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June 28, 2023


IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein



Author to whom correspondence should be addressed.

Vaccines 2023, 11(5), 991; https://doi.org/10.3390/vaccines11050991

Vaccines is an international, peer-reviewed, open access journal published monthly online by MDPI. The American Society for Virology (ASV) is affiliated with Vaccines and their members receive a discount on the article processing charges.


Received: 2 April 2023 / Revised: 12 May 2023 / Accepted: 15 May 2023 / Published: 17 May 2023

(This article belongs to the Special Issue SARS-CoV-2: Immune Tolerance and Autoimmune Diseases after COVID-19 Vaccination and Its Related Adverse Events)

この記事は「SARS-CoV-2: COVID-19ワクチン接種後の免疫寛容と自己免疫疾患とその関連有害事象に関する特別号」に所属しています。



Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with comorbidities has recently been questioned, and increasing evidence has shown that, as with many other vaccines, they do not produce sterilizing immunity, allowing people to suffer frequent re-infections.


sterilizing immunity 殺菌免疫

Additionally, recent investigations have found abnormally high levels of IgG4 in people who were administered two or more injections of the mRNA vaccines. HIV, Malaria, and Pertussis vaccines have also been reported to induce higher-than-normal IgG4 synthesis. Overall, there are three critical factors determining the class switch to IgG4 antibodies: excessive antigen concentration, repeated vaccination, and the type of vaccine used. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects.

さらに、最近の調査では、mRNAワクチンを2回以上注射した人に異常に高いレベルの免疫グロブリンG4 (IgG4)が見つかりました。HIV、マラリア、百日咳ワクチンも、通常よりも高いIgG4合成を誘導することが報告されています。全体として、IgG4抗体へのクラス切り替えを決定する3つの重要な要素があります:過剰な抗原濃度、繰り返しのワクチン接種、および使用されるワクチンの種類。免疫グロブリンG4 (IgG4)レベルの増加は、免疫グロブリンE(IgE)誘発効果を阻害することによってアレルゲン特異的免疫療法の成功時に起こるのと同様に、免疫の過剰活性化を防ぐことによって保護的な役割を果たす可能性があることが示唆されています。

Immunoglobulin G4 (IgG4):免疫グロブリンG4 (IgG4)

IgEは免疫グロブリンの一種です。 身体のなかに入ってきたアレルギーの原因物質(アレルゲン)に対して働きかけ、身体を守る機能を持つ抗体です。

allergen-specific immunotherapy アレルゲン特異免疫療法

However, emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.



IgG4,antibodies; mRNA,vaccines; immuno-tolerance; auto-immunity; SARS-CoV-2; COVID-19

免疫グロブリンG4 (IgG4),抗体、mRNA、ワクチン、免疫寛容、自己免疫、新型コロナウイルス、新型コロナウイルス感染症


Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination

SARS-CoV-2 mRNAワクチンの反復接種により、非炎症性のスパイク特異的IgG4抗体へのクラス切り替えが起こる。


Anti-spike IgG4 rises from obscurity


The four human IgG subclasses have distinct effector properties due to differences in binding Fc receptors and activating complement. The serum concentration of human IgG4 is normally lower than either IgG1, IgG2, or IgG3.


Fc受容体(Fcじゅようたい、Fc receptor、FcR)とは免疫グロブリン(抗体)分子のFc部位に対する受容体タンパク質であり、細胞表面に存在する。免疫グロブリン分子であるIgG、IgA、IgE、IgMに対する受容体をそれぞれFcγR、FcαR、FcεR、FcμRと呼ぶ。フリー百科事典『ウィキペディア(Wikipedia)』より

effector properties :エフェクター特性

Irrgang et al. did a longitudinal analysis of the level of spike-specific antibodies from each IgG subclass in recipients of the SARS-CoV-2 BNT162b2 mRNA vaccine. Anti-spike IgG4 as a fraction of total anti-spike IgG rose by 6 months after the second vaccination and increased further after a third vaccine dose.

Irrgangら SARS-CoV-2 BNT162b2 mRNAワクチンの接種者における各IgGサブクラスからのスパイク特異的抗体のレベルを縦断的に分析しました。抗スパイクIgG全体の割合としての抗スパイクIgG4は、2回目のワクチン接種後に6か月増加し、3回目のワクチン接種後にさらに増加しました。

Serum antibody effector activity assessed by antibody-dependent phagocytosis or complement deposition was less after the third dose than after the second dose.


Serum antibody effector activity:血清抗体エフェクター活性
phagocytosis 食作用

complement 補体

Further studies are needed to determine how emergence of an IgG4 anti-spike response influences vaccine-induced protection from SARS-CoV-2 infection. ?IRW






膜性腎症の病因I IgG サブクラスおよび細胞性免疫からの考察

ヒト IgG は 4 つのサブクラスに分類される。このうち IgG4 は血中濃度が最も低く,全 IgG に対する割合は,最 も高い IgG1 が 50 %以上であるのに対し IgG4 は 5 %以下 である。抗体産生のクラススイッチは IgG3,IgG1,IgG2, IgG4 の順番で行われ,このうち IgG1 は Th1 サイトカイン で,IgG4 は Th2 サイトカインで誘導される。






Th1細胞(-さいぼう、英: Th1 Cell)は、CD4+T細胞(いわゆるヘルパーT細胞)の亜群であり、インターフェロン-γやインターロイキン-12(IL-12)の刺激を受けることによりナイーブT細胞とよばれる抗原タンパク質との接触経歴を持たないT細胞からの分化が誘導される。T細胞をはじめとした免疫系の細胞はサイトカイン産生能を有しているがTh1細胞により産生されるインターフェロン-γ(IFN-γ)をはじめとしたサイトカインは特にTh1サイトカインと呼ばれ、マクロファージや細胞障害性T細胞(CTL)などの細胞を活性化してウイルスや細胞内抗原の除去、自己免疫疾患の発症、抗腫瘍免疫を担う細胞性免疫などに関与していることが知られている。同様にナイーブT細胞から分化するTh2細胞はIL-4などのいわゆるTh2サイトカインを産生し、Th1細胞とTh2細胞はサイトカインを放出することにより互いの機能を抑制しあっている。

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June 20, 2023


How to Stimulate the Vagus Nerve



Looking for Ways to Stimulate the Vagus Nerve to Reduce Stress?


Importance of the Vagus Nerve


The vagus nerve is the longest nerve in the body, connecting the brain to the neck, heart, lungs, spleen and the digestive system. It has many functions within those body systems with vital involvement in sensory and movement functions and a major role in balancing the nervous system, which is the focal point of this article.


Balancing the Nervous System


Try to think of the Vagus nerve as an on/off switch between the sympathetic and parasympathetic nervous system, your stress response fight or flight and your rest and digest response. On the sympathetic side, turning the switch ON when experiencing a stressful event, the vagus nerve is involved in increasing the heart rate, blood pressure, energy levels, allows you to be more alert and focused, accelerates breathing, and redirects blood flow from the digestive system to the brain and muscles. We can become faster, stronger, react quicker to a “dangerous” situation. Energy is not “wasted” on digestive functions! On the parasympathetic side, turning the switch OFF to get back into the rest and digest phase, it lowers blood pressure, heart rate, slows breathing, instills a sense of calmness and relaxation to body and mind.


Remember that in a stressful situation blood flow to the digestive system is going to be decreased, slowing down digestive functions. That is an important factor when considering that many of us stay in a state of “stress response” for prolonged periods of time. The Vagus nerve is in constant communication between the gut and the brain, and is also involved in sending anti-inflammatory information to the body. Hence, unmanaged stress can add to digestive and inflammatory issues.


Stimulating the Vagus Nerve


When the Vagus nerve gets stimulated it releases a substance called “Vagusstoff”, also named acetylcholine, a neurotransmitter that plays an important role in our capacity to calm down, to switch from our stress response back into our rest and digest response. The vagus nerve communicates the state of our organs back to the brain. The higher our vagal tone, the better our emotional and physical wellbeing, the better our ability to stay in control during stressful situations and exercising adequate response. Low vagal tone makes it difficult to “switch back” into a calm and relaxed state and may be associated with chronic inflammation, negative moods and emotions, feeling isolated, increased heart rate and blood pressure, digestive issues – just to name a few.




vagal tone :ベーガル・トーン(迷走神経の活性度)

How Do I know I have low vagal tone?


A useful indicator (also called hearth coherence) is the difference in heart rate between inhaling (when the blood gets oxygenated) and exhaling. The greater the difference in heart rate, the higher the vagal tone.


hearth coherence:ハート・コヒーランス

Practices Commonly Used to Stimulate the Vagus Nerve may include:


Deep Breathing Practices


Deep and slow diaphragmatic breathing, raising the belly when breathing in, holding the breath for few counts, exhaling by releasing all air out of the lungs until it feels the belly is sinking against the spine (exhaling for longer counts than breathing in) is a helpful practice to stimulate the vagus nerve. The more we practice deep breathing every single day, the easier it will be to use this technique during a stressful event, to help our nervous system back into a calmer state.


OM Chanting


When chanting Om, a vibration sound is felt in the vocal cords which may stimulate the vagus nerve which runs down at the back of the throat. Chanting Om has been indicated as having positive cardiovascular benefits, reducing feelings of stress and helping the body enter a relaxed state of mind, lowering blood pressure, slowing heart rate, instilling a sense of inner calm, opening the Crown Chakra and self-realization. If chanting is new to you, you may want to start practicing with guidance. Several good videos can be found on YouTube.


Singing & Laughing


Singing in the shower or car, playing Karaoke, watching a funny movie or comedy show, talking with friends who are sure to make you laugh are a fun and great way to stimulate the vagus nerve.


Cold Water


Splashing cold water into your face, running it over the inside of the wrists, turning the shower on cold for the last 30 seconds are great ways to boost vagal tone (and support the immune system).


Probiotics & Balanced Nutrition


Supporting gut health can greatly impact our overall health (digestive health, immune system, emotional balance). The gut is often referred to as the “second brain” because it produces neurotransmitters such as serotonin and dopamine which play an important role in regulating mood. It is estimated that the digestive tract creates 90% of our serotonin levels. What affects our gut also affects the brain and vice versa. Fortifying the body with balanced nutrition and probiotics may support vagal tone.


Essential Oils


Essential oils can calm the autonomic nervous system by engaging the vagus nerve. Calming essential oils include Lavender, Roman Chamomile, Melissa, Sandalwood, Cedarwood, Vetiver, Patchouli, Rose, Neroli, Lemon, and Ylang Ylang to name some of the most commonly used. Inhaling essential oils (from the palms of the hands or diffused) has the most immediate and profound effect.




Movements requiring a complex level of coordination (Fast Walking, Jogging, Yoga, Thai Chi and other Eastern movement practices) help stimulate the vagal tone, synchronizing internal and external rhythms with thoughts and emotions.


Training the Taste Buds


The vagus nerve is involved in our sense of taste. Consciously tasting foods and beverages, reflecting on what we like or dislike, differentiating nuances of sweet, savory or spicy and learning to discern whether we are sensing true hunger or just craving something because of stress or need for emotional gratification, helps train the vagus nerve.


Regular practice and consistency makes all the difference!


Incorporating some of these techniques, may strengthen vagal tone which can positively impact our ability to manage stress, balance mood, support digestion, and improve overall feelings of wellbeing.



vagal toneを迷走神経緊張と訳していたがどうもニュアンスが違うではないのかと、投稿にあたり、再度検索をしてみたところ下記の記事にであい、ベーガル・トーン(迷走神経の活性度)にしました。





迷走神経は英語で「ベガス・ナーブ(Vagus nerve)」、そこから転じて、迷走神経の活性度を「ベーガル・トーン(Vagal tone)」といいます。迷走神経は、いわば副交感神経の「元締め」のようなもの。その迷走神経の活性度を上げること、つまりベーガル・トーンを上げることが、副交感神経を優位にする有効な戦略になるというわけです。


オーム(ओम् om、または ॐ oṃ〈オーン〉)は、バラモン教をはじめとするインドの諸宗教において神聖視される呪文。

ヴェーダを誦読する前後、また祈りの文句の前に唱えられる。 ウパニシャッドにおいては、この聖音は宇宙の根本原理であるブラフマンを象徴するものとされ、特に瞑想の手段として用いられた。

また、この聖音 は「a」、「u」、「m」の3音に分解して神秘的に解釈される。これは、サンスクリット語ではaとuが隣り合うと同化して長母音oになるという音韻法則があるからである。

例えば『ブリハッド・アーラニヤカ・ウパニシャッド』では「a」は『リグ・ヴェーダ』、「u」 は『サーマ・ヴェーダ』、「m」 は『ヤジュル・ヴェーダ』の三ヴェーダを表し、「aum」全体でブラフマンを表すと解釈された。




この聖音は後に仏教にも取り入れられ、密教では真言の冒頭の決まり文句(オン)として、末尾のスヴァーハー(ソワカ)と共に多用された(例えば「オン アビラウンケン ソワカ」で大日如来の真言)。 また、仏教の経典『守護国界主陀羅尼経』では「a」は法身、「u」は報身、「m」は応身の三身を象徴し、すべての仏たちはこの聖音を観想する事によって成仏すると説かれる。







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June 19, 2023


Neuromodulation of Neural Oscillations in Health and Disease



Department of Biomedical Engineering, Columbia University, ET 351, 500 W. 120th Street, New York, NY 10027, USA


Over the past few decades, advances in electroencephalography (EEG) recordings and brain stimulation has permitted an unprecedented view of how specific brain structures communicate as well as organize complex cognitive functions. Specifically, neurotransmitters (including norepinephrine, acetylcholine, and dopamine) have all been shown to have an impact on neural oscillations throughout the brain, linking them to changes in cognitive functions such as memory, attention, and executive function.


While these interactions are still widely unexplored, their appearance in neurological disorders through cross-frequency coupling (CFC) brings light to the vital role they play in orchestrating healthy brain function. This brief review serves to highlight the important role each neuromodulatory system plays in changing widespread neural networks, emphasizing their involvement in health and disease to help inform more translational brain stimulation technologies.

これらの相互作用はまだ広く解明されていませんが、周波数間カップリング (CFC) を介した神経障害におけるそれらの出現は、健康な脳機能を調整する上でそれらが果たす重要な役割に光をもたらします。この簡単なレビューは、広範な神経回路網の変化において各神経調節システムが果たす重要な役割を強調し、より多くのトランスレーショナル脳刺激技術に情報を提供するために健康と病気への関与を強調するのに役立ちます。

cross-frequency coupling (CFC) :周波数間カップリング (CFC)



Using EEG and local field potentials (LFPs) as an index of large-scale neural activities, research has been able to associate neural oscillations in different frequency bands with markers of cognitive functions, goal-directed behavior, and various neurological disorders. While this gives us a glimpse into how neurons communicate throughout the brain, the causality of these synchronized network activities remains poorly understood.


local field potentials (LFPs):局所場電位(LFP)
goal-directed behavior 目標指向行動

Moreover, the effect of the major neuromodulatory systems (e.g., noradrenergic, cholinergic, and dopaminergic) on brain oscillations has drawn much attention. More recent studies have suggested that cross-frequency coupling (CFC) is heavily responsible for mediating network-wide communication across subcortical and cortical brain structures, implicating the importance of neurotransmitters in shaping coordinated actions. By bringing to light the role each neuromodulatory system plays in regulating brain-wide neural oscillations, we hope to paint a clearer picture of the pivotal role neural oscillations play in a variety of cognitive functions and neurological disorders, and how neuromodulation techniques can be optimized as a means of controlling neural network dynamics.

さらに、脳の振動に対する主要な神経調節系(例えば、ノルアドレナリン作動性、コリン作動性、およびドーパミン作動性)の効果が多くの注目を集めています。より最近の研究では、周波数間カップリング (CFC) が皮質下および皮質の脳構造にわたるネットワーク全体のコミュニケーションを仲介することに大きく関与していることが示唆されており、協調行動の形成における神経伝達物質の重要性が示唆されています。脳全体の神経振動を制御する上で各神経調節系が果たす役割を明らかにすることで、神経振動がさまざまな認知機能や神経障害において果たす重要な役割と、神経回路網のダイナミクスを制御する手段として神経調節技術を最適化する方法をより明確に描きたいと考えています。



neuromodulation; EEG; noradrenergic system; cholinergic system; dopaminergic system; pupil-linked arousal; neural oscillations; cross-frequency coupling; vagus nerve stimulation; neurological disorders

神経調節、脳波、ノルアドレナリン系、コリン系、ドーパミン系、瞳孔連動性覚醒、神経振動、周波数間カップリング (CFC)、迷走神経刺激、神経障害


1.はじめに 1-1

Neural oscillations are thought to be an essential driver of interaction, communication, and information transmission throughout the brain [1,2,3]. Evolution has maximized the role these oscillations play in regulating and controlling neuronal functions, driving the synchronization of widespread neural networks in the brain. The EEG provides the most popular non-invasive methods to record neural oscillations, summating the local field potentials of thousands of neurons in cortical structures [4,5]. Not only does this tool characterize the “global” brain state as a time series of voltage potentials, but also allows researchers to analyze these oscillatory waveforms through frequency domain analysis. Studies have suggested that distinct EEG frequency bands (Delta, Theta, Alpha, Beta, Gamma) are generated from unique neural populations across a variety of brain regions [6].

神経振動は、脳内の相互作用、コミュニケーション、情報伝達の重要な伝達機構であると考えられている[1,2,3]。進化は、これらの振動が神経細胞機能の調節と制御に果たす役割を最大限に高め、脳内の広範な神経ネットワークの同期を促進した。脳波は、神経振動を記録する最も一般的な非侵襲的方法であり、皮質構造における何千ものニューロンの局所電位を合計する[4,5]。このツールは、電位差の時系列として「グローバルな」脳の状態を特徴付けるだけでなく、周波数領域分析によってこれらの振動波形を分析することも可能である。研究では、異なる脳波の周波数帯(デルタ、シータ、アルファ、ベータ、ガンマ)が、さまざまな脳領域にわたる固有の神経集団から生成されることが示唆されています [6]。

This characterization shows the ability of different brain structures to generate specific neural oscillatory patterns, permitting synchronization and frequency coupling [6]. Assessing the effect of oscillatory changes both globally and locally throughout the brain can uncover the important and/or causal role of various neuromodulatory processes [7]. Cross-frequency coupling (CFC), resulting from coupling between various neural circuits and/or different types of neurons through chemical or electrical synapses, has recently become a more prominent topic [8,9]. Components of CFC such as phase?phase and phase?amplitude coupling have been shown to have a large influence on cognitive processes including attention, learning, and short- and long-term memory [10,11].

この特徴は、異なる脳構造が特定の神経振動パターンを生成し、同期と周波数結合を可能にする能力を示しています[6]。脳内の全体的および局所的な振動変化の影響を評価することで、様々な神経調節プロセスの重要な役割や因果関係を明らかにすることができます[7]。最近、化学的または電気的シナプスを介した様々な神経回路や異なる種類のニューロン間の結合に起因する周波数間カップリング(CFC)が、より顕著な話題となっている [8,9]。周波数間カップリング(CFC)の構成要素である位相-位相および位相-振幅結合は、注意、学習、短期・長期記憶などの認知過程に大きな影響を与えることが示されている[10,11]。

phase?phase and phase?amplitude coupling : 位相-位相および位相-振幅結合

Additionally, the phase?amplitude synchronization of these high and low frequency bands plays a prominent role in facilitating neural communication and neural plasticity [12,13,14,15]. Neurological diseases and conditions can often be associated with an abnormal oscillatory desynchronization or type of CFC, unveiling the importance that synchronized neural networks have in carrying out normal brain function [16]. While largely misunderstood, this network-wide communication seems to be an instrumental part of the coordination and regulation of cognitive abilities. More recently, neural stimulation techniques such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS) have been incorporating types of CFC analysis to better understand the effects of phase-coupled neuromodulation [17,18,19,20]. By leveraging the causal effects of neuromodulation on cognitive functions, these tools are focusing on real-time oscillation analysis to optimize the effectiveness of stimulation across brain regions [21].

さらに、これらの高周波数帯と低周波数帯の位相振幅同期が、神経伝達や神経可塑性を促進する上で重要な役割を果たしています[12,13,14,15]。神経学的な疾患や状態は、しばしば異常な振動の非同期化や周波数間カップリング(CFC)のタイプと関連することがあり、正常な脳機能を遂行する上で同期した神経ネットワークが重要であることが明らかにされています [16]。大きく誤解されているようだが、このネットワーク全体のコミュニケーションは、認知能力の調整と調節に不可欠な要素であるようだ。最近では、迷走神経刺激(VNS)や脳深部刺激療法(DBS)などの神経刺激技術が、位相結合神経調節の効果をよりよく理解するために、周波数間カップリング(CFC)分析の一種を組み込んでいます[17,18,19,20]。認知機能に対する神経調節の因果関係を活用することで、これらのツールは、脳領域全体における刺激の効果を最適化するために、リアルタイムの振動解析に焦点を当てている[21]。

phase?amplitude synchronization:位相振幅同期
Deep Brain Stimulation; DBS脳深部刺激療法(DBS)

Introduction  1-2

はじめに  1-2

The neuromodulatory systems, including the noradrenergic, cholinergic, and dopaminergic systems, play a pivotal role in the regulation and synchronization of neural oscillations. These systems provide direct axonal projections to most structures of the brain, regulating various brain functions through the release of neurotransmitters [22,23,24,25] (Figure 1a). Specifically, norepinephrine, acetylcholine, and dopamine are all implicated in the formation of complex decision making and executive functions [26]. Through their activation and inhibition, each neuromodulatory system has been seen to change the oscillatory behavior of widespread neural networks, implicating changes in cortical structures as well as in different frequency bands [27]. Recently, more work has been conducted that focuses on how cross-frequency coupling can be affected by neuromodulation, with phasic or tonic neurotransmitter release causing synchronization or desynchronization in EEG waveform features such as power, amplitude, phase and frequency [28]. These experiments are often using optogenetic manipulation in conjunction with LFP recordings, providing insights into how particular neuromodulatory centers can have a profound effect on neural oscillations, even in indirectly coupled brain regions. Another non-invasive biometric measure, pupil size, has also been implicated in having a key role in indexing neuromodulation, potentially serving as a new indirect modality in understanding the widespread effect of different arousal states on neural oscillations and behavior [29,30,31,32,33,34].

神経振動の制御と同期化には、ノルアドレナリン系、コリン系、ドーパミン系などの神経調節系が極めて重要な役割を担っています。これらの系は、脳のほとんどの構造物に直接軸索投射を行い、神経伝達物質の放出を通じて様々な脳機能を調節しています[22,23,24,25](図1a)。特に、ノルエピネフリン、アセチルコリン、ドーパミンは、複雑な意思決定や実行機能の形成に関与している [26]。それぞれの神経調節系は、その活性化と抑制を通じて、広範な神経ネットワークの振動挙動を変化させ、皮質構造や異なる周波数帯域での変化に関与していることが確認されている[27]。最近では、ニューロンモジュレーションによって周波数間カップリング(CFC)がどのように影響されるかに焦点を当てた研究が行われており、位相性または緊張性の神経伝達物質放出によって、パワー、振幅、位相、周波数などの脳波EEG波形の特徴に同期化または非同期化が生じることが分かっている [28].これらの実験は、局所電場電位LFP記録と連動した光遺伝学的操作を用いることが多く、間接的に結合した脳領域であっても、特定の神経調節中枢が神経振動に大きな影響を与えることができるという洞察を与えている。また、非侵襲的な生体指標である瞳孔の大きさも、神経調節の指標として重要な役割を果たすことが示唆されており、異なる覚醒状態が神経振動や行動に及ぼす広範な影響を理解するための新しい間接的モダリティとなる可能性があります [29,30,31,32,33,34].

LFP:local field potential, LFP:局所電場電位
局所電場電位(local field potential, LFP)は、脳内から記録される比較的低周波の振動電位で、頭蓋表面から記録される脳波の元となる信号である ...

Figure 1. Anatomical representations of each neuromodulatory system and CFC visualization: (a) Anatomical locations and projections of the three neuromodulatory systems: the noradrenergic system (left), dopaminergic system (middle), and cholinergic system (right). (b) A cartoon illustrating theta?gamma phase?amplitude coupling (PAC).

図1. 神経調節系の解剖学的表現と周波数間カップリング (CFC) (CFC)の可視化:(a)3つの神経調節系、ノルアドレナリン系(左)、ドーパミン系(中)、コリン系(右)の解剖学的位置と突起。(b) シータ・ガンマの位相・振幅結合(PAC)を説明する漫画イラストデザイン

This review will focus on how these three neuromodulatory systems can individually modulate neural oscillations, looking specifically at how their activation can change large-scale neural network synchrony in cognitive functions and neurological disorders. This phenomenon has yet to be fully understood, and looking at how each system’s activation or inhibition affects large scale oscillatory patterns may help uncover the origin and causality of complex behaviors and neurological disorders. These insights will hopefully inform a new direction of research that looks to further investigate how neuromodulation could improve and/or shape brain functions through changing large-scale neural oscillations.



概要|大阪大学医学部附属病院 未来医療開発部未来医療センター (osaka-u.ac.jp)




Tensorpacによる位相-振幅カップリング (PAC) 推定


周波数間カップリング (CFC) について
パワースペクトル密度 (PSD) 推定
位相-振幅カップリング (PAC) 推定

周波数間カップリング (CFC) について

近接する神経細胞の集団活動によって生じる電位変化を電場電位(field potential) といい,脳波計(EEG), 皮質脳波(ECoG), 脳磁図(MEG)等で計測できる.細胞集団の同期した活動は様々な周波数の振動として計測される.その周波数が属する周波数帯域に応じて,次のような名称がついている.

Gamma (γ?) > 30 Hz
Beta (β?) 12-30 Hz
Alpha (α?) 8-12 Hz
Theta (θ?) 4-8 Hz
Delta (δ?) 0.5-4 Hz

周波数間カップリング (cross-frequency coupling; CFC) とは,異なる周波数帯域の振動の間における相互作用の総称である.次の図は(Jirsa & M?ller. Frontiers in Computational Neuroscience. 2013)からの引用であり,様々なCFCを示している.Aでは振動Xの振幅(amplitude)の2乗(=power)が赤線,位相(phase)の基準が縦点線で示されている.B-FはXの振幅や位相に対してY1-Y5の振幅や位相,周波数が変調されている様子を表している.ここで因果関係は明らかでないので各YからXが変調されている場合もある.GはY5-Y6間での周波数における変調を示している.

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June 11, 2023


Theta wave


https://en.wikipedia.org/wiki/Theta wave

From Wikipedia, the free encyclopedia


Theta waves generate the theta rhythm, a neural oscillation in the brain that underlies various aspects of cognition and behavior, including learning, memory, and spatial navigation in many animals.[1][2] It can be recorded using various electrophysiological methods, such as electroencephalogram (EEG), recorded either from inside the brain or from electrodes attached to the scalp.


At least two types of theta rhythm have been described. The hippocampal theta rhythm is a strong oscillation that can be observed in the hippocampus and other brain structures in numerous species of mammals including rodents, rabbits, dogs, cats, and marsupials. "Cortical theta rhythms" are low-frequency components of scalp EEG, usually recorded from humans. Theta rhythms can be quantified using quantitative electroencephalography (qEEG) using freely available toolboxes, such as, EEGLAB or the Neurophysiological Biomarker Toolbox (NBT).

シータ律動には、少なくとも2つのタイプがあることが知られている。海馬シータ律動は、齧歯動物、ウサギ、イヌ、ネコ、有袋類など多数の哺乳類の海馬や他の脳構造で観察できる強い振動である。"皮質シータ律動 "は、通常ヒトから記録される頭皮脳波の低周波数成分である。シータ律動は、脳機能画像解析用ソフト(EEGLAB)や神経生理学的バイオマーカーツールボックス(NBT)などの自由に利用できるツールボックスを使って、定量的脳波検査(qEEG)で定量化することができる。

hippocampal theta rhythm:海馬のシータ律動
rodents 齧歯動物
eeglab 脳機能画像解析用ソフト
Neurophysiological 神経生理学的
Biomarker Toolbox バイオマーカーツールボックス

In rats, theta wave rhythmicity is easily observed in the hippocampus, but can also be detected in numerous other cortical and subcortical brain structures.Hippocampal theta waves, with a frequency range of 6–10 Hz, appear when a rat is engaged in active motor behavior such as walking or exploratory sniffing, and also during REM sleep.[3] Theta waves with a lower frequency range, usually around 6–7 Hz, are sometimes observed when a rat is motionless but alert. When a rat is eating, grooming, or sleeping, the hippocampal EEG usually shows a non-rhythmic pattern known as large irregular activity or LIA. The hippocampal theta rhythm depends critically on projections from the medial septal area, which in turn receives input from the hypothalamus and several brainstem areas. Hippocampal theta rhythms in other species differ in some respects from those in rats. In cats and rabbits, the frequency range is lower (around 4–6 Hz), and theta is less strongly associated with movement than in rats. In bats, theta appears in short bursts associated with echolocation.


rhythmicity 律動性(周期的に一定の動作を繰り返す様子)
REM sleep ;レム睡眠
REM(rapid eye movement):急速眼球運動
medial septal area 内側中隔領域

In humans, hippocampal theta rhythm has been observed and linked to memory formation[4][5] and navigation.[6] As with rats, humans exhibit hippocampal theta wave activity during REM sleep.[7] Humans also exhibit predominantly cortical theta wave activity during REM sleep.[8] Increased sleepiness is associated with decreased alpha wave power and increased theta wave power.[8] Meditation has been shown to increase theta power.[9]


The function of the hippocampal theta rhythm is not clearly understood. Green and Arduini, in the first major study of this phenomenon, noted that hippocampal theta usually occurs together with desynchronized EEG in the neocortex, and proposed that it is related to arousal.Vanderwolf and his colleagues, noting the strong relationship between theta and motor behavior, have argued that it is related to sensorimotor processing. Another school, led by John O'Keefe, have suggested that theta is part of the mechanism animals use to keep track of their location within the environment. Another theory links the theta rhythm to mechanisms of learning and memory (Hasselmo, 2005). These different theories have since been combined, as it has been shown that the firing patterns can support both navigation and memory.[10]

海馬のシータ律動性の機能は、明確に理解されていない。GreenとArduiniは、この現象に関する最初の主要な研究で、海馬のシータは通常、新皮質の脱同期脳波と一緒に起こることを指摘し、それが覚醒と関連していることを提案した。Vanderwolfらは、シータと運動行動の間に強い関係があることに注目し、感覚運動処理に関係すると主張した。また、ジョン・オキーフを中心とする別の学派は、シータ波は動物環境内の自分の位置を把握するためのメカニズムの一部であると提唱している。また、シータ律動性を学習や記憶のメカニズムと関連付ける説もあります(Hasselmo, 2005)。その後、発火パターンがナビゲーションと記憶の両方をサポートすることが示されたため、これらの異なる理論は統合された[10]。

desynchronized 脱同期
desynchronized sleep 脱同期睡眠
Neocortex 新皮質
motor behavior:運動行動

In human EEG studies, the term theta refers to frequency components in the 4–7 Hz range, regardless of their source. Cortical theta is observed frequently in young children.[11] In older children and adults, it tends to appear during meditative, drowsy, hypnotic or sleeping states, but not during the deepest stages of sleep. Theta from the midfrontal cortex is specifically related to cognitive control and alterations in these theta signals are found in multiple psychiatric and neurodevelopmental disorders.[12]


midfrontal cortex  内側前頭皮質

研究成果「学ぶほど頭がよくなる仕組みがわかった 」


研究成果「学ぶほど頭がよくなる仕組みがわかった 」





増大特集 学習と記憶――基礎と臨床


 海馬では,動物の行動状況に応じてさまざまな周波数帯域の脳波が観察される。探索行動時やレム睡眠中にはシータ活動(4〜12Hz)やガンマ活動(30〜80Hz)1-3),摂じ行動時やノンレム(徐波)睡眠中には鋭波関連リップル活動(80〜250Hz)が観察される4)。また神経細胞が病的な過興奮状態に陥ると,てんかん発作(3〜5Hz)が誘発される。このような脳波は,ニューロン群が同じタイミングで発火する「同期」と,ニューロン群が形成する律動性すなわち「リズム」による「同期的リズム活動」の反映と考えられる。この同期的リズム活動が動物の行動や脳の状態と密接に連関するという事実は,多数の神経細胞が一斉に律動的に活動することが脳神経回路の基本的な性質であり,これが脳機能の円滑な遂行に重要な役割を果たすことを示唆している。例えば,記憶のシナプスメカニズムのin vitroモデルである海馬LTP(長期増強)がシータ帯域の周波数を利用した刺激により効率的に惹起される5)ことなどからも,記憶・学習のメカニズムにおける同期的リズム活動の生理学的意義が推測できる。また,in vivo自由行動動物において,海馬のリズム活動が空間認知や記憶に本質的に関与していることも,最近明らかにされてきている2,6)。







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June 08, 2023


Effects of inhaling essential oils of Citrus limonum L., Santalum album, and Cinnamomum camphora on human brain activity







Essential oil inhalation has various effects on the human body. However, its effects on cognitive function and the neural basis remain unclear. We aimed to investigate the effects of inhaling lemon, sandalwood, and kusunoki essential oils on human brain activity and memory function using multichannel electroencephalography and brain source activity estimation.




Participants performed a letter 2-back working memory task during electroencephalography measurements before and after essential oil inhalation. Brain activation, task difficulty, concentration degree, and task performance were compared among the essential oils and a fragrance-free control.




Task performance significantly improved after lemon essential oil inhalation. Lemon essential oil inhalation resulted in delta and theta band activation in the prefrontal cortex, including the anterior cingulate gyrus and orbitofrontal cortex, superior temporal gyrus, parahippocampal gyrus, and insula. During inhalation, persistent alpha band activation was observed in the prefrontal cortex, including the anterior cingulate gyrus. Sandalwood essential oil inhalation led to beta and gamma band activation in the prefrontal cortex, including the anterior cingulate gyrus.




Our findings demonstrate that different essential oils have specific effects on brain activity related to emotion and memory processing.


Keywords: Cinnamomum camphora; Citrus limonum L; Santalum album; essential oil; human brain.



1 序論

Inhaling essential oils reduces stress (Chamine & Oken, 2016; Heuberger et al., 2006; H?ferl et al., 2016; Kim et al., 2011; Motomura et al., 2001; Shimada et al., 2011; Toda & Morimoto, 2008), maintains concentration (Ho & Spence, 2005; Kaneki et al., 2005), and improves sleep (Fismer & Pilkington, 2012; Hirokawa et al., 2012) and dementia symptoms (Ballard et al., 2002; Holt et al., 2003; Smallwood et al., 2001) in humans. Human cognitive functions, including perception, attention, memory, language, thought, and emotion, collectively facilitate higher-order processing, including decision making and creativity. Inhaling essential oils reduces stress (Chamine & Oken, 2016; Heuberger et al., 2006; H?ferl et al., 2016; Kim et al., 2011; Motomura et al., 2001; Shimada et al., 2011; Toda & Morimoto, 2008), maintains concentration (Ho & Spence, 2005; Kaneki et al., 2005), and improves sleep (Fismer & Pilkington, 2012; Hirokawa et al., 2012) and dementia symptoms (Ballard et al., 2002; Holt et al., 2003; Smallwood et al., 2001) in humans. Human cognitive functions, including perception, attention, memory, language, thought, and emotion, collectively facilitate higher-order processing, including decision making and creativity. The effects of essential oil inhalation on these functions and their neural basis remain unclear. A study on the relationship between essential oil inhalation and cognitive function (Moss et al., 2008) reported that inhaling peppermint oil improved memory function. Moreover, an electroencephalography (EEG) study reported that inhaling lavender oil significantly attenuated alpha band (8-10 Hz) EEG activity in the parietal and posterior temporal brain regions (Masago et al., 2000). Moreover, inhaling lavender oil significantly increased beta band (21-30 Hz) EEG activity in the frontal region (Diego et al., 1998). Although some studies have reported on the effects of lemon oil inhalation on stress (K omiya et al., 2006) and pain reduction (Ikeda et al., 2014) and on the neural mechanisms underlying these effects, they were mostly conducted on rodents. Previous studies have used physiological indices associated with the autonomic nervous system, including heart rate and skin conductance response, to analyze the stress-reducing effects of sandalwood oil inhalation (Heuberger et al., 2006; H?ferl et al., 2016); however, none reported on cognitive function and human brain activity.

精油の吸入は、ストレスを軽減し(Chamine & Oken, 2016; Heuberger et al., 2006; H?ferl et al., 2016; Kim et al., 2011; Motomura et al., 2001; Shimada et al., 2011; Toda & Morimoto, 2008)、集中力を維持(Ho & Spence, 2005; Kaneki et al、 2005)、睡眠改善(Fismer & Pilkington, 2012; Hirokawa et al., 2012)、認知症改善(Ballard et al. 知覚、注意、記憶、言語、思考、感情を含む人間の認知機能は、集合的に意思決定や創造性を含む高次の処理を促進します。精油の吸入がこれらの機能およびその神経基盤に及ぼす影響については、依然として不明な点が多い。精油の吸入と認知機能の関係に関する研究(Moss et al.、2008年)は、ペパーミントオイルの吸入が記憶機能を改善することを報告した。さらに、脳波の研究では、ラベンダーオイルの吸入により、頭頂部および後頭部の脳領域におけるアルファバンド(8-10Hz)の脳波活動が有意に減衰することが報告されている(Masago et al.、2000年)。さらに、ラベンダーオイルを吸入すると、前頭部のβ帯(21-30Hz)
の脳波活動が有意に上昇した(Diego et al., 1998)。レモンオイルの吸入によるストレス軽減効果(小宮ら、2006)や疼痛軽減効果(池田ら、2014)、およびこれらの効果の基盤となる神経機構について報告した研究もあるが、その多くはげっ歯類を用いて行われたものであった。これまでの研究では、心拍数や皮膚コンダクタンス反応など自律神経系に関連する生理指標を用いて、サンダルウッドオイル吸入のストレス軽減効果を解析しているが(Heuberger et al., 2006; H?ferl et al., 2016)、認知機能や人間の脳活動について報告しているものはなかった。

skin conductance:皮膚コンダクタンス

電気皮膚活動EDAの伝統的な理論は皮膚の汗腺の状態で皮膚抵抗が変化することに基づく。汗は交感神経系によってコントロールされているため[4]、皮膚コンダクタンスは心理的または身体的興奮の兆候だというものだ。 もし自律神経系の交感神経側が興奮した場合、汗腺の活動は活発化され、皮膚コンダクタンスの上昇につながる。このように、皮膚コンダクタンスは感情的または交感神経系の反応の指標になりうる[5]。ガルバニック皮膚反応ウィキペディア(より

The limbic system, which is close to the olfactory nerve, is considered the most important pathway for direct signal transmission from the olfactory nerve to the brain after intranasal absorption (Kandel et al., 2012). The limbic system comprises the hippocampus, which controls memory functions (Burgess et al., 2002; Phelps, 2004), and the amygdala (Davis & Whalen, 2001; Phelps, 2004) and anterior cingulate cortex (Bush et al., 2000), which control emotional functions. Therefore, essential oil inhalation may influence memory and emotional functions in humans. In this study, we focused on memory function while examining the effects of essential oil inhalation on cognitive function and human brain activity.

嗅神経に近い大脳辺縁系は、経鼻吸収後に嗅神経から脳へ直接信号を伝達する最も重要な経路と考えられている(Kandel et al.、2012)。大脳辺縁系は、記憶機能を司る海馬(Burgess et al., 2002; Phelps, 2004)、感情機能を司る扁桃体(Davis & Whalen, 2001; Phelps, 2004)および前帯状皮質(Bush et al., 2000)からなります。したがって、精油の吸入は、ヒトの記憶や感情機能に影響を与える可能性がある。本研究では、精油の吸入が認知機能やヒトの脳活動に及ぼす影響を調べながら、記憶機能に着目した。

anterior cingulate cortex :前帯状皮質

EEG measurements acquired at high temporal resolutions can reveal the time course of brain activation after essential oil inhalation. Moreover, multichannel head-surface EEG with exact low-resolution brain electromagnetic tomography (Pascual-Marqui et al., 2011; Pascual-Marqui et al., 1994) can facilitate brain source activity estimation, including that within deep brain regions, such as the hippocampus and anterior cingulate cortex (Cannon et al., 2005; Pizzagalli et al., 2004).

高時間分解能で取得した脳波測定は、精油吸入後の脳活性化の時間経過を明らかにすることができる。さらに、正確な低解像度脳電磁トモグラフィーを用いた多チャンネル頭表脳波(Pascual-Marqui et al., 2011; Pascual-Marqui et al., 1994)により、海馬や前帯状皮質などの脳深部領域内のものを含む脳源活動の推定が容易になる(Cannon et al., 2005; Pizzagalli et al.)

Here, we aimed to evaluate the effects of inhaling lemon, sandalwood, and kusunoki (i.e., camphor) essential oils on human brain activity and memory function using EEG and a working memory task. Numerous brain regions are involved in working memory. Additionally, specific EEG frequencies are involved in human working memory functions. Working memory activity in the delta band could be associated with the frontal lobe (de Vries et al., 2018; Zarjam et al., 2011) and parahippocampal gyrus (Imperatori et al., 2013). Moreover, numerous studies have demonstrated the importance of the theta band in the prefrontal cortex, especially in the medial prefrontal cortex (Gevins et al., 1998; Hsieh & Ranganath, 2014; Jensen & Tesche, 2002; Meltzer et al., 2008; Onton et al., 2005; Sauseng et al., 2010). We hypothesized that essential oil inhalation would activate EEG signals in the frequency bands of the brain regions involved in working memory task performance. This is the first study to investigate the effects of essential oil inhalation on the human brain, including the deep regions, using a memory demanding task.

そこで、レモン、サンダルウッド、クスノキの精油の吸入がヒトの脳活動や記憶機能に及ぼす影響を、脳波とワーキングメモリ課題を用いて評価することを目的としました。ワーキングメモリには多数の脳領域が関与している。さらに、特定の脳波周波数がヒトのワーキングメモリ機能に関与している。デルタ帯のワーキングメモリ活動は、前頭葉(de Vries et al., 2018; Zarjam et al., 2011)および海馬傍回(Imperatori et al., 2013)に関連する可能性があります。さらに、多くの研究が、前頭前皮質、特に内側前頭前皮質におけるシータ帯の重要性を示している(Gevins et al., 1998; Hsieh & Ranganath, 2014; Jensen & Tesche, 2002; Meltzer et al., 2008; Onton et al., 2005; Sauseng et al., 2010).我々は、精油の吸入により、ワーキングメモリ課題の遂行に関与する脳領域の周波数帯の脳波信号が活性化すると仮定した。精油の吸入が深部領域を含むヒトの脳に及ぼす影響を、記憶負荷の高い課題を用いて検討した初めての研究である。

frontal lobe 前頭葉
prefrontal cortex 前頭前皮質
medial prefrontal cortex 内側前頭前皮質
parahippocampal gyru : 海馬傍回



前帯状皮質(ぜんたいじょうひしつ、英: Anterior cingulate cortex ACC)は、帯状皮質の前部で、脳の左右の大脳半球間の神経信号を伝達する線維である脳梁を取り巻く"襟"のような形をした領域である。

この領域には背側部 (ブロードマンの脳地図における24野) と腹側部 (ブロードマンの脳地図における32野) が含まれている。前帯状皮質は血圧や心拍数の調節のような多くの自律的機能の他に、報酬予測、意思決定、共感や情動といった認知機能に関わっているとされている。


海馬は大脳側頭葉の内側部で側脳室下角底部に位置し、エピソード記憶等の顕在性記憶の形成に不可欠な皮質部位である(図1)。記憶形成に関与する側頭葉皮質部位には、嗅内野、傍海馬台、前海馬台、海馬台、海馬(アンモン角)、歯状回がある。また、海馬台、海馬、歯状回に、脳梁上部に位置し、中隔方向に連続する構造物である脳梁灰白層を加えて集合的に海馬体 (hippocampal formation) と呼ぶ。


海馬傍回(かいばぼうかい、英: Parahippocampal gyrus)または海馬回(かいばかい、英: hippocampal gyrus)は海馬の周囲に存在する灰白質の大脳皮質領域。大脳内側面の脳回のひとつである。この領域は記憶の符号化及び検索において重要な役割を担っている。この領域の前部は嗅周皮質 (perirhinal cortex) 及び、嗅内皮質 (entorhinal cortex) を含んでいる。海馬傍皮質 (parahippocampal cortex) という用語は海馬傍回の後部と紡錘状回の内側部を指して用いられる。







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June 06, 2023


Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity




Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory, and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and, in particular, whether stimulus-driven high-frequency oscillations play a role in odor processing is unknown.


high-frequency oscillations 高周波振動(γ・ガンマ帯域を超える80 Hz以上の脳波活動である。)

Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that 3 key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: Odor induces theta, beta, and gamma rhythms in human piriform cortex.We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting that they are critical for odor identity perception in humans.


gamma:γ波(ガンマ波)30-100 Hz:認知や記憶などの高次脳機能との関係

We also found that the amplitude of high-frequency oscillations is organized by the phase of low-frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.

また、高周波振動の振幅は、匂いがある場合にのみ、匂いを嗅ぎ始める直後の低周波信号の位相によって組織化されることもわかりました。我々の知見は、シータ振動に関するこれまでの研究を補強し、ヒト梨状皮質のガンマ振動が匂いの同定の知覚に重要であることを示唆し、ヒト脳の匂いに対する特徴的な電気生理学的応答の堅牢な同定を構成する。 今後の研究では、私たちが特定した明確な振動が匂い刺激の明確な知覚的特徴を反映しているかどうかが決定されます。
















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June 02, 2023


New Insights Into How the Brain Processes Scents



Featured Neuroscience June 6, 2017

Summary: Theta oscillations may play an important role in olfactory processing, a new study reports.


Source: Northwestern Medicine.


Theta oscillations, a type of rhythmic electrical activity that waxes and wanes four to eight times per second, may play a fundamental role in processing scent in the human brain, according to a new study recently published in Neuron.


The use of intracranial EEG recordings in patients with medically resistant epilepsy allowed Jay Gottfried, MD, PhD, professor of Neurology, and his team to characterize, for the first time, the time-frequency dynamics of odor processing in the human piriform cortex, a region in the brain important for smell.


intracranial EEG recordings ; 頭蓋内脳波記録

The study we did here was to understand what happens at the microstructural level of the human brain when you smell an odor, Gottfried said. The advantage of the approach is we can record the physiological rhythms of the brain using these electrodes in this unique and rare patient population.


They found that odors could be decoded as early as 110 milliseconds from a person’s first sniff.


A lot of people think that the sense of smell is a very slow sense, so this study highlights the speed of the sense of smell and relates it to its biological underpinnings, Gottfried said.


Heidi Jiang, a graduate student and the first author of the study, obtained electrophysiological recordings while patients took part in a cued odor detection task.

本研究の筆頭著者である大学院生のハイディ ジャンは、患者が手がかりとなる匂い検出課題に参加している間に電気生理学的記録を取得しました。

electrophysiological recordings :電気生理学的記録

Jiang and Gottfried found that odor stimulation enhanced theta waves in the piriform cortex, in each of seven patients. Under conditions where patients smelled odorless air, the scientists observed no change in theta waves. Across four different odors, the physiological features of the theta waves could be used to distinguish between each odor.


Based on this rhythmic activity, we can decode which smell the patient has encountered, Gottfried said. These oscillations contain critical information about whether the smell is strawberry, peanut butter, chocolate or garlic, and this information is already available to the brain within a very rapid timeframe.


Additionally, with electrodes in the piriform cortex and hippocampus, they found the presence of odor caused both regions to fall into a synchronized rhythm, suggesting that theta oscillations facilitate the coordination and exchange of information between those two areas.


What is neat about this finding is that the hippocampus is a central hub through which memories can be reactivated and retrieved ? like what ice cream you ate, when you ate it, and where you ate it. Its possible that the hippocampus is able to telegraph some of that information to the piriform cortex to facilitate olfactory processing, Gottfried said.


As noted above, the subjects in the study were patients with medically resistant epilepsy who had existing electrode implants placed for purely clinical considerations, but gave the scientists an opportunity to gather detailed electrophysiological data.


A lot of our work has used fMRI techniques to relate brain activity patterns in the human brain to different odor perceptual states such as memory, but the fMRI work provides a very limited understanding of the mechanisms and timing that support the sense of smell. So it has been a special opportunity to work with these rare epilepsy patients at Northwestern, Gottfried said.


functional magnetic resonance imaging, fMRI 磁気共鳴機能画像法(fMRI

Previous research has shown that theta oscillations are a dominant rhythm in rodent brains, in line with the rapid breathing rate of rats and mice. Gottfried found that while the human brain oscillates at this same theta timescale, humans breathe at a much slower rate.


It poses a question in my mind that, for humans, theta isnt simply something that falls in line with the breathing cycle, but rather might be a more fundamental rhythm for odor processing in the brain, Gottfried said.


A Type of Timekeeping Mechanism


In terms of functional significance, Gottfried believes these oscillations might serve as an internal clock in the brain.


The brain doesnt really have access to an external time reference, and across numerous studies there is more and more evidence to suggest it is the oscillations in the brain that are time-keeping mechanisms, Gottfried said. The brain may use these oscillations to segment information into malleable packets of information.


Malleable 変容可能性

Gottfried said in future studies, he wants to understand more about the importance of theta oscillations in contributing to odor perception and test the hypothesis that theta rhythms might serve as a clock for regulating brain dynamics.




Theta Oscillations Rapidly Convey Odor-Specific Content in Human Piriform Cortex




Odor elicits theta power selectively in human piriform cortex within 500 ms of sniff ok


Presence (versus absence) of odor enhances piriform-hippocampal theta phase locking


phase locking 位相ロック

Odor-specific content can be decoded from piriform oscillations as early as 110 ms


ms・milli second: ミリセカンド, ミリ秒 1秒は1000msとなります。







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