0-1 star Wasted resources

Research that wasted resources

A study of visual perception that didn’t inform us about human conscious awareness

gettingwell4 0-1 star Wasted resources, Cerebrum, Limbic system, Lower brain ,

This 2015 Vanderbilt study with a Princeton reviewer stated that they found “compelling evidence” related to:

“How the brain begets conscious awareness.

Identifying the fingerprints of consciousness in humans would be a significant advancement for basic and medical research, let alone its philosophical implications on the underpinnings of the human experience.”

Let’s begin with the “conscious” part of the study’s conscious awareness goal. A summary article of 105 studies entitled Evolution of consciousness: Phylogeny, ontogeny, and emergence from general anesthesia that I curated found:

“The core of human consciousness appears to be associated primarily with phylogenetically ancient structures mediating arousal and activated by primitive emotions.”

The current study ignored the evolutionary bases of human consciousness and didn’t include any limbic system and lower brain areas. The researchers’ biases were further indicated by the statement from their press release:

“Focal theories contend there are specific areas of the brain that are critical for generating consciousness, while global theories argue consciousness arises from large-scale brain changes in activity.”

The researchers were in the “global” camp of this unnecessary divide.

Let’s next examine the “awareness” part of the study’s conscious awareness goal. The subjects were 24 students in a visual perception experiment that used fMRI. The visual events that were perceived went into the “aware” bucket and the others into the “unaware” bucket.

The study’s subject selection criteria and experiment seemed a little odd for developing “compelling evidence” related to “how the brain begets conscious awareness.” By equating visual perception with awareness, the researchers excluded the contributions of other senses and methods of awareness.

Would it follow from the study’s methodology that blind people can’t be consciously aware?

The supplementary material showed that 7 of the 24 subjects’ results for one experimental condition, and 12 – half – of the subjects’ results for another condition were excluded because they apparently had problems reporting confidence in their visual perception. I wonder why the reviewer agreed that it was appropriate to discard half of the subjects’ experimental results?

Whatever else it was that the study found, the researchers didn’t reach their goal of developing “compelling evidence” related to “how the brain begets conscious awareness.”

http://www.pnas.org/content/112/12/3799.full “Breakdown of the brain’s functional network modularity with awareness”

A study on online cooperation with limited findings

gettingwell4 0-1 star Wasted resources, Cerebrum, Limbic system, Lower brain ,

This 2015 Cambridge/Oxford study found:

“Global reputational knowledge is crucial to sustaining a high level of cooperation and welfare.”

Basically, the subjects learned how to “game” a cooperative online game, and the researchers drew up their findings.

To me, the study demonstrated part of the findings of the Reciprocity behaviors differ as to whether we seek cerebral vs. limbic system rewards study, the part where the cerebrum was active in:

“Reputation-based reciprocity, in which they help others with good reputations to gain good reputations themselves.”

The current study ignored how people’s limbic system and lower brain areas may have motivated them to cooperate.

I didn’t see how excluding people’s emotional involvement when cooperating with others improved the potential reach of this study’s findings. Doesn’t a person’s willingness to cooperate in person and in online activities usually also include their emotional motivations?

The findings can’t be applied generally to cooperative motivations and behaviors that the researchers intentionally left out of the study. The study’s findings applied just to the artificial environment of their experiment, and didn’t provide evidence for how:

“Cooperative behavior is fundamental for a society to thrive.”

http://www.pnas.org/content/112/12/3647.full “The effects of reputational and social knowledge on cooperation”

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.

Pulling on the chain of causes and effects with insulin resistance

gettingwell4 0-1 star Wasted resources, Cortisol, Dopamine, Neurochemicals, Stress , , ,

This 2015 Harvard rodent study found multiple undesirable symptoms and attributed the cause to insulin resistance, which is itself a symptom.

Humans most often develop the symptom of insulin resistance due to causes other than genetics, such as a result of abnormal eating behaviors, which are symptoms of other causes.

Use of insulin-resistant-due-to-genetics mice may have misdirected the researchers to lose focus that their ultimate task was to find ways that their research can help humans. If helping humans was the researchers’ focus, it may have occurred to them to develop evidence for how “something” caused symptoms such as abnormal eating behaviors, that in turn caused a symptom of insulin resistance.

The study’s unexamined causes included why genetically insulin-resistant mice developed symptoms of anxiety and depressive-like behaviors between early adulthood and late middle age. Examples of undesirable symptoms described in the supplementary material included:

  • Higher body weight in late middle age, especially in females;
  • Depressive-like behavior in both sexes by late middle age;
  • Higher corticosterone levels in both sexes by late middle age, even when unstressed; and
  • Higher corticosterone levels in late middle age when stressed, especially in males.

It’s remarkable how researchers consistently get caught in a loop of studying only symptoms, paying little attention to studying causes, then suggesting various medications and treatments to suppress the studied symptoms.

It’s not surprising then that there’s no explanation of why and how symptoms develop. The study designs seldom include trying to show causes for the effects in the first place!

http://www.pnas.org/content/112/11/3463.full “Insulin resistance in brain alters dopamine turnover and causes behavioral disorders”

Losing track of what are symptoms and what are causes with serotonin and stress

gettingwell4 0-1 star Wasted resources, Limbic system, Neurochemicals, Serotonin, Stress, Thalamus ,

I’m starting to appreciate just how far down the rabbit hole researchers can go when they focus on symptoms and ignore causes.

This 2014 Duke study found that low-serotonin mice were more susceptible to stress than normal mice.

Okay so far, except that the study used transgenic mice that only had 20-40% of normal serotonin.

Humans most often develop low-serotonin symptoms for causes other than genetics, such as a second-order result of being subjected to childhood maltreatment and stress.

Use of the low-serotonin-due-to-genetics mice may have misdirected the researchers to lose focus that their ultimate task was to find ways that their research can help humans. If helping humans was the researchers’ focus, it may have occurred to them to show how stress caused “something” that caused low serotonin.

A second finding was that following exposure to stress, the low-serotonin mice didn’t respond to a standard antidepressant, fluoxetine. SSRI medications usually act to increase serotonin transmission, i.e. treat the symptom of low serotonin.

Stress was again not viewed as a cause of “something” that caused low serotonin. Stress was viewed as the reason that the medication didn’t work.

If helping humans was the researchers’ focus, it may have occurred to them that humans may not need medication to treat the low-serotonin symptom if the “something” that stress caused that keeps the low-serotonin symptom in place was removed.

A third finding was that inhibiting the lateral habenula area (proximal to the thalamus) with a drug relieved some depression-like behavior of the low-serotonin mice.

Okay, but one of the researchers went on to say:

“The next step is to figure out how we can turn off this brain region in a relatively non-invasive way that would have better therapeutic potential.”

Would everything would be fine if the low-serotonin mice just stopped displaying symptoms such as the depression-like behavior? Why no focus on causes, no forward thinking that maybe humans wouldn’t want part of their limbic system that performed many other functions to “turn off” just to suppress a symptom?

The researchers apparently didn’t realize their situation viz-à-viz the rabbit hole, as they circled back to the initial finding to develop a fourth finding – a possible reason that low-serotonin mice were more susceptible to stress was because a signaling molecule, β-catenin, wasn’t produced in a pathway that may be involved in resilience.

The news coverage added one more researcher quote:

“If we can identify what’s both upstream and downstream of β-catenin we might be able to come up with attractive drug targets to activate this pathway and promote resilience.”

If we treat a third-order symptom, the signaling molecule, everything will be alright?

Which leads me to ask:

http://www.pnas.org/content/112/8/2557.full “Brain 5-HT deficiency increases stress vulnerability and impairs antidepressant responses following psychosocial stress”

If research treats “Preexisting individual differences” as a black box, how can it find causes for stress and depression?

gettingwell4 0-1 star Wasted resources, Epigenetics, Immune system, Stress ,

This 2014 research studied both humans and rodents to provide further evidence on the physiology of defeat. The researchers demonstrated that with mice:

“Bone marrow transplants of stem cells that produce leucocytes lacking IL-6 (the cytokine interleukin 6) or when injected with antibodies that block IL-6 prior to stress exposure, the development of social avoidance was reduced.”

The researchers also showed in humans that standard antidepressants didn’t act to lower IL-6.

So, what were we to make of this finding?

“Preexisting differences in the sensitivity of a key part of each individual’s immune system to stress confer a greater risk of developing stress-related depression or anxiety.”

  • Was it sufficient for the researchers and the news articles covering the research to treat “preexisting differences” as a black box that nobody could enter to find causes for the effects of “developing stress-related depression or anxiety?”
  • Did things happen in each individual’s history to cause the “preexisting differences” or was each individual born that way?
  • Why was the research directed at symptoms with no mention of any underlying causal factors?

It wasn’t sufficient for the researchers to carry on their experiments with assumptions that there weren’t early-life causes for the above symptoms. Such a pretense leads to the follow-on pretense that later-life consequences weren’t effects of causes, but were instead, mysteries due to “preexisting individual differences.”

http://www.pnas.org/content/111/45/16136.full “Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress”

An example of how we are unaware of some of the unconscious bases of our decisions

gettingwell4 0-1 star Wasted resources, Beliefs, Cerebrum, Limbic system, Lower brain , ,

This 2014 human study provided details of how we are unaware of some of the unconscious bases of our decisions:

“We show that unconscious information can be accumulated over time and integrated with conscious elements presented either before or after to boost or diminish decision accuracy.

The unconscious information could only be used when some conscious decision-relevant information was also present.

Surprisingly, the unconscious boost in accuracy was not accompanied by corresponding increases in confidence, suggesting that we have poor metacognition for unconscious decisional evidence.”

I wouldn’t agree that these findings apply as broadly as the researchers said they did during interviews.

The first reason is that the researchers restricted the study to the subjects’ cerebrums’ visual processing. In everyday life, though, our limbic systems and lower brains are also very much involved with visual processing.

As an example, have you ever taken a nature walk where you instinctually jumped back from a vague initial impression only to find that the object was a stick? I’ve done that many times, and our shared human instincts operating with the limbic system and lower brain saved me once in childhood from stepping on a copperhead snake.

Secondly, the researchers limited the term “unconscious” to mean below visual perception of the subjects’ cerebrums.

What if, for example, the study’s visual cues included emotional content that involved the subjects’ limbic systems? The researchers may have able to develop a basis for findings that applied to common operations such as making decisions that are influenced by unconscious emotional content.

The third reason to not apply the findings as broadly as the researchers may have desired is that the researchers limited the term “metacognition” to operations of the the subjects’ cerebrums. We know that Task performance and beliefs about task responses are solely cerebral exercises, which accurately describes the metacognition experiment.

As an example of how people’s metacognitions are much broader than just their cerebrums, I take a crowded train to and from work everyday. It’s fairly straightforward to understand people’s actions, body postures, and facial expressions in terms of the combined metacognition operations of their entire brains.

Also, the metacognition finding sample size may have been too small by involving only five subjects.

http://www.pnas.org/content/111/45/16214.full “Unconscious information changes decision accuracy but not confidence”

If rodent training had beneficial epigenetic effects, how can the next step be human gene therapy?

gettingwell4 0-1 star Wasted resources, Epigenetics, Memory , ,

This 2014 rodent study detailed significant and lasting epigenetic DNA methylation in the hippocampus part of the limbic system as a result of fear-extinction training.

The researchers missed the boat when explaining in interviews how their research could apply to humans. What I understood from the interviews was that the researchers were focused on targeting human genes with some outside action.

Recommending human gene therapy smelled like an agenda. If these epigenetic modifications were induced by training in rodents, wouldn’t the next step be research into reversal training or therapeutic activity for humans?

The researchers also found:

“Importantly, these effects were specific to extinction training and did not occur in mice that had been fear conditioned, followed by a single reactivation trial, therefore arguing against the possibility that such epigenetic modifications are nonspecifically induced by the retrieval or reconsolidation of the original fear memory.”

This was fine for rodent studies where the origins of both the disease and the cure were all exerted externally. I didn’t see that it necessarily applied to humans.

After all, we’re not lab rats. We can perform effective therapy that doesn’t involve some outside action being done to us.

http://www.pnas.org/content/111/19/7120.full “Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation”

What happens next after a detox program predictably fails?

gettingwell4 0-1 star Wasted resources, Beliefs, Limbic system, Lower brain, Memory, Primal Therapy , ,

This 2014 study was a misguided example of looking solely at the presenting parts of a person’s condition rather than the whole historical person.

What did this study’s researchers decide after finding:

“Alcohol-dependent subjects..remained with high scores of depression, anxiety, and alcohol craving after a short-term detoxification program.”

Was it that the detox program didn’t work because it dealt with suppressing symptoms rather than addressing causes?

NO!

The researchers decided:

“Gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.”

The researchers proceeded on some trendy, in-vogue aspect of their patients with which to tinker.

The researchers ignored that the correlation of the new treatment course didn’t show causation. They also ignored underlying causes for the ineffectiveness of the preceding treatments of symptoms.

Hard to see how the reviewer believed that this study would advance science.

Meanwhile, the researchers continued to ignore the elephants in the room: the relationships of the patients’ histories and their pain.

http://www.pnas.org/content/111/42/E4485.full “Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity”

If research provides evidence for the causes of stress-related disorders, why only focus on treating the symptoms?

gettingwell4 0-1 star Wasted resources, Brainstem, Cortisol, Hippocampus, Hypothalamus, Limbic system, Locus coeruleus, Lower brain, Memory, Neurochemicals, Stress , , ,

This 2014 rodent research reliably induced many disorders common to humans. Here are some post-birth problems the researchers caused, primarily by applying different types of stress, as detailed in the study’s supplementary material:

Yet the researchers’ goal was to identify a brain receptor for:

“Novel therapeutic targets for stress-related disorders.”

In other words, develop new drugs to treat the symptoms.

Where are the studies that have goals to prevent these common problems being caused in humans by humans?

Where is the research on treatments to reverse the enduring physiological impacts to stress by treating the causes?

What do you think of this excerpt?

“Accumulating evidence suggests that traumatic events particularly during early life (e.g., parental loss or neglect) coupled with genetic factors are important risk factors for the development of depression and anxiety disorders.

Moreover, the brain is particularly vulnerable to the effects of stress during this period.

Maternal separation in rodents is a useful model of early-life stress that results in enduring physiological and behavioral changes that persist into adulthood, including increased hypothalamic–pituitary–adrenal (HPA)–axis sensitivity, increased anxiety, and visceral hypersensitivity.”

http://www.pnas.org/content/111/42/15232.full “GABAB(1) receptor subunit isoforms differentially regulate stress resilience”

Are stress-induced epigenetic changes to DNA inherited across generations?

gettingwell4 0-1 star Wasted resources, Amygdala, Brain development, Cortisol, Epigenetics, Limbic system, Memory, Neurochemicals, Stress , , , , ,

This 2014 Geneva/Cambridge plant study ended by stating:

“The unequivocal demonstration of transgenerational transmission of environmentally-induced epigenetic traits remains a significant challenge.

One of the critical activities erasing stress memories is conserved between plants and mammals.”

However, the researchers didn’t demonstrate that their findings were broadly applicable for mammals or organisms other than the specific plant variety they studied. Possible reasons for these limited findings were given in a 2015 Australian study referenced by Mechanisms of stress memories in plants:

“The majority of DNA methylation analyses performed in plants to date have focused on Arabidopsis, despite being relatively depleted of TEs [transposable elements] (15–20% of the genome) and being poorly methylated compared to other plant genomes.

These studies have lacked the resolution to provide the specific context and genomic location of the changes in DNA methylation.”

There are also significant differences in how epigenetic inheritance across generations may operate among different species per Epigenetic reprogramming in plant and animal development.

Neither the current study nor the above review addressed the behavioral aspect of stress-induced epigenetic inheritance across generations. For example, the behavior of a mother whose DNA was epigenetically changed by stress can induce the same epigenetic changes to her child’s DNA when her child is stressed per One way that mothers cause fear and emotional trauma in their infants:

“Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups’ stress response paired with the cue to induce amygdala-dependent learning plasticity.”

http://www.pnas.org/content/111/23/8547.full “Identification of genes preventing transgenerational transmission of stress-induced epigenetic states”

We feel anxious even when making a choice from multiple good options

gettingwell4 0-1 star Wasted resources, Cerebrum, Limbic system, Lower brain

This 2014 Harvard/Princeton research studied brain areas as people made choices among multiple good options:

“Our results show that choice conflict can at least lead to substantial short-term anxiety, that this anxiety increases with the number and value of one’s options (potentially enhanced by time pressure), and that it is not attenuated by awareness of the objectively negligible costs of a “bad” choice.”

There was a problem with the way the researchers evaluated “positive feelings” through the subjects’ computerized self-reporting. The subjects’ cerebral assessments of “positive feelings” didn’t match their limbic system functional MRI measurements.

These discrepancies showed that what the subjects assessed weren’t emotions originating from their limbic system or lower brains. “Positive feelings” were, instead, constructs of the subjects’ cerebrums.

“This is what I think I should be feeling” may have been a more appropriate characterization of the subjects’ assessments.

The study had better accuracy when fMRI measurements showed that limbic system areas were more activated in people who self-reported feeling more conflicted at the time they made their choice. The conflicted subjects were also more likely than subjects whose limbic system areas weren’t similarly activated, to reverse their choice when given the opportunity.

http://www.pnas.org/content/111/30/10978.full “Neural correlates of dueling affective reactions to win–win choices”

Problematic research on human happiness

gettingwell4 0-1 star Wasted resources, Beliefs, Cerebrum, Limbic system, Lower brain

This 2014 UK study provided an example of researchers inappropriately ignoring the limbic system and lower brains when allegedly researching emotions. Only cerebral areas were measured and considered in the researchers’ efforts to measure the subjects’ happiness.

Efforts to determine emotions by cerebral measurements seldom reveal what people actually feel. What’s measured is a construct of people’s cerebrums – a proxy for their emotions – that may not have anything to do with what people actually feel at the time.

It may have been more appropriate to characterize the subjects’ self-reports of happiness as “This is what I think I should tell the researchers about what I think I should feel.”

What we think we should feel is separate from what we actually feel. Limbic system and lower brain measurements need to be taken and considered when subjects self-report degrees of happiness if the researchers intend to draw conclusions about feelings of happiness.

“We show that emotional reactivity in the form of momentary happiness in response to outcomes of a probabilistic reward task is explained not by current task earnings, but by the combined influence of recent reward expectations and prediction errors arising from those expectations.”

It was the researchers’ cerebral exercise of expectations and prediction errors to find:

“Moment-to-moment happiness reflects not just how well things are going, but whether things are going better than expected.”

Informed by the Using expectations of oxytocin to induce positive placebo effects of touching is a cerebral exercise study, I consider the current study to be one big demonstration of how researchers can be fooled by a positive placebo effect!

http://www.pnas.org/content/111/33/12252.full “A computational and neural model of momentary subjective well-being”

Problematic research: Is sleep deprivation a therapy for depression? Seriously?

gettingwell4 0-1 star Wasted resources, Limbic system

This 2013 Zurich study provided details of depression symptoms, particularly in limbic system structures.

As often happens when researchers are absorbed in studying symptoms, there was nothing about treating the causes, in this case, of depression.

Sleep deprivation as a viable therapy for enduring depression? Is that or drugs really all that science has to offer for depression?

http://www.pnas.org/content/110/48/19597.full “Sleep deprivation increases dorsal nexus connectivity to the dorsolateral prefrontal cortex in humans”

Problematic research on the hippocampus part of the limbic system

gettingwell4 0-1 star Wasted resources, Hippocampus, Limbic system, Memory

This 2014 UK human study of the CA3 region of the hippocampus found:

“Individual differences in subjective mnemonic experience can be accurately predicted from measurable differences in the anatomy and neural coding of hippocampal region CA3.”

I emailed the authors as follows:

“I read the “CA3 size predicts the precision of memory recall” study, and I wondered how it could be used to help people.

I am not a scientist; I am a software developer by trade. I read the abstracts of each new issue of PNAS with an eye to how studies can help people, which I think is an implied reason to publicly fund research.

The study’s supporting information reveals that the participants scored no emotional involvement with the tasks’ memories. This variable thus did not influence the finding that the contexts of participants’ memories were not a factor.

Could it be that the study’s findings apply to only non-emotional memories, and that context could be a factor in memories that involve emotions?

Given the large role of the hippocampus in our emotional memories, would it not have been realistic to include emotional content in the study? Was it a design decision to not involve the participants’ emotions?

The study found that memory retrieval confusion increased with a participant’s smaller CA3 size. We know from studies such as http://www.pnas.org/content/109/9/E563.full “Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum” and its references that emotional experiences influence CA3 anatomy.

Could it be that the study’s participants were not all sampled from the same brain population?”

http://www.pnas.org/content/111/29/10720.full “CA3 size predicts the precision of memory recall”

Let’s not miss a big clue! Embryonic precursor transplants in adult hippocampus

gettingwell4 0-1 star Wasted resources, Brain development, Hippocampus, Limbic system ,

This 2014 rodent study induced “multiple psychosis-relevant phenotypes“ by disrupting specific functions of the hippocampus. The researchers then “cured” the brain disorders:

“Transplanting interneuron progenitors derived from the embryonic medial ganglionic eminence into adult hippocampus mitigates these abnormalities.”

However, full function of the hippocampus wasn’t restored.

I disagree that this study’s findings:

“Support a rationale for targeting limbic cortical interneuron function in the prevention and treatment of schizophrenia.”

People with schizophrenia aren’t lab rats and shouldn’t be treated as such. They often don’t need something externally done to them to recover from brain disorders.

Doesn’t the fact that embryonic precursors to the adult brain helped “cure” the abnormalities tell us where to look for the disorders’ beginnings? Let’s not miss a big clue as to when brain disorders may start.

http://www.pnas.org/content/111/20/7450.full “Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition”