Month: February 2015

The effects of early-life stress are permanent alterations in the child’s brain circuitry and function

gettingwell4 4-5 stars Advanced knowledge, Amygdala, Brain development, Cortisol, Limbic system, Memory, Neurochemicals, Stress ,

The sobering application of this 2013 rodent study’s finding was that if the limbic systems of human children weren’t already permanently damaged before they entered an orphanage, the orphanage experience would probably do that to them:

“The current study manipulates the type and timing of a stressor and the specific task and age of testing to parallel early-life stress in humans reared in orphanages.

The results provide evidence of both early and persistent alterations in amygdala circuitry and function following early-life stress.

These effects are not reversed when the stressor is removed nor diminished with the development of prefrontal regulation regions.”

http://www.pnas.org/content/110/45/18274.full “Early-life stress has persistent effects on amygdala function and development in mice and humans”

One way that mothers cause fear and emotional trauma in their infants

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

This 2014 rodent study showed that infants learned to fear specific items in the environment that their mothers feared. The imprinting memory happened at a stage in the infants’ lives when they hadn’t yet developed the physiology to respond to the environment with fear on their own.

The learning cue was the mothers’ fear response – in this case, her distress odor, even when the mother was not present – coupled with the infants’ stress. The fear memory was stored in the infants’ amygdalae:

“These memories are acquired at younger ages compared with amygdala-dependent odor-shock conditioning and are more enduring following minimal conditioning.

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.”

There’s no scientific reason why this and related studies shouldn’t inform researchers who ignore the earliest stages of human life when studying limbic system disorders in humans.

For an example of researchers choosing to NOT be informed, look at Is this science, or a PC agenda? Problematic research on childhood maltreatment and its effects.

http://www.pnas.org/content/111/33/12222.full “Intergenerational transmission of emotional trauma through amygdala-dependent mother-to-infant transfer of specific fear”

Is this science, or a PC agenda? Problematic research on childhood maltreatment and its effects

gettingwell4 < 0 Detracted from science, Amygdala, Brain development, Epigenetics, Hippocampus, Limbic system, Lower brain, Memory, Stress ,

This 2013 Wisconsin human study’s goal was to assess effects of childhood trauma using both functional MRI scans and self-reported answers to a questionnaire. The families of the study’s subjects (64 18-year-olds) participated with researchers before some of the teenagers were born.

How could the teenagers give answers that described events that may have taken place early in their lives, before their cerebrums were developed, around age 4? Even if the subjects were old enough to remember, would they give accurate answers to statements such as:

“My parents were too drunk or high to take care of the family.

Somebody in my family hit me so hard that it left me with bruises or marks.”

knowing that affirmative answers would prompt a visit to their family from a government employee?

Although some data may have been available, data from the teenagers’ prenatal, birth term, infancy, and early childhood wasn’t part of the study design. Intentional dismissal of early influencing factors ignored applicable research!

No

Was the study’s limited window due to the political incorrectness of placing importance in the development environment provided by the subjects’ mothers? The evidence was there for those willing to see.

One clue of ignored early traumatic events was provided by the lead researcher’s quote in news coverage:

“These kids seem to be afraid everywhere,” he says. “It’s like they’ve lost the ability to put a contextual limit on when they’re going to be afraid and when they’re not.”

This finding of “fear without context” possibly described the later-life effects of traumas that were encountered in utero and during infancy. A pregnant woman’s terror and fear can register on the fetus’ lower brain and the amygdala from the third trimester onward.

Storing a memory’s context is one of the functions that the hippocampus performs. Because the hippocampus develops later than the amygdala, though, it would be unable to provide a context for any earlier feelings and sensations such as fear and terror.

The researchers attempted to place the finding of unfocused fear into later stages of child development without doing the necessary research. They tried to force this finding into the subjects’ later development years by citing rat fear-extinction and other marginally related studies.

But citing these studies didn’t make them applicable to the current study. Cause and effect wasn’t demonstrated by noting various “is associated with” findings.

Was this science? Was it part of furthering an agenda like protecting publicly funded jobs?

Was this study published to make a contribution to science? Were the peer reviewers even interested in advancing science?

And what about the 64 18-year-old subjects? If the lead researcher’s statement was accurate, did these teenagers receive help that addressed what they really needed?

http://www.pnas.org/content/110/47/19119.full “Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence”

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

How mothers-to-be program lifelong low testosterone into their unborn male children

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Testosterone

This 2014 rodent study was one of many on how pregnant mothers-to-be epigenetically program their developing children. The enduring changes made to the male fetuses in the womb led to lifelong low testosterone, which produces a variety of ill health effects:

“Leydig cells do not develop until puberty but the team showed that their function is impaired if their stem cell forefathers are exposed to reduced levels of testosterone in the womb.

There is increasing evidence that a mother’s diet, lifestyle and exposure to drugs and chemicals can have a significant impact on testosterone levels in the womb.”

http://www.pnas.org/content/111/18/E1924.full “Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells”

When recognition memory is independent of hippocampal function

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

This 2014 human study provided additional details on the specialized brain circuits we have for recognizing faces.

Damage to the hippocampus didn’t impair recognition of new faces, “..but only at a short retention interval. Recognition memory for words, buildings, famous faces, and inverted faces was impaired.”

http://www.pnas.org/content/111/27/9935.full “When recognition memory is independent of hippocampal function”

Conserved epigenetic sensitivity to early life experience in the hippocampus

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

This 2012 human study was done by McGill University, whose researchers in Canada are at the forefront of epigenetic studies. The subject was epigenetic DNA methylation in the hippocampus of people who experienced abuse as children and who also committed suicide.

Comparisons were made with rats that were stressed in early life to identify genomic regions that are epigenetically changeable in response to a range of early life experiences.

http://www.pnas.org/content/109/Supplement_2/17266.full “Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus”

Left–right dissociation of hippocampal memory processes in mice

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

This 2014 rodent study provided more details on the CA3 segment of the hippocampus:

“Silencing of either the left or right CA3 was sufficient to impair short-term memory…

Only left CA3 silencing impaired performance on an associative spatial long-term memory task, whereas right CA3 silencing had no effect.”

http://www.pnas.org/content/111/42/15238.full “Left–right dissociation of hippocampal memory processes in mice”

Hippocampal mechanisms involved in the enhancement of fear extinction caused by exposure to novelty

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

This 2014 Brazilian rodent study provided more information on the workings of the hippocampus. The researchers measured the effects of re-experiencing a fear within a specific context:

“Within a restricted time window, a brief exposure to a novel environment enhances the extinction of contextual fear.

The enhancement of extinction by the exposure to novelty depends on hippocampal gene expression..on hippocampal but not amygdalar processes.”

http://www.pnas.org/content/111/12/4572.full “Hippocampal molecular mechanisms involved in the enhancement of fear extinction caused by exposure to novelty”

Rebooting the brain with anesthesia: Implications for Primal Therapy and evolution

gettingwell4 4-5 stars Advanced knowledge, Anterior cingulate cortex, Brain development, Brainstem, Hypothalamus, Limbic system, Locus coeruleus, Lower brain, Memory, Primal Therapy, Thalamus , , ,

Here are some paragraphs from a 2013 summary article of 105 studies entitled Evolution of consciousness: Phylogeny, ontogeny, and emergence from general anesthesia:

“The emergence of consciousness (from anesthesia) (as judged by the return of a response to command) was correlated primarily with activity of the brainstem (locus coeruleus), hypothalamus, thalamus, and anterior cingulate (medial prefrontal area). Surprisingly, there was limited neocortical involvement that correlated with this primitive form of consciousness.

In the sleep study, midline arousal structures of the thalamus and brainstem also recovered function well before cortical connectivity resumed. Thus, the core of human consciousness appears to be associated primarily with phylogenetically ancient structures mediating arousal and activated by primitive emotions, in conjunction with limited connectivity patterns in frontal–parietal networks.

The emergence from general anesthesia may be of particular interest to evolutionary biology, as it is observed clinically to progress:

  1. from primitive homeostatic functions (such as breathing)
  2. to evidence of arousal (such as responsiveness to pain or eye opening)
  3. to consciousness of the environment (as evidenced by the ability to follow a command)
  4. to higher cognitive function.

Regarding ontogeny of H. sapiens, peripheral sensory receptors are thought to be present from 20 wk of gestation in utero. The developmental anlage of the thalamus is present from around day 22 or 23 postconception, and thalamocortical connections are thought to be formed by 26 wk of gestation. Around the same time of gestation (25–29 wk), electrical activity from the cerebral hemispheres shifts from an isolated to a more continuous pattern, with sleep–wake distinctions appreciable from 30 wk of gestation.

Both the structural and functional prerequisites for consciousness are in place by the third trimester, with implications for the experience of pain during in utero or neonatal surgery.“

I recently came out of anesthesia after being anesthetized for three hours during rotator cuff surgery. I felt pain, and went into a primal reliving of a painful memory.

I interpret the event as a reliving of my birth experience because of the following:

  • The beginning point was complete anesthetization as it was at my birth. My mother was completely anesthetized, so I, weighing less than one twentieth of her, was also completely anesthetized.
  • I felt a great urge and impulse to “get out” as it was at my birth. The attending nurse told me the next day that she called over another person to help her restrain me in the post-op chair.
  • I had a great need for oxygen and started breathing rapidly as it could have been at my birth. The nurse told me the next day that she was already giving me oxygen, and per the monitors, I didn’t need more oxygen.
  • I had to frequently “spit up” as it could have been at my birth. There was nothing in my current situation to cause me to expectorate.
  • My lower brain and limbic system were in control, as I thrashed, cried and moaned. I probably used primarily the same brain areas as what were the developed parts of my brain at birth.

The attending nurse told me the next day when I called her that she followed the established protocol, which was to get me out of the experience. She intentionally distracted me away from my pain. I was instructed to sit still, to think of some place pleasant, and to calm down.

I heard her as though she was at the other end of a tunnel at first, and then started to comply as I regained cognitive awareness.

I understand how such a powerful event could present a danger to a patient. It didn’t occur to me until the next day to tell the nurse of relevant history, that I’ve had relivings while in therapy, and wasn’t in the same danger that her regular patients may have been.

Even if I had said something, however:

  • Neither the anesthesiologist nor the attending nurse had a method of understanding how an evolutionary-determined sequential process – such as rebooting a person’s brain after prolonged anesthesia – may have therapeutic benefits.
  • They had no training to recognize aspects of neurobiologic therapeutic value in what was going on inside of me during this event, as a therapist in Dr. Arthur Janov’s Primal Therapy has.
  • The default response per medical protocol would be to shut down a patient’s expressions of their feelings.

As a result, my experience of this event was pretty much the opposite of what happens in Primal Therapy. Although I didn’t feel harmed, my reliving wasn’t therapeutic, as previous re-experiencings had been. The reliving’s progression through my levels of consciousness was purposely interrupted, and approached from a non-therapeutic direction.

Unlike my experience of coming out of anesthesia, Dr. Arthur Janov’s Primal Therapy isn’t something the patient is thrown into and potentially overwhelmed by their feelings. It’s a gradual process where the patient is in control.

This summary study showed that existing science is already in alignment with the background of Primal Therapy, that the core of human consciousness is in the limbic system and lower brain structures. My anesthesia experience showed that medical professionals are familiar with at least the outward signs of a primal reliving.

The challenge seems to be how to use this complementary knowledge for people’s benefit. What can be done with therapeutic re-experiencing so that people aren’t burdened with the continuing adverse effects of traumas?

How can scientists and medical professionals get the eyes to see what’s in front of them?

Weakening memories by mispredicting their contexts

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

This 2014 human study showed that:

“Item memories are weakened when they are mispredicted by their context..weakening of the synapses that support the item’s representation in memory.

Note that our use of the term “pruning” is not meant to imply that traces are being deleted completely from memory.“

Connecting the dots, two studies showed that our memories are formed within specific contexts and that our memories have contexts with specific places and times.

http://www.pnas.org/content/111/24/8997.full “Pruning of memories by context-based prediction error”

How painful long-lasting memories are stored and why they are so strong

gettingwell4 2-3 stars Required further work, Amygdala, Cortisol, Limbic system, Memory, Neurochemicals, Stress , ,

This 2014 rodent study provided evidence for a portion of the neurophysiology that underlies how painful long-lasting memories are stored and why they are so strong. The amygdala was the brain area studied.

The researchers were misguided in news coverage by focusing on solutions such as external mechanisms to forget these memories. The researchers should think in terms of how their research can help people who can help themselves instead of having something externally done to them.

After all, we’re humans who can participate in therapy, not lab rats who need to be fixed.

http://www.pnas.org/content/111/51/E5584.full “Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation”

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”

Early emotional experiences change our brains: Childhood maltreatment is associated with reduced volume in the hippocampus

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

This 2011 human study by the grandfather of hippocampus stress studies, Martin Teicher, quantified childhood maltreatment using the Adverse Childhood Experiences study and Childhood Trauma Questionnaire scores:

“The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG [dentate gyrus] subfields, and were not mediated by histories of major depression or posttraumatic stress disorder.

These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.”

The evidence is clear that early emotional experiences change our brains. There are seldom valid reasons for researchers to exclude emotional content when designing human brain studies, especially studies that involve the hippocampus.

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”

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”

Problematic research: Hippocampal memory reactivation during rest supports upcoming learning of related content

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

This 2014 human study involved the subjects replaying hippocampal memories in the limbic system while in a restful state.

The researchers found that intentional replaying made memories stronger, and improved understanding of future related material.

However, the researchers excluded emotional memories from this study. See the human Emotional memories and out-of-body–induced hippocampal amnesia study as an example of why emotional memories are necessary in order to properly study the hippocampus. Also see Problematic research on memory for why excluding emotional memories yields questionable findings.

http://www.pnas.org/content/111/44/15845.full “Memory reactivation during rest supports upcoming learning of related content”