Month: June 2015

Do scientists have to perpetuate memes in order to keep their jobs?

gettingwell4 < 0 Detracted from science, Amygdala, Anterior cingulate cortex, Beliefs, Cerebrum, Hippocampus, Limbic system, Thalamus , , ,

I was disgusted by this 2015 Korean human study.

Is the current state of science such that researchers won’t be funded unless there’s an implicit guarantee that their studies will produce politically correct findings? It seemed that the primary reason for the study’s main finding of:

“Neural markers reflecting individual differences in human prosociality”

was to perpetuate that non-causal, non-explanatory meme.

Per If research treats “Preexisting individual differences” as a black box, how can it find causes for stress and depression? it wasn’t sufficient in 2015 to pretend that there are no early-life causes for the observed behavior and fMRI scan results of the subjects. Such a pretense leads to the follow-on pretense that later-life consequences are not effects, but are instead, a “mystery” due to “individual differences.”

The researchers asserted:

“Our present findings shed some light on the mystery of human altruism.”

Weren’t the findings of the People who donated a kidney to a stranger have a larger amygdala 2014 study of extraordinary altruists big enough clues for these researchers to feature the amygdala in the fMRI scans?

The main experiment had the female, college student, right-handed subjects try to “reduce the duration of exposure to stressful noise.” Why weren’t brain areas that are especially susceptible to stress like the hippocampus featured in the fMRI scans?

The secondary reason for the study seemed to be to perpetuate the harmful “self-sacrifice = good, individuality = bad” meme.

The main reason this meme is harmful is that it condones a subset of people’s unconscious act outs. People are encouraged to avoid conscious awareness both of who they really are and of what drives their feelings, thoughts, and actions.

Despite not asking the subjects directly about either their motivations or their histories, these researchers asserted that the study demonstrated:

“The automatic and intuitive nature of prosocial motivation.”

What was largely observed were the subjects’ unconscious act outs, not some higher-order functions as the researchers mischaracterized them.

Similar to Who benefits when research promotes a meme of self-sacrifice? I suspect that a major motivation behind scientific justification for memes like the self-sacrifice promoted by this study is to rush people past what really happened in their lives.

I wonder what value we would place on the “social norms internalized within an individual” if we felt and honestly understood our real history.

This study and the Do you know a stranger’s emotional motivations for smiling? study had the same reviewer, and shared several of the burden-of-proof problems. Both studies demonstrated a lack of researcher interest in finding causes for the observed effects.

What was the agenda with these researchers and the reviewer? Why would the researchers glorify factors that cause difficulties when one tries to live a life of one’s own choosing?

http://www.pnas.org/content/112/25/7851.full “Spatial gradient in value representation along the medial prefrontal cortex reflects individual differences in prosociality”

Dopamine may account for differences in cognitive performance

gettingwell4 2-3 stars Required further work, Anterior cingulate cortex, Cerebrum, Dopamine, Hippocampus, Limbic system, Memory, Neurochemicals, Thalamus ,

This 2015 German human study found:

“Dopamine may account for adult age differences in brain signal variability.”

The researchers administered amphetamine to the subjects to boost their dopamine levels, and measured their cognitive performance on several working memory tests under fMRI:

“Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult..”

brain signal variability levels when on speed.

The order of the tests also influenced the results. Older adults who received amphetamine during the initial series of tests performed better on placebo during the second series of tests.

As is often done, the researchers focused on effects and not causes. I didn’t see questionnaires or investigation into possible historical or biological factors for reduced dopamine levels, leaving the researchers with age as the only correlated-but-not-causative explanation.

http://www.pnas.org/content/112/24/7593.full “Amphetamine modulates brain signal variability and working memory in younger and older adults”

How brains mature during critical periods

gettingwell4 5+ stars Premium, Brain development, Epigenetics, Hippocampus, Limbic system , , , ,

This 2015 German rodent study found:

“Once silent synapses are consolidated in any neural circuit, initial experience-dependent functional optimization and critical periods end.

Silent synapses are thought to be immature, still-developing excitatory synapses.”

The number of silent synapses related to visual processing was measured at ~50% at eye opening. Visual experience reduced this to 5% or less by adulthood in the study’s control group. Removing a protein in the subjects’ hippocampus silenced the synapses back up to ~50%, even in adults.

Critical periods are:

“Characterized by the absolute requirement for experience in a restricted time window for neural network optimization.

Although some functions can be substantially ameliorated after the CP [critical period], they are rarely optimally restored.”

Two human studies were cited on critical periods in second-language and musical skills development, Sensitive periods in human development: Evidence from musical training (not freely available).

The researchers generalized their findings as:

“Experience-dependent unsilencing of silent synapses constitutes an important general maturational process during CPs of cortical development of different functional domains and suggest an interplay with inhibitory circuits in regulating plasticity.”

http://www.pnas.org/content/112/24/E3131.full “Progressive maturation of silent synapses governs the duration of a critical period”

Unconscious stimuli have a pervasive effect on our brain function and behavior

gettingwell4 5+ stars Premium, Brain development, Cerebrum, Epigenetics, Limbic system, Lower brain, Memory, Primal Therapy , , , , ,

This 2015 Swedish human study, performed at the institution that awards the Nobel Prize in Physiology or Medicine, found:

“Pain responses can be shaped by learning that takes place outside conscious awareness.”

Images of neutral male faces were used as conditioning stimuli which the subjects were trained to associate with levels of pain.

The concluding sentence of the study:

“Our results demonstrate that conscious awareness of conditioned stimuli is not required during either acquisition or activation of conditioned analgesic and hyperalgesic responses, and that low levels of the brain’s hierarchical organization are susceptible for learning that affects higher-order cognitive processes.”

From the study’s abstract:

“Our results support the notion that nonconscious stimuli have a pervasive effect on human brain function and behavior and may affect learning of complex cognitive processes such as psychologically mediated analgesic and hyperalgesic responses.”

Principles of Dr. Arthur Janov’s Primal Therapy related to this study’s findings are:

  • Experiences associated with pain can be remembered below our conscious awareness.
  • Unconscious memories associated with pain, when activated, have varying forms of expression as they pass up through our levels of consciousness.
  • These memories, when activated, have effects on our feelings, thinking, health, brain functioning, and behavior that are usually below our conscious awareness.

I’ll use one of Dr. Janov’s 2011 blog posts, On Being Alone, to show an example of how the study’s findings of:

  • “Conscious awareness of conditioned stimuli is not required during either acquisition or activation of conditioned..responses” and
  • “Nonconscious stimuli have a pervasive effect on human brain function and behavior”

are seen through the lens of Primal Therapy:

Unconscious memories associated with the pain of being left alone may be stored, especially in the developing brain, in our lower brain areas below conscious awareness: “Pain of being left alone a lot in childhood and infancy, added to the ultimate aloneness right after birth when no one was there for the newborn. That imprints a primal terror where a naïve, innocent and vulnerable baby has no one to lean on, to be held by, to snuggle up to, to be comforted. To be loved.”
As we develop, the cumulative memories associated with the pain of being left alone, when activated, may affect our feelings, thoughts, and behavior: “And that also has multiple meanings: no one wants me; there is no one there for me: no one wants to be with me; I have no love and no one who cares. One races to phone others so as not to feel alone. One runs from the feeling and struggles mightily not to be alone. Or, depending on earlier events one stays alone out of that same feeling. These are by and large the depressives.”
Although memories associated with the pain of being left alone may be formed in our early lives, they remain decades later, and can be activated below our conscious awareness: “When something in the present occurs which is similar to an old feeling “I am all alone and no one wants me,” the old feelings are triggered off..and the whole feeling rises toward conscious/awareness where it must be combated. Either the person wallows in the feeling and is overwhelmed by it even when she doesn’t even know what “it” is. Or the compounded feeling drives the act-out, forcing the person into some kind of social contact.”

A PNAS commentary on the study stated:

“Pain, analgesia, and hyperalgesia represent higher-order cognitive functions.”

and attempted to draw conclusions from this reasoning.

The commentator was incorrect regarding pain. I didn’t see where this study showed or even postulated that pain was always a higher-order cognitive function. In fact, the researchers cited a sea slug study and stated:

“It would not be surprising if vestiges of simpler nonconscious processes would also be operative under some conditions.”

Maybe it would have provided clarifications if the researchers specifically defined “low” and “higher” used throughout the study in statements such as the closing sentence:

“Low levels of the brain’s hierarchical organization are susceptible for learning that affects higher-order cognitive processes.”

http://www.pnas.org/content/112/25/7863.full “Classical conditioning of analgesic and hyperalgesic pain responses without conscious awareness”

This post has somehow become a target for spammers, and I’ve disabled comments. Readers can comment on other posts and indicate that they want their comment to apply here, and I’ll re-enable comments.

The effects of inescapable, uncontrollable, repeated stress on the hippocampus

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Cerebrum, Cortisol, Epigenetics, Glutamate, Hippocampus, Limbic system, Neurochemicals, Stress , , ,

This 2015 MIT rodent study found:

“Behavioral stress impairs cognitive function via activation of a specific direct neural circuit from the basolateral amygdala to the dorsal hippocampus. Moreover, we delineate a molecular mechanism by which behavioral stress is translated to hippocampal dysfunction via a p25/Cdk5 (cyclin-dependent kinase 5)-dependent pathway and epigenetic alterations of neuroplasticity-related gene expression.”

The researchers made several intermediate findings to develop their main finding:

1. “Repeated stress is accompanied by

  • generation of p25,
  • up-regulation and phosphorylation of glucocorticoid receptors,
  • increased HDAC2 [the gene encoding the histone deacetylase 2 enzyme] expression, and
  • reduced expression of memory-related genes [most, but not all that were tested] in the hippocampus.”

2. “BLA [basolateral amygdala] activation is both necessary and sufficient for stress-associated molecular changes and memory impairments.”

3. “This effect [2. above] relies on direct glutamatergic projections from the BLA to the dorsal hippocampus.”

4. “p25 generation is necessary for the stress-induced memory dysfunction.”

From the Results section:

“Control mice showed a significant preference for the novel over the familiar object or location, whereas RFS [repetitive foot shock]-treated mice performed no better than chance.”

The subject adult mice underwent:

“Inescapable, uncontrollable repeated stress.”

Do humans also experience impaired “cognitive function” and “hippocampal dysfunction” and “epigenetic alterations of neuroplasticity-related gene expression” caused by “inescapable, uncontrollable repeated stress”?

And what are the real histories of people who aren’t curious, who don’t show “a significant preference for the novel over the familiar object or location”?

http://www.pnas.org/content/112/23/7291.full “Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway”

Measuring the signal-to-noise ratio of a brain neuron

gettingwell4 2-3 stars Required further work, Hippocampus, Limbic system, Thalamus

This 2015 study found that a single brain neuron’s

“Spiking history is often a more informative predictor of spiking propensity than the signal or stimulus activating the neuron.

Characterizing the reliability with which neurons represent and transmit information is an important question in computational neuroscience.”

Three of the four brain neuron areas studied were of the limbic system: a rat thalamus, a monkey hippocampus, and a human subthalamus area.

http://www.pnas.org/content/112/23/7141.full.pdf “Measuring the signal-to-noise ratio of a neuron” (pdf file is linked because the html has errors)

An inhibitory gene that affects alcohol binge behavior

gettingwell4 2-3 stars Required further work, Beliefs, Cerebrum, Dopamine, Limbic system, Lower brain, Neurochemicals, Thalamus , , ,

This 2015 La Jolla rodent study found that an inhibitory gene affected alcohol binging behavior:

“Our study reveals the behavioral impact of this cellular effect, whereby the level of GIRK3 [the gene] expression in the VTA [ventral tegmental area] tunes ethanol intake under binge-type conditions: the more GIRK3, the less ethanol drinking.”

GIRK3-silenced mice still binged, though, and got alcohol’s rewarding effects through dopamine’s other neural pathways.

High concentrations of the gene were found in the thalamus part of the limbic system of wild-type mice, the control group. Per the study’s title, this gene presumably contributes to the thalamus’ overall function of gating information from limbic system and lower brain areas to reach the cerebrum and vice versa.

And the potential causes for reduced GIRK3 expression are..?? Hopefully – someday – researchers will be focused on finding causes for abnormal gene expression rather than being content to just study effects of abnormal gene expression. Until then, the usual practice of considering only the effects led these researchers to:

“Believe that a compound selectively targeting GIRK3-containing channels may hold promise for reducing alcohol consumption in heavy binge drinkers.”

http://www.pnas.org/content/112/22/7091.full “GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol”

Epigenetic changes in the developing brain change behavior

gettingwell4 4-5 stars Advanced knowledge, Brain development, Epigenetics, Hippocampus, Limbic system, Neurochemicals, Serotonin, Stress , , , , ,

This 2015 review cited 143 studies to tie together findings in epigenetic chemistry and behavioral neuroscience.

In addition to studies I’ve previously curated, other research included:

  • a 2012 study which completely abolished mouse maternal behavior by silencing a gene encoding an estrogen receptor;
  • a 2012 study which found that stress-induced changes in the rat hippocampus were heritable;
  • a 2014 study that distinguished between transgenerational and intergenerational epigenetic effects such as:

    “in utero exposure to nutritional status, stress, or toxic environmental factors that act on the developing embryo and its germ line”

  • a 2013 study that showed how genomic imprinting coordinated:

    “Genetic coadaptation where beneficially interacting alleles evolve to become coinherited.”

The current status of research incorporating both epigenetic chemistry and behavioral neuroscience was summed up as:

“A large number of behavioral epigenetic studies attempt to correlate epigenetic marker changes at global levels and in mixed populations of cells with phenotypic changes.

Specific changes at specific gene levels and at single cell levels correlating with behavioral changes remain largely unknown.”

http://www.pnas.org/content/112/22/6789.full “Epigenetic changes in the developing brain: Effects on behavior”

RNA as a proxy signal for context-specific biological activity

gettingwell4 2-3 stars Required further work, Brain development, Cerebrum, Hippocampus, Hypothalamus, Limbic system, Thalamus , ,

This 2015 Harvard/MIT rodent study was of long (more than 200 nucleotides) noncoding (non-protein coding) RNAs (ribonucleic acids). These are of interest because:

“Within the mammalian body, the largest repertoire and diversity of lncRNA genes outside the germ line occurs in the brain, where lncRNAs exhibit regional and cell-specific localization.

The expression patterns of lncRNAs may serve as a proxy signal for important, context-specific biological activity.”

The researchers explained what they could and couldn’t determine with current techniques and technologies:

“The whole-gene ablation method used here is often a first approach to determine the functionality of a locus.

Although each of these loci contains a lncRNA, it is important to consider that any observation resulting from this strategy could reflect the loss of any regulatory element in the deleted region.

The rate of lncRNA gene discovery has significantly outpaced our ability to evaluate both the physiological significance and function of these genes. It is difficult to predict whether the loss of any particular lncRNA locus will present a phenotype, but crucial information on the spatiotemporal dynamics of expression from each locus can provide significant direction and focus to downstream mechanistic studies by highlighting those loci most likely to have a physiological impact.

It is important to stress that no single method exists that can account for all possible mechanisms of action of a noncoding locus. Within these limits, the phenotypes observed after ablation of specific lncRNA loci confirm that expression of this class of noncoding RNAs can serve as a proxy signal to identify functional genomic loci with physiological relevance to disease and development, independent of whether this activity is directly ascribed to a functional lncRNA molecule.”

http://www.pnas.org/content/112/22/6855.full “Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain”

Stress in early life can alter physiology and behavior across the entire lifespan

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Brain development, Cerebrum, Cortisol, Epigenetics, Hippocampus, Immune system, Limbic system, Memory, Neurochemicals, Stress, Testosterone , , , , , , , ,

I’ll quote a few sections of this 2014 summary of 111 studies concerning stress, including the authors’ research:

“The brain is the central organ of stress and adaptation to stressors because:

  • It not only perceives what is threatening or potentially threatening and initiates behavioral and physiological responses to those challenges,
  • But also is a target of the stressful experiences and the hormones and other mediators of the stress response.

The stress history of parents is a significant factor in the resilience of their offspring.

Environmental stress transduces its effects into lasting changes on physiology and behavior, which can vary even among genetically identical individuals.

Stress in early life can alter physiology and behavior across the entire lifespan.

Structural stress memory is even more apparent with regard to gene expression in stress-sensitive brain regions like the hippocampus.

Individual history is important and that there is a memory of stress history retained by neurons at the cellular level in regions like the hippocampus.

Stress has a number of known effects on epigenetic marks in the brain, producing alterations in DNA methylation and histone modifications in most of the stress-sensitive brain regions examined, including the hippocampus, amygdala, and prefrontal cortex.”

It seemed to be taboo to note that most of – and the largest of – detrimental effects of stress occurred during womb-life in the mother’s environment. The authors instead opted for a politically correct “the stress history of parents” phrase.

Referenced studies had findings relevant to the earliest periods of life, including Figure 1:

interactions

“Those organs that show the highest levels of retrotransposon [a repeat element (mobile DNA sequences often involved in mutations) type formed by copy-and-paste mechanisms] activity, such as the brain and placenta, also seem to be both steroidogenic and steroid-sensitive.”

However, Figure 1 was given a beneficial context, and other studies’ findings weren’t mentioned in their contexts of detrimental effects on fetuses of mothers who were stressed while pregnant.

http://www.pnas.org/content/112/22/6828.full “Stress and the dynamic genome: Steroids, epigenetics, and the transposome”