61 replies to this topic

[abelard lindsay]

I'm starting this thread to investigate strategies for positively modulating or improving fluid intelligence. This is different from learning and memory. How So? Let's ask Wikipedia:

http://en.wikipedia....id_intelligence

Fluid intelligence or fluid reasoning is the capacity to think logically and solve problems in novel situations, independent of acquired knowledge. It is the ability to analyze novel problems, identify patterns and relationships that underpin these problems and the extrapolation of these using logic. It is necessary for all logical problem solving, especially scientific, mathematical and technical problem solving. Fluid reasoning includes inductive reasoning and deductive reasoning.

And Dual-n-Back is mentioned as a way to improve fluid intelligence.. This is very very familiar territory arorund here.

In a controversial study, Susanne M. Jaeggi and her colleagues at the University of Michigan, found that healthy young adults who practiced a demanding working memory task (dual n-back) approximately 25 minutes per day for between 8 and 19 days, had statistically significant increases in their scores on a matrix test of fluid intelligence taken before and after the training than a control group who did not do any training at all. [Jaeggi, Susanne M.; Buschkuehl, Martin; Jonides, John; and Perrig, Walter J. (2008). "Improving fluid intelligence with training on working memory." PNAS- Proceedings of the National Academy of Sciences]
A second study conducted at the University of Technology in Hangzhou, China, supports Jaeggi's results independently. After student subjects were given a 10 day training regime based on the dual n-back working memory theory, the students were tested on Raven's Standard Progressive Matrices. Their scores were found to have increased significantly. [Qiu Feiyue; Wei Qinqin (2010). "Study on Improving Fluid Intelligence through Cognitive Training System Based on Gabor Stimulus" Information Science and Engineering]

For the record, I can get 80% on D3B and 40% on D4B with only a little practice.

Great.. But....... I think I can do better. Let's examine the science.

The problem with studying fluid intelligence is that mice don't have a whole lot of it. So most of the research has been using humans doing tests with functional MRIs trying to figure out what's going on in their brains.

http://www.ncbi.nlm....pubmed/22745498

A lateral prefrontal cortex (LPFC) region's activity was found to predict performance in a high control demand working memory task and also to exhibit high global connectivity. Critically, global connectivity in this LPFC region, involving connections both within and outside the frontoparietal network, showed a highly selective relationship with individual differences in fluid intelligence.

A special case of superior fluid intelligence occurs in austic savants. What's going on here?

http://www.ncbi.nlm....pubmed/18646626

On the other hand, the reduced inter-regional collaboration could lead to a disinhibitory enhancement of neural activity and connectivity in local cortical regions. In addition, enhanced connectivity in the local brain regions is partly due to the abnormal organization of the cortical network as a result of developmental and pathological states. This enhanced local connectivity results in the specialization and facilitation of low-level cognitive processing.

So we are talking about development of cortical networks. Increasing connectivity could be the mechanism that might provide something.

http://en.wikipedia....efrontal_cortex

It is also widely believed that the size and number of connections in the prefrontal cortex relates directly to sentience, as the prefrontal cortex in humans occupies a far larger percentage of the brain than any other animal. And it is theorized that, as the brain has tripled in size over 5 million years of human evolution,^[30] the prefrontal cortex has increased in size sixfold.^[31]

Sentience... That's neat stuff.

Anyway.. Laying the groundwork for this thread here... Will follow up with more research.

Edited by abelard lindsay, 06 July 2012 - 04:52 AM.

[abelard lindsay]

It appears that recently (2010) they've figured out ways to measure fluid intelligence in mice.

http://www.ncbi.nlm....pubmed/19607858

This work with laboratory animals has coincided with human imaging studies (briefly reviewed here) which suggest that common brain structures (e.g., prefrontal cortex) mediate the efficacy of selective attention and the performance of individuals on intelligence test batteries. In total, this evidence suggests an evolutionary conservation of the processes that co-vary with and/or regulate "intelligence" and provides a framework for promoting these abilities in both young and old animals.
...
Despite the colloquial (c.f. commercial) contention that “brain exercises” and “smart drugs” can enhance fluid intelligence in normal adults, these claims have rarely been subjected to empirical test, beyond the observation that such treatments have small task-specific benefits. (It is noted that many of the commercial “brain exercise” programs that are marketed to the public make claims of effectiveness based on improvement of performance on a common pre- and post-test of cognitive function, a result that is attributable to a simple practice effect.) In fact, decades of rigorous empirical research has found little evidence that environmental variables influence intelligence test performance in any systematic way (Gray et al., 2003).

"Interesting" perspective.

Continuing on....

A principal component analysis was performed to assess the entire data set described above. One factor accounted for 44% of the total variance in cognitive performance across the six learning tasks. On this factor, short-term memory duration loaded at a negligible level (.14), simple span abilities loaded at a moderate level (.50), and our measure of selective attention loaded strongly (.78). Given the good separation of simple span and selective attention that we believe these procedures support, these results (consistent with that from the human literature) suggest that simple span and controlled attention may act in unison (but to varying extents) to regulate the relationship between working memory and general cognitive abilities.

It seems that the researcher is saying that "selective attention" is a good test of fluid intelligence. For mice they used an odor discrimination test to measure this capability and mix it up with visual cues to confuse the mice. For people they use the "Stroop Test" (http://en.wikipedia....iki/Stroop_test).

Unfortunately, this study has not been cited extensively Probably because it came out very recently. Thus, the "selective attention" tests described in his study are not in wide use. However, the finding that "selective attention" is one of the hallmarks of "fluid intelligence" can be used to search for more information about factors that influence "selective attention" capabilities as a way to pursue enhancement of "fluid intelligence".

Edited by abelard lindsay, 06 July 2012 - 06:21 AM.

[gizmobrain]

Fluid intelligence or fluid reasoning is the capacity to think logically and solve problems in novel situations, independent of acquired knowledge. It is the ability to analyze novel problems, identify patterns and relationships that underpin these problems and the extrapolation of these using logic.

The above definition describes the one area where I excel above those around me, both when I was in school and in the workplace.

Anecdotally speaking... I am terrible at Dual-N-back. It actually hurts my brain to train on Dual-N-back because I'm so bad at it. I wonder if that means that my fluid intelligence would improve even more I increased my Dual-N-back capabilities? I already "think outside the box" enough to get myself in trouble. I wonder if this aspect of my psyche would increase? That could be bad

[sparkk51]

Abelard Lindsay, would the double trouble game on cambridgebrainsciences.com be a suitable indicator of fluid intelligence?

[middpanther88]

Tag. (waiting to find the mechanisms to be unearthed to see if potential nootropic combos can increase it)

[abelard lindsay]

Abelard Lindsay, would the double trouble game on cambridgebrainsciences.com be a suitable indicator of fluid intelligence?

"Double Trouble" is a good test because it is a stroop effect test and thus a test for selective attention. I am really bad at that one. "Odd One Out" is also a good test because it's a pattern matching task intended to mimic some standardized fluid intelligence tests.

If you want to see fluid intelligence in action, watch Salam Khan of Khan Academy do very laborious mathematical calculations that can take 10 minutes or so. He does these quickly, by hand and rarely makes any mistakes.

[Batou]

However, current findings cast doubt on both the clinical relevance of working memory training programs and their utility as methods of enhancing cognitive functioning in typically developing children and healthy adults.

http://psycnet.apa.o...0.1037/a0028228

However, as of 2010, a Georgia Institute of Technology (US) review of the world-wide literature "concluded that, as of yet, the results are inconsistent and this is likely driven by inadequate controls and ineffective measurement of the cognitive abilities of interest."^[

http://en.wikipedia....memory_training

Studies like these are why I'm a bit sceptical about working memory training.

[abelard lindsay]

Going along the stroop test line of inquiry. There are some neuro-anatomical findings with regards to where processing is taking place:

http://www.ncbi.nlm....pubmed/22750124

We manipulated an arrow-word version of the
Stroop
task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict.

So dorsal anterior cingulate cortex (dACC) talks to the left interior frontal junction and posterior parietal cortex. To figure out what to answer on the stroop test.

Hmm.. so how do we modulate dACC to make it work better?

http://www.ncbi.nlm....pubmed/22549117

N-Acetylcysteine Normalizes Glutamate Levels in Cocaine-Dependent Patients: A Randomized Crossover Magnetic Resonance Spectroscopy Study.

...
Proton magnetic resonance spectroscopy ((1)H MRS) was used to investigate Glu changes in the dorsal anterior cingulate cortex (dACC) after a single dose of NAC in cocaine-dependent patients and normal controls.
In an open-label, randomized, crossover study, 8 cocaine-dependent patients and 14 healthy controls underwent two scan sessions: one group receiving no compound and the other following a single administration of 2400 mg NAC.
...
The Barratt Impulsiveness Scale was administered to examine the relation between dACC Glu levels and impulsivity. In the medication-free condition, Glu levels in the dACC were significantly higher in cocaine-dependent patients compared with healthy controls. After administration of NAC, Glu levels were reduced in the cocaine-dependent group, whereas NAC had no effect in healthy controls. Higher baseline Glu levels were associated with higher impulsivity, and both were predictive of greater NAC-induced Glu reduction. The current findings indicate that NAC can normalize elevated Glu levels in cocaine-dependent patients

So the Barratt Impulsiveness Scale isn't the stroop test. Still we find that NAC is working to normalize glutamate levels in cocaine addicted brains specifically in the dACC. I take NAC everyday, just for liver health and as an anti-oxidant. It doesn't really do anything special for me. So probably not a winner.

Still.... NAC has always been one of those things with interesting neurological effects that was overlooked. Searching through the forum I see some people are having pretty powerful beneficial effects (http://www.longecity...774#entry464774). Some other people say it's has strong neurological effects (http://www.longecity...xpected-effect/). Hmm.. Still needs more testing.

Seems that the dACC is related to ADHD too (http://www.ncbi.nlm....pubmed/22424873). Seems that since dACC is inolved in implulse control that it's checking with the other parts of the brain before answering on the test. More on this here: (http://www.ncbi.nlm....pubmed/21515388)

Another study about the dACC and glutamate
http://www.ncbi.nlm....pubmed/22411802

Resting-state glutamate level in the anterior cingulate predicts blood-oxygen level-dependent response to cognitive control.
..
More specifically, individuals with low resting-state glutamate levels in the dACC showed an increased blood-oxygen level-dependent (BOLD) response when the task demands were high, whereas high-glutamate individuals showed the opposite pattern of an increased BOLD response when the task demands were low.

Next post I'll explore the other stroop test parts of the brain.

Edited by abelard lindsay, 07 July 2012 - 05:28 AM.

[FrankMH]

Credibility of these sorts of tests notwithstanding, this - one the latest - certainly is interesting (and incidentally contains Stroop tasks):

http://www.ncbi.nlm....les/PMC3313479/

[abelard lindsay]

So 1200mg of NAC today increased my double trouble scores.

Avg 39.75 (n=4, 3 over the last week and 1 this morning before taking NAC) vs 48 (n=2, 30 minutes after taking the test). So a 20% improvement. It felt a lot easier to do the test and NAC was the only thing taken since I woke up.

Edited by abelard lindsay, 07 July 2012 - 08:29 PM.

[sparkk51]

my record on double trouble is 112

Edited by sparkk51, 08 July 2012 - 12:34 AM.

[abelard lindsay]

I plugged my before and after 1200mg NAC scores into an online t-test calculator (http://www.graphpad....alcs/ttest1.cfm).

The results were considered to be "extremely statistically significant" according to this tool. This is for a paired test.

Here's the data
Before : [37,41,40,41] vs After: [46,50,48,49] (I took 2 more tests a little later)

Edited by abelard lindsay, 08 July 2012 - 01:49 AM.

[middpanther88]

I don't get how NAC suddenly works for you Abelard if you said previously, " I take NAC everyday, just for liver health and as an anti-oxidant. It doesn't really do anything special for me. So probably not a winner."

[abelard lindsay]

I don't get how NAC suddenly works for you Abelard if you said previously, " I take NAC everyday, just for liver health and as an anti-oxidant. It doesn't really do anything special for me. So probably not a winner."

The "Probably Not A Winner" was just my initial gut reaction based on previously taking 600mg a day mixed with all my other supplements. This mixing made it hard to distinguish its effects. For the experiment I took a single dose of 1200mg and did not take any other supplements. I was surprised that it helped so much with my poor stroop test performance in particular. My earlier comments were also skeptical about its effects because NAC doesn't have a obvious and pronounced psychotropic effect like say Methelyne Blue or Noopept does.

Edited by abelard lindsay, 08 July 2012 - 04:14 AM.

[Overman]

Abelard Lindsay, would the double trouble game on cambridgebrainsciences.com be a suitable indicator of fluid intelligence?

"Double Trouble" is a good test because it is a stroop effect test and thus a test for selective attention. I am really bad at that one. "Odd One Out" is also a good test because it's a pattern matching task intended to mimic some standardized fluid intelligence tests.

If you want to see fluid intelligence in action, watch Salam Khan of Khan Academy do very laborious mathematical calculations that can take 10 minutes or so. He does these quickly, by hand and rarely makes any mistakes.

I've been lurking in these forums forever, here's to my first post.

Anywho. Abelard, I wouldn't say that Khan's lessons are a demonstration of fluid intelligence. I'd say they're something like the opposite (per the provided definition, the key factor being novelty), as he is clearly well experienced with the subjects he deals with, and therefore he's most likely utilizing whatever neural mechanism is responsible for tasks which are learned--- not those which are unfamiliar.

I don't get how NAC suddenly works for you Abelard if you said previously, " I take NAC everyday, just for liver health and as an anti-oxidant. It doesn't really do anything special for me. So probably not a winner."

The "Probably Not A Winner" was just my initial gut reaction based on previously taking 600mg a day mixed with all my other supplements. This mixing made it hard to distinguish its effects. For the experiment I took a single dose of 1200mg and did not take any other supplements. I was surprised that it helped so much with my poor stroop test performance in particular. My earlier comments were also skeptical about its effects because NAC doesn't have a obvious and pronounced psychotropic effect like say Methelyne Blue or Noopept does.

In the interest of scientific consideration: There are many factors which contribute to cognitive ability, and in my opinion it seems a hasty presumption to say that the results of your stroop test on this particular morning can be attributed to the NAC without careful consideration of the many other possibilties. For example, adrenaline can enhance short term memory, so perhaps it has some effect on working memory too (although I'm certain it varies per individual). From what I understand adrenaline/cortisol are higher in the morning for most people. Also, diet leading up to the test, exposure to allergens, quality of sleep, your expectations or assesments of your capabilites before or during the test, the possible cognitive detriments caused by some portion of your test-day- excluded regimen, and so on.

Hard to convey tone here, and hope I haven't come off harshly. I just want to support the scientific merit that attracted me to the forums in the first place.



Btw the Ciltep stack is great--excellent find.

[Overman]

This study may have some interesting implications.

After' class='bbc_url' title='External link' rel='nofollow external'>http://www.nature.com/nrn/journal/v11/n9/abs/nrn2884.html']After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.

→ source (external link)

I

I have the full pdf, feel free to pm for full text (educational purposes only of course).


Now, IQ has been correlated with fluid intelligence, and IQ has also been correlated with the number of words heard in the first three years of life. We know that neuroplasticity is on average at its highest point during the first 6-8 years, and this fact has been cited as the enabling affective factor that early life exposure to vocabulary has on IQ. So, given these things, it's fairly reasonable to assume (hypothesis alert) that early life neuroplasticity and the corresponding environmental factors have an impact on fluid intelligence throughout one's life.

Per the hypothesized increase in neuroplasticity driven by psychedelic compounds in the aforementioned paper, there exists some merit in the notion that training on cognitively demanding tasks whilst using psychedelics may result in lasting cognitive enhancements.

Feedback?


(Ethical side point) As is frequently proposed in other contexts by bioethicists, if the above hypothesis were to be confirmed, the possible implications of widespread lasting cognitive enhancement would demand the rescheduling of the compounds mentioned in the cited paper solely (but not only) on the grounds of increasing net well being of humanity.

[gizmobrain]

Psilocybin has finally found it's way back into scholarly studies, since it is hard to ignore how well it works for a host of issues. I think we will see some interesting things from it in the next few years.

That being said, most of the psychedelics that have shown positive results are also illegal to obtain or grow with the purpose of being consumed in the United States. That creates an immediate barrier to entry for me and many others. Not to mention, anything that causes a "trip" where one would need to be supervised to prevent harm to themselves or others (no matter how mild), causes barriers to entry for most, given the taboo involved.

I think what needs to be established is whether the "trip" is what increases the cognitive functions, or if it is the chemical functions taking place. If this is the case, can we isolate the cognitive boosting aspect away from the hallucinating effects? If so, I think we are one step closer to seeing legal acceptance of the drug. At this point, I think it is assumed that the hallucination is part of the cognitive improving process, but it would be interesting to see some research to determine this validity.

I'm wondering if something oneirogenic, like Calea Zacatechichi, could be used to achieve cognitive gains along the same line? Basically, instead of being awake and hallucinating, you would be asleep and dreaming. Maybe that would be something to research into, given that dreaming is culturally accepted

[Overman]

Agreed on your first and second points zr, the barrier does currently exist, and for now will be problematic. I was merely suggesting a theoretical extension of the ideas in the thread, and obviously don't recommend anyone take unknown compounds in highly variable settings; especially since this sort of engagement with x compound/s would (in a typical instantiation) hardly be the sort of experience that could result in what we're talking about.

As far as separating the chemical mechanism which induces neuroplasticity from the subjective experience of hallucinating and the other obvious divergences from baseline, I'm inclined to think that this would be rather difficult-though not impossible.

If researchers could identify every interaction between x compound and existing biology, then somehow (this is the difficult part) identify a different compound or means of intervention (tms,tdcs,deep brain stimulation, or an as-of-yet non existent neurotreatment interface) which mimics each individual interaction (quite many I imagine), and then finally do a trial by error with every possible configuration of interventions to determine which among them is most capable (with the least side effects) of producing the desired effects on neuroplasticity; then yes, I propose it would be possible to determine/utilize some means which is not currently illegal and which does not result in a multitude of sometimes undesired side effects.


As far as this herb, I know nothing of it, but offhandedly it would seem that the possible long term effects on quality of sleep could be quite severe (even a small deficiency could result in larger problems over time). This possibility, coupled with the fact that input seems to be a necessary could prevent that from panning out. However, it could be that the induced neural states at night may result in the same neurological configuration which is correlated with neuroplasticity.

Also as far as the culturally accepted thing... I don't want to worry myself there because when something unusual makes its way into the mainstream it usually happens with reluctance, and also seems to first become a cultural imperative for one reason or another--(pants for example lol, or books which socrates was purportedly unfond of, for they 'dulled the minds of the youth' (or something to that effect))

In addition this forum (aside from the general health sections which are a tiny bit more mainstream) in general is pretty out there relative to cultural norms, and whenever I get into conversations about nootropics with the uninitiated, I get the look I'm sure everyone around here has. So I say, let us create the imperative for the (clears throat) Luddites, and have them join us or fall further and further behind.

[brainslugged]

As far as fluid intelligence goes, I am horrible.

It took me about 5 games of 2back before I could even do 3back at all, and even then, I didn't ever get past 50% on 3back before I got frustrated and quit.

My number span is only 6, and my spacial span is only 7.

Odd one out is the worst. My top score is only 12. I just can't do it.
For one thing, I have a hard time scanning the objects. I can't focus on them for some reason. I have a hard time scanning 2d objects in general. Things like word-searches are hell to me. Objects in real life are fine(still not amazing, but maybe a bit above average), just not when it is on a paper or computer screen.
Then, when I think I have found the right object, it is wrong. I could SWEAR that the object in the odd one sometimes, but it is not. I don't know if I am not looking at all the other objects or if there is a flaw in my comparisons.

It really kills me when I do below average on a cognitive test. I did very well in high-school, and my IQ was tested to be in the mid 130s, so I would expect myself to do okay at least.

[sparkk51]

As far as fluid intelligence goes, I am horrible.

It took me about 5 games of 2back before I could even do 3back at all, and even then, I didn't ever get past 50% on 3back before I got frustrated and quit.

My number span is only 6, and my spacial span is only 7.

Odd one out is the worst. My top score is only 12. I just can't do it.
For one thing, I have a hard time scanning the objects. I can't focus on them for some reason. I have a hard time scanning 2d objects in general. Things like word-searches are hell to me. Objects in real life are fine(still not amazing, but maybe a bit above average), just not when it is on a paper or computer screen.
Then, when I think I have found the right object, it is wrong. I could SWEAR that the object in the odd one sometimes, but it is not. I don't know if I am not looking at all the other objects or if there is a flaw in my comparisons.

It really kills me when I do below average on a cognitive test. I did very well in high-school, and my IQ was tested to be in the mid 130s, so I would expect myself to do okay at least.

You're right, these tests are very inconclusive at determining your overall cognition. I hope you aren't reffering to an IQ test you had taken online.

[brainslugged]

You're right, these tests are very inconclusive at determining your overall cognition. I hope you aren't reffering to an IQ test you had taken online.

No, I am referring to one I had to take for schools for the advanced program. I have yet to find an online IQ test that even gives semi-realistic tests.

I do want to improve my fluid intelligence, still. I will be monitoring this thread.

[FrankMH]

I took a military Stanine Aptitude test last year in order to fast-track my career, and fell short on 'Central Information Processing' and 'Strategic Task Management'. It wasn't really a shocker; I'm aware I have executive function and working memory issues. I was kind of shocked to see that my short term memory score was my best attribute. I guess I just can't seem to juggle multiple streams of that short term memory.

My scores:

Strategic Task Management: 2
Visual and Auditory perception: 3
Short term memory and capacity: 6
Spatial reasoning: 4
Symbolic reasoning: 4
Central Information Processing: 2

Funnily enough, they weight Central Information Processing quite heavily relative to everything else.

The Test Centre advisor said that it was pointless coming back as I have past my peak (29) and that it would be very unlikely that I could improve my scores. I'd love to prove him wrong.but I fear he's probably right.

I'd love to see something emerge with significant effects on executive function. I'll continue to monitor, research, experiment and help if I can.

.

[abelard lindsay]

As far as fluid intelligence goes, I am horrible.

It took me about 5 games of 2back before I could even do 3back at all, and even then, I didn't ever get past 50% on 3back before I got frustrated and quit.
...
It really kills me when I do below average on a cognitive test. I did very well in high-school, and my IQ was tested to be in the mid 130s, so I would expect myself to do okay at least.

I do pretty bad at some of the tests but I can score in the 99% on the spatial ones. Not everyone is good at everything. Intelligence is not a single variable but multi-dimensional.

In the interest of scientific consideration: There are many factors which contribute to cognitive ability, and in my opinion it seems a hasty presumption to say that the results of your stroop test on this particular morning can be attributed to the NAC without careful consideration of the many other possibilties. For example, adrenaline can enhance short term memory, so perhaps it has some effect on working memory too (although I'm certain it varies per individual). From what I understand adrenaline/cortisol are higher in the morning for most people. Also, diet leading up to the test, exposure to allergens, quality of sleep, your expectations or assesments of your capabilites before or during the test, the possible cognitive detriments caused by some portion of your test-day- excluded regimen, and so on.

IMHO, the stack so far is unimpressive. It took several months of digging around in the research before I got somewhere with the CILTEP stack.

Edited by abelard lindsay, 08 July 2012 - 11:17 PM.

[abelard lindsay]

Back to the research. Let's look at the left inferior frontal junction which is what the dACC talks to when taking the stroop test.

http://brain.oxfordj...ain.awr311.long

Although the analysis revealed task-specific frontoparietal networks, it consistently showed that hypometabolism in one region in the left lateral prefrontal cortex—the inferior frontal junction area—was related to performance in the various neuropsychological tests. This brain region has recently been related to the three component processes of cognitive control—working memory, task switching and inhibitory control

The "left inferior frontal junction" is a region in the "inferior frontal junction". I'll just look at the "interior frontal junction" because the left vs right material is very sparse.

http://www.cell.com/...1305001385?cc=y

Cognitive control processes refer to our ability to coordinate thoughts and actions in accordance with internal goals. In the fronto-lateral cortex such processes have been primarily related to mid-dorsolateral prefrontal cortex (mid-DLPFC). However, recent brain-imaging and meta-analytic studies suggest that a region located more posterior in the fronto-lateral cortex plays a pivotal role in cognitive control as well. This region has been termed the inferior frontal junction area and can be functionally and structurally distinguished from mid-DLPFC.

So enhanced "cognitive control" is more or less synonymous with what we're looking for. That being task-switching,working memory and inhibitory control. Basically, being able to stay on track and focused on a line of reasoning without getting distracted by irrelevant information.

This part of the brain also shows up as a bottleneck in information processing.
http://www.ncbi.nlm....pubmed/21825137

We conclude that a unified attentional bottleneck, including the inferior frontal junction, superior medial frontal cortex, and bilateral insula, temporally limits operations as diverse as perceptual encoding and decision-making.

Now I'm starting to think that the optimization of the "cortical network" that I referred to earlier might be a direction to go in, since all these fluid intelligence processes seem to involve a lot of coordination between different areas of the brain.

For example:

http://www.ncbi.nlm....pubmed/21568635

Overlapping activity for switching between abstract rules versus response hands was present in the inferior frontal junction area of the posterolateral frontal cortex. This region, however, showed very distinct patterns of functional connectivity depending on the content of the switch: Increased functional connectivity with anterior prefrontal, superior frontal, and hippocampal regions was present for abstract rule switching, whereas response hand switching led to increased coupling with motor regions surrounding the central sulcus.

Apparently the more D2 receptors one has, the harder it is to switch tasks. The inferior frontal junction area makes an appearance here.

http://www.ncbi.nlm....pubmed/20962241

We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks: noncarriers of the A1 allele of the DRD2/ANKK1-TaqIa polymorphism, associated with higher DRD2 density, show increased task-switching costs, increased prefrontal switching activity in the inferior frontal junction area, and increased functional connectivity in dorsal frontostriatal circuits, relative to A1 allele carriers. A DRD2 haplotype analysis in the same sample confirmed these results, indicating an association between high D2 density and increased task-switching effort.

So a D2 antagonist might help here. I wonder if there's anything that's not a powerful anti-psychotic that is a d2-antagonist. Not something to mess around lightly with as d2 indirectly controls prolactin.


http://en.wikipedia.org/wiki/Prolactin

Pituitary prolactin secretion is regulated by endocrine neurons in the hypothalamus, the most important ones being the neurosecretory tuberoinfundibulum (TIDA) neurons of the arcuate nucleus, which secrete dopamine to act on the dopamine-2 receptors of lactotrophs, causing inhibition of prolactin secretion.

Hmm.. Vitex Angus, normally a PMS herb is a d2 antagonist:

http://www.ncbi.nlm....pubmed/11081988

At least Vitex is pretty widely taken. Then there are all the very odd Chinese herbal preparations that are also d2 antagonists.

http://www.ncbi.nlm....pubmed/16819167

http://www.ncbi.nlm....pubmed/19604496 (Proposed Schizophrenia medication)

I would not recommend taking these yet. Some of these more esoteric chinese herbal preparations have been known to have significant side effects. Vitex has been around since the ancient greeks and was traditionally used as an anti-aphrodisiac, thus the coloquial name "chaste tree". Anyway, this is probably not the way to go as higher prolactin levels via d2 antagonists will increase the male refractory period so this might be trading better fluid intelligence for less sexual desire and all the other problems that come with hyper-prolactima.

This is pretty much what will happen with any d2 antagonist so this is more or less a dead-end. Back to the drawing board.

D2 antagonists are also considered as treatment options for schizophrenia. Interestingly enough, schizophrenics have decreased activation in the inferior frontal junction.

http://www.ncbi.nlm....pubmed/19336793

At baseline, the patient group showed significantly attenuated activation within the anterior cingulate gyrus, left pre-/postcentral gyrus and inferior frontal junction. At follow-up, there was a significant increase in activation in the left inferior frontal junction associated with a decrease in positive symptoms, suggesting this region plays a role in the development of these symptoms.

All this makes me think. What is the D2 receptor activation doing besides modulating prolactin? Could there be a downstream mechanism of action that causes its activation to interfere with task switching? Could the beneficial effects of D2 antagonism on task switching be achieved without affecting prolactin?

Hmm.... Will have to explore this more...

Edited by abelard lindsay, 09 July 2012 - 12:52 AM.

[telight]

It seems that higher doses, strangely, Vitex tends to decrease prolactin : http://www.ncbi.nlm..../pubmed/9021345

Edited by telight, 09 July 2012 - 01:30 AM.

[middpanther88]

http://herbs.maxforu...al-life-nzt-48/ might prove interesting

[Batou]

Abelard,

Here's a large study that's been done, linking brain regions to intelligence. Not sure if you've seen it, I thought you might find it interesting.

http://news.illinois...AronBarbey.html

[abelard lindsay]

Now here's an interesting study on d2 antagonists:

http://www.ncbi.nlm....5?dopt=Abstract

Impaired set-shifting and dissociable effects on tests of spatial working memory following the dopamine D2 receptor antagonist sulpiride in human volunteers.

...

RESULTS:
Sulpiride impaired performance of the delayed-response task both without distraction and with task-relevant distraction. By contrast, the drug protected against deficits from task-irrelevant distraction seen in the placebo group. Task set-switching was also impaired by sulpiride, with participants being slower to respond on switch trials compared with non-switch trials. There was also a trend for attentional set-shifting to be impaired following sulpiride. In contrast, self-ordered SWM performance was enhanced by sulpiride on the second test session only.

Hmm... So d2 antagonists helped in some instances and hurt in others.

http://www.jneurosci...0/42/14205.long

The study of Laakso et al. (2005) provides an important link between the finding of impaired switching performance and increased neural effort for high DRD2 density in the present study and impaired task switching for individuals under the DRD2 antagonist sulpiride (Mehta et al., 2004). The putative adaptive increase in dopamine synthesis in A1 carriers might explain why genetically determined low DRD2 density is not necessarily associated with decreased DRD2 signaling as evoked by transient pharmacological interventions. Instead, adaptively increased dopamine signaling in A1 carriers might evoke a more salient gating signal, facilitating the updating of task representations in prefrontal cortex.

Wandering back over to the gene d2 association study we find the scientist suggesting that a smaller population of DRD2 receptors maintains the same level of DRD2 signalling via greater dopamine synthesis.

So... The idea being that fewer D2 receptors in the superior task switchers causes more dopamine production creating better task switching performance.

So that's great for people who were born that way, but then the question becomes will a normal brain up-regulate dopamine production in the presence of a d2 antagonist and if so do we even want that?

More sulpride tests:
http://www.ncbi.nlm....pubmed/15671126

Tasks that did not emphasize WM were spatial and non-spatial trial-and-error learning, long-term spatial memory and emotional memory. After dopamine D2 receptor blockade, performance was not impaired on the spatial WM (SWM) task, but was impaired on the auditory counting task with distraction. Sulpiride did not impair, but rather appeared to enhance trial-and-error learning overall. Thus, we were unable to support the notion that dopaminergic modulation preferentially influences spatial over non-spatial processing during learning. In addition, recognition was impaired in the emotional memory task after encoding on drug compared to placebo. These findings question the precise role of dopamine D2 receptor modulation on WM, and highlight the need for sensitive tests to study dopaminergic modulation of emotional processing.

Hmm... Maybe d2 antagonism isn't the right place to look. There's improvement and degradation of performance on certain tasks. Maybe this is just too broad of a mechanism.

Edited by abelard lindsay, 09 July 2012 - 06:56 AM.

[Batou]

Selective D4 agonist?

http://en.wikipedia.org/wiki/A-412,997

[gizmobrain]

Yeah, I was going to say that D2 antagonism probably wouldn't be too great, given that d2 receptors in the anterior cingulate cortex have been linked to motivation and drive. Decreased D2 receptor binding has been linked to Schizophrenia. So, out of the box thinking and novel solutions may increase, but at what cost?

D4 agonism looks nice, since I never responded well to methylphenidate (puked every time I took it).

Edited by zrbarnes, 09 July 2012 - 04:26 PM.