中古合作，促進(jìn)全球精準(zhǔn)腦健康

我出生在美國，父親在美行醫(yī)。古巴革命勝利后，我的家人于1962年回到了古巴。我們?nèi)叶枷Ｍ麨閯?chuàng)造一個新的、更公正的社會作出貢獻(xiàn)。

20世紀(jì)80年代末，古巴神經(jīng)科學(xué)中心與中國建立合作

20世紀(jì)60年代末，作為一名醫(yī)學(xué)生，我與紐約大學(xué)的Erwin Roy John教授一起，利用古巴的第一臺計算機（1970年）開創(chuàng)了量化腦電圖（qEEG）技術(shù)。時至今日，我們的目標(biāo)仍是創(chuàng)造一種在群體層面協(xié)助診斷和管理大腦疾病的工具。1977年，我們在《自然》上發(fā)表了一篇神經(jīng)計量學(xué)的論文，這即是我們本次合作的成果。我需要繼續(xù)強化醫(yī)學(xué)訓(xùn)練，這促使我從醫(yī)學(xué)專業(yè)畢業(yè)后開始學(xué)習(xí)數(shù)學(xué)。后來，我領(lǐng)導(dǎo)的團(tuán)隊為世界上首批qEEG設(shè)備之一，即MEDICID系統(tǒng)構(gòu)建了硬件和軟件。

這一系列設(shè)備被引進(jìn)到古巴的公共衛(wèi)生系統(tǒng)，并最終在1990年進(jìn)入中國以及歐洲與拉丁美洲的其他幾個國家。1990年，我們與我的孿生兄弟Mitchell J. Valdes-Sosa一起成立了古巴神經(jīng)科學(xué)中心（CNEURO）。作為一個研究、開發(fā)、生產(chǎn)、醫(yī)療服務(wù)和商業(yè)化的一體化機構(gòu)，古巴神經(jīng)科學(xué)中心率先創(chuàng)建了古巴國家臨床神經(jīng)生理學(xué)網(wǎng)絡(luò)，并發(fā)起了一些倡議，如基于事件相關(guān)電位的國家聽力篩查計劃，以及國家治療學(xué)習(xí)障礙計劃。

Pedro A. Valdes-Sosa （古巴），古巴科學(xué)院院士、拉丁美洲科學(xué)院院士。2015年起，擔(dān)任中國電子科技大學(xué)生命科學(xué)與技術(shù)學(xué)院教授。

在20世紀(jì)末，古巴神經(jīng)科學(xué)中心的領(lǐng)導(dǎo)人已經(jīng)確信，為在管理全球大腦疾病方面產(chǎn)生可衡量的影響，亟須建立國際聯(lián)盟。出于種種考慮，中國成為這個聯(lián)盟的自然候選人。在此先提一句，我的家庭與中國有著緊密聯(lián)系。20世紀(jì)50年代，我的一位叔叔作為革命學(xué)生領(lǐng)袖訪問了中國，見到了周恩來總理。兩國建交后，我的母親在古巴教授第一批訪問古巴的中國人西班牙語。更重要的是，隨著中國經(jīng)濟(jì)實力和國際影響力的提升，兩國關(guān)系也越發(fā)牢固，造福人民是兩國的共同目標(biāo)。

因此，古巴神經(jīng)科學(xué)中心在20世紀(jì)80年代末開始與中國的機構(gòu)建立合作關(guān)系，引進(jìn)了第一批qEEG系統(tǒng)。90年代，我第一次訪問中國，擔(dān)任中國早期qEEG會議的外方主席，后來還開設(shè)了關(guān)于古巴MEDICID系統(tǒng)的課程。2011年，我和朋友——中國科學(xué)院的蔣田仔和電子科技大學(xué)的堯德中訪問了北京和成都。在他們的幫助下，我了解了中國腦科學(xué)的宏偉計劃，發(fā)現(xiàn)了中國和古巴兩國在神經(jīng)科學(xué)上的互補性，并決心努力增進(jìn)與中國機構(gòu)的合作。隨著工作關(guān)系的推進(jìn)，我開始越來越多地待在中國。2015年，我被電子科技大學(xué)聘為神經(jīng)信息學(xué)的特聘教授。

2015年，中國—古巴聯(lián)合實驗室成立

中國—古巴生物技術(shù)會議期間，在中國和古巴高層領(lǐng)導(dǎo)人的支持下，作為古巴神經(jīng)科學(xué)中心和電子科技大學(xué)合作進(jìn)程的關(guān)鍵點，2015年中國—古巴聯(lián)合實驗室在電子科技大學(xué)成立。我被任命為聯(lián)合實驗室的主任。我的任務(wù)是：在電子科技大學(xué)創(chuàng)建一個高度國際化的實驗室，促進(jìn)國際合作；繼續(xù)開發(fā)以腦連接為重點的新的生物物理方法，將其用于神經(jīng)影像學(xué)；使神經(jīng)影像學(xué)，特別是qEEG技術(shù)在所有衛(wèi)生系統(tǒng)應(yīng)用；建立國際網(wǎng)絡(luò)，服務(wù)于全球精準(zhǔn)腦健康。

2015年以來所發(fā)生的一切證明了我們的計劃正在逐漸實現(xiàn)。很幸運，我得到了電子科技大學(xué)和中國科研機構(gòu)的支持。中國—古巴聯(lián)合實驗室已經(jīng)成為電子科技大學(xué)最國際化的實驗室之一，其學(xué)生和工作人員來自古巴、中國、坦桑尼亞、盧旺達(dá)、巴基斯坦、也門和尼日利亞，已經(jīng)有3名博士生和17名碩士生從這里畢業(yè)。實驗室已經(jīng)在索引期刊上發(fā)表了70多篇論文，其中許多見刊《自然》系列雜志。我們還建立起一個個性化醫(yī)療院士站，來自古巴的5位院士參與其中，共形成8篇論文。

隨著這一國際平臺的建立，2017年，在哈瓦那舉行的一次會議之后，魁北克研究基金會醫(yī)學(xué)部、古巴環(huán)境與科技部、中國國家自然科學(xué)基金委員會批準(zhǔn)了中國（成都）—加拿大—古巴腦計劃項目（C-C-C項目），以創(chuàng)建一個神經(jīng)影像和神經(jīng)信息學(xué)平臺。該平臺可為協(xié)調(diào)尋找衰老相關(guān)疾病的生物標(biāo)志物和治療方法、招募全球領(lǐng)先的大腦項目、激勵中低收入國家奠定基礎(chǔ)。

古巴國家電視新聞播出了最近在哈瓦那科學(xué)中心舉辦的古巴大腦項目啟動儀式，古巴總統(tǒng)Miguel D az-Canel也出席了本次儀式。C-C-C項目被推介給古巴政府和公眾，強調(diào)了與中國開展國際合作的價值。

很明顯，對跨國腦成像網(wǎng)絡(luò)的需求在C-C-C項目之后不斷增加，這將有助于解決神經(jīng)科學(xué)領(lǐng)域一些最重要的問題。信息技術(shù)在數(shù)據(jù)共享方面的最新進(jìn)展、資助者的鼎力支持以及蓬勃發(fā)展的開放科學(xué)文化，為有意義的國際科學(xué)參與帶來了新的希望。

2019年，全球人腦圖表聯(lián)盟創(chuàng)建

事實證明，由于各種技術(shù)、組織、倫理和社會政治原因，全球科學(xué)家聚集在一起合作是十分困難的。我們必須同心協(xié)力，依靠科學(xué)家、技術(shù)開發(fā)人員和資助者共同制定戰(zhàn)略來實現(xiàn)這一目標(biāo)。因此，C-C-C項目需要將合作經(jīng)驗擴(kuò)展到其他國家，包括美國、歐洲、亞洲和澳大利亞的合作伙伴。這促使我和蒙特利爾神經(jīng)研究所的Alan Evans在2019年創(chuàng)建了國際人腦圖表聯(lián)盟（GBC）。作為C-C-C的延伸，GBC專注于人類神經(jīng)影像學(xué)及其與基因組學(xué)和行為數(shù)據(jù)的集成，以加速我們對大腦狀態(tài)的時空動力學(xué)的理解。這些知識對于理解神經(jīng)發(fā)育、神經(jīng)可塑性和疾病進(jìn)展至關(guān)重要。在最初的戰(zhàn)略決策中，EEG是首選的神經(jīng)影像技術(shù)，因為其具有低成本、便攜性和非侵入性的優(yōu)勢。因此，這些發(fā)現(xiàn)可以作為轉(zhuǎn)化研究的橋梁，滿足得不到充分服務(wù)的人群的需求。相信我們的研究結(jié)果可以成為中低收入國家進(jìn)行全球精準(zhǔn)腦健康研究的基礎(chǔ)，為那些精神疾病負(fù)擔(dān)最重但也最難獲得昂貴成像技術(shù)的地方提供幫助。

GBC已經(jīng)吸引了包括世界衛(wèi)生組織在內(nèi)的9個國際組織的150多名研究人員，他們來自23個國家。我們的合作產(chǎn)出了一些論文，這些論文現(xiàn)已被列入《神經(jīng)成像》雜志中關(guān)于全球健康的特刊。其中有兩項合作項目值得一提，它們均強調(diào)了多國合作的必要性和可能性，可以使中低收入國家受益。

第一個項目是巴巴多斯、美國、加拿大和古巴之間的合作，旨在研究僅發(fā)生在生命第一年的蛋白質(zhì)能量營養(yǎng)不良的終身影響。一項獨一無二的49年追蹤研究為對早期蛋白質(zhì)能量營養(yǎng)不良的參與者在學(xué)齡時和45年后成年時進(jìn)行qEEG研究提供了可能性。

qEEG能夠清楚地識別這兩個年齡段的大腦功能障礙。研究結(jié)果顯示，早期qEEG老化的指標(biāo)似乎與早期認(rèn)知衰退有關(guān)。由于全球兒童營養(yǎng)不良情況的增多，這一發(fā)現(xiàn)可推動開發(fā)疾病進(jìn)展模型和生物標(biāo)志物以預(yù)防這些后果。在所述的營養(yǎng)不良研究中，qEEG的效用強調(diào)了擁有全球有效的qEEG規(guī)范性數(shù)據(jù)的重要性。

要強調(diào)的第二個項目是GBC多國項目，該項目為來自9個國家的超過1564人創(chuàng)建了黎曼規(guī)范，涵蓋了從5歲到97歲的年齡范圍。

通過創(chuàng)建平臺來擁有一個科學(xué)焦點，用以解決重要的技術(shù)問題并產(chǎn)生全球影響，這是一種困難的平衡行為。現(xiàn)代神經(jīng)科學(xué)擁有大量理論、建模和神經(jīng)影像技術(shù)，但其中許多設(shè)備在中低收入國家是不容易獲得的。

幸運的是，近年來，由于對腦計劃的投入增加，一系列數(shù)字和神經(jīng)技術(shù)的使用得到加強，這可能有助于我們彌合不同國家間的差距。這將為中低收入國家的神經(jīng)科學(xué)家和臨床醫(yī)生提供合作機會，而這些人恰恰是以往在全球伙伴關(guān)系倡議中被忽視的群體。

擴(kuò)展合作推動腦科學(xué)發(fā)展

我對未來的期望是竭力推動低成本、可負(fù)擔(dān)的神經(jīng)影像技術(shù)在中低收入國家的部署，推動大腦疾病研究發(fā)展，并希望減少巨大的心理健康負(fù)擔(dān)。

我有意建立一個中國—古巴聯(lián)合實驗室，作為“一帶一路”倡議的一部分，在兩國范圍內(nèi)研究老齡化并推出高科技產(chǎn)品。這一想法在成都、上海等地受到極大歡迎，一些科研機構(gòu)公開表明了對這項合作倡議的興趣。之后，我想把合作擴(kuò)展到其他國家，如墨西哥、巴西、巴基斯坦和馬來西亞。

我希望能夠繼續(xù)推動GBC，鞏固中國和古巴在開發(fā)適合中低收入國家的技術(shù)方面的效用。我還希望為腦電圖規(guī)范、營養(yǎng)不良的大腦后果、癡呆癥和帕金森病的早期生物標(biāo)志物、兒童和青少年大腦發(fā)育的縱向生物標(biāo)志物，以及CIBD（新冠肺炎誘發(fā)的大腦疾病）等創(chuàng)立項目。

CIBD的項目說明了開發(fā)可擴(kuò)展技術(shù)以幫助診斷大腦功能障礙的重要性和挑戰(zhàn)性。由于需要篩查和管理的人數(shù)眾多，大腦研究的目標(biāo)有必要進(jìn)行革命性的改變。我和Mitchell Valdes-Sosa、Alan Evans、蒲慕明共同撰寫了一篇呼吁在這一領(lǐng)域采取國際行動的文章，發(fā)表在了《國家科學(xué)評論》上。

在提供足夠的資源和可能的社會影響以開展研究方面，世界上任何一個國家都不能和中國媲美。盡管前路漫漫，但我為中國和中國同事給予我支持而感到幸運。我結(jié)識了許多至交好友。中國政府對我的努力給予了極大的支持，我為獲得2017年度中國政府友誼獎以及受邀參加中華人民共和國成立70周年慶?；顒佣陡凶院?。

I was born in the United States, where my father practiced medicine. However, my family returned to Cuba in 1962, following the triumph of the Cuban Revolution. The entire family was motivated by the desire to contribute to creating a new and more just society.

In the Late 1980s, Cuban Neuroscience Center Started Cooperation with China

As a medical student in the late 1960s, jointly with Prof. Erwin Roy John from NYU, I harnessed the first Cuban computer (1970) to pioneer methods for the quantitative analysis of the electroencephalogram (qEEG). Our objective was (and still is) to create tools that can assist in the diagnosis and management of Brain disorders at population levels. This collaboration resulted in a “Science” paper on Neurometrics in 1977. I had to complement my medical training, and this prompted me to study mathematics after graduating from medicine. I later led the team that built the hardware and software for one of the first qEEG devices in the world, the MEDICID system.

This family of equipment was introduced into Cuba’s public health system and eventually reached China in 1990, as well as several other countries, including Europe and Latin America. We founded the Cuban Neuroscience Center (CNEURO) in 1990 with my twin brother Mitchell J. Valdes-Sosa as an institution carrying out the complete cycle of research, development, production, medical services, and commercialization. CNEURO spearheaded the creation of the Cuban National Network for Clinical Neurophysiology and launched initiatives like the national hearing screening program using Event-related potentials and a national program for detecting and treating learning disabilities.

At the end of the 20th century, the leaders of CNEURO had become convinced that international alliances were required to achieve our goal of having a measurable effect on the management of the staggering global burden of brain disorders. For many reasons, China was a natural candidate for this alliance. First, my family had close ties with China. In the 1950s, one of my uncles visited the new China as a revolutionary student leader and met Premier Zhou Enlai. In Cuba, my mother taught Spanish to the first Chinese to visit Cuba after mutual diplomatic recognition. More importantly, as China’s economy and international influence developed, so did the strong relations between the two nations, which shared similar goals of benefitting their populations.

As a result, CNEURO initiated relations with Chinese institutions in the late 1980s, introducing, as I already mentioned, some of the first qEEG systems used here. I visited China for the first time in the 1990s to be the foreign chair of an early Chinese qEEG conference and later give a course on the Cuban MEDICID systems. My first encounters followed these initial contacts in 2011 during a visit to Beijing and Chengdu with my friends Tianzi Jiang from the Chinese Academy of Sciences and Dezhong Yao of University of Electronic Science and Technology of China (UESTC). Owing to them, I learned about the ambitious plans for Chinese Brain Science, discovered the complementary nature of Cuban and Chinese neuroscience, and began working to increase the international relations of the Chinese institutions I worked with. As our working relations grew, I started spending more time in China. In 2015, UESTC appointed me a Distinguished Professor of Neuroinformatics.

In 2015, the China-Cuba Joint Lab was Established

As a culmination of this integration process of the work of CNEURO and UESTC, the China-Cuba Joint Lab at UESTC was created in 2015 during the China-Cuba Bi-National meeting for Biotechnology with the enthusiastic support of high-level Cuban and Chinese leaders. Designated as the first Director of the Joint Lab, this coincided with my appointment as a foreign expert at UESTC. The tasks that UESTC and CNEURO charged me with were: To create a highly international laboratory within UESTC that would foster international collaborations. To continue developing new biophysical methods for Neuroimaging with emphasis on Brain Connectivity. To introduce neuroimaging, particularly qEEG methods applicable in any health system. To establish international networks that would work for Global Precision Brain Health.

What has occurred since 2015 has vindicated our intentions. I have been fortunate in the support received by UESTC and the Chinese Scientific establishment. The China-Cuba Joint Lab has become one of the most international ones of UESTC, with students and staff from Cuba, China, Tanzania, Rwanda, Pakistan, Yemen, and Nigeria. We have graduated 3 Ph.D Students and 17 Master’s students. The lab has published over 70 papers in indexed journals, many of them from the Nature family. With UESTC, we also established an Academician Station for Personalized Medicine that brought five Academicians from Cuba, resulting in eight collaborative papers.

With this international platform in place, in 2017, following a meeting in Havana, the Fonds de recherche du Québec - Santé (FRQS), the Ministry of Science, Technology, and Environment (CITMA) of Cuba, and the National Science Foundation of China (NSFC) approved the so-called China (Chengdu)-Canada-Cuba Brain Mapping Project (CC-C Project) to create a Neuroimaging and Neuroinformatics Platform (NNP) that would set the stage for the coordinated search for biomarkers and treatments for aging-related disorders in the three countries, the recruitment for this research of the leading global brain projects as well as stimulating initiatives in Low- and Middle-Income Countries (LMIC) .

The launch of the most recent Cuban Brain Project at the Scientific Pole of Havana was broadcasted on the Cuban National TV News in the presence of the Cuban President Miguel Díaz-Canel. The C-C-C project was conveyed to the Cuban Government and the general public, thereby underscoring the value of international collaboration with China.

Following the C-C-C Project, it became evident that there is a rising demand for transnational brain imaging networks that will help us tackle some of the biggest questions in neuroscience. Recent advancements in information technology to mediate data-sharing, dedicated support from funders, and a burgeoning culture of Open Science offer new hope for meaningful scientific engagement internationally.

Pedro A. Valdes-Sosa教授獲得2017年度中國政府友誼獎

In 2019, the Global Brain Consortium was Created

Bringing scientists across the globe together to collaborate has proven difficult for various technical, logistical, ethical, and socio-political reasons. We must work together—scientists, technology developers, and funders to devise strategies to make this happen. Therefore, the C-C-C needed to extend the experience of collaboration across other borders and include partners of the US, Europe, Asia, and Australia. This led Alan Evans from the Montreal Neurological Institute and me to create the Global Brain Consortium (GBC) in the year 2019. As an extension of the C-C-C, the GBC focuses on human neuroimaging and its integration with genomics and behavioral data to accelerate our understanding of the spatiotemporal dynamics of brain states. This knowledge will be essential for comprehending neurodevelopment, neuroplasticity, and disease progression. EEG was chosen as the preferred neuroimaging technique in an initial strategic decision. This position was due to the advantages of EEG in terms of low-cost effectiveness, portability, and non-invasiveness. Therefore, the findings can serve as a translational research bridge to address the needs of underserved populations. We believe that our results can be the basis for global precision brain health research in LMIC, making a difference where the burden of mental disorders is highest but access to where expensive imaging technologies is most limited.

The GBC has engaged over 150 researchers from 23 countries and nine international organizations, including the World Health Organization. Our collaboration has generated papers that have now been included in a special issue about Global Health in Neuroimage. Two of the collaborations published in that issue should be mentioned because they underscore the need and possibility of multinational collaborations that can benefit LMIC.

The first example is a collaboration between Barbados, the United States, Canada, and Cuba to study the lifelong effects of Protein Energy Malnutrition (PEM) that occurs only in the first year of life. A unique 49-year longitudinal study offered the possibility of studying the qEEG of participants with early PEM at school age and when they were adults 45 years later.

The qEEG enabled the clear identification of brain dysfunctions at both ages, with what appear to be indicators of early qEEG aging related to early cognitive decline as a conclusive result. As a result of the increase in child malnutrition globally, this finding may pave the way to develop disease progression models and biomarkers to help prevent these consequences. The utility of qEEG demonstrated in the described malnutrition study underscores the importance of having globally valid qEEG normative data.

The second result we want to highlight is the GBC multinational Project, which created Riemannian norms for over 1,564 persons from 9 countries, covering the age range from 5 to 97 years.

It’s a difficult balancing act to create a platform that allows us to have a scientific focus, tackle important technology issues, and have a global impact. Modern neuroscience has a considerable arsenal of theoretical, modeling, and neuroimaging technologies, but many of these devices are not readily available in LMIC.

Fortunately, access to an array of digital and neuro-technologies, which has been enhanced in recent years due to the investment of the Big Brain initiatives, may help us bridge this essential gap. This will open collaborative opportunities for neuroscientists and clinicians in LMIC who have previously been overlooked in global partnership initiatives.

Expand Cooperation and Promote the Development of Brain Science

My expectation for the future is to push harder for the deployment of low-cost, affordable neuroimaging technologies in LMIC to study brain disorders and potentially decrease the enormous mental health burden.

I intend to establish a China-Cuba Joint Lab as part of the Belt and Road Initiative to study aging and launch high technological products in both countries. This idea has been received with great enthusiasm in Chengdu, Shanghai, and other places, where several scientific institutions publicly declared their interest in a joint initiative. Later, I would like to extend the collaboration to other countries like Mexico, Brazil, Pakistan, and Malaysia.

I wish, of course, to boost the Global Brain Consortium (GBC), cementing China and Cuba’s role in developing technologies appropriate for LMIC. I also wish to build our programs for EEG norms, Brain Consequences of Malnutrition, Early Biomarkers of Dementia and Parkinson’s, Longitudinal biomarkers of child and adolescent brain development, and COVID induced Brain Disorders (CIBD).

This last program of CIBD illustrates the importance and challenges of developing scalable technologies to aid in diagnosing brain dysfunctions. The sheer number of people that need to be screened and managed necessitates a revolutionary change in the objectives of brain research. Mitchell Valdes-Sosa, Alan Evans, Mu-ming Poo, and I wrote a call to international action in this field, which was published in the National Science Review.

There is nowhere in the world that provides possibilities to carry out research with adequate resources and possible social impact as China. Although there is still much to accomplish, I feel truly fortunate for the support given by China and my Chinese colleagues. I have made beautiful friends. The Chinese Government has been extremely supportive of my efforts. I am particularly proud of receiving the 2017 Chinese Government Friendship Award and being invited to participate in the parade to commemorate the 70th anniversary of the PRC.