Bit of an idea for possible CURE. Has some weight to it.

[mgrade]

The synapse is not as much of a tangible concept as a neuron. There are extracellular fluids generally that take up much of the synaptic cleft. I can see the synapses getting damage aside from this "transmission fluid" and the

elementary usage of the voltage gating system (and transmitters, etc. themselves).

( <it looks like the very full potential is -100 to 300mV). But aside from surviving a split second lightning strike, massive swings would end up being very detrimental to life. The electrical force/potential is largely maintained by the body's natural adherence to equilibrium (so things never get to high or too low, generally).

Observing non-spiking differences in mV in the synapse is very hard because it always seems to be within normal range, because to sustain human life there can be no other way (generally). Another way to look at the regulation of the body is:

if Lance Armstrong injected him self with ACTH, to improve performance, they would not be able to prove he was "doping" because the level never goes too far from the normal range, and everything could be explained with reactions to environmental stressors.

resting V seems to be just below -70 mV

with spikes at or around +40 to +50 mV

refer to this article, and the diagrams and the other article below:

http://bioserv.fiu.e...vous_system.htm

[mgrade]

OK ----I'm still learning----but:

[mgrade]

I'm not nearly fully, 100% understanding this stuff but read this and keep re-explaining it until everybody understands:

(....plus I'm sick with upper respiratory infection; cut me some slack)

http://en.wikipedia....brane_potential

[VisualDude]

plus I'm sick with upper respiratory infection; cut me some slack

In that case we forgive you, lol

This is a good point as well. But maybe the damage is somewhere else that just damage to the nuerons, maybe it has to do with damage related to the synapses etc...

In general (or at least when I'm posting) neuron "damage/injury" are lumped together whether it is synapses (part of neuron), axon, or main body.

Some neuronal damage is "demyelination" with is damage to the axon and will alter its future durability as well as its signal getting to all the synapses that it is connected to. My 'toxic encephalopathy' involves this (according to the nature of the chemicals exposed to). MS involves demyelination from auto-immune attacks. http://en.wikipedia....inating_disease [Note the importance of B12]

"Burning" is largely a synaptic event. Using Parkinson's as an example, synapses are damaged (at least 3 known mechanisms). The neurons rarely die but function poorly (loss of connections). Since the neurons are still alive, MRI scans do not show any problem. It takes PET scans (and the like) which reveal metabolic activity in order to 'image' a problem.

So dopamine issues that some may have with HPPD would probably involve burnt synapses. And it makes sense that with other neurotransmitters as well, that if the firing activity exceeded the 'cleanup' (metabolic) activity, free radicals will burn then.

On average, each neuron has 1000 synaptic connections !!! [ Trivia Time: With Alzheimer's disease, 1000 neurons die each day ... 1,000,000 connections ]

Neurons are strange little buggers ... if they fire too much they die from metabolic waste inside, and yet if the don't fire enough, they die from inactivity.

So you can see that if enough synaptic or axonal damage has occured, then the cell can't fire frequently enough to survive.

And then there are changes (plasticity) caused by the altered activity (the way plasticity is stimulated). So HPPD is complex to say the least ... and very individualistic as Jay posted.

[Guest]

http://www.ncbi.nlm.nih.gov/m/pubmed/21921840/

[Guest]

http://www.neurotransmitter.net/twoa.html

[mgrade]

When referring to synapse, it is not only limited to the synaptic cleft but includes parts pre- and post-synaptic.

[mgrade]

They say the next-generation antipsychotics are either the 5HT-inverse agonists or Glutamate Positive Allosteric Modulator (or Selective mGluR agonists [or <in my mind> partial antagonists]):

metabotropic glutamate receptors

Different mGluR subtypes are found predominantly in different parts of the body. For example, mGluR₄ is located only in the brain, in locations such as the thalamus, hypothalamus and caudate nucleus.^[19] All mGluRs except mGluR₆ are thought to exist in the hippocampus and entorhinal cortex.^[13]

The Entorhinal Cortex (EC) is a major part of the hippocampal formation of the human brain, and is reciprocally connected with the hippocampus.

The hippocampal formation, which consists of the hippocampus, perirhinal cortex, the dentate gyrus, the subicular areas and EC forms one of the most important parts of limbic system. It is an infolding of the parahippocampal gyrus into the inferior (temporal) horn of the lateral ventricle.

Group I

The mGluRs in group I, including mGluR₁ and mGluR₅, are stimulated most strongly by the excitatory amino acid analog L-quisqualic acid.^[5][15] Stimulating the receptors causes the associated enzyme phospholipase C to hydrolyzephosphoinositide phospholipids in the cell's plasma membrane.^[2][5][8] This leads to the formation of inositol 1,4,5-trisphosphate (IP3) and diacyl glycerol. Due to its hydrophilic character, IP3 can travel to the endoplasmic reticulum, where it induces, via fixation on its receptor, the opening of calcium channels increasing in this way the cytosolic calcium concentrations. The lipophilic diacylglycerol remains in the membrane, acting as a cofactor for the activation of protein kinase C.

These receptors are also associated with Na⁺ and K⁺ channels.^[5] Their action can be excitatory, increasing conductance, causing more glutamate to be released from the presynaptic cell, but they also increase inhibitory postsynaptic potentials, or IPSPs.^[5] They can also inhibit glutamate release and can modulate voltage-dependent calcium channels.^[8]

Group I mGluRs, but not other groups, are activated by 3,5-dihydroxyphenylglycine (DHPG),^[13] a fact that is useful to experimenters because it allows them to isolate and identify them.

Group II & Group III

The receptors in group II, including mGluRs 2 and 3, and group III, including mGluRs 4, 6, 7, and 8, (with some exceptions) prevent the formation of cyclic adenosine monophosphate, or cAMP, by activating a G protein that inhibits the enzymeadenylyl cyclase, which forms cAMP from ATP.^{[2][4][5][16]} These receptors are involved in presynaptic inhibition,^[8] and do not appear to affect postsynaptic membrane potential by themselves. Receptors in groups II and III reduce the activity of postsynaptic potentials, both excitatory and inhibitory, in the cortex.^[5]

The chemicals 2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) and eglumegad activate only group II mGluRs, while 2-amino-4-phosphonobutyrate (L-AP4) activates only group III mGluRs.^[13] Several subtype-selective positive allosteric modulators that activate only the mGlu2 subtype, such as Biphenylindanone A, have also now been developed.

LY-341,495 and MGS-0039 are drugs that act as a selective antagonist blocking both of the group II metabotropic glutamate receptors, mGluR₂ and mGluR₃.^[17] RO4491533 acts as a negative allosteric modulator of mGluR₂ and mGluR₃.^[18]

(reference: http://www.nature.co...nrd2571_T2.html, http://en.wikipedia....tamate_receptor)

[mgrade]

Of course, this brings you back to the whole "stress and neurogenesis" model.

[mgrade]

Can anyone find the actual Phase III (or Phase II) Trials of Pimavanserin with all the charts for efficacy, etc. ??

[Fawkinchit]

asdf

[mgrade]

Initially, I had that feeling -------but i fought thru it and now that i am over the hump, i'm doing good. That's a bad feeling and it is related to (stress, sex, etc.) hormones.

[mgrade]

Gata1 silencing, caspases (programmed cell death), depression, cancer........

I got the ingredients now make me some dinner.........lol

**plus look at Emapunil (AC-5216, XBD-173)

[mgrade]

There has been very little research medically done on the Corpus Callosum in terms of maintaining its health.

I wonder if anybody has any insight?

[mgrade]

I had mentioned indoles, aromatics, and dyes.

Benzodiazepines were discovered by a dye chemist from Poland. He moved to the US to join a drug company; he tested a number of compounds he had worked with in his dye research in Poland (now on wild monkeys). One compound was found to have a calming effect. That drug was Chlordiazepoxide. This was the discovery of the next generation of drugs for anxiety. It was synthesized from work on a chemical dye, quinazolone-3-oxides.

(So ......HA! .....told you so! )

[mgrade]

Link: Triptans, Indole, Aromatics, Dyes, Quinazolone (~dye), Benzodiazepines, Quinine, Quinidine (ion channel blocker), Ion Channels,

P-GcP etc

(You should see the link now if you haven't yet.........if you have than i am totally obnoxious).

[mgrade]

Today: I am looking into ion channels, electrophysiological resistance/conductivity,

cellular and synaptic pH, and drugs often used in ER and/or hospitals.

Drugs like atropine, quinidine, valium + ativan IV, epinephrine, etc.

Atropine: Deadly Nightshade

Quinidine: dyes/aromatics

Ativan: dyes/aromatics

Epinephrine: precursor role of Nutrasweet to synthesize

and

Perfumes, Shit-smells, Flower-Smells, Grape Flavor (Kool-aid, Crush, Bubblicious), Different Dyes and Coloring

--------------> All related to Serotonin (5HTP)

and

Nutrasweet, flavonoid biosynthesis base, meat, chicken, fish, eggs,nuts, cheese, legumes, milk, potatoes, bread, pasta, and corn, breast milk,

----------------> precursors to dopamine, norepinephrine, and epinephrine

(sorry about reiteration )

[mgrade]

The Answer To All Your Dreams!!!

[shaolinbomber]

http://en.wikipedia....tical_resonance

Recurrent thalamo-cortical resonance

"Recurrent thalamo-cortical resonance is an observed phenomenon of oscillatory neural activity between the thalamus and various cortical regions of the brain. It is proposed by Rodolfo Llinas and others as a theory for the integration of sensory information into the whole of perception in the brain.^[1][2] Thalamocortical oscillation is proposed to be a mechanism of synchronization between different cortical regions of the brain, a process known as temporal binding.^[3] This is possible through the existence of thalamocortical networks, groupings of thalamic and cortical cells that exhibit oscillatory properties."

"The thalamus in this system acts as both the gate for sensory input to the cortex as well as the site for feedback from cortical pyramidal cells, implying a processing role in sensory perception in addition to its function in directing information flow."

"Reticular neurons (RE), on the other hand, are highly interconnected and have their own intrinsic oscillatory properties. These neurons are capable of inhibiting thalamocortical activity via their direct connections to TCs. Corticothalamic neurons are the cortical neurons that TC neurons synapse on. These cells are glutaminergic excitatory cells that exhibit increasing activity as they become more depolarized. This activity is described as "bursting", firing in the gamma range at rates between 20 and 50 Hz."

Now i'm wondering if these http://neuronbank.or...eticular_neuron could be part of the inhibitory interneuron theory presented by Dr. Abraham. This is relevant because that is (or atleast was) his primary theory in trying to explain what causes HPPD and the visuals. The theory says that these inhibitory interneurons had been changed somehow and were no longer functioning properly by inhibiting our vision and that is what is causing all of the visuals.

These Thalamic reticular neurons would fit this description quite nicely for an inhibitory interneuron in the visual cortex.

If I understand this theory correctly, then the thalamocortical feedback loop receives information from our sensory input of the eyes, yet perhaps in the case of an HPPDer the correct inhibitory responses to this sensory input is not functioning properly and we're left with too much sensory input resulting in afterimages, trails, floaters (when, in a young healthy human, there should be none or very little) and so on.

"Thalamic cells synapse on apical dendrites of pyramidal cells in the cortex. These pyramidal cells reciprocally synapse back on thalamic neurons. Each loop is self-contained and modulated by sensory input. Inhibitory interneurons both in the cortex and the reticular nucleus of the thalamus regulate circuit activity."

"The lateral geniculate nucleus, known as the major relay center from the sensory neurons in the eyes to the visual cortex, is found in the thalamus and has thalamocortical oscillatory properties,^[7] forming a feedback loop between the thalamus and the visual cortex. Sensory input can be seen to modulate the oscillatory patterns of thalamocortical activity while awake. Visual perception is no exception, and stimulation from light sources can be seen to cause direct changes in the amplitude of the thalamocortical oscillations as measured by EEG."

Then we have basically the proposed theory that I have stated yet put into a scientific model to be presentable to the scientific community.

Thalamocortical dysrhythmia

"Thalamocortical dysrhythmia (TCD) is a proposed explanation for certain cognitive disorders. It occurs upon the disruption of normal gamma-band electrical activity between the cortex and thalamic neurons during awakened, conscious states.^[13] This disorder is associated with diseases and conditions such as neuropathic pain, tinnitus, and Parkinson’s disease^[14] and is characterized by the presence of unusually low-frequency resonance in the thalamocortical system. TCD is associated with disruption of many brain functions including , and motor control and occurs when thalamocortical neurons become inappropriately hyperpolarized, allowing T-type calcium channels to activate and the oscillatory properties of the thalamocortical neurons to change.^[13] A repeated burst of action potentials occurs at lower frequencies in the 4–10 Hz range. These bursts can be sustained by inhibition from the thalamic reticular nucleus and may cause an activation of cortical regions that are normally inhibited by gamma-band activity during resonance column formation. While the effect of the deviation from normal patterns of gamma oscillatory activity during conscious perception is not entirely settled, it is proposed that the phenomenon can be used to explain chronic pain in cases where there is no specific peripheral nerve damage."

Here is the wiki link about it.:http://en.wikipedia.org/wiki/Thalamocortical_dysrhythmia

[VisualDude]

Dr A: "Studies of HPPD patients with qEEG mapping show that the disorder is represented by disinhibition in the cerebral cortex". Disinhibition means without proper controls and restraints.

The thalamus is not part of the cerebral cortex. All sensory signals go through the thalamus (except pain).

Paraphrasing another paper posted on the forum, it did attribute many HPPD symptoms as cerebral hyperactivity can be from incorrect or insufficient information getting from the retina - which would implicate retina -> optic nerves -> thalamus -> etc.

There are lots of feedback and feedforward systems in the brain, and thus oscillation (brain waves are oscillations)

Certainly everything that visual (etc) signals go through experience some processing. Signals split, go all over the place, get sub-processed here-there-and-everywhere, and then eventually get pasted together in some meaningful way we call perception. http://en.wikipedia....wiki/Perception Perception starts at infancy as hardwiring. Then plasticity and memories begin forming. Eventually here we are now, "meaning-making-machine" with perception based on past experience (memory).

For whatever reasons we get scrambled, distorted info (snow, bending, ...) and either our brains learn how to integrate "the-new-way", or signals "clean-up", or we keep experiencing "the-light-show"

Note: Sorry, no further info about Orville P Vunder.

[mgrade]

What's up with this??

[EmIly]

Ok first pic someone save the child. 2nd pic your life could always be worse.

[mgrade]

Is that a hernia?............And 2nd guy, this guy IS Beavis.....lol

[Fawkinchit]

Dr A: "Studies of HPPD patients with qEEG mapping show that the disorder is represented by disinhibition in the cerebral cortex". Disinhibition means without proper controls and restraints.

The thalamus is not part of the cerebral cortex. All sensory signals go through the thalamus (except pain).

Paraphrasing another paper posted on the forum, it did attribute many HPPD symptoms as cerebral hyperactivity can be from incorrect or insufficient information getting from the retina - which would implicate retina -> optic nerves -> thalamus -> etc.

There are lots of feedback and feedforward systems in the brain, and thus oscillation (brain waves are oscillations)

Certainly everything that visual (etc) signals go through experience some processing. Signals split, go all over the place, get sub-processed here-there-and-everywhere, and then eventually get pasted together in some meaningful way we call perception. http://en.wikipedia....wiki/Perception Perception starts at infancy as hardwiring. Then plasticity and memories begin forming. Eventually here we are now, "meaning-making-machine" with perception based on past experience (memory).

For whatever reasons we get scrambled, distorted info (snow, bending, ...) and either our brains learn how to integrate "the-new-way", or signals "clean-up", or we keep experiencing "the-light-show"


Note: Sorry, no further info about Orville P Vunder.

 

asdf

[mgrade]

I doubt antipsychotics would help in cases that only have visual symptoms. As for anxiety, dr/dp, dissociation, paranoia, hyper-vigilance, hallucinations, psychosis, antipsychotics will work.....but they carry a lot of side effects. I have tried Zyprexa, Abilify, and Risperdone. I have been on Haldol for an instance, also. They are MEAN drugs. Tranq's.

For 5ht2a inverse agonists, look at Acadia Pharmaceuticals and the drug Pimavanserin.

This is the closest drug to being approved in the US. At 40mg, it seems to show a 20% increase in effectiveness as compared to placebo. In November, another trial result will come out.

Perhaps there may be something to these inverse agonists but the study was small and did not make its "endpoint".