and thus the conclusion was that there was reduced myelination in those areas which meant reduced signal transmission speed and more signal leak . It is notable that that study too used DTI and Tract based Spatial statistics (TBSS) analysis method to arrive at their conclusions.
Regular readers of this blog will know my fanaticism for Autism and Psychosis as opposites on a continuum theory. This new paper nicely fits in with my last post linking creativity/psychosis and white matter/myelination, I had as much surmised that Autism would show the opposite effect and have high FA and decreased Dr. It is heartening to note when such a relation is found and reported- goes to show the strength and ability to make predictions of the theory.
However, I would also like to point out and highlight that I believe Autistic spectrum is characterized by another type of ability – the savantic intelligence- that may be directly due to this white matter /excess myelination effect. Perhaps the signals travel so fast that decisions are made locally without the time available to get other far-0off regions involved- thus giving attention to details but inability to link disparate regions and ideas.
Weinstein, M., Ben-Sira, L., Levy, Y., Zachor, D., Itzhak, E., Artzi, M., Tarrasch, R., Eksteine, P., Hendler, T., & Bashat, D. (2010). Abnormal white matter integrity in young children with autism Human Brain Mapping DOI: 10.1002/hbm.21042
Ben Bashat, D., Kronfeld-Duenias, V., Zachor, D., Ekstein, P., Hendler, T., Tarrasch, R., Even, A., Levy, Y., & Ben Sira, L. (2007). Accelerated maturation of white matter in young children with autism: A high b value DWI study NeuroImage, 37 (1), 40-47 DOI: 10.1016/j.neuroimage.2007.04.060
Jung, R., Grazioplene, R., Caprihan, A., Chavez, R., & Haier, R. (2010). White Matter Integrity, Creativity, and Psychopathology: Disentangling Constructs with Diffusion Tensor Imaging PLoS ONE, 5 (3) DOI: 10.1371/journal.pone.0009818
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More brains and bonkers connection: thinking out of a broken box
May 24th

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We have covered many studies linking creativity with Psychosis and this new study by Manzano et al provides further corroborating evidence.
Dopamine has been linked with psychosis and is now also being increasingly being linked with creativity, especially divergent creativity and thinking style.
Divergent thinking is influenced by dopaminergic function. Reuter [6] found a correlation between divergent thinking (the Inventiveness battery of the Berliner Intelligenz Struktur Test) and polymorphisms of the dopamine D2 receptor gene–DRD2 TAQ IA. Higher creativity scores were observed in carriers of the A1 allele. This polymorphism is unrelated to general intelligence [7], [8], which suggests that it is more specifically related to Glr (“long-term storage and retrieval”). This finding is in line with functional imaging research showing the D2 system to be involved in attentional set shifting and response flexibility, which are important components of divergent thinking [9]. Furthermore, the finding indicates that divergent thinking is related to regional differences in D2 densities, since the DRD2 TAQ IA polymorphism has been shown to modulate D2 binding potential (D2BP) in both striatal [10] and extrastriatal regions [11].
Divergent thinking is traditionally measured using alternate uses test, for eg., in which a familiar object like brick is provided and subjects asked to name novel use for that object. The responses are marked for creativity as per the follwoing criterion:
- Fluency–the number of valid responses;
- Originality–how frequent the participant’s responses were among the responses of the rest of the sample;
- Flexibility–the number of semantic categories produced;
- Switching–the number of shifts between semantic categories;
- and Elaboration–how extensive each response is (if the task involves producing more than single words)
The main findings of the study was that dopamine D2 binding potential (D2BP) receptor density in thalamus correlated negatively with divergent thinking and creativity scores. Here is how the authors interpret the results:
Based on the current findings, we suggest that a lower D2BP in the thalamus may be one factor that facilitates performance on divergent thinking tasks. The thalamus contains the highest levels of dopamine D2 receptors out of all extrastriatal brain regions [33], [45]. Decreased D2BP in the thalamus has been suggested, firstly, to lower thalamic gating thresholds, resulting in decreased filtering and autoregulation of information flow [31] and, secondly, to increase excitation of cortical regions through decreased inhibition of prefrontal pyramidal neurons [46], [47], [48]. The decreased prefrontal signal-to-noise ratio may place networks of cortical neurons in a more labile state, allowing them to more easily switch between representations and process multiple stimuli across a wider association range [49]. This state, which we hereforth will refer to as the “creative bias”, could benefit performance on tasks that involve continuous generation and (re-)combination of mental representations and switching between mind-sets. The creative bias could also explain why the different measures of divergent task performance correlate: A decreased signal-to-noise ratio in thalamus would decrease information gating and possibly increase fluency; decreased signal-to-noise ratio in cortical regions should better enable flexibility and switching between representations; similarly, the associative range should be widened and selectivity should be decreased which might spur originality and elaboration.
Besides carrying benefits related to fluency and switching, the decreased signal-to-noise ratio associated with the creative bias should be disadvantageous in relation to tasks that require high levels of selective attention. Some support for this prediction can be taken from Dorfman [50] who showed that the greater a person’s divergent thinking scores, the slower his or her reaction times were on a negative priming task requiring the inhibition of interfering information. Furthermore, the creative bias may also bring a risk of excessive excitatory signals from the thalamus overwhelming cortical neurotransmission, with ensuing cognitive disorganization and positive symptoms [30]. It is thus tempting to suggest that dopaminergic modulation of neurotransmission mediated through dopamine D2-receptors could be one of the mechanisms which associate creativity with positive psychotic symptoms. Interestingly, positive symptoms are not necessarily related to problems in executive function, at least not to the same extent as negative symptoms [51], which indicates that in the creative individual “blind variation” might be affected without a concomitant decline in “selective retention”. It can be speculated that aberrant thalamic function may promote unusual associations, as well as improved performance on divergent thinking tests in healthy individuals, in the absence of the detrimental effects typically associated with psychiatric disorders. In other words, thinking outside the box might be facilitated by having a somewhat less intact box.
In plain English speak, the same decreased signal-to-noise ratio in perfrontal regions that gives rise to creativity also gives rise to proneness to psychosis. The more the noise that is introduced the greater the chances that the ideas generated by ‘blind variation’ are more creative; if the ‘selective retention’ procedure is also defective or loosened to an extent, it may result in psychopathology and psychosis, while if intact it leads to creativity. Thus while one factor , that of loosening of associations, flexibility and set switching is common to both psychosis and creativity, the defects in selective retention may be the crucial factor that distinguishes brains from bonkers.
de Manzano, ?., Cervenka, S., Karabanov, A., Farde, L., & Ullén, F. (2010). Thinking Outside a Less Intact Box: Thalamic Dopamine D2 Receptor Densities Are Negatively Related to Psychometric Creativity in Healthy Individuals PLoS ONE, 5 (5) DOI: 10.1371/journal.pone.0010670
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The Creativity-dopamine (b)linkage: more brains and bonkers connections
Apr 14th

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Creativity is certainly different from intelligence; it is usually gauged as the ability to make novel and useful unique contributions to a field. Creativity itself is not a unified construct but can be broken into convergent creativity (involving more focused approach) and divergent creativity (involving more widening and loosening of associations).
It has been evident for quite some time that there is a connection between insanity (especially bipolar/schizophrenia spectrum) and creativity , especially as evidenced by the creative bent of schizotypal people. See for example this article covering a recent study that looks at exactly the same issue. However, most of these studies rely on a unitary construct of creativity that does not do full justice to the correlations that could be found if convergent and divergent creativity was distinguished and effect of intelligence was factored out. The new study by Hommel, B. does just that.
Schizophrenia/psychosis as many will know from their elementary neuroscience knowledge is associated with dopamine dysfunction; specifically it is believed that high baseline dopamine levels are there in schizophrenics/psychotics. So it was not unreasonable for Hommel et al to hypothesize that dopamine should have some relation with creativity possible higher dopamine associated with high creativity. However, dopamine has shown an inverse U relation for many other factors and thus they were cautious and tried to fit both linear and quadratic graphs to their data. But we are moving ahead of ourselves. Before they could find the underlying relation between dopamine and creativity, they had to measure these things accurately.
They measured dopamine using Eye Blink Rate (EBR): that is how many time you blink in a minute. For creativity , they measured Convergent Creativity using a remote association task (don’t go by the name …the task has only one answer and measures convergent thinking) . for eg. a subject is given three words (say time, hair, stretch) and have to come up with a word that is commonly related to all three (answer: long) . this reliably measures creativity but of he convergent type. For Divergent thinking , they administered the Alternate Uses task (AUT),a task that requires one tocome up with novel uses of everyday objects like brick, toothpaste etc. The responses to AUT were further coded for fluency (how easily one could come up with alternatives measured by total no. of responses) , flexibility(the number of different categories used or how remote the mind wandered) and elaboration (the level of detail surrounding the use). They also measured fluid intelligence using Raven’s progressive matrices.
They then conducted experiments (administered the tests to subjects) , collected data and analyzed the results. The main findings of interest to us is that they found a inverse u shaped relation between dopamine (EBR) and flexibility dimension fo divergent thinking. This effect was present even when the effect of intelligence was factored out. thus both low dopamine, as well as too much dopamine is detrimental to flexible divergent thinking/creativity and schizotypals , placed precariously between normals and psychotics are best placed to be the most creative as they presumably have the optimum dopamine levels. the authors also argue that schizophrenics dopamine levels should not be brought down indiscreetly by using anti-psychotics (which reduce dopamine levels) but they should be brought in the optimum range of dopamine functioning. this obviously has immense importance and treatment implications. No wonder creative people feel stiffed when on anti-psychotics- their dopamine levels are being brought down way too much.
The other interesting finding was that dopamine (EBR) was negatively ad linearly related to convergent thinking. Thus, it is evident that convergent creativity and divergent creativity are different constructs and while dopamine has a complex quadratic relationship with divergent thinking, that with convergent thinking is linear though not very comforting. It seems that as dopamine levels increase the ability to narrow focus diminishes and this would be concordant with other studies linking dopamine to ADHD for example.
Overall, a view of how brains and bonkers are two sides of the same coin is emerging and it is exciting to note that many previous inconsistencies in literature around this issue may have to do with not differentiating and decomposing creativity into its many components and not looking for inverse u shaped effects.
Chermahini SA, & Hommel B (2010). The (b)link between creativity and dopamine: Spontaneous eye blink rates predict and dissociate divergent and convergent thinking. Cognition PMID: 20334856
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