A study that provided evidence for basic principles of Primal Therapy

This 2015 Northwestern University rodent study found:

“Fear-inducing memories can be state dependent, meaning that they can best be retrieved if the brain states at encoding and retrieval are similar.

Memories formed in a particular mood, arousal or drug-induced state can best be retrieved when the brain is back in that state.

“It’s difficult for therapists to help these patients,” Radulovic said, “because the patients themselves can’t remember their traumatic experiences that are the root cause of their symptoms.”

The best way to access the memories in this system is to return the brain to the same state of consciousness as when the memory was encoded.”

The study demonstrated one method of activating neurobiological pathways with a drug to remove a hippocampal memory’s protection, which played a part in enabling subjects to relive their remembered experiences. This rodent study’s methods  weren’t designed to therapeutically access similarly protected memories with humans.

From the Northwestern press release:

“There are two kinds of GABA [gamma-Aminobutyric acid] receptors. One kind, synaptic GABA receptors, works in tandem with glutamate receptors to balance the excitation of the brain in response to external events such as stress.

The other population, extra-synaptic GABA receptors, are independent agents.

If a traumatic event occurs when these extra-synaptic GABA receptors are activated, the memory of this event cannot be accessed unless these receptors are activated once again.

“It’s an entirely different system even at the genetic and molecular level than the one that encodes normal memories,” said lead study author Vladimir Jovasevic, who worked on the study when he was a postdoctoral fellow in Radulovic’s lab.

This different system is regulated by a small microRNA, miR-33, and may be the brain’s protective mechanism when an experience is overwhelmingly stressful.

The findings imply that in response to traumatic stress, some individuals, instead of activating the glutamate system to store memories, activate the extra-synaptic GABA system and form inaccessible traumatic memories.”

I’d point out that “can’t remember” and “inaccessible traumatic memories” phrases used above were in reference to what’s usually called “memory” i.e., a recall initiated by the cerebrum.

The study’s findings should inform memory-study researchers if they care to understand how emotional memories can be formed and re-experienced.

The study provided evidence for fundamentals of Dr. Arthur Janov’s Primal Therapy, such as:

  • Experiences associated with pain can be remembered below our conscious awareness.
  • The retrieval and re-experiencing of emotional memories can engage our lower-level brain areas without our higher-level brain areas’ participation.

The obvious nature of this study’s straightforward experimental methods made me wonder why other researchers hadn’t used the same methods decades ago.

Use of this study’s methodology could have resulted in dozens of informative follow-on study variations by now, and subsequently found whether subjects’ physiological, behavioral, and epigenetic measurements differed from control group subjects, as in:

“miR-33 is downregulated in response to gaboxadol [the drug used to change subjects’ brain state] and modulates its effects on state-dependent fear.”

See Resiliency in stress responses for abstracts of three follow-on papers by these researchers.

http://www.nature.com/neuro/journal/v18/n9/full/nn.4084.html “GABAergic mechanisms regulated by miR-33 encode state-dependent fear”

MP3 with lead researcher Dr. Jelena Radulovic: http://www.thenakedscientists.com/HTML/specials/show/20150825/

Leaky gates, anxiety, and grocery store trips without buying list items

An interview with Jeff Link, the editor of Dr. Arthur Janov’s 2011 book “Life Before Birth: The Hidden Script that Rules Our Lives” with Ken Rose:

“Even further confirmation for some of the views of Janov, that maybe weren’t widely accepted for a time, it’s new research now being done into memory and what a lot of scientist are seeing, a lot of different studies is that memory reactivates the same neuroimpulses that were initially firing off when the event happened.

So a traumatic event when you remember it, the act of remembering it is actually creating a neuromirror of what went on initially.

In a lot of ways that is what Primal Therapy is attempting to do; is to go back to that place and reconnect, or as it’s sometimes referred to, reconsolidate the brain state so that real healing can take place.”

Transcript (part 4 of 6): http://cigognenews.blogspot.com/2015/09/ken-rose-on-life-before-birth-part-46.html

MP3: http://www.pantedmonkey.org/podcastgen/download.php?filename=2011-12-15_1300_what_now_jeff_link.mp3

A hippocampal protein that increases when stress increases

This 2015 Michigan human/rodent study found:

“Gene expression profiling in postmortem human brain and studies using animal models have implicated the fibroblast growth factor (FGF) family in affect regulation and suggest a potential role in the pathophysiology of major depressive disorder (MDD).

We show that FGF9 expression is up-regulated in the hippocampus of individuals with MDD, and that FGF9 expression is inversely related to the expression of FGF2.”

The researchers went down the evolutionary scale from human findings to replicate many of the findings with rodents:

“We found that chronic social defeat stress, an animal model recapitulating some aspects of MDD, leads to a significant increase in hippocampal FGF9 expression.

Collectively, these results suggest that high levels of hippocampal FGF9 play an important role in the development or expression of mood and anxiety disorders.”

http://www.pnas.org/content/112/38/11953.full “Fibroblast growth factor 9 is a novel modulator of negative affect”

Adverse effects of inflammation and stress on hippocampal synapses

This dense and highly-jargoned 2015 rodent study found:

“The suppression of BDNF [brain-derived neurotrophic factor] signaling, LTP [long-term potentiation], and memory may be driven by an increased sensitivity to IL-1β [the proinflammatory cytokine interleukin 1β] that occurs directly at synapses.”

The researchers reversed the adverse effects of IL-1β after they induced stress and inflammation. Blocking IL-1β when there wasn’t stress or inflammation, however, also caused adverse effects:

“Interestingly, administration of AS1 [the compound that blocked the proinflammatory responses] in the absence of LPS [the bacterial compound used to stress the subjects’ immune systems] treatment also impaired OLM [the object location memory test where control group rodents exhibited a preference for a novel location over a familiar location].

This finding is consistent with the notion that endogenous IL-1β at physiologically low levels may be essential for hippocampal memory function.”

The researchers asserted:

“Our data reveal a previously unidentified mechanism that explains the age-related vulnerability of hippocampal function to impairment by inflammation.”

Instead of couching their findings with a non-causal “age-related” term, could the researchers have specifically identified causes?

“IL-1β activates different pathways via AcP (proinflammatory) or AcPb (prosurvival) IL-1 receptor subunits.

This study demonstrates that the IL-1 receptor subunit system undergoes an age-dependent reconfiguration in hippocampal synapses.

This previously undescribed reconfiguration, characterized by an increase in the AcP/AcPb ratio, is responsible for potentiating impairments of synaptic plasticity and memory by IL-1β.”

What were the underlying causes for the relatively increased AcP activation over AcPb activation? The researchers didn’t say. Their explanations were left hanging at a correlated-but-not-causal “age-dependent” level rather than a “mechanism that explains.”

http://www.pnas.org/content/112/36/E5078.full “Synapse-specific IL-1 receptor subunit reconfiguration augments vulnerability to IL-1β in the aged hippocampus”

A mechanistic study of neurotransmitters in the hippocampus

This 2015 UK rodent study found:

“A mechanistic understanding of how alterations in dopamine and NMDAR [a type of glutamate receptor that participates in excitatory neurotransmission] function can lead to the disruption of hippocampal–PFC [prefrontal cortex] functional connectivity.

These results show how dopaminergic activation induces long-term hypofunction of NMDARs, which can contribute to disordered functional connectivity, a characteristic that is a hallmark of psychiatric disorders such as schizophrenia.”

One of the experiments applied theta-frequency (5 Hz) waves to the rats’ hippocampi and dampened the electrical activity of the NMDAR type of glutamate receptor.

However, this effect of theta waves was dependent on the activation of D2 dopamine receptors. The study’s findings should inform researchers who treat brain waves as base causes of behavior in studies such as What’s an appropriate control group for a schizophrenia study?

This study’s findings may also inform researchers of studies such as the What causes disconnection between the limbic system and the cerebrum? of a neurochemical basis for “the disruption of hippocampal–PFC functional connectivity.”

http://www.pnas.org/content/112/35/11096.full “Disruption of hippocampal–prefrontal cortex activity by dopamine D2R-dependent LTD of NMDAR transmission”

We first recognize familiar faces with our limbic system

This 2015 Belgian human study found:

“Medial temporal lobe structures (perirhinal cortex, amygdala, hippocampus) and anterior inferior temporal cortex responded abruptly when sufficient information for familiar face recognition was accumulated.

Activation in ventral occipitotemporal face-preferential regions increased with visual information, independently of long-term face familiarity.

[The researchers] isolated the discriminative neural responses to unfamiliar and familiar faces by slowly increasing visual information (i.e., high-spatial frequencies) to progressively reveal faces of unfamiliar or personally familiar individuals.”

A limitation of the study was, however:

“Behavioral data were acquired from only 11 subjects because of a technical error.”

http://www.pnas.org/content/112/35/E4835.full “Neural microgenesis of personally familiar face recognition”