2022年脑科学与类脑智能发展态势

脑科学是理解人和自然的“终极疆域”,现已成为重要的科学和技术前沿领域之一。该文主要从研究计划、研究进展、产品研发与产业发展的视角分析2022年脑科学与类脑智能领域的进展,并对未来发展趋势加以展望。2022年,美国、中国等国家/地区的脑计划取得较大进展;在脑图谱绘制、脑发育与脑认知功能解析、脑疾病机制探索及类脑智能技术与产品开发方面取得重要研究突破;脑疾病药物研发管线丰富,将推动相关产业快速发展。未来,借助各类新技术,研究人员将在多尺度解析脑认知功能,识别其中的功能障碍,开发出多种有效的脑疾病治疗药物;脑科学与人工智能等领域相互借鉴,推动类脑智能领域快速发展并广泛应用;数据治理和伦理安全的突破有助于脑科学与类脑智能研究的良性发展。     

空间脑科学研究的回顾与展望

人类大脑是自然界最复杂的系统之一.大脑结构与功能之谜是人类认识自身的终极疆域,对于推动科技创新发展与人类文明进步具有极其重要的意义.载人航天是现代科技革命的重要领域之一,美国、俄罗斯等航天大国已利用空间资源开展脑科学研究.我国空间站的建设,将提供空间脑科学研究的系统创新平台,极大地推进中国空间脑科学计划进程.本文综述了在空间环境或模拟空间环境下,脑发育及生物学机制、认知规律与机制、生物节律和睡眠对脑功能的影响、群脑协同等方面的空间脑科学研究进展,并简述和展望了我国空间脑科学研究的发展方向.     

脑科学和脑功能MR成像

目的：在对大脑认知功能进行脑功能成像研究之中,随着磁共振成像技术的发展,人们现在可以对脑的认知功能,如视觉、运动、语言和记忆等功能中枢进行成像。本文首先介绍了脑科学的发展历程,并从脑功能MR成像的方法出发,分析了其成像机理,探讨了用脑功能MR成像为手段对脑科学—认知科学进行的方法研究,最后对脑功能MR成像应用于脑科学的研究作了展望。     

编者按: 脑成像与脑网络

揭示脑的奥秘是人类面临的最大挑战之一。神经元是构成神经系统结构与功能的基本单位。神经元与神经元之间通过突触实现信息交互,并构成神经环路或神经网络。神经环路有局部的,也有跨脑区或长程的,甚至全脑尺度的。神经环路则是脑实现神经信息处理的基本单元。若干神经环路构成脑网络。脑网络研究已经成为脑功能与脑疾病研究领域的热点。 在国家自然科学基金委员会和科技部“973计划”等项目的支持下,我国科学家在这一领域已经开展了卓有成效的工作。2011年第393次香山科学会议“脑网络组及其临床应用的前沿科学问题”曾对此进行过比较深入的研讨。为促进对该领域现状及发展的了解,本期汇集了2篇述评和2篇研究论文,作为脑成像与脑网络专题发表,以飨读者。 利用9.4T功能磁共振成像(fMRI)获得轻度麻醉状态下大鼠静息状态及刺激激活的数据,通过互相关分析构建节点之间的相关系数矩阵并计算相应的网络参数,赖永秀等人报道了大鼠感觉运动系统静息态脑网络的研究成果,发现感觉运动系统在静息态时的脑网络具有小世界属性。 扩散磁共振成像(dMRI)的出现为大脑结构与功能研究提供了全新的检测手段,雷皓等报道了小动物高分辨扩散磁共振成像数据分析方法,为小动物脑dMRI研究提供了统一图像模板与完善的计算方法,对于检测神经纤维微观结构的变化,以及临床诊断,将具有极其重要的意义。 神经环路功能变化的实时在体监测是研究脑网络不可或缺的手段,曾绍群等评述了基于声光偏转器的快速无惯性随机扫描双光子显微成像技术的研究进展及发展趋势,指出该技术的进一步发展将为神经活动观测提供一种全新的方法,从而极大地推动脑科学研究的发展。 针对哺乳动物全脑的神经元网络成像,龚辉等从空间分辨率、探测范围、数据配准和成像速度等方面评述了光学显微水平全脑成像方法的研究进展,并讨论所面临的挑战。他们指出,要在全脑尺度获取突起水平分辨率的结构与功能数据,光学成像方法最为成熟。华中科技大学研制的MOST系统,率先获得了一系列高分辨率的完整大脑解剖数据集,该成果将在神经元网络的构建和脑功能与疾病研究中发挥重要作用。 我们期待更多、更好的有关脑成像与脑网络的论文发表,以更广泛和深入地促进我国脑科学研究领域的学术交流。     

日本“脑科学时代”计划纲要简介

随着世纪之交的来临,对脑的奥妙的探索越来越受到人们的重视,脑科学将在21世纪的自然科学的发展中占据重要的地位。90年代以来,欧美都相继开展了大规模的脑科学研究计划。在这个历史背景下,日本经过长时间酝酿后,于1996年推出了“脑科学时代”（TheAgeofBrainScience）庞大计划纲要（以下简称“纲要”）,拟在20年内,以每年1000亿日元的支持强度,大力推进脑研究,将使日本的脑科学达到甚至领先于国际水平。“纲要”由三个部分组成。首先分析了目前国际脑科学研究现状及日本施科学研究中存在的问题;其次,针对脑科学未来的发展方向…     

综述: 光学显微水平全脑成像方法的研究进展

在全脑水平研究哺乳动物复杂的脑神经网络是现代脑科学的重要研究目标之一,但由于缺乏合适的研究方法,已有的研究还局限于高等动物的局部脑回路或低等动物的脑网络．为了实现大范围的高分辨三维成像,近10年来,发展出了一些光学显微成像新方法,已经或有希望应用于哺乳动物全脑的神经元网络成像研究中．本文对上述方法进行了归纳和比较,综述了各种成像技术在空间分辨率、探测范围、数据配准和成像速度等方面的性能表现及面临的挑战．     

我国脑科学研究战略部署及发展情况浅析

脑科学研究对于人类不断认识自身与世界有着重要意义,近年来主要发达国家纷纷制订脑科学研究规划,加大对脑科学研究的投入,力图占领这一领域的研究制高点,并推动相关产业的进步。分析了世界脑科学发展的总体态势,介绍了我国脑科学研究的总体部署和突出进展,并探讨了脑科学研究的发展前景。     

神经功能成像及其在重大脑疾病中的应用

根据第101期双清论坛"神经功能成像及其在重大脑疾病中的应用"的报告内容,简述了功能神经成像技术与方法的现状与发展趋势,介绍了近年来基于成像技术的重要脑科学研究成果和临床转化研究面临的挑战,并提出了神经功能成像及其在重大脑疾病应用中的主要研究方向和科学问题的设想.     

编者按: 脑与认知科学研究的现状与前沿

研究和揭示大脑在生理和病理状态下的工作机制,一直是脑与认知科学的重要研究内容和目标.虽然脑与认知科学领域已经取得了一系列重要的研究成果,但仍然面临巨大的挑战.因此,各国都在加大投入,推动技术创新,开展多学科交叉、多层次的脑与认知科学研究.2013年美国启动脑科学     

也谈谈“中国脑计划”

正最近两年,"脑科学"、"脑计划"成了热门词语.似乎周围的人都在谈论脑科学,科研一线的脑科学家们在谈论,其他领域的科学家们、非科学家们也在谈论脑科学.在广泛谈论脑科学的同时,大家谈论更多的是"中国脑计划",逐步从开始的"应不应该做",到后来的"应该做哪些领域、做哪些技术".第一个问题,就不需要过多探讨了.即使没有欧洲、美国、加拿大、日本等纷纷启动的脑计划,中国也一直在做脑科学相关的研究.从国家自然科学基金委员会、科学技术部、中国科学院等,都一直在支     

脑机接口：现状，问题与展望

本文综述现有脑机接口技术的最新发展，并讨论这些脑机接口技术的局限和存在的问题，如高估人类个体大脑的功能、对大脑信息存储方式缺乏了解等. 基于大脑信息存储的“二维码”模型，我们认为目前的脑机接口技术方案仅适用于一些简单的应用场景，如了解受测者的情绪变化、生命活动的状态，以及控制体外器械等，而无法通过脑机接口技术获取脑内诸如记忆与思考等信息的精准细节. 我们也提出，向大脑输入信息的脑机接口技术有较大的发展空间，比如发展具有多种调控效果、物理和生化技术结合的深脑刺激装置，有可能广泛应用于抑郁症、癫痫等脑疾病的治疗，以及应用于短期脑力的增强. 本文对于目前的脑机接口研究领域具有一定的警示和启发意义.     

The distribution of melanopsin (OPN4) protein in the human brain

Until now, melanopsin (OPN4) – a specialized photopigment being responsive especially to blue light wavelengths – has not been found in the human brain at protein level outside the retina. More specifically, OPN4 has only been found in about 2% of retinal ganglion cells (i.e. in intrinsically photosensitive retinal ganglion cells), and in a subtype of retinal cone-cells. Given that Allen Institute for Brain Science has described a wide distribution of OPN4 mRNA in two human brains, we aimed to investigate whether OPN4 is present in the human brain also at protein level. Western blotting and immunohistochemistry, as well as immunoelectron microscopy, were used to analyse the existence and distribution of OPN4 protein in 18 investigated areas of the human brain in samples obtained in forensic autopsies from 10 male subjects (54 ± 3.5 years). OPN4 protein expression was found in all subjects, and, furthermore, in 5 out of 10 subjects in all investigated brain areas localized in membranous compartments and cytoplasmic vesicles of neurons. To our opinion, the wide distribution of OPN4 in central areas of the human brain evokes a question whether ambient light has important straight targets in the human brain outside the retinohypothalamic tract (RHT). Further studies are, however, needed to investigate the putative physiological phototransductive actions of inborn OPN4 protein outside the RHT in the human brain.     

Small RNAs in Human Brain Development and Disorders

Small RNA is a variable and abundant type of non-coding RNAs in brain. The function of these RNAs is mainly unknown. A specific class of small RNA, microRNA, is dynamically regulated in neurogenesis and in embryo brain development. The genes for synaptic formation and some mental retardation disorders are putative targets for microRNA predicted by computational algorithms. The molecular pathways for mental development, common forms of autisms, schizophrenia, and affective disorders have yet to be elucidated. The hypothesis proposed here is that small regulatory RNAs, specifically microRNAs, play a role in human brain development and pathogenesis of brain disorders, especially of neurodevelopmental conditions. Pilot tests using comprehensive arrays of microRNAs demonstrate that microRNAs derived from postmortem human brains are applicable for microRNA expression profiling. The abundant expression of many regulatory small RNAs in human brain implies their biological role that must be tested by functional assays in neurons and by genetic and comparative expression profiling.     

Characterization of an Initiating Cell-Free Protein Synthesis System Derived from Rabbit Brain

Abstract: Protein synthesis in the brain is known to be affected by a wide range of treatments. The detailed analysis of the mechanisms that are involved would be facilitated by the development of cell-free translation systems derived from brain tissue. To date, brain cell-free systems have not been fully characterized to demonstrate a capacity for initiation of translation. The following criteria were utilized to demonstrate that a cell-free protein synthesis system derived from rabbit brain was capable of initiation in vitro : (a) sensitivity of cell-free translation to the initiation inhibitor aurintricarboxylic acid (ATA); (b) binding of [³⁵S]Met-tRNA_f to 40S and 80S initiation complexes; (c) incorporation of labeled initiation methionine into high-molecular-weight proteins; and (d) the association of labeled exogenous mRNA with polysomes. The optimum conditions for amino acid incorporation in this system were 4 mM-Mg²⁺, 140 mM-K⁺, and pH 7.55. Incorporation was dependent on the addition of ATP, GTP, and an energy-generating system. Cell-free protein synthesis reflected the normal process, since a similar spectrum of proteins was synthesized in vitro and in vivo. This initiating cell-free translation system should have wide application in the analysis of the mechanisms whereby various treatments affect protein synthesis in the brain.     

Brain Amino Acids During Hyponatremia In Vivo: Clinical Observations and Experimental Studies

Hyponatremia is a highly morbid condition, present in a wide range of human pathologies, that exposes patients to encephalopathic complication and the risk of permanent brain damage and death. Treating hyponatremia has proved to be difficult and still awaits safe management, avoiding the morbid sequelae of demyelinizing and necrotic lesions associated with the use of hypertonic solutions. During acute and chronic hyponatremia in vivo, the brain extrudes the excessive water by decreasing its content of electrolytes and organic osmolytes. At the cellular level, a similar response occurs upon cell swelling. Among the organic osmolytes involved in both responses, free amino acids play a prominent role because of the large intracellular pools often found in nerve cells. An overview of the changes in brain amino acid content during hyponatremia in vivo is presented and the contribution of these changes to the adaptive cell responses involved in volume regulation discussed. Additionally, new data are provided concerning changes in amino acid levels in different regions of the central nervous system after chronic hyponatremia. Results favor the role of taurine, glutamine, glutamate, and aspartate as the main amino acid osmolytes involved in the brain adaptive response to hyponatremia in vivo. Deeper knowledge of the adaptive overall and cellular brain mechanisms activated during hyponatremia would lead to the design of safer therapies for the hyponatremic patient.     

On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis

The most serious consequence of sterol 27-hydroxylase deficiency in humans [cerebrotendinous xanthomatosis (CTX)] is the development of cholestanol-containing brain xanthomas. The cholestanol in the brain may be derived from the circulation or from 7alpha-hydroxylated intermediates in bile acid synthesis, present at 50- to 250-fold increased levels in plasma. Here, we demonstrate a transfer of 7alpha-hydroxy-4-cholesten-3-one across cultured porcine brain endothelial cells (a model for the blood-brain barrier) that is approximately 100-fold more efficient than the transfer of cholestanol. Furthermore, there was an efficient conversion of 7alpha-hydroxy-4-cholesten-3-one to cholestanol in cultured neuronal and glial cells as well as in monocyte-derived macrophages of human origin. It is concluded that the continuous intracellular production of cholestanol from a bile acid precursor capable of rapidly passing biomembranes, including the blood-brain barrier, is likely to be of major importance for the accumulation of cholestanol in patients with CTX. Such a mechanism also fits well with the observation that treatment with chenodeoxycholic acid, which normalizes the level of the bile acid precursor, results in a reduction of cholestanol-containing xanthomas even in the brain.     

Emerging Bioelectronics for Brain Organoid Electrophysiology

Human brain organoids are generated from three-dimensional (3D) cultures of human induced pluripotent stem cells and embryonic stem cells, which partially replicate the development and complexity of the human brain. Many methods have been used to characterize the structural and molecular phenotypes of human brain organoids. Further understanding the electrophysiological phenotypes of brain organoids requires advanced electrophysiological measurement technologies to achieve long-term stable 3D recording over the time course of the organoid development with single-cell, millisecond spatiotemporal resolution. In this review, first, we briefly introduce the development, generation, and applications of human brain organoids. We then discuss the conventional methods used for characterizing the morphological, genetic, and electrical properties of brain organoids. Next, we highlight the need for characterizing electrophysiological properties of brain organoids in a minimally invasive manner. In particular, we discuss recent advances in the multi-electrode array (MEA), 3D bioelectronics, and flexible bioelectronics and their applications in brain organoid electrophysiological measurement. In addition, we introduce the recently developed cyborg organoids platform as an emerging tool for the long-term stable 3D characterization of the brain organoids electrophysiology at high spatiotemporal resolution. Finally, we discuss the perspectives of new technologies that could achieve the high-throughput, multimodal characterizations from the same brain organoids.     

Brain and testis: more alike than previously thought?

Several strands of evidence indicate the presence of marked similarities between human brain and testis. Understanding these similarities and their implications has become a topic of interest among the scientific community. Indeed, an association of intelligence with some semen quality parameters has been reported and a relation between dysfunctions of the human brain and testis has also been evident. Numerous common molecular features are evident when these tissues are compared, which is reflected in the huge number of common proteins. At the functional level, human neurons and sperm share a number of characteristics, including the importance of the exocytotic process and the presence of similar receptors and signalling pathways. The common proteins are mainly involved in exocytosis, tissue development and neuron/brain-associated biological processes. With this analysis, we conclude that human brain and testis share several biochemical characteristics which, in addition to their involvement in the speciation process, could, at least in part, be responsible for the expression of a huge number of common proteins. Nonetheless, this is an underexplored topic, and the connection between these tissues needs to be clarified, which could help to understand the dysfunctions affecting brain and testis, as well as to develop improved therapeutic strategies.     

射频热疗技术在脑胶质瘤治疗中的应用进展

近几年,射频(radio frequency,RF)热疗技术以其靶向、微创、效果好,副作用少等特点,在临床治疗中,尤其是恶性肿瘤的治疗方面,取得了巨大的发展。随着研究的逐步深入,射频热疗技术越来越受到人们的重视,其应用范围也逐渐宽泛。脑胶质瘤呈广泛侵袭性生长,尤其是Ⅲ～Ⅳ级胶质瘤,具有高度间变的生长特点,术后复发快,手术加放化疗的平均生存期仅为8～11个月,严重威胁人类健康,是神经外科治疗领域中最难治疗的肿瘤。因而有关恶性脑胶质细胞瘤发生、发展及治疗的研究一直是神经外科领域的热点之一。本文就射频热疗技术的基本原理、脑胶质瘤治疗现状、射频热疗技术在脑胶质瘤治疗方面的应用,最新研究方向及进展做一综述。