On Primal Therapy with Drs. Art and France Janov

Experiential feeling therapy addressing the pain of the lack of love.

The hypothalamus couples with the brainstem to cause migraines

This 2016 German human study with one subject found:

“The hypothalamus to be the primary generator of migraine attacks which, due to specific interactions with specific areas in the higher and lower brainstem, could alter the activity levels of the key regions of migraine pathophysiology.”

The subject underwent daily fMRI scans, and procedures to evoke brain activity. She didn’t take any medications, and suffered three migraine attacks during the 31-day experimental period.

Neuroskeptic commented:

“The dorsal pons has previously been found to be hyperactive during migraine. It’s been dubbed the brain’s ‘migraine generator.’ Schulte and May’s data suggest that this is not entirely true – rather, it looks like the hypothalamus may be the true generator of migraine, while the brainstem could be a downstream mediator of the disorder.

A hypothalamic origin of migraines would help to explain some of the symptoms of the disorder, such as changes in appetite, that often accompany the headaches.”

The above graphic looks like the result of feedback mechanisms that either didn’t exist or inadequately handled the triggering event. Other examples of the hypothalamus lacking feedback or being involved in a deviated feedback loop include:

There are many unanswered questions with a one-person study, of course. Addressing the cause of this painful condition would find out when, where, and how a person’s hypothalamus became modified to express migraine tendencies.

I’d guess that migraine tendencies may appear as early as the first trimester of pregnancy, given that a highly functional hypothalamus is needed for survival and development in our earliest lives. Gaining as much familial and historical information as possible from the person would be necessary steps in therapies that address migraine causes.

http://blogs.discovermagazine.com/neuroskeptic/2016/05/22/pinpointing-origins-of-migraine/ “Pinpointing the Origins of Migraine in the Brain”

The current paradigm of child abuse limits pre-childhood causal research

As an adult, what would be your primary concern if you suspected that your early life had something to do with current problems? Would you be interested in effective treatments of causes of your symptoms?

Such information wasn’t available in this 2016 Miami review of the effects of child abuse. The review laid out the current paradigm mentioned in Grokking an Adverse Childhood Experiences (ACE) score, one that limits research into pre-childhood causes for later-life symptoms.

The review’s goal was to describe:

“How numerous clinical and basic studies have contributed to establish the now widely accepted idea that adverse early life experiences can elicit profound effects on the development and function of the nervous system.”

The hidden assumption of almost all of the cited references was that these distant causes can no longer be addressed. Aren’t such assumptions testable here in 2016?

As an example, the Discussion section posed the top nine “most pressing unanswered questions related to the neurobiological effects of early life trauma.” In line with the current paradigm, the reviewer assigned “Are the biological consequences of ELS [early life stress] reversible?” into the sixth position.

If the current paradigm encouraged research into treatment of causes, there would probably already be plenty of evidence to demonstrate that directly reducing the source of the damage would also reverse the damaging effects. There would have been enough studies done so that the generalized question of reversibility wouldn’t be asked.

Aren’t people interested in human treatments of originating causes so that their various symptoms don’t keep bubbling up? Why wouldn’t research paradigms be aligned accordingly?

The review also demonstrated how the current paradigm of child abuse misrepresents items like telomere length and oxytocin. Researchers on the bandwagon tend to forget about the principle Einstein expressed as:

“No amount of experimentation can ever prove me right; a single experiment can prove me wrong.”

That single experiment for telomere length arrived in 2016 with Using an epigenetic clock to distinguish cellular aging from senescence. The seven references the review cited for telomere length that had “is associated with” or “is linked to” child abuse findings should now be viewed in a different light.

The same light shone on oxytocin with Testing the null hypothesis of oxytocin’s effects in humans and Oxytocin research null findings come out of the file drawer. See their references, and decide for yourself whether or not:

“Claimed research findings may often be simply accurate measures of the prevailing bias.”

http://www.cell.com/neuron/fulltext/S0896-6273%2816%2900020-9 “Paradise Lost: The Neurobiological and Clinical Consequences of Child Abuse and Neglect”

The effects of imposing helplessness

This 2016 New York rodent study found:

“By using unbiased and whole-brain imaging techniques, we uncover a number of cortical and subcortical brain structures that have lower activity in the animals showing helplessness than in those showing resilience following the LH [learned helplessness] procedure. We also identified the LC [locus coeruleus] as the sole subcortical area that had enhanced activity in helpless animals compared with resilient ones.

Some of the brain areas identified in this study – such as areas in the mPFC [medial prefrontal cortex], hippocampus, and amygdala – have been previously implicated in clinical depression or depression-like behavior in animal models. We also identified novel brain regions previously not associated with helplessness. For example, the OT [olfactory tubercle], an area involved in odor processing as well as high cognitive functions including reward processing, and the Edinger–Westphal nucleus containing centrally projecting neurons implicated in stress adaptation.

The brains of helpless animals are locked in a highly stereotypic pathological state.”

Concerning the study’s young adult male subjects:

“To achieve a subsequent detection of neuronal activity related to distinct behavioral responses, we used the c-fosGFP transgenic mice expressing c-FosGFP under the control of a c-fos promoter. The expression of the c-fosGFP transgene has been previously validated to faithfully represent endogenous c-fos expression.

Similar to wild-type mice, approximately 22% (32 of 144) of the c-fosGFP mice showed helplessness.”

The final sentence of the Introduction section:

“Our study..supports the view that defining neuronal circuits underlying stress-induced depression-like behavior in animal models can help identify new targets for the treatment of depression.”

Helplessness is both a learned behavior and a cumulative set of experiences during every human’s early life. Therapeutic approaches to detrimental effects of helplessness can be different with humans than with rodents in that we can address causes.

The researchers categorized activity in brain circuits as causal in the Discussion section:

“Future studies aimed at manipulating these identified neural changes are required for determining whether they are causally related to the expression of helplessness or resilience.”

Studying whether or not activity in brain circuits induces helplessness in rodents may not inform us about causes of helplessness in humans. Our experiences are often the ultimate causes of helplessness effects. Many of our experiential “neural changes” are only effects, as demonstrated by this and other studies’ induced phenotypes such as “Learned Helplessness” and “Prenatally Restraint Stressed.”

Weren’t the researchers satisfied that the study confirmed what was known and made new findings? Why attempt to extend animal models that only treat effects to humans, as implied in the Introduction above and in the final sentence of the Discussion section:

“Future studies aimed at elucidating the specific roles of these regions in the pathophysiology of depression as well as serve as neural circuit-based targets for the development of novel therapeutics.”

http://journal.frontiersin.org/article/10.3389/fncir.2016.00003/full “Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression” (Thanks to A Paper a Day Keeps the Scientist Okay)

Advance science by including emotion in research

This 2015 analysis of emotion studies found:

“Emotion categories [fear, anger, disgust, sadness, and happiness] are not contained within any one region or system, but are represented as configurations across multiple brain networks.

For example, among other systems, information diagnostic of emotion category was found in both large, multi-functional cortical networks and in the thalamus, a small region composed of functionally dedicated sub-nuclei.

The dataset consists of activation foci from 397 fMRI and PET [positron emission tomography] studies of emotion published between 1990 and 2011.”

From the fascinating Limitations section:

“Our analyses reflect the composition of the studies available in the literature, and are subject to testing and reporting biases on the part of authors. This is particularly true for the amygdala (e.g., the activation intensity for negative emotions may be over-represented in the amygdala given the theoretical focus on fear and related negative states). Other interesting distinctions were encoded in the thalamus and cerebellum, which have not received the theoretical attention that the amygdala has and are likely to be bias-free.

Some regions—particularly the brainstem—are likely to be much more important for understanding and diagnosing emotion than is apparent in our findings, because neuroimaging methods are only now beginning to focus on the brainstem with sufficient spatial resolution and artifact-suppression techniques.

We should not be too quick to dismiss findings in ‘sensory processing’ areas, etc., as methodological artifacts. Emotional responses may be inherently linked to changes in sensory and motor cortical processes that contribute to the emotional response.

The results we present here provide a co-activation based view of emotion representation. Much of the information processing in the brain that creates co-activation may not relate to direct neural connectivity at all, but rather to diffuse modulatory actions (e.g., dopamine and neuropeptide release, much of which is extrasynaptic and results in volume transmission). Thus, the present results do not imply direct neural connectivity, and may be related to diffuse neuromodulatory actions as well as direct neural communication.”

Why did the researchers use only 397 fMRI and PET studies? Why weren’t there hundreds or thousands of times more candidate studies from which to select?

The relative paucity of candidate emotion studies demonstrated the prevalence of other researchers’ biases for cortical brain areas. The lead researcher of the current study was a coauthor of the 2016 Empathy, value, pain, control: Psychological functions of the human striatum, whose researchers mentioned that even their analyses of 5,809 human imaging studies was hampered by other imaging-studies researchers’ cortical biases.

Functional MRI signals depend on the changes in blood flow that follow changes in brain activity. Study designers intentionally limit their findings when they scan brain areas and circuits that are possibly activated by human emotions, yet exclude emotional content that may activate these areas and circuits.

Here are a few examples of limited designs that led to limited findings when there was the potential for so much more:

It’s well past time to change these practices now that we’re in 2016.

This study provided many methodological tests that should be helpful for research that includes emotion. It showed that there aren’t impenetrable barriers – other than popular memes, beliefs, and ingrained dogmas – to including emotional content in studies.

Including emotional content may often be appropriate and informative, with the resultant findings advancing science. Here are a few recent studies that did so:

http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1004066 “A Bayesian Model of Category-Specific Emotional Brain Responses”

Lifelong effects of stress

A 2016 commentary A trilogy of glucocorticoid receptor actions on two 2015 French rodent studies started out:

“Glucocorticoids (GCs) belong to a class of endogenous, stress-stimulated steroid hormones..they have wide ranging physiologic effects capable of impacting metabolism, immunity, development, stress, cognition, and arousal.

GCs exert their cellular effects by binding to the GC receptor (GR), one of a 48-member (in humans) nuclear receptor superfamily of ligand-activated transcription factors.”

The French studies were exceedingly technical. The first GR SUMOylation and formation of an SUMO-SMRT/NCoR1-HDAC3 repressing complex is mandatory for GC-induced IR nGRE-mediated transrepression:

“GCs acting through binding to the GR are peripheral effectors of circadian and stress-related homeostatic functions fundamental for survival.

Unveils, at the molecular level, the mechanisms that underlie the GC-induced GR direct transrepression function mediated by the evolutionary conserved inverted repeated negative response element. This knowledge paves the way to the elucidation of the functions of the GR at the submolecular levels and to the future educated design and screening of drugs, which could be devoid of undesirable debilitating effects on prolonged GC therapy.”

The companion study Glucocorticoid-induced tethered transrepression requires SUMOylation of GR and formation of a SUMO-SMRT/NCoR1-HDAC3 repressing complex stated:

“GCs have been widely used to combat inflammatory and allergic disorders. However, multiple severe undesirable side effects associated with long-term GC treatments, as well as induction of glucocorticoid resistance associated with such treatments, limit their therapeutic usefulness.”

It’s funny that even when researchers study causes, they often justify their efforts in terms of outcomes that address effects. Is an etiologic advancement in science somehow unsatisfactory in and of itself?

Once in a while I get a series of personal revelations while reading scientific publications. Paradoxically, understanding aspects of myself has seldom been sufficient to address historical problems.

Thoughts are only where some of the effects of problems show up, and clarifying my understanding can – at most – tamp down these effects. The causes are elsewhere, and addressing them at the source is what ultimately needs to happen.

A few glucocorticoid-related items to ponder:

  • How has stress impacted my life? When and where did it start?
  • Why do I feel wonderful after taking prednisone or other anti-inflammatories? What may be the originating causes of such effects?
  • Why have prolonged periods of my life been characterized by muted responses to stress? How did I get that way?
  • Have I really understood why I put myself into stressful situations? What will break me out of that habit?
  • Why do the feelings I experience while under stressful situations feel familiar? Does my unconsciousness of their origins have something to do with “homeostatic functions fundamental for survival?”
  • Why haven’t I noticed that symptoms of stress keep showing up in my life? There are “physiologic effects capable of impacting metabolism, immunity,” etc. but I don’t do something about it?
  • How else may stress impact my biology? Brain functioning? Ideas? Behavior?

State-dependent brain functions and adrenaline

This 2015 German/Italian rodent study investigated:

“How a specific neuromodulatory input may influence the information content and the readout of cortical information representations of sensory stimuli.

The locus coeruleus (LC) is a brainstem neuromodulatory nucleus that likely plays a prominent role in shaping cortical states via a highly distributed noradrenaline release in the forebrain. In particular, the LC:

  • contributes to regulation of arousal and sleep;
  • it is involved in cognitive functions such as vigilance, attention, and selective sensory processing; and
  • it modulates cortical sensory responses and cortical excitability.

An important addition of our work to previous models of state dependence was the inclusion of the contribution of an important neuromodulator—the noradrenergic system. Our results support the hypothesis that the temporal structure of LC firing causally influences cortical dynamics.

Our work highlights the importance of timing of LC burst: suitably timed LC burst (for example, triggered by an alerting stimulus) can very rapidly trigger transitions into excitable cortical states, which in turn decrease the threshold for cortical responses and thus dynamically facilitate the processing of salient or attended events.

State dependence may either:

  • force neurons to transmit information only using codes that are robust to state fluctuations (e.g., relative firing rates), or may
  • force downstream neurons to gain information about the state of the networks sending the sensory messages and then to use the knowledge of state to properly interpret neural responses.

Our results suggest that the latter information transmission scheme is feasible, because detecting state by either monitoring the dynamics of cortical ongoing activity alone or by also monitoring the dynamics of noradrenergic modulation substantially increased the amount of information about sensory stimuli in the late response components relevant for behavior.”

The study added to the evidence that state dependencies can’t be overlooked in explanations of brain function and resultant physical and mental activity. Locus coeruleus neural activity “can very rapidly trigger transitions into excitable cortical states..and thus dynamically facilitate the processing of salient or attended events.”

Adrenaline from the locus coeruleus produced a state of arousal in multiple brain and body areas tied into the subjects’ sympathetic nervous systems. Such internal state changes may be accompanied by state-dependent memories, following the findings of What can cause memories that are accessible only when returning to the original brain state?

The study highlighted the capability of a lower brain structure to influence other brain areas. Its findings should inform researchers in attention and behavior studies, especially when investigating causes of certain attention and behavior difficulties.

http://www.pnas.org/content/112/41/12834.full “Modeling the effect of locus coeruleus firing on cortical state dynamics and single-trial sensory processing”