The right dose of green tea’s theanine can help you to …

Chisel Your Awareness
By down-regulating the startle response

By Will Block

T he neurological phenomenon known as Prepulse Inhibition (PPI) occurs when a weaker stimulus (prepulse) inhibits an organism’s reaction to a succeeding strong startling stimulus (pulse). This is true for humans as well as other species. Although the stimuli involved are usually acoustic, tactile stimuli, and light stimuli also are among the prepulses. PPI is a positive response that when amplified in humans can make a large difference in learning by honing awareness, lucidity, and even make for more efficient thinking. Just as a sculptor removes with chisel what stands in the way of the artist’s vision, so too can you remove what blocks the clarity of your vision by cleaning nonessentials from your doors of awareness.

Theanine Can Help Control the Gates of Awareness

In a new study, 14 healthy Japanese adults underwent PPI testing — as a measure of what can trigger sensorimotor gating — 90 minutes after an oral intake of L-theanine (hereafter theanine), an amino acid uniquely found in white and green tea.1 As with the sculptor simile, sensorimotor gating is beneficial because it allows us to neurologically filter out redundant or unnecessary stimuli, to separate in our brains what is important from what is not. Excess or trivial stimuli are screened or “gated out” of awareness. Without such abilities, we would function like preconceptual children, unable to distinguish the wheat from the chaff in the bombardment of environmental stimuli on our minds. The researchers observed that theanine had a significant effect on PPI suggesting that theanine increases sensorimotor gating in humans.


The researchers observed
that theanine had a significant effect
on PPI suggesting that
theanine increases sensorimotor
gating in humans.


The Cushions of Consciousness

Sensorimotor gating prevents an overload of irrelevant information in the higher cortical centers of the brain, the pulvinar nuclei of the thalamus. These cushions (derived from the Latin word for cushion, pulvinus) of consciousness play a major role in attention, and filter out superfluous information. Although sensorimotor gating is automatic for the most part, it also occurs within attentional processes.

The term sensory gating has been used interchangeably with sensorimotor gating, but the two are distinct constructs. When you’re at a cocktail party (with lots of noise generated by multiple simultaneous conversations) it is possible for you to volitionally inhibit input from environmental stimuli, while still processing sensory input from the attended stimulus. This means that you can hone in on one conversation and exclude others. This so-called cocktail party effect demonstrates sensory gating in hearing, but your other senses also go through similar processes that protect primary cortical areas from being overwhelmed.

Sensorimotor Gating


Acoustic Startle Set Up (PPI): A test of anxiety and sensori­motor gating, at the University of Toronto
The study was double blinded. There was no significant relationship between the dose of theanine and the startle magnitude or the habituation of startle response. The plasma concentrations of theanine correlated with the dose of theanine. The observed effect with 200 – 400 mg of theanine on PPI suggested that theanine at a particular dose range increases sensorimotor gating in humans.

According to the researchers, “The reduction of the amplitude of startle reflects the ability of the nervous system to temporarily adapt to a strong sensory stimulus when a preceding weaker signal is given to warn the organism.”

PPI has been found to occur in various species extending from mice to humans. While the range of adaptation affects numerous systems, it is easiest to measure the muscular reactions, because they are routinely reduced as a result of the nervous inhibition.

Dampening the Startle Response with Prepulse


Figure 1. Prepulse inhibition: preceding stimulus attenuates the startle response.
The startle response is a defensive response to sudden or threatening stimuli, and is associated with negative affect. It can be suppressed when its stimulus is preceded by a weak non-startling prepulse (see Fig. 1). This constitutes the PPI process. The level by which such a prepulse inhibits the startle reflex in PPI is used as a degree of sensorimotor gating. Thus, excessive or trivial stimuli are screened or “gated out” of awareness, so that an individual can focus attention on the most salient aspects of the stimulus-laden environment.

Insufficient PPI in Neuropsychiatric Disorders

Several neuropsychiatric disorders are characterized by abnormalities in the cortico-striato-thalamic-pontine circuitry that result in deficient PPI. In schizophrenia, PPI has been proposed as a measure of information-processing abnormalities. After treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, amantadine, ketamine, memantine, among other drugs, PPI varies. This indicates that PPI is governed not only by dopamine inducers, but also by glutamatergic neurotransmission. Deficits of prepulse inhibition manifest in the inability to filter out unnecessary information. In addition to schizophrenia, such deficits are noted in patients suffering from illnesses like Alzheimer’s disease, and in people under the influence of drugs, surgical manipulations, or mutations.

Returning to the study, of the 14 healthy adults — seven men and seven women — whose mean age was 31.0 ± 7.0 years and mean body mass index was 22.5 ± 2.8 (normal). Two out of the 14 subjects smoked at least 10 cigarettes per day (possible confounders) and participants were interviewed for enrollment using the Japanese version of the Mini-International Neuropsychiatric Interview (MINI) by psychiatrist researchers to exclude those with psychiatric illness or who had suffered severe head injury.


The observed effect with
200 – 400 mg of theanine on PPI
suggested that theanine at a
particular dose range increases
sensorimotor gating in humans.


Administration of Theanine and Measurement of PPI

Theanine was given to each participant four times, at 0, 200, 400, and 600 mg in a randomized order, the amounts of which were blinded, at the four administration times. The half-life of theanine ranges from 58 to 74 minutes in humans and the washout period takes at least 2 days.

The effect of theanine on brain activity in the subjects began to appear 30 minutes after oral administration. Based on these findings, theanine was administered 1.5 hours prior to the PPI test.

Blood samples were obtained immediately before the PPI test, and the plasma concentration of theanine was determined. Startle reflex of the subjects to acoustic stimuli was measured. The two smokers refrained from smoking for at least 20 min prior to the test.

Broadband white noise was produced as background noise, and was sustained throughout the session. Acoustic startle stimuli of the broadband white noise were presented through headphones. Altogether, 35 trials of startle response were recorded during each session, segregated into three blocks. In the first block, startle response of the subjects to a pulse [sound pressure 115 dB; duration 40 milliseconds (ms)] alone was recorded five times. In the second block, the startle response to the same pulse with or without a prepulse (sound pressure 86 or 90 dB; duration 20 ms; lead interval [onset to onset] 60 or 120 ms) was measured five times for each condition.

The trial conditions were presented in a random order, and in the final block, startle response to pulse alone was measured five times. The intertrial intervals [15 seconds (s) on average, range 10 – 20 s] were randomly changed. The entire session lasted approximately 15 minutes. The analysis of PPI of the subjects was based on the mean of the five trials for each trial type.

The researchers obtained measures of the startle response to pulse-alone trials, habituation of the startle response during the session, and % PPI (the higher the %, the greater the inhibition of the startle). PPI tests were conducted by examiners who were blind to the dose of theanine.

Upon examining the effect of theanine on the % PPI, startle magnitude, and habituation, the researchers ran repeated measures, capturing covariance analysis for each metric with lead intervals, sound pressure, and dose of theanine as within-subjects factors, sex as a between-subjects factor, and age and bodyweight as covariates, followed by corrected pairwise comparisons as post-hoc tests. In other words, the researchers went to great lengths to produce quality data.

The Japanese scientists evaluated the effect of theanine on the startle magnitude and habituation with repeated measures, including sex, age, and bodyweight as covariates. They calculated the association between the plasma concentration of theanine and PPI metrics of subjects by a partial correlation analysis with age as a control variable. We also examined the association between the dose of oral administration and the plasma concentration of theanine, using a correlation test.

There was a significant interaction between the dose of theanine and sound pressure in the effect on % PPI. But there was no significant interaction between the dose of theanine and lead interval, nor between sex and lead interval or between sex and sound pressure.

When the prepulse sound pressure was 90 dB (comparable to a motorcycle at 25 feet), the % PPI was significantly increased by theanine. When the lead interval was 60 ms, there was a significant difference in the % PPI between the baseline and the 200 mg administration and between the baseline and the 400 mg administration.

The Higher the %, the Greater the Startle Inhibition

With the conditions of 120 ms and 90 dB, there was a significant difference in % PPI between the baseline and the 400 mg administration. There was a significant positive correlation between the plasma theanine concentration and the administered dose.

It was found that 200 mg or 400 mg of theanine increased the % PPI, while 600 mg of theanine did not. Only the lower range of theanine significantly affected the PPI of the. To the best knowledge of the Japanese researchers, this is the first study to obtain evidence of the effects of theanine on sensorimotor gating in humans.

Galantamine Reverses Deficits In PPI

It has recently been found that galantamine, but not donepezil, reversed isolation rearing-induced deficits of prepulse inhibition (PPI),* and sensory information-processing, in mice.1 Japanese researchers at Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan unexpectedly found that the galantamine-induced improvements in PPI deficits were prevented by the muscarinic acetylcholine receptor (mAChR) antagonists scopolamine and telenzepine (preferential for M1 subtype of mAChR), but not by nicotinic acetylcholine receptor (nAChR) antagonists.2


* Prepulse Inhibition (PPI) is a neurological phenomenon in which a weaker prestimulus (prepulse) inhibits the reaction of an organism to a subsequent strong startling stimulus (pulse). Deficits of prepulse inhibition manifest in the inability to filter out unnecessary information; they have been linked to abnormalities of sensorimotor gating, the state-dependent regulation of transmission of sensory information to a motor system. Such deficits are noted in patients suffering from illnesses like schizophrenia and Alzheimer’s disease.


References

  1. Koda K, Ago Y, Kawasaki T, Hashimoto H, Baba A, Matsuda T. Galantamine and donepezil differently affect isolation rearing-induced deficits of prepulse inhibition in mice. Psychopharmacology (Berl) 2008 Feb;196(2):293 – 301.
  2. Ago Y. Beneficial effect of galantamine on sensory information-processing deficits. Yakugaku Zasshi 2010 Oct;130(10):1305 – 10.

Effects Attributable to the Chemical Structure of Theanine

The effects of theanine on PPI were thought to be attributable to its chemical structure (i.e., as a glutamate derivative), owing in part to the knowledge that theanine has weak affinities for NMDA receptors. NMDA (N-methyl-D-aspartate receptor), a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function. In keeping with this notion, one study suggests that glutamate can act either as a brake or as an accelerator of dopamine, serotonin, and noradrenaline systems, resulting in either increased or decreased information flowing to the cortex. The narrow dose range for theanine-induced changes in PPI may result from the ambivalent action of glutamatergic transmission. The researchers observed the effect with 200 – 400 mg of theanine on % PPI. This finding is in accordance with a previous study using memantine, a dopamine agonist as well as an NMDA antagonist.

Previous studies showed that a low dose of memantine increased PPI, whereas a high dose reduced PPI compared to controls in both rats and humans. These points indicate that the ratio of the dopamine agonist to NMDA antagonist effects of memantine differed at the doses they administered: a predominant NMDA antagonism at a low dose of memantine leads to increased PPI; and more prominent dopamine agonist effects at a high dose oppose these NMDA blockade effects.

Furthermore, theanine is known to have affinities for glutamatergic receptors, and also to increase brain gamma-aminobutyric acid (GABA), serotonin, and dopamine levels. This suggests that theanine exerts its effects, at least in part, through an ambivalent action of the glutaminergic system.


It was found that 200 mg or 400 mg
of theanine increased the % PPI,
while 600 mg of theanine did not.


Selective Attention

The startle response can be suppressed by the right dose of theanine which invokes a weak non-startling prepulse, in the process known as prepulse inhibition (PPI). The degree to which such a prepulse inhibits the startle reflex in PPI is used as a measure of sensorimotor gating, by which excess or trivial stimuli are screened or ‘gated out’ of awareness, so that an individual can focus attention on the most salient aspects of the stimulus-laden environment. PPI may also operate as a safety mechanism that can prevent us from overreactions that could lead to dangerous accidents.

Taurine Helps Remodel Your Sleepscape

Durk Pearson & Sandy Shaw have touted theanine for a wide variety of properties (see “Theanine: Neuroprotective, Stress Reducing, Sleep Quality Improver” in the August 2013 issue). “It can pass the blood-brain barrier and, in fact, has been shown to have neuroprotective effects in the brain that include protection against the injury induced by transient forebrain neuronal ischemia, oxidative stress in the brain, reduced brain cell death due to stroke in mice and reduced stress induced by a mental arithmetic task in human volunteers [references removed].”

In the above referenced article, Durk & Sandy also cite other studies that suggest and show that theanine can induce feelings of relaxation and improved sleep quality while reducing physiological stress responses during stress-producing tasks in human subjects. Furthermore, they write, although theanine has been linked to improved sleep quality, it has also been reported to produce no drowsiness in humans.

Reference

  1. Ota M, Wakabayashi C, Matsuo J, Kinoshita Y, Hori H, Hattori K, Sasayama D, Teraishi T, Obu S, Ozawa H, Kunugi H. Effect of L-theanine on sensorimotor gating in healthy human subjects. Psychiatry Clin Neurosci. 2014 May;68(5):337-43.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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