LONGECITY

Since we've run out of interesting approaches with regards to the stroop test, it's back to the coritcal network.

http://www.ncbi.nlm....pubmed/20655484

The roles of GABAB receptors in cortical network activity.
...

In contrast, we have only recently begun to appreciate the roles of slow inhibition via GABA(B) receptors in the control of cortical network activity. Here, we provide a framework for understanding the contributions of GABA(B) receptors in helping mediate, modulate, and moderate different types of physiological and pathological cortical network activity. We demonstrate how the slow time course of GABA(B) receptor-mediated inhibition is well suited to help mediate the slow oscillation, to modulate the power and spatial profile of gamma oscillations, and to moderate the relative spike timing of individual neurons during theta oscillations. We further suggest that GABA(B) receptors are interesting therapeutic targets in pathological conditions where cortical networkactivity is disturbed, such as epilepsy and schizophrenia.

So Gaba B receptors modulate the cortical network... Hmm wonder if there have been any nootropic related findings here.

Hmm... Looking around Gaba B agonists have serious addiction and side effect issues, so not going to go there.

Maybe we should go back and look at glutamate again in the dAAC:

Oh wow look what we got from June 2012!

Eur J Pharmacol. 2012 Jun 15;685(1-3):59-69. Epub 2012 Apr 20.
A novel glycine transporter-1 (GlyT1) inhibitor, ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole), improves cognition in animal models of cognitive impairment in schizophrenia and Alzheimer's disease.
Harada K, Nakato K, Yarimizu J, Yamazaki M, Morita M, Takahashi S, Aota M, Saita K, Doihara H, Sato Y,Yamaji T, Ni K, Matsuoka N.
Source
Pharmacology Research Labs., Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. katsuya.harada@jp.astellas.com
Abstract
Hypofunction of brain N-methyl-d-aspartate (NMDA) receptors has been implicated in psychiatric disorders such as schizophrenia and Alzheimer's disease. Inhibition of glycine transporter-1 (GlyT1) is expected to increase glycine, a co-agonist of the NMDA receptor and, consequently, to facilitate NMDA receptor function. We have identified ASP2535 (4-[3-isopropyl-5-(6-phenyl-3-pyridyl)-4H-1,2,4-triazol-4-yl]-2,1,3-benzoxadiazole) as a novel GlyT1 inhibitor, and here describe our in vitro and in vivo characterization of this compound. ASP2535 potently inhibited rat GlyT1 (IC(50)=92 nM) with 50-fold selectivity over rat glycine transporter-2 (GlyT2). It showed minimal affinity for many other receptors except for μ-opioid receptors (IC(50)=1.83 μM). Oral administration of ASP2535 dose-dependently inhibited ex vivo [(3)H]-glycine uptake in mouse cortical homogenate, suggesting good brain permeability. This profile was confirmed by pharmacokinetic analysis. We then evaluated the effect of ASP2535 on animal models of cognitive impairment in schizophrenia and Alzheimer's disease. Working memory deficit in MK-801-treated mice and visual learning deficit in neonatally phencyclidine (PCP)-treated mice were both attenuated by ASP2535 (0.3-3mg/kg, p.o. and 0.3-1mg/kg, p.o., respectively). ASP2535 (1-3mg/kg, p.o.) also improved the PCP-induced deficit in prepulse inhibition in rats. Moreover, the working memory deficit in scopolamine-treated mice and the spatial learning deficit in aged rats were both attenuated by ASP2535 (0.1-3mg/kg, p.o. and 0.1mg/kg, p.o., respectively). These studies provide compelling evidence that ASP2535 is a novel and centrally-active GlyT1 inhibitor that can improve cognitive impairment in animal models of schizophrenia and Alzheimer's disease, suggesting that ASP2535 may satisfy currently unmet medical needs for the treatment of these diseases.
Copyright © 2012 Elsevier B.V. All rights reserved.

So improving glycine availability by inhibiting the transporter improved NMDA receptor function which leads to better working memory.


How do we increase glycine availability?

Maybe just taking it straight? Is this safe?
http://en.wikipedia....eurotransmitter

...
There is some evidence showing that 3000 milligrams of glycine before bedtime improves sleep quality.[15]....

Animal and human foods

Other markets for USP grade glycine include its use an additive in pet food and animal feed. For humans, glycine is sold as a sweetener/taste enhancer. Food supplements and protein drinks contain glycine. Certain drug formulations include glycine to improve gastric absorption of the drug....

So it's used in foods and just checking around it appears to be a pretty common unremarkable supplement.

Let's see if we can find more evidence for glycine's health benefits...

Well they fed high dosages to rats and watched for excito-toxicity and didn't find any:

http://www.ncbi.nlm....pubmed/11343684

Chronic high-dose glycine nutrition: effects on rat brain cell morphology.

Shoham S, Javitt DC, Heresco-Levy U.

Source

Research Department, Ezrath Nashim-Herzog Memorial Hospital, Jerusalem, Israel.

AbstractBACKGROUND:
Facilitation of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission via administration of glycine site agonists of the NMDA receptor (e.g., glycine, D-serine), and glycine transport inhibitors may represent an innovative pharmacologic strategy in schizophrenia; however, given the potential involvement of NMDA receptors in the neurotoxicity of excitatory amino acids, possible neurotoxic effects of glycinergic compounds need to be explored. Furthermore, studying brain adaptations to chronic administration of glycine site agonists may provide insights into the therapeutic mechanisms of these drugs.METHODS:
Adult rats were randomized to one of three nutritional regimens (no glycine supplementation, 1 g/kg/day, or 5 g/kg/day glycine supplementation) and to one of three treatment durations (1, 3, or 5 months). Serum glycine and serine levels at sacrifice and brain sections were examined using histologic markers of neurodegeneration (cresyl violet and silver impregnation staining) and immunohistochemical staining of glial fibrillary acidic protein, microtubule-associated protein, and neurofilament 200. To explore additional neural adaptations to high-dose glycine treatment, immunostaining was also performed for class B, N-type Ca(2+) channels.RESULTS:
Serum glycine levels increased dose dependently during glycine nutrition, whereas serine levels were not changed. In hippocampal dentate gyrus, the percentage of hypertrophied astrocytes transiently increased at 1 month. At 3 and 5 months of glycine treatment, the density of class B, N-type Ca(2+) channels was reduced in parietal cortex and hippocampus. No evidence of neuronal or glial cell excitotoxic damage or degeneration was registered at either of the treatment intervals studied.CONCLUSIONS:
These findings demonstrate for the first time that in vivo administration of high-dose glycine may induce brain morphological changes without causing neurotoxic effects. A reduction in density of class B, N-type Ca(2+) channels in specific brain regions may represent one general adaptation to long-term, high-dose glycine treatment.

Notice that they were giving 1g/kg dosages or 5g/kg dosages. Which are HUGE and no evidence of excitotoxicity.

What are Class B, N-Type Ca(2+) Channels anyway?

http://en.wikipedia....calcium_channel

These control the release of neurotransmitters. Blockade of which is being considered as a potential treatment for alcoholism.

They also had astrocyte hypertrophy. Which means enlargment of astrocytes which are gilial cells around the brain.

http://www.ncbi.nlm....pubmed/22046366

Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy , a hallmark of brain aging.

So not good.


So anyway... Taking 1g/kg or 5g/kg of Glycine is not something I'm going to do. The LD50 is roughly 7g/kg so these are huge doses they were giving these mice for months. However, it looks like a reasonable thing for me to test at normal supplement dosages (e.g 3g daily or less).

Searching around the forum found these cautions about glycine supplements in certain individuals.

http://www.longecity...ion-to-glycine/

That's why it's generally good practice to start with low dosages when taking new supplements.

Apparently your average can of Tuna has roughly 1g of glycine in it.

http://www.dietandfi...-in-glycine.php
Edited by abelard lindsay, 10 July 2012 - 03:59 AM.

What about D-Serine instead of Glycine?

What about D-Serine instead of Glycine?

Might work, from what I've read on that thread it seems that D-Serine is a more direct route to the effect I was trying to get with Glycine.

Are you still thinking it's sentience-related?

So it looks like adding D-Serine is a good addition to working memory. It would be good to take with the CILTEP stack since now you have something working on memory and also fluid intelligence/working memory.

I think I am going to order my first D-Serine

I'll order once these flock of people give me the green light.

Yeah, honestly, it might be a bust. An expensive bust. But I will keep you guys updated if you want to wait.
Edited by zrbarnes, 14 July 2012 - 06:14 PM.

Yeah it really looks to tick a few of those nice boxes. I'm still waiting on an E-Mail response apropos achieving International delivery.

I was concerned about d-serine's ability to cross the BBB, but this sort of negates that entirely. Zrbarnes, this should comfort you some.

http://www.ncbi.nlm....pubmed/16253803


Also, do let us know how your trial goes.

Thread research go dead?

Let's revive this thread

I'm back....

http://www.ncbi.nlm....pubmed/22832821

A gene (MAOA) on human chromosome X, significantly affected brain activity in a network of frontal, parietal and occipital regions. Increased activity in this network, but not in caudate nucleus or anterior prefrontal regions, was correlated with VSWM capacity, which in turn predicted externalizing (aggressive/oppositional) symptoms, with higher WM capacity associated with fewer externalizing symptoms

So low MAOA activity is associated with poor working memory and agressive behavior.

http://www.ncbi.nlm....pubmed/22832821

CONCLUSION:
The high-activity MAOA allele is protective against ASP [Anti-Social Personality]among whites with no history of physical abuse, lending support to a link between MAOA expression and antisocial behavior.

Hmm.. Wonder if high MAOA activity is associated with better working memory.

http://www.ncbi.nlm....pubmed/21983350

We found that carriers of 5-HTTLPR and MAOA-uVNTR alleles recently implicated in executive processing showed a more efficient executive control of working memory-related performance as evidenced by reaction time, error rate as well as N2 and P3b event-related potential measures. This impact was further supported by interactions with the NET polymorphism.

So what's with MAOA-uVNTR

http://www.ncbi.nlm....pubmed/19941049

The catechol-O-methyltransferase (COMT) gene contains a functional polymorphism (Val158Met) affecting the activity of the enzyme, and the monoamine oxidase A (MAOA) gene contains a VNTR polymorphism (MAOA-uVNTR) that affects the transcription of the gene.

We found that the COMT x MAOA interaction significantly predicted full scale (FSIQ) and performance (PIQ) IQ scores (P = 0.039, 0.011); the MAOA-uVNTR significantly predicted FSIQ,
...
Our finding that gene-gene interaction between COMT and MAOA predicts the intelligence of ADHD boys in China is intriguing but requires replication in other samples.

So now we have COMT MAOA and 5-HTTLPR in play

Well maybe not 5-HTTLPR
http://www.ncbi.nlm....pubmed/21302344

Neither MAOA nor 5HTTLPR polymorphisms showed significant effects on cognitive function. In boys but not girls, there was a modest but statistically significant interaction between MAOA and COMT genotypes such that increased prefrontal catecholamine availability was associated with better working memory.

http://www.ncbi.nlm....pubmed/15817751

Male mice that have either the COMT or the MAOA gene knocked out show elevated aggression. The allele that codes for the lower enzymatic activity of COMT has been associated with elevated aggressive behavior in several samples of psychiatric patients. Similarly, the alleles that code for the lower activity of MAOA were associated with the development of aggressive behavior in maltreated male children in a large birth cohort study.

So more COMT and MAOA activity make for lower agression and better working memory. Have you ever known a math or physics nerd with an uncontrollable temper?

COMT along with MAOB degrades dopamine. I wonder if MAOB inhibitors improve working memory?

Not coming up with a whole lot on this...


Hmm.. Well how about good ol' DRD1? Peaks around the 3rd decade of life.

http://www.ncbi.nlm....15/?tool=pubmed

The DRD1 protein peak in expression appears to occur a few years later in life than that of mRNA expression. DRD1 is critical to PFC cognitive functioning and in particular working memory [37] and these cognitive processes may not fully mature until the third decade of life [38,39] Thus, the change in DRD1 from periadolescence into young adulthood happens during a time in development when the cortex and our cognitive behaviour are also maturing suggesting that DA-DRD1 may have an integrative role in higher cortical function.

The Wisconsin Card Sorting test looks to be an interesting test of executive function and working memory.

http://en.wikipedia....rd_sorting_test

http://www.ncbi.nlm....10/?tool=pubmed

Inverted U-shaped relation between prefrontal D1 receptor availability and Wisconsin Card Sorting Test performance, indicating that too little or too much D1 receptor stimulation impairs working memory or set shifting.

Hmm... Here's a connection between NMDARs, MAO-A and agression. Maybe there's some sort of interaction here that contributes to the working memory/agression connection.

http://www.ncbi.nlm....pubmed/22723698

...

Ok that's enough digging around in pubmed for tonight.
Edited by abelard lindsay, 05 August 2012 - 04:33 AM.

Influence of dopaminergic and serotoninergic genes on working memory in healthy subjects.
Wiłkość M, Hauser J, Tomaszewska M, Dmitrzak-Weglarz M, Skibińska M, Szczepankiewicz A, Borkowska A.
Source
Department of Clinical Neuropsychology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland. monikawilkosc@gmail.com
Abstract
Working memory is an ability to keep information in short-term memory and manipulate them 'on line'. Working memory is also involved in complex frontal executive functions. The role of dopaminergic system in modulating working memory processes in prefrontal cortex is well established. Also the role of serotoninergic receptors is postulated. The purpose of this study was to assess the association between the polymorphisms of dopaminergic (DRD1, DRD3, DRD4, COMT) and serotoninergic (SERT--serotonin transporter, 5HT2A, 5HT2C) genes' polymorphisms and performance on WCST in 200 volunteers from the Polish population. We found the association between DRD1, DRD4, COMT and SERT genes polymorphisms and the performance on WCST. The results obtained in the study indicate that dopaminergic and serotoninergic genes may play a role in modulating the executive function and working memory processes in healthy subjects. The pattern of this influence may be different in males and females. Moreover, the relationship between the efficacy of prefrontal cognitive function and genes polymorphisms may differ between healthy subjects and schizophrenic patients.

Lets get this thread back on track!
Im really confused about the differened "kinds" of working memory tough, and seems like differened abstracts relate to differened functions and as has been indicated some things like D2 antagonists are both impairing and improving.
Will have to do some more research

just started the cambridge brain thing, it makes my head hurt, im gonna be doing it as a daily exercise from now on and see what affects nootropics have on the trend.
Edited by rmo, 09 August 2012 - 06:21 AM.

just started the cambridge brain thing, it makes my head hurt, im gonna be doing it as a daily exercise from now on and see what affects nootropics have on the trend.

You mean Double Trouble? What's your high score on that one?

Hi all. Been reading through this thread. Very interesting so far. I joined the cambridge brain thing too, but I'm not sure its a good gauge of ability. It seems highly training-dependent to me. Tonight I tried odd one out and managed to train myself from an initial 14 up to 26.

just started the cambridge brain thing, it makes my head hurt, im gonna be doing it as a daily exercise from now on and see what affects nootropics have on the trend.

You mean Double Trouble? What's your high score on that one?

i just got that as well, but i have to agree with noodly about the cambridge testing, most of the tests that have huge discrepancies around test results are usually just because theyre poorly designed, or are reliant on trying to figure out the mechanics (esp. odd one out)

just started the cambridge brain thing, it makes my head hurt, im gonna be doing it as a daily exercise from now on and see what affects nootropics have on the trend.

You mean Double Trouble? What's your high score on that one?

i just got that as well, but i have to agree with noodly about the cambridge testing, most of the tests that have huge discrepancies around test results are usually just because theyre poorly designed, or are reliant on trying to figure out the mechanics (esp. odd one out)

Yeah, most of the scores increase drastically with familiarity. The memory tests are pretty much the only ones that seem to stabilize for me.

I have been using something called PEBL for my testing/benchmarking recently (except ones where I have to continue on Cambridge for continuity). It doesn't give the neat graph form, and you may need to be just a little familiar with computers (just looking in the program folder to find the results, nothing you can't learn if you never use computers), but the tests are more "official" and have more research behind them (and there are a ton of them). I only use it for benchmarking. I don't think training with it would have much effect.

Take a look at it if you have time
http://pebl.sourcefo...et/battery.html

How do we increase glycine availability?

DMG (dimethylglycine) is basically the amino acid glycine attached to two methyl groups while TMG, also known as betaine, has three methyl groups. Commonly these methyl groups are added to homocysteine, converting it into the amino acid methionine which is then converted to SAMe, a nutrient available over the counter which has been used as a powerful antidepressant. DMG plays a crucial role in the respiratory cycle of the cells, transporting oxygen and serving as a potent methyl donor. DMG acts as a building block for the synthesis of many important substances such as choline, SAM-e, the amino acid methionine, several hormones, neurotransmitters, and DNA.
The formation of the neurotransmitters norepinephrine and dopamine requires a methyl group donated by SAMe. Dopamine enhances sex drive.

http://www.raysaheli...hylglycine.html

Let us consider COMT Inhibition:

http://www.biomedcen...1-2350/8/34/#B1

A substitution of valine (Val) by methionine (Met) at codon 158 affects the activity of the COMT enzyme, and individuals with the Val/Val genotype have a three- to fourfold higher activity of the COMT enzyme than those with Met/Met genotype

http://www.ncbi.nlm....pubmed/18213617

All individuals were genotyped for the rs4680 (Val158Met) polymorphism at the COMT gene. Met carriers showed near-significant better performance in the LNS compared with Val/Val individuals (F = 3.9, df = 1, P = 0.046). Moreover, the analysis for linear trend found that Met allele carriers showed significantly better performance than Val/Val individuals (B = 0.58 P = 0.031), although evidence for a linear trend was not found

LNS(Letter-Number Sequencing) is a test of working memory in the Wechsler Adult Intelligence Scale

So those with weaker COMT (Met) activity scored better than those with stronger COMT activity (Val).

Devin Thayer already did a lot of the research for me on this one:

http://www.longecity...ibitor-synergy/

(I speculated that COMT inhibition was bad on this thread, but I revisited MAO vs COMT inhibition safety a bit on the LTP thread and decided the evidence wasn't there to show it was an issue -> http://www.longecity...696#entry528696)

Looking at some of the studies from Devin's Thread:

http://www.ncbi.nlm....les/PMC2674329/

we found that epigallocatechin-3-gallate (EGCG), a common tea polyphenol, is an exceptionally strong inhibitor of human COMT-mediated O-methylation of 2-OH-E₂ and 4-OH-E₂, with IC₅₀ values at approximately 70 nM [13–16]
...
In summary, of the three coffee polyphenols tested, chlorogenic acid has the highest inhibition potency, with IC₅₀ values of 0.2–0.8 μM for inhibiting the methylation of 4-OH-E₂ and 0.8–1.4 μM for inhibiting the methylation of 2-OH-E₂.

For reference Quercetin and Fisetin are somewhat weaker.
http://www.ncbi.nlm....pubmed/15100171

The IC(50) values for quercetin and fisetin were 0.9 to 1.5 microM and 3.3 to 4.5 microM, respectively, for inhibiting the O-methylation of 2-OH-E(2), and 0.5 to 1.2 microM and 2.6 to 4.2 microM, respectively, for inhibiting the O-methylation of 4-OH-E(2)

Edited by abelard lindsay, 21 August 2012 - 09:46 AM.

So I was hunting around for any sort of Wisconsin Card Sorting Test stuff and found this interesting study:

http://www.ncbi.nlm....pubmed/22353286

The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD.
....
Executive function was tested at 3 weeks post-surgery using a rat analogue of Wisconsin card sorting test called the Extra Dimensional/Intra Dimensional (ED/ID) set-shifting task. The results demonstrated that performance by the pre-motor rat model of PD was equivalent to that of the control groups in the simple and the compound discriminations as well as the intra-dimensional set-shifting. However the PD group exhibited attentional set-shifting deficits similar to those observed in PD patients.
....
Additionally, sodium butyrate, a short chain fatty acid derivative and inhibitor of class I and II histone deacetylase (HDACi), was tested as a potential therapeutic agent to mitigate the pre-motor cognitive deficits in PD. The results indicated that the sodium butyrate treatment not only effectively alleviated the set-shifting deficits, but also improved the attentional set formation in the treated rats.

So we have a new mouse fluid intelligence test the Extra Dimensional/Intra Dimensional (ED/ID) set-shifting task to look at and an interesting short chain fatty acid: Sodium butyrate.

Interesting stuff, this sodium butyrate.

http://www.ncbi.nlm....pubmed/21597935

Synergistic effects of sodium butyrate, a histone deacetylase inhibitor, on increase of neurogenesis induced by pyridoxine and increase of neural proliferation in the mouse dentate gyrus.
....
Sodium butyrate in combination with pyridoxine robustly enhanced cell proliferation and neurogenesis induced by the increase of neural proliferation in the dentate gyrus, showing that sodium butyrate treatment distinctively enhanced development of neuroblast dendrites. These results indicate that an inhibition of HDAC synergistically promotes neurogenesis induced by a pyridoxine and increase of neural proliferation.

So... What does the Dentate gyrus do again. It's not the Pre-Frontal Cortext after all.

http://www.ncbi.nlm....pubmed/23348108

In this review article the emphasis will be on the role of the DG (dorsal and ventral) in supporting memory based on the operation of specific processes. Based on the development of computational models of dorsal dentate gyrus (dDG) and behavioral evidence based on dysfunction of dDG, this review will show that the dDG mediates mnemonic processing of spatial information. The processes subserved by dDG include (a) the operation of conjunctive encoding of multiple sensory inputs, implying an integration of sensory inputs to determine a spatial representation, and (b) pattern separation of spatial (especially metric) information, involving the reduction of interference between similar spatial locations © pattern separation of context (d) importance of context in object recognition, and (e) temporal integration and remote memory and spatial pattern separation based in part on neurogenesis. In addition the ventral dentate gyrus (vDG) mediates mnemonic processing of odor information as indicated by odor pattern separation.

So mainly spatial decoding and spatial working memory.

Hmm.. Some speculation on some more interesting behavior, at least for this thread:

http://www.ncbi.nlm....pubmed/17765738

A potential role of the DG in mediating processes, such as recall of sequential information and short-term memory as well as temporal order for remote memory, are also discussed.

So now a word of caution. Hippocampal Neurogenisis can also be caused by Ischemia, leading to a reduction in short-term memory.

http://www.ncbi.nlm....pubmed/17345578

Differential response to ischemia in adjacent hippocampalsectors: neuronal death in CA1 versus neurogenesis in dentate gyrus.
...
Ischemia induces Ca(2+) mobilization, calpain activation, lysosomal membrane disruption, and cathepsin release, which all occur specifically in the CA1 sector and cause neuronal death. In the postischemic DG, a vascular niche has been implicated in adult neurogenesis, in that adventitial cells of the DG microvascular environment provoke postischemic up-reguation of neurogenesis with the aid of brain-derived neurotrophic factor and polysialylated form of the neural cell adhesion molecule

So I'm a little cautious on the sodium butyrate. Looking around the web some schizophrenics have mixed results. Some people claim it's a great anti-depressant.

The schizophrenic results are worth exploring as schizophrenia is characterized by short-term memory disruption.

http://www.ncbi.nlm....pubmed/22917204

OBJECTIVE:
Disruption within the working memory (WM) neural network is considered an integral feature of schizophrenia. The WM network, and the dorsolateral prefrontal cortex (DLPFC) in particular, undergo significant remodeling in late adolescence. Potential interactions between developmental changes in the WM network and disease-related processes for schizophrenia remain unclear. The aim of this study was to determine whether DLPFC activation and functional connectivity are impaired during WM in patients with early-onset schizophrenia (EOS; age of onset <18 years).

I'll have to investigate a bit more on this angle.

Ok Sodium Butyrate isn't as weird as I thought. Seems to be pretty common in butter and cheese.

http://www.ncbi.nlm..../pubmed/8497370

We have studied the effect of butyrate on mammary tumorigenesis by 7,12-dimethylbenz(a)anthracene. As reported previously, a high incidence of mammary tumors was observed in rats fed a basal diet containing 20% margarine. However, the enhancing effect of margarine was inhibited when sodium butyrate was supplemented in the high margarine diet. Sodium butyrate did not cause any effect when it was supplemented in the basal diet. The result suggests a possibility that a part of the inhibitory effect of butter on mammary tumorigenesis, which we had previously reported, was caused by butyrate milk lipids.

This reminds me of the infamous "butter mind" experiment.

http://quantifiedsel...arithmetic-and/

At the last Bay Area Quantified Self Show&Tell, Seth Roberts presented new findings on his “Arithmetic and Butter” experiment. Seth does arithmetic problems every morning as a measure of his brain function. He found that eating half a stick of butter every day shaved 30 milliseconds off his time to solve the problems. Does butter improve brain function, or is Seth endangering his life, as a cardiologist in the audience worried? Catch the excitement in the video below.

So what foods are high in Butyrate?

http://www.livestron...gh-in-butyrate/

Whole Grains
...
Fruits and Vegetables
...
Milk Fat
...
Food Flavors
..

hmmm... This need more exploration.
Edited by abelard lindsay, 28 January 2013 - 07:25 AM.

Jaeggi and her colleagues claimed that they were able to improve fluid intelligence by training working memory. Subjects who trained their working memory on a dual n-back task for a period of time showed significant improvements in working memory span tasks and fluid intelligence tests such as the Raven's Progressive Matrices and the Bochumer Matrices Test after training compared to those without training. The current study aimed to replicate and extend the original study in a well-controlled experiment that could explain the cause or causes of such transfer if indeed the case. There were a total of 93 participants who completed the study, and they were assigned to one of three groups—passive control group, active control group and experimental group. Half of the participants were assigned to the 8-day condition and the other half to the 20-day condition. All participants completed a battery of tests at pre- and post-tests that consisted of short timed tests, a complex working memory span and a matrix reasoning task. Although participants' performance on the training task improved, results from the current study did not suggest any significant improvement in the mental abilities tested, especially fluid intelligence and working memory capacity, after training for 8 days or 20 days. This does not support the notion that increasing one's working memory capacity by training and practice could transfer to improvement on fluid intelligence as asserted by Jaeggi and her colleagues.

Anyone seen this study? Looks like it's from December.

http://www.sciencedi...160289612000839

Also just found a thread about this study: http://www.longecity...y-young-adults/
Edited by bobz1lla, 21 February 2013 - 06:43 AM.

Although this thread was an interesting concept, I believe it took a wrong turn at the very beginning. The wikki definition has some positive sides to it, but it ends up as defining it as something close to Excutive Function. I would suggest that that is the wrong way to approach it. Executive Function and Working Memory have been looked into extensively, but they cannot really even start to illustrate what Fluid Intelligence would truly have to be. Nor would most scientific studies do much good as Fluid Intelligence would be represented only by the best of the best scientists for example, and there is not a large group willing to be studied there.

One way to go about finding out about Fluid Intelligence would be to read popular books written by Nobel Prize winning and near prize winning scientists toward the end of their career when they a far more open in their real thinking processes. At that point they don't have to guard what they say or worry about all the taboos that would offend other less successful scientists. You see, there is a Hidden Game in all science communities, and part of fluid intelligence is avoiding the pitfalls without letting those taboos stop you from doing great science.

Fluid Intelligence by my definition is to have broad insight along with experience that is gained by exchanging information with other very sharp people in your speciality, and more importantly related and distant areas of expertise. the variables are vast, too vast to be studied in individual studies without a large amount of foundation knowledge, which can best be gained by actually reading these top scientists when they are most open and informal.

So what is this Fluid Intelligence that separates the best scientists from the merely analyitical scientists who have great Executive Function and Working Memory? How do they talk inside their trusted groups when they don't have to be guarded? Hint: It goes beyond math skills and logic, although these people are well grouded in those areas. Is there a brain area that talks to other areas that gets this "insight" level going? that's what Fluid Intelligence is you know, solid to great analytic skills backed up by insight. Insight is the critical difference that makes the difference though.
Edited by OverDu, 02 June 2013 - 02:02 PM.

This does start with Executive Function and Working Memory as one brain scientist looks at those as the exploring/searching part of the brain, and it is dopamine driven (as you people know), but it has to be balanced by inhibitory or GABA to function right. It works like this: the dopamine search affective parts of the brain gets entranced by novel problems and it goes into overdrive trying to solve the problem or problems. One uses all of ones logical and analytic abilities to follow every path, but often the novel problems do not give in in a straight forward manner to these efforts. Yet scientists with broad knowledge outside their specialty and connections with experts in close fields, and even apparently distant sciences -- their minds keep looking in a relaxed fasion even while asleep or doing recreational activities. Eventually an Aha! moment may hit them and give them a new key to solving the problem or problems.

David Perkins the Harvard "learning about learning" expert wrote a whole book about these searches called, "The Eureka Effect."

Let's continue this amazing exploratory thread!

Picking this back up again:

http://www.ncbi.nlm....pubmed/14764884

Science. 2004 Feb 6;303(5659):853-6.

Selective D2 receptor actions on the functional circuitry of working memory.
Wang M, Vijayraghavan S, Goldman-Rakic PS.
Author information

Abstract

Prefrontal neurons engaged by working memory tasks express a sequence of phasic and tonic activations linked to a train of sensory, mnemonic, and response-related events. Here, we report that the dopamine D2 receptor selectively modulates the neural activities associated with memory-guided saccades in oculomotor delayed-response tasks yet has little or no effect on the persistent mnemonic-related activity, which is instead modulated by D1 receptors. This associates the D2receptor with a specific component of working memory circuitry and fractionates the modulatory effects of D1 and D2 receptors on the neural machinery of a cognitive process.

PMID: 14764884 [PubMed - indexed for MEDLINE]

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Maybe looking at the downstream intracellular aspects of D1 and D2 agonism will yield some fruit.

D2:
http://en.wikipedia....ine_receptor_D2

This G protein-coupled receptor inhibits adenylyl cyclase activity.

D1:
http://en.wikipedia....ine_receptor_D1

This G protein-coupled receptor stimulates adenylate cyclase and indirectly activates cyclic AMP-dependent protein kinases.

Ahhh.. Adenylyl cylcase again. That's the ATP -> cAMP enzyme..... So d1 agonism and d2 antagonism should be synergistic with CILTEP. How is that related to short term memory then?

Another dead end... Sort of...
Edited by abelard lindsay, 05 January 2014 - 04:30 AM.

You are taking this butyrate thing from the wrong angle. Its not about eating it in its pure form its more about eating the substrate for the bacteria to produce it :-)

http://www.ncbi.nlm....pubmed/21450362

Inulin-type fructans are not digested and reach the human colon intact, where they are selectively fermented by the colon microbiota, in particular bifidobacteria. As a result, they are converted, directly or indirectly, to short-chain fatty acids and other organic acids, as well as gases, and lead to both bifidogenic and butyrogenic health-promoting effects.

So we have oligofructans or oligosaccharides and the like and we have something even better: resistant starch which one good form to use is potatoe starch or potatoe flour. It comes to the colon intact and can change the colonies of bacteria in your colon to allow "good" bacteria to grow there and to help them produce more of the sodium butyrate.

Here's a primer from one of the paleoblogs out there:

http://freetheanimal...ml<br /><br />Pretty interesting stuff, what do you guys think?

Still curious Abelard!

Regarding intelligence. I think the biggest contributors are working memory and processing speed. The biological manifestation of working memory is the DLPFC's ability to focus selectively and I believe that WM training can cover this base. But I'm interested in processing speed, and namely myelination. My experience with noots that increase myelination is super high lucidity and fast processing. I've been looking into the relationship between myelin, N-acetyl aspartate and intelligence. I hypothesize that N-acetyl aspartate may be able to be increase to achieve higher intelligence. Hopefully abelard can make sense of some of these studies.