Memory

A missed opportunity to study odor-evoked emotional memories

gettingwell4 0-1 star Wasted resources, Anterior cingulate cortex, Cerebrum, Hippocampus, Limbic system, Memory

The researchers of Can a study exclude the limbic system and adequately find how we process value? published another study. In this 2015 human study, subjects were monitored with fMRI scans while making choices on the identity and pleasantness of rewarding food odors.

I feel that the researchers missed quite a few good opportunities to advance science. Instead of making peripheral assessments of limbic system areas and citing numerous other studies, they could have included emotional content in their study and drawn their own conclusions.

Consider these opportunities:

  • Wouldn’t the odors used in the study such as chocolate cake and pizza and strawberry and potato chips – and other “comfort” foods – potentially be associated with emotional responses?
  • Don’t most humans have memories that include pleasant food odors?
  • Wouldn’t it have been informative to ask the subjects during fMRI scans to identify what emotions were evoked by the pleasant food odors?
  • Wouldn’t these resultant fMRI scans be expected to potentially show more strongly activated limbic system areas, given the hippocampus’ position as the seat of emotional memories?
  • Wouldn’t the additional emotional responses and memories and subsequent limbic system area activations potentially influence the subjects’ value judgments?

Instead, the researchers peripherally included limbic system areas in the study. The supplementary material included passages such as:

“Identity-specific value signals were found in not only the OFC, [orbitofrontal cortex] but also the ACC [anterior cingulate cortex] and hippocampus.”

Like the previous study, the current study’s focus was to provide evidence that areas of the cerebrum were in control when people made value judgments. The term “value” in the current study meant:

“the pleasantness of the odor.”

Like the previous study, areas of the limbic system weren’t addressed until the tail end of the supplementary material. The researchers cited other studies in an attempt to dismiss the role of the ACC in making value judgments, then said:

“Although we are unable to distinguish between these alternative explanations, our findings suggest that value-related signals in ACC—whether signed or unsigned—are specific to the identity of the expected outcome.”

Since the current study found that “identity” was encoded by cerebral areas, the above sentence was written to nudge the reader into inferring that the cerebrum dominated value judgments of “the pleasantness of the odor.”

The researchers similarly cited other studies in the last paragraph instead of specifically discussing how they studied the participation of the hippocampus part of the limbic system. They then speculated that the hippocampus’ contributions to value judgments in the current study were explained by the referenced studies:

“We speculate that the hippocampus is involved in retaining sensory-based information about specific rewards, which may be linked to value-based representations in OFC for later consolidation.”

Like the previous study, the researchers were begrudgingly diverted away from their focus on cerebral areas when they were forced to acknowledge the limbic system’s contributions to value judgments of “the pleasantness of the odor.”

http://www.pnas.org/content/112/16/5195.full “Identity-specific coding of future rewards in the human orbitofrontal cortex”

Problematic research that ignored the hippocampus as the seat of emotional memories

gettingwell4 < 0 Detracted from science, Cerebrum, Hippocampus, Limbic system, Memory

If this 2015 human study from the San Diego Veterans Administration developed findings of any note, I didn’t see them.

Like other studies, this study ignored the hippocampus’ position as the seat of emotional memories. The experiments were designed to not contain any emotional content.

The researchers mainly wanted to fight a 60-year old battle on whether or not the hippocampus contributed to spatial processing. They ignored all the research on place cells, such as:

to name three of the hundreds of place cell studies available.

By ignoring these and other studies, the researchers declared:

“We have not found evidence that this is the case.”

The lead researcher continued with speculations that couldn’t be verified with the current experiments’ data:

“We think they can do these spatial tasks because these tasks can be managed within short-term memory functions, supported by the frontal lobe of the neocortex.

The spatial tasks that we can do with our neocortex using short-term memory must be performed by the hippocampus in rats.”

Basically, the rest of the scientific world must supply irrefutable evidence (which will be ignored) but the reader can just take the lead researcher’s words as fact for what’s going on inside human and rodent brains, although:

  • No fMRI scans were performed during the experiments,
  • No hard measurements were taken.

The findings were based on observations of six subjects:

  • With hippocampal lesions of unspecified duration,
  • Drawing pictures, and
  • Narrating what they imagined about a playground.

I wonder what the reviewers saw in this study that factually advanced science. Did the statement:

“These results support the traditional view that the human hippocampus is primarily important for memory.”

convey something new? Make a contribution to science?

Studies like this one not only detract from science. They are also a waste of resources that supposedly the Veterans Administration have in short supply.

The design and data of such studies are not able to reach levels where they can provide evidence of causes and effects of anything within their scope. That’s a good indication of some other agenda in play.

http://www.pnas.org/content/112/15/4767.full “Memory, scene construction, and the human hippocampus”

Why is it so difficult to live your own life?

gettingwell4 5+ stars Premium, Memory, Primal Therapy ,

This 2015 Princeton/German study of fish schooling behavior reminded me of one of the difficulties an individual has in living a life of their own choosing. The study showed that the way social animals have evolved makes the individual likely to do what the group does.

Before looking at some details of the study, I’ll point out a natural pro and con of an individual going along with the crowd. A major survival advantage is that a predator won’t find it as easy to single out an individual from the group.

A major survival disadvantage is that a group is easily manipulated into a fate that each individual wouldn’t experience on their own. Here’s one instance of such an event:
Alfred Jacob Miller “Hunting buffalo” 1837

The difference in this study as compared with other literature on the subject was that there were a lot of equations presented:

“We demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur.

Establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.”

Does this sound like it could apply to humans?

“We define susceptibility as the likelihood of a fish responding given that it observes the initiator.

An individual will be more likely to respond (is more susceptible) if it:

  • Is strongly connected to the initiator (short path length), and
  • Has neighbors which are strongly connected to each other.

Shortest paths represent most probable paths.”

This passage definitely applied to humans:

“Such waves of evasion can spread extensively or may rapidly die out, resulting in a broad distribution of cascade magnitudes (number of responding individuals), a property shared with other spreading processes [e.g., neural activity, human communication].

In contrast to analyses of social contagion for online social networks, such as Twitter and Facebook, individuals’ proximity to the core of the network is not predictive of social influence.”

Schooling and herding behaviors are largely no longer needed for humans to survive in today’s world. However, these can be seen all day every day.

Why are such leftover behaviors still around? They are certainly misplaced from their original contexts.

The places and times in which these actions and reactions were relevant to survival have passed. They don’t make sense in other contexts in the present.

To lead to answers, purchase Dr. Arthur Janov’s 2011 book “Life Before Birth: The Hidden Script that Rules Our Lives” and read the passages listed in the index under the “survival” term. I’ll quote the beginning of a paragraph from page 52:

“What’s happening here is that the body, in the interest of survival, is continually reacting to imprinted memory..”

An individual may find it difficult to live a life of their own choosing due to external influences such as those presented in this study. There are also difficulties in living your own life that have other origins, as delineated by principles of Primal Therapy.

http://www.pnas.org/content/112/15/4690.full “Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion”

Can you give emotionally informed yet reasoned responses to moral questions within 3 seconds?

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

Could you give a 3-second informed decision that reflected your true feelings about this statement?

“Inflicting emotional harm is just as bad as inflicting physical harm.”

Could you then express your confidence about your answer on a 1-7 scale within 1 second? How about your 3-second response to this statement:

“Developing a child’s character is central to raising it good.”

The researchers of this 2015 Swedish study asserted that it:

“Demonstrates that moral choices are no different from their preferential and perceptual counterparts; they are highly constrained and coupled to the immediate environment through sensory interaction.”

The subjects’ moral choices about statements such as:

“One should never intentionally harm another person.”

weren’t weighted any differently than their “top of the head” answers to questions such as:

“Is Denmark larger than Sweden?”

There was a time limit of 3 seconds for the subjects to answer 63 “moral” and 35 “factual” questions. The subjects were asked to express their confidence in the answer during an additional 1-second time frame. Answers after these time limits were discarded.

In the supplementary material, the researchers:

“Justified our design. When no time-out condition was included, 33% of participants realized that their eye movements were influencing the timing of the trial.”

So the 3-second time frame was imposed to keep the subjects from gaming the experiment. The experiment’s time limit of 3 seconds didn’t have anything to do with properly modeling moral decision-making.

The time period wasn’t the only questionable area. The researchers focused on eye gaze as the important homogenous factor influencing the subjects as they made their “moral” choices.

However, one person’s eye gaze is not necessarily the same as the next person’s, as demonstrated by studies such as:

An individual’s attention and perception that are incorporated into their eye gaze are behaviors that may have many differing historical components. For example, one subject may have kept their gaze on the:

“Value animals equally.”

answer to the:

“Animal welfare should not be valued equally with human welfare.”

question because their initial reaction involved their cuddly pet. Another subject may have kept their gaze on the same answer because their initial reaction involved a stray dog that attacked them.

Did the study shed light on its initial statement?

“Moral cognition arises from the interplay between emotion and reason.”

I didn’t see that the study’s design allowed its subjects to produce emotionally informed yet reasoned responses to the 98-question battery.

http://www.pnas.org/content/112/13/4170.full “Biasing moral decisions by exploiting the dynamics of eye gaze”

Are hippocampal place cells controlled by theta brain waves from grid cells?

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

This 2015 Canadian rodent study tried to establish that grid cells in the medial entorhinal cortex generated brain waves in the theta frequency range that controlled place cells in the hippocampus part of the limbic system.

The researchers stated:

“Our results deviate from the prediction.”

but a commentary Do the spatial frequencies of grid cells mold the firing fields of place cells? said the researchers:

“Obtained fascinating results, largely supporting the model.”

What’s fascinating to me is the volume of studies on the hippocampus that ignore its position as the seat of emotional memories. Human experiments involving the hippocampus are usually designed to not contain any emotional content.

Two studies showed functions of hippocampal place cells:

A summary study of 118 other studies What do grid cells contribute to place cell firing? provided additional information on grid cells and hippocampal place cells, head direction cells, boundary cells, and cells that encode object locations.

The summary study related to the current study by stating that the research through early 2014 arguably found:

“Grid and place cell firing patterns are not successive stages of a processing hierarchy, but complementary and interacting representations that work in combination.”

http://www.pnas.org/content/112/13/4116.full “Place field expansion after focal MEC inactivations is consistent with loss of Fourier components and path integrator gain reduction”

Neural plasticity trumps genetics in the hippocampus part of the limbic system

gettingwell4 2-3 stars Required further work, Brain development, Epigenetics, Hippocampus, Limbic system, Memory , ,

This 2015 rodent study used a genetic strain of mice that was bred to not express a gene that enabled long-term memory in the hippocampus. The mice were not memory-impaired, however, due to their brains’ neural plasticity.

The researchers found:

“Deletion of genes in organisms does not always give rise to phenotypes because of the existence of compensation.

The current work provides an example of how a complex brain system may adjust to the effects of gene deletion to recover function.”

The Early human brain development can be greatly modified by environmental factors study showed even greater plasticity in another part of the human brain where the people faced much larger obstacles than gene deletion.

I view this finding as a cautionary tale to reference any time a study comes out stating that A and B genes are found to cause X and Y symptoms or behavior. Researchers don’t have enough evidence in 2015 to unequivocally describe what rodent brains are capable of, much less human brains.

The researchers implied how they kept faith in their work with the phrase:

“The compensatory mechanism is imperfect and does not fully restore cGKII-dependent function.”

Is perfection the standard to which their research is also held?

http://www.pnas.org/content/112/10/3122.full “Network compensation of cyclic GMP-dependent protein kinase II knockout in the hippocampus by Ca2+-permeable AMPA receptors”

Why do we cut short our decision-making process?

gettingwell4 5+ stars Premium, Beliefs, Cerebrum, Dopamine, Limbic system, Memory, Neurochemicals, Serotonin , , ,

This 2014 Zurich study found that people adapt their goal-directed decision-making processes in certain ways.

First, the researchers found that the subjects usually acted as though the computational cost of evaluating all outcomes became too high once the process expanded to three or more levels. Their approach to a goal involved developing subgoals. For example, for a three-level goal:

“Level 3 was most frequently decomposed into a tree of depth 2 followed by a depth-1 tree.”

A level 3 tree had 24 potential outcomes (24 outcomes = 3*2x2x2) whereas a level 2 tree followed by a level 1 tree had 10 potential outcomes (10 outcomes = 2*2×2 + 1*2).

Second, the subjects memorized and reused subgoals after their initial formation. The researchers found that this practice didn’t produce results significantly different than the optimal solutions, but that could have been due to the study’s particular design. The design also ensured that the subjects’ use of subgoals wasn’t influenced by rewards.

Further:

“It is known that nonhuman primate choices, for instance, depend substantially on their own past choices, above and beyond the rewards associated with the decisions. Similar arguments have been made for human choices in a variety of tasks and settings and have been argued to be under dopaminergic and serotonergic control.”

Third, ALL 37 subjects were unwilling to evaluate decisions that had initial large losses, even if they could see that the path to reach the optimal solution went through this loss outcome! The researchers termed this behavior “pruning” and stated:

“Pruning is a Pavlovian and reflexive response to aversive outcomes.”

The lead author relied on a previous study he coauthored to elaborate on the third finding. One statement in the previous study was:

“This theory predicts excessive pruning to occur in subjects at risk for depression, and reduced pruning to occur during a depressive episode.”

The current study’s subjects were screened out for depressive conditions, though. They were somewhat conditioned by the study design, but not to the extent where their behavior could be characterized as Pavlovian responses.

Fourth, the subjects’ use of larger subgoals wasn’t correlated to their verbal IQ.

So, what can we make of this research?

  1. Are shortcuts to our decision processes strictly a cerebral exercise per the first and second findings?
  2. Do we recycle our decision shortcuts like our primate relatives, uninfluenced by current rewards?
  3. Or is it rewarding to just not fully evaluate all of our alternatives?
  4. Do all of us always back away from decisions involving an initial painful loss, even when we may see the possibility of gaining a better outcome by persevering through the loss?
  5. Is it true that we excessively cut decision processes too short – such that many of our decisions are suboptimal – when we’re on our way to becoming depressed?
  6. Are we overwhelmed when depressed such that we don’t summon up the effort to cut short or otherwise evaluate decisional input?

Let me know your point of view.

http://www.pnas.org/content/112/10/3098.full “Interplay of approximate planning strategies”

Fear extinction is the learned inhibition of retrieval of previously acquired responses

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Cerebrum, Epigenetics, Hippocampus, Limbic system, Memory

This 2014 rodent study showed that fear extinction doesn’t depend on memory retrieval:

“These results show that extinction and retrieval are separate processes and strongly suggest that extinction is triggered or gated by the conditioned stimulus even in the absence of retrieval.”

Key to my understanding this finding came from a definition in another summary study by the authors, The learning of fear extinction, where they stated:

“Extinction is the learned inhibition of retrieval of previously acquired responses.”

These two studies and Hippocampal mechanisms involved in the enhancement of fear extinction caused by exposure to novelty should inform researchers of studies such as If rodent training has beneficial epigenetic effects, how can the next step be human gene therapy? of desirable alternative treatments, rather than proceeding from rodent training directly to human gene therapy.

http://www.pnas.org/content/112/2/E230.full “Extinction learning, which consists of the inhibition of retrieval, can be learned without retrieval”

A biologically relevant event can drive long-term memory in a single training session

gettingwell4 2-3 stars Required further work, Brain development, Dopamine, Epigenetics, Memory, Neurochemicals

This 2014 fruit fly study found:

“A biologically relevant event such as finding food under starvation conditions or being poisoned can drive long-term memory in a single training session.”

I don’t think that we need to discover at these extremes, though, whether or not the finding has human applicability.

We do know from the Dutch hunger winter of 1944 study referenced in the Non-PC alert: Treating the mother’s obesity symptoms positively affects the post-surgery offspring study that prenatal exposure to famine had lifelong ill effects on the children. The exposed children had epigenetic DNA changes – a form of long-term memory – from their mothers’ starvation, which resulted in relative obesity compared with their unexposed siblings.

http://www.pnas.org/content/112/2/578.full “Distinct dopamine neurons mediate reward signals for short- and long-term memories”

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 pay attention to the present through the windows of perception that we’ve developed from our past

gettingwell4 4-5 stars Advanced knowledge, Memory, Primal Therapy , ,

My paraphrase of the 2013 study’s findings:

  • We pay attention to the present through the windows of perception that we’ve developed from our past;
  • The rest of the world is blocked by our consciousness’ perceptual thresholds.

It was good to read an attention study that didn’t zap the subjects’ brains.

http://www.pnas.org/content/111/4/E417.full “Prestimulus oscillatory power and connectivity patterns predispose conscious somatosensory perception”

Our long-term memory usually selects what we pay closer visual attention to

gettingwell4 2-3 stars Required further work, Memory

This 2014 human study at Vanderbilt found that our long-term memory usually selects what we pay closer visual attention to:

“Improvements in attentional tuning were accompanied by changes in an electrophysiological signal hypothesized to index long-term memory.”

The focus was on electrical fields, leading to predictable statements:

“Follow-up studies using neuroimaging techniques are needed to identify definitively the brain areas and associated networks responsible for the rapid changes in perceptual attention we observed.”

The researchers also found that 20 minutes of electrical brain stimulation helps tune perceptual attention. Is it in vogue that attention studies like this one and Can psychologists exclude the limbic system and adequately study awareness and social cognition? seemed to need gadgets that zapped the subjects’ brains?

http://www.pnas.org/content/112/2/625.full “Enhancing long-term memory with stimulation tunes visual attention in one trial”