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Sandeep Gautam is a psychology and cognitive neuroscience enthusiast, whose basic grounding is in computer science.

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Best of Tweets: 20-05-09

I am starting an experimental new feature today called Best of Tweets. Many other bloggers do weekly link fests and I had somehow refrained form doing one myself. Using twitter, I am able to share many more links that I find interesting instantly , but I know that many of you are not on twitter; so perhaps a weekly best of tweets post that aggregates the best of my tweets for the past week may be useful to the mouse trap blog readers. Do tell me via comments whether you find this useful.Remember that this is a manually compiled by me list of best of tweets and is not auto generated, so I am putting some additional efforts here.

Without further ado, here is the best of tweets for week ending 20-05-09:

  1. RT @Wildcat2030: In defense of distraction–it’s not a bug, it’s a feature of a new techno-nomadic culture. (via @LynJ)
  2. Debates on free will / perchance or predetermined / now silence reigns, courtesy free won’t #haiku #scaiku (ver 2) #philosophy (for the background of this tweet go read the 4 way convesration I had on twitter on free-will yesterday)
  3. I believe in a libertarian free will concept and thus found the recent Nature article based on randomness in… re:
  4. a 5 part npr series on brain/spirituality RT @kdwashburn: Great interactive graphic on the brain and spirituality:
  5. RT @kdwashburn: “reading someone else’s attention involves the same brain circuits that control one’s own attention” 
  6. Yes! 50 Scientifically Proven Ways to Be Persuasive
  7. Narrative gravity /go spin a yarn/define yourself . via @LeadonYoung: & #scaiku 
  8. Creativity ,esp. musical / ‘a seething cauldron of ideas’/ Jonah peeps in your brain : : #scaiku #haiku #science
  9.  Triune Ethics: On Neurobiology and Multiple Moralities « Neuroanthropology
  10. Your will is free / not everything is a reaction/ behold the fly acting random! #scaiku #science #haiku #cognitive 
  11. Depression and Mania / which one comes first / a serpent eating its tail ? : #scaiku #science #haiku
  12. psychosis or a dream/ hard to tell/an overactive default network : #scaiku #haiku #science
  13. “We can’t control the world, but we can control how we think about it”: Mischel . Sounds a lot like Viktor Frankl.
  14. via @anibalmastobiza : cool genomic imprinting paper that predates Badcock/Crespi’s work on Autism/Psychosis

Attention allocation / Same as action selection/ New insight on ADHD #haiku #scaiku

The title of my above post is a scaiku (scientific haiku in 140 chars on twitter) that I posted last night on twitter.I am using this title as the inspiration for this post is twitter itself.

Last night, after a hard day full of tweeting (yes tweeting and keeping up with all the friends’ tweets is a lot of hard work- go check the 4-way conversation I had on cosnsciousness and free will), I was not able to relax myself, but found myself in a constant state of distraction and restlessness, and getting up in middle of night to update my status.  Of course I have heard of twitter addiction and would rubbish that off; but I could not rubbish off the unique demands on attention and juggling that twittering makes on you. First off, you need to read a lot of tweets and find the needle in the haystack- the tweets that need to be retweeted/replied to and ignore/forget the rest of them as soon as possible. Secondly, I at least, juggle constantly between windows and tabs of tweetdeck and other application trying to do optimal scavenging (feeding off good content tweeted by others) and foraging (finding a good tweetable link myself).

So to sum up, I found that twitter had taxed, at least yesterday, my attentional system- leading to a habitual distractibility and also my motor system hat had constantly flitted between open windows and tabs leading to a habitual distractibility. I am sure that was a very short term and temporary phenomenon, but that set me thinking  I have already devoted an entire post to how attention allocation and action selection may be similar and have drawn many parallels. The fundamental problem in  both the cases is to choose an action/ stimuli to attend to, that can maximize the rewards from the world/ predictability of the world.  At any given time, there are many more stimuli to attend to and acts to indulge in than are the attentional/intentional resources required for the same and thus one has to choose between alternatives. Mathematicaly, different acts have different probabilities associated with them that they would lead to a rewarding state- this wave function needs to be collapsed such that only one act is actually intended. One way to do is my maximizing Utility (ExV) associated with different acts and choosing the maximal one always; another solution is to randomly choose an act from the given set  in accordance with  the probability distribution  that is a function of their utilities.I believe that instead of maximizers most of us are staisficers and especially in time-sensitive decisions go for an undeliberate choice that does’nt actually maximize the utility over all possible behavioral acts, but choses one of them randomly/probabilistically as per their prior known probabilities of rewards. Thus, we can be both maximizers as well as satisficers and which system we engage depends both on situational factors as well as our personality tendencies/ habits.

Anyway that was a lot of digression from the main line of argument. To continue with the digression for some more time, if one extends the analogy to attending to stimuli, on can either attend to stimuli that leads to greatest predictability (P= ExR) ;  or one can attend to a stimuli from a given set in accordance with a probability distribution that is a function of their prior predictabilities. again I haven’t even got into Bayesian models where thing should get more complicated; suffice it to note for now that both attention-allocation and action-selection involve choosing an act / stimuli from a set.

A look at the Utility function of acts (U=ExV) and  Predictability function of stimuli (P = ExR) , immediately outlines the importance of dopamine in the above choosing mechanism as it encodes both (reward) expectancy as well as incentive salience/Value for acts;  on the attentional side of things, it should encode  both the strength of conditioned association (E) as well as (stimuli) Relevance for minimizing surprise. As such it should detect novelty in stimuli that can indicate that things have changed and the internal model needs updating. 

I also talked in my last post about a general energy level that leads to more propensity to indulge in operant acts and a general arousal level that leads to more propensity to attend to external stimuli. Today I want to elaborate on that concept using ADHD as a guide – ADHD has primarily two varieties (and in most general case both co-exist) – the inattentive type and the hyperactive-impulsive type. In the inattentive type, one is easily distracted or to put in my conceptualization – has a high baseline arousal leading to more frequent monitoring to the world/ external stimuli . The attention-reallocation happens faster than controls and may be triggered by irrelevant stimuli too. In the hyperactive-impulsive type,  one is overly active and impulsive or to put in mu conceptualization- has a high baseline energy level leading to more frequent shifts in activities and possibly triggering unvalued acts (impulses that are not really rewarding) .

It is important to note that dopamine and dopamine mediated regions like smaller PFC, cerebellum and basal ganglia, dopamine related genes like DAT1 and DRD4  and Ritalin that works primarily on dopamine have been implicated in ADHD.  All the above points to a dopamine signalling aberration in ADHD. Once one embraces the overarching framework of action-allocation and action-selection as similar in nature and possibly involving dopamine neurons, it is easy to see why ADHD children should have both hyperactive-impulsive and inattentive syndromes and subgroups.

Child Psychology: The Mouse Trap turns 3

The Mouse Trap turns 3 today. It was exactly three years and 334 posts earlier that the Mouse Trap was born. The Mouse Trap has indeed learnt to walk on its own and has also developed adequate linguistic skills in the meantime. The toddler years are all but over, as it now becomes more playful and enters play age of early childhood. Already people are demanding that it not be developmentally delayed, but start indulging in rich imaginative pretend play with topics being requested like symbolic interactionsim and social epistemology.

Some stock taking and reality check is in store. The wiki page on toddler lists the following last milestones for 25-36 months and I hope the Mouse trap is doing fine. To recap:

  1. Speaking in sentences: Hopefully the strands of mouse trap blog posts now form more cohesive sentences (like the theme of autism-psychosis, stage theories etc) and are not disjointed phrases and one-off utterances.
  2. Ability to be independent to primary care giver: I hope that the reader partcipation has increased and with more reader participatory initiatives like Skribit suggestions, Google FriendConnect etc., the Mouse Trap is able to become more and more independent of its primary caregiver, that is me, and instead make deep attachments with other secondary caregivers like its prized readers and subscriber base.
  3. Easily learns new words, places and people’s names: Hopefully as the Mouse trap matures, it is learning to expand its horizons and foraying into topics left hitherto untouched; with better reader connect features , like twitter/Frinedfeed etc it is surely remembering peoples names and where they come form!
  4. Anticipates routines: The mouse trap hopefully has learnt to anticipate the routine articles and topics that its readership likes to read and is doing a decent job on that score. do suggest your topics if the mouse trap doesn’t anticipate them!
  5. Toilet learning continues : Once th emouse trap might have been suffering from blogorrehea, but now it knows that passing motion (posting articles) once a week is adequate enough an dthat one should write a article only when one is full of it! There does exist scope for more routinized daily motion passing though!!
  6. Plays with toys in imaginative ways: I am experimenting a lot with social media (my favorite web 2.0 toy) so as to engage more readers in a conversation. If you have any imaginative ideas of how to play with this toy, do let me know!!
  7. Attempts to sing in-time with songs: Hopefully, the mouse trap has learnt to sing in tune with the zeitgeist of the day; though here I believe Mouse trap more has an original, unsynchronised with others voice and singing profile. Hope to change that and be more in sync with what others in the science blogosphere are singing (but definitely not the atheism/evolution debate which just bores me)

So, the Mouse trap is just about doing fine. It has been consistently featured in wikio top 100 science blogs, is amongst the top 5 blogs in India as ranked by, has a google page rank of 6 and has a subscriber base of close to 450 dedicated RSS feed subscribers, besides those that visit it daily on web via search. Also , the twitter followers of @sandygautam are increasing steadily and have reached 450 and the rate at which they are growing it seems they’ll grow way beyond the Mouse trap feed subscribers. With micro-blogging and twitter/ FriendFeed, I have found a new way to share links and ideas and deepen conversations and connect with my readers, that was not possible with just the Mouse Trap.

I would also like to take this opportunity to encourage all feed subscribers to join me at twitter (@sandygautam) to keep up to date on links that I don’t find exciting enough to write a blog post about or do not have much to add to, but which still are related to theme of what I write about and would make for a good read and need to be shared. I would also encourage new as well as veteran readers and subscribers, just for today,  to visit the mouse trap blog on the web and not in their feed readers (to celebrate its B’day, you are invited to the party at the web) so that they can become familiar with new social media tools I have put together on the Mouse Trap blog, like the ‘recommended by readers’ widget, the ‘top posts by PostRank’ widget or the ‘suggest topics to write’ widget.

Lastly as a primary caregiver, though my investment in the mouse trap has been more and my pride consequently in its progress has been immense; I must also thank all the other caregivers like you , the reader, or the peers like the other science blogs that have provided a safe and playful environment in which the Mouse Trap could flower or learn by peer play/ imitation learning. You all are a part and parcel of the Mouse Trap blog, so thanks everyone and take pride in your child’s development and maturation and now that it becomes more independent come forward and supplant the primary caregiver and let it achieve its full potential! Amen!

Read the Mouse Trap on your Kindle

Amazon today broadened their kindle blog offerings and I have used that facility to make the Mouse Trap blog feed available on the Kindle. I am not sure how many of the Mouse trap blog readers do indeed possess a kindle and whether they would find it useful to read the blog with a monthly subscription fee of 1.99 dollars; but there was no option to have a say and make the Mouse Trap blog feed available for free, so that’s what we have ended up with. You can always continue to read the blog freely using other means, but experimenting with a 14 day free kindle trial may be a good idea! More details here.

If you do subscribe using kindle , do let me know your experience via the comments.

synaptic plasticity: angelman’s/autism and psychosis

There is a recent article in Nature Neuroscience by Philpot et al regarding how experience-dependent synaptic plasticity is downregulated in Angelmans’ syndrome and perhaps in Autism too, as the Ube3a gene involved is implicated in both disorders.

First a little history about Angelman– it is a disorder caused by deletion/lack of a maternally imprinted UBE3a gene in chromosomal region 15q11-q13 . It is typically contrasted with Prader-Willi syndrome which is caused by a paternally imprinted gene malfunction in the same chromosomal region. Christopher Badcock has used this to contrast Autism (related to Angelman) and Psychosis (more common in PWS) to argue that Autism and Psychosis are due to a genomic imprinting tug of war between fathers and mothers genes.

I have written about Badcock’s and Crespi’s thesis before and how it fits in with my views on Autism and Psychosis; suffice it to say that I am seeing the new study primarily from this prism of Autism and Psychosis dichotomy.

First , let us see what the study tells us:

It uses mouse model that contains silenced maternal Ube3a genes (Ube3a m-p+ mouse), thus trying to make a mouse model of Angelman.

What it found was:

1)    Ube3a expression was markedly reduced in Ube3am-/p+ mice compared with wild-type mice in all three brain regions (visual neocortex, hippocampus,cerebellam). Consistent with previous observations, this attenuation was brain specific, as Ube3a was highly expressed in the liver of both Ube3am+/p- and Ube3am-/p+ mice.

2) To determine the physiological consequences of Ube3a loss on neocortical development, we examined the developmental acquisition of spontaneous excitatory synaptic transmission by recording miniature excitatory postsynaptic currents (mEPSCs) in layer 2/3 pyramidal neurons of visual cortex (see Supplementary Table 1 online for intrinsic membrane properties of recorded neurons). Consistent with previous findings24, 25, mEPSC amplitudes decreased and frequency increased during development in wild-type mice . Just before eye opening (postnatal day 10, P10), mEPSC frequency and amplitude were indistinguishable between wild-type and Ube3am-/p+ mice . Thereafter, mEPSC frequency failed to develop normally in Ube3am-/p+ mice

3)Although dark rearing had no measurable effect on mEPSC amplitude in wild-type mice at P25 , sensory deprivation strongly attenuated the normal developmental increase in mEPSC frequency in wild-type mice . In contrast, dark rearing did not affect mEPSC amplitude or frequency in Ube3am-/p+ mice. Consequently, mEPSC frequency in normally reared Ube3am-/p+ mice was not significantly different from that of dark-reared wild-type mice . These findings demonstrate that, although Ube3a is not necessary for the initial sensory-independent establishment of synaptic connectivity, it is selectively required for experience-dependent maturation of excitatory circuits.

4)We therefore compared the properties of neocortical long-term depression (LTD) and LTP at layer 2/3 synapses in visual cortex of wild-type and Ube3am-/p+ mice at both young (P25) and adult (P100) ages. Because layer 2/3 pyramidal neurons receive major inputs from layer 4 pyramidal neurons, layer 2/3 field potentials were evoked by layer 4 stimulation . We began by measuring LTD in young mice using a standard stimulation protocol (1 Hz for 15 min). Although LTD was reliably induced in young wild-type mice, it was absent in young Ube3am-/p+ mice . We also observed deficits in LTP induction. A relatively weak induction protocol (three 1-s trains of 40-Hz stimulation) elicited LTP in young wild-type mice, but failed to reliably induce LTP in young Ube3am-/p+ mice . To test whether the neocortex of Ube3am-/p+ mice was capable of expressing LTP, we also applied a strong LTP stimulation protocol (two 1-s trains of 100-Hz stimulation). This protocol consistently induced LTP in both Ube3am-/p+ and wild-type mice. Thus, as with LTP deficits in hippocampus8, 9, the LTP induction machinery is impaired in the visual cortex of Ube3am-/p+ mice and this deficit in LTP can be overcome with strong stimulation.

5)To determine whether the plasticity deficits in Angelman syndrome mice persisted into adulthood, we tested LTD and LTP in adults (P100). In adult wild-type mice, LTD induced by 1-Hz stimulation was absent, as expected27, whereas LTP could be induced with strong stimulation. In adult Ube3am-/p+ mice, however, neither of these protocols were effective at modifying synaptic strength. These results indicate that wild-type mice show attenuated neocortical plasticity as they mature and that this attenuation of plasticity is more severe in the absence of Ube3a . Furthermore, these data indicate that plasticity defects in Angelman syndrome mice persist into adulthood.

..and so on (go read the full paper)

In a nutshell, what they found was that in presence of visual stimuli, the plasticity (measured by LTP/LTD ) of visual cortex was adversely affected. As sensory stimulus would normally be available while developing, this would adversely affect the plasticity in adolescence/ critical periods and also continue into adulthood.

Thus, Autism/ Angelman are charechterised by less synaptic plasticity in adulthood and during critical development periods. Paradoxically, this loss of synaptic plasticity is concomitant on their it being experience-dependent or having sensory stimuli. If the organism is sensory deprived, it may still retain the normal synaptic plasticity exhibited by similar sensory deprived normal people.

How does this relate to Psychosis? If my thesis is correct that autism and Psychosis are opposites, then I would predict that in either prader-willi or in Psychosis (scheziphrenia etc) there should be excessive experience-dependent plasticity. I was glad to learn that I am not the first one to make that proposition, but someone back in 1995 has argued for Hippocampal synaptic plasticity as an endophenotyoe for Episodic Psychosis. I now quote heavily form that article.

Here is the abstract:

Structural change in the hippocampal formation has become popular as a proposed neurobiological substrate for schizophrenic disorders. It is postulated that behavioral plasticity in the form of long-term potentiation of hippocampal synaptic transmission is an attractive putative mechanism for the mediation of transient psychosis. Moreover, the disturbed hippocampal neuroarchitecture found in schizophrenic brain may be susceptible to potentiation and dysfunctional to the degree that delusions and hallucinations develop. Partial and selective blockade of the receptors mediating potentiation may prove to be an efficient means of preventing psychotic episodes and avoiding further damage to the involved network. Basic research, utilizing experimental models such as intraventricular kainic acid injection, may help to clarify the anatomical and physiological substrate of psychosis.

The Main thesis of the paper is:

1. Anatomical, physiological, pharmacological, and behavioral findings are most consistent with the view that neuropathological changes within the limbic system, specifically within the hippocampal formation, may represent a biological substrate of schizophrenia.

2. The biological mechanism underlying transient psychosis may be long-term potentiation (LTP) of synaptic transmission within the hippocampal formation.

3. The effects of dopamine manipulation on these behaviors may be mediated by direct actions on the compromised limbic system of the psychotic patient.


Associative plasticity within hippocampus occurs in the form of long-term potentiation (LTP), an experience-dependent increase in synaptic efficacy. Experimentally, LTP is produced by tetanic stimulation of afferent systems (Bliss and Lomo 1973) and has been shown to facilitate simple associative learning (Berger 1984) but disrupt more complex forms of associative plasticity (Robinson et al 1989). Hippocampal LTP has been observed to occur as a consequence of stimulus pairings in classical conditioning (Weisz et al 1984) and appears to be mediated by N-methyl-Daspartate (NMDA) receptors (Harris et al 1984). Pharmacological blockade of NMDA receptors has been shown to disrupt learning and memory in a variety of forms, including simple associations (Stillwell and Robinson 1990), spatial learning (Morris et al 1986; Heale and Harley 1990; Shapiro and Caramanos 1990), conditioned fear (Miserendino et al 1990; Kim et al 1991), olfactory memory (Staubli et al 1989) and gustatory memory (Welzl et al 1990). Some evidence, however, suggests that deficits involve motor impairment as well as disrupted learning (Keith and Rudy 1990)

Hippocampal function is particularly sensitive to neurochemical modulation, and the expression of monoamine receptors in the temporal lobe is altered in schizophrenics (Joyce 1993). Antipsychotics that reduce endogenous dopamine levels (Losonczy et al 1987) exert significant effects on the hippocampus and LTP. Trifluoperazine inhibits induction of LTP in hippocampus (Finn et al 1980), whereas the dopamine antagonist domperidone has been shown to prevent the maintenance of LTP (Frey et al 1990). Long-term effects of antipsychotic drugs include functional supersensitivity of hippocampal pyramidal neurons (Bijak and Smialowski 1989). Thus, individuals with deranged hippocampal neuroarchitecture would be prone to cognitive dysfunction (including, perhaps, perceptual distortion and other schizophrenic symptoms), differentially susceptible to stress, and responsive to amelioration of symptoms via dopamine antagonism. It may be more than coincidence that the time lag between administration of antipsychotic medication (which results in near immediate decrement in dopamine levels) and the attenuation of psychotic symptoms weeks later (Kane 1987) is remarkably consistent with the time parameters of LTP decay (Douglas and Goddard 1975). Also, the selective disruption of “weak” associative responses by antipsychotic drugs (van der Heyden and Bradford 1988) is consistent with interactions between NMDA-receptor blockade and stimulation intensity on induction of LTP (Reed and Robinson 1991).

From the above, at least to me, it is clear that anti-psychotics may work by decreasing LTP/LTD that is enhanced in episodic psychosis. A propensity towards increased experience-dependent enhancement of synaptic palsticty may be at work here and paradoxically the same approach of sensory deprivation, as in Angelman/ Autism may work here too.

Here is the summary:

In summary, potentiation of hippocampal synaptic transmission may be the neurophysiological basis of episodic psychosis. (Post [1993] has proposed a similar process in the amygdala as a useful model in understanding the progression of recurrent affective disorders.) More selective blockade of the NMDA receptor, which mediates LTP, may prove an effective means of attenuating positive symptoms and preventing further accrual of cellular damage in hippocampus.

In my own summation, I am convinced that we would find more synaptic plasticity in Psychotic people and that hyper-plasticity to hypo-plasticity is another dimension on which the autistics and psychotics differ and this again is a result of the genomic imprinting mediated tug-pf-war between the maternal and paternal genomes.
PORT, R., & SEYBOLD, K. (1995). Hippocampal synaptic plasticity as a biological substrate underlying episodic psychosis Biological Psychiatry, 37 (5), 318-324 DOI: 10.1016/0006-3223(94)00128-P
Koji Yashiro, Thorfinn T Riday, Kathryn H Condon, Adam C Roberts, Danilo R Bernardo, Rohit Prakash, Richard J Weinberg, Michael D Ehlers & Benjamin D Philpot (2009). Ube3a is required for experience-dependent maturation of the neocortex Nature Neuroscience

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