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The brain is the most complex part of human body. It is the source of intelligence and human behavior. Understanding how the brain works is essential for treatment of neurological disorders and development of more powerful artificial intelligence algorithms. To investigate its function, novel neurotechnologies are needed to record large-scale neural activity at high spatiotemporal resolution. Besides that, computational models could also be built to investigate possible mechanisms for neural activities at different levels. This dissertation presents research work on novel neurotechnologies and computational frameworks based on machine learning and biophysical modeling for investigation of brain functions. Chapter 1 presents a flexible insertable transparent microelectrode array (Neuro-FITM) for simultaneous electrical recordings from hippocampus and wide-field calcium imaging of dorsal cortex. We successfully recorded simultaneous activity of large-scale cortex and hippocampus. Using two-stage tensor component analysis and decoding analysis with support vector machines, we demonstrated distinct associations between hippocampus and cortex during hippocampal sharp-wave ripples.Chapter 2 presents a compact closed-loop optogenetics system based on transparent graphene microelectrode array. We extensively investigated light-induced artifacts for graphene electrodes and gold electrodes. We also validated the system for different frequencies of interest for neural recordings. The developed system can be used for various applications involving optogenetic stimulation and electrophysiological recordings.Chapter 3 presents the decoding of cortex-wide brain activity using surface electrical recordings over the cortex. We performed simultaneous local electrical recording and wide-field calcium imaging in awake mice. Using recurrent neural network, we demonstrated successful decoding of pixel-level cortical activity using locally recorded surface potentials. These results show that locally recorded surface potentials indeed contain rich information of large-scale neural activities.Chapter 4 presents a biophysical model for coupled network of hippocampal CA1 and prefrontal cortex to study mechanisms of memory trace transfer and reactivation. We found that stored memory traces in cortex can be retrieved through two different mechanisms, namely cell-specific inputs and non-specific spontaneous activities. Our study presents mechanistic explanations for memory transfer and retrieval.Chapter 5 is the conclusion of this dissertation. The future directions of neurotechnologies and computational models for neuroscience research are discussed

Scanning neurotechnology: what is being developed, where and by whom?Neurotechnology's developments hold profound implications for human identity, autonomy, privacy, behavior, and well-being,i.e. the very essence of what it means to be human.Since 2013, government investments in this field have exceeded$6 billion. Private investment has also seen significant growth,with annual funding experiencing a 22-fold increase from 2010 to 2020, reaching $7.3 billion and totaling $33.2 billion.This investment has translated into a 35-fold growth in neuroscience publications between 2000-2021 and 20-fold growth in innovations between 2000-2020, as proxied by patents. However, not all are poised to benefit from such developments, as big divides emerge.This report targets policy makers, researchers, patentanalysists, scientists, technology enthusiasts, ethicists, and anyone interested in the intersection of neuroscience, technology, and society. This report sheds light on the neurotechnology ecosystem,that is, what is being developed, where and by whom, and informs about how neurotechnology interacts with other technological trajectories, especially Artificial Intelligence.The report underscores the need for evidence in support of policy making and calls for the ethical governance of neurotechnology, to ensure that its development and deployment respects human rights, fundamental freedoms and human dignity, safeguarding individuals and societies.

Contains fulltext : 292128.pdf (Publisher’s version ) (Open Access) The rise of neurotechnologies, especially in combination with artificial intelligence (AI)-based methods for brain data analytics, has given rise to concerns around the protection of mental privacy, mental integrity and cognitive liberty - often framed as 'neurorights" in ethical, legal, and policy discussions. Several states are now looking at including neurorights into their constitutional legal frameworks, and international institutions and organizations, such as UNESCO and the Council of Europe, are taking an active interest in developing international policy and governance guidelines on this issue. However, in many discussions of neurorights the philosophical assumptions, ethical frames of reference and legal interpretation are either not made explicit or conflict with each other. The aim of this multidisciplinary work is to provide conceptual, ethical, and legal foundations that allow for facilitating a common minimalist conceptual understanding of mental privacy, mental integrity, and cognitive liberty to facilitate scholarly, legal, and policy discussions. 15 mei 2023 21 p.

Neuromodulation by Focused Ultrasound (NeuroFUS) is a state-of-the-art, non-invasive brain and nerve modulation method with high spatial resolution and precision. This OSF.IO Project is intended to provide an open access and resource sharing forum to make these methods more accessible to scientists, engineers, physician's, and medical device professionals.

Learning changes the activity of neurons across multiple brain regions, but the significance of this distributed organization remains poorly understood, owing in part to the difficulty of observing brain-wide activity patterns in commonly used mammalian model systems. This review discusses the promise of using the small and optically accessible nervous system of larval zebrafish to study the brain-wide networks that encode experience. I discuss the opportunities and challenges of studying learning and memory in the larval zebrafish, the lessons learned from recent studies of brain-wide imaging during experience-dependent behavior, and the potential for using zebrafish neurotechnology to understand the physiological principles and behavioral significance of distributed memory networks.

This brief presents multimodal neural interface circuits for diverse interaction with neuronal cell populations in the human brain. The next-generation neural interface system based on advanced circuits that can perform neural recording and stimulation in multiple modalities is indispensable to advance neuroscience and neurotechnology. Seven key circuit topologies used for interfacing with neural networks are reviewed: 1) electrical recording circuits for monitoring action potentials and local field potentials, 2) electrical stimulation circuits delivering electric charges to neuronal cells, 3) chemical recording circuits for monitoring neurotransmitters, 4) impedance measurement and 5) optical imaging circuits to characterize cell distributions and cellular morphologies, 6) optogenetics-based neural recording circuits and 7) neural stimulation circuits for conducting a cell-type-specific study of heterogeneous cell populations.

Most of the studies employing neuroimaging have focused on cortical and subcortical signals individually to obtain neurophysiological signatures of cognitive functions. However, understanding the dynamic communication between the cortex and subcortical structures is essential for unraveling the neural correlates of cognition. In this quest, magnetoencephalography (MEG) and electroencephalography (EEG) are the methods of choice because they are non-invasive electrophysiological recording techniques with high temporal resolution. Sophisticated MEG/EEG source estimation techniques and network analysis methods developed recently can provide a more comprehensive understanding of the neurophysiological mechanisms of fundamental cognitive processes. Used together with noninvasive modulation of cortical-subcortical communication, these approaches may open up new possibilities for expanding the repertoire of non-invasive cognitive neurotechnology.

The COVID-19 pandemic and its resulting health and safety concerns caused the cancellation of many engineering education opportunities for high school students. To expose high school students to the field of neural engineering and encourage them to pursue academic pathways in biomedical engineering, the Center for Neurotechnology (CNT) at the University of Washington converted an in-person summer camp to a fully online program (Virtual REACH Program, VRP) offering both synchronous and asynchronous resources. The VRP is a five-day online program that focuses on a different daily theme (neuroscience, brain-computer interfaces, electrical stimulation, neuroethics, career/academic pathways). Each day, the VRP starts with a live videoconference meeting (lecture and interactive discussion) with a CNT faculty member. The online lectures are supported by at-home learning resources (e.g., text, videos, activities, quizzes) embedded within a digital book created using the Pressbook platform. An online bulletin board (Padlet) is also used by students to share artifacts and build community. Program evaluation will be conducted by an external evaluator. A summative survey will collect information on participants’ experiences in the VRP and will help inform future iterations of the program. Although significant time was required to create a digital book, the VRP will reach a larger audience than the prior in-person program and resulted in the creation of learning tools that can be used in the future.

Deep Brain Stimulation (DBS) is an FDA-approved treatment for symptoms of motor disorders—with experimental use for psychiatric disorders. DBS, however, causes a variety of side effects. Moral philosophers question DBS’s influence on users’ experiences of authenticity, identity, and/or autonomy. These characterizations of DBS, however, may not make sense of how DBS complicates, rather than simply impedes or bolsters, users’ abilities to exercise agency. Empirical work exploring DBS users’ lived-experiences and feminist accounts of relational autonomy demonstrate that the issues users face are better characterized in terms of the user’s relationship to their stimulator, that is, in terms of “relational agency.”

Producción Científica, Background and objective. Neurotechnologies have great potential to transform our society in ways that are yet to be uncovered. The rate of development in this field has increased significantly in recent years, but there are still barriers that need to be overcome before bringing neurotechnologies to the general public. One of these barriers is the difficulty of performing experiments that require complex software, such as brain-computer interfaces (BCI) or cognitive neuroscience experiments. Current platforms have limitations in terms of functionality and flexibility to meet the needs of researchers, who often need to implement new experimentation settings. This work was aimed to propose a novel software ecosystem, called MEDUSA©, to overcome these limitations. Methods. We followed strict development practices to optimize MEDUSA© for research in BCI and cognitive neuroscience, making special emphasis in the modularity, flexibility and scalability of our solution. Moreover, it was implemented in Python, an open-source programming language that reduces the development cost by taking advantage from its high-level syntax and large number of community packages. Results. MEDUSA© provides a complete suite of signal processing functions, including several deep learning architectures or connectivity analysis, and ready-to-use BCI and neuroscience experiments, making it one of the most complete solutions nowadays. We also put special effort in providing tools to facilitate the development of custom experiments, which can be easily shared with the community through an app market available in our website to promote reproducibility. Conclusions. MEDUSA© is a novel software ecosystem for modern BCI and neurotechnology experimentation that provides state-of-the-art tools and encourages the participation of the community to make a difference for the progress of these fields. Visit the official website at https://www.medusabci.com/ to know more about this project., Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación/10.13039/501100011033/' y el Fondo Europeo de Desarrollo Regional (FEDER) grants (PID2020-115468RB-I00 and RTC2019-007350-1)

BACKGROUND: A long-held goal of vision therapy is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists. METHODS: We implanted an intracortical microelectrode array consisting of 96 electrodes in the visual cortex of a 57-year-old person with complete blindness for a 6-month period. We measured thresholds and the characteristics of the visual percepts elicited by intracortical microstimulation. RESULTS: Implantation and subsequent explantation of intracortical microelectrodes were carried out without complications. The mean stimulation threshold for single electrodes was 66.8 ± 36.5 μA. We consistently obtained high-quality recordings from visually deprived neurons and the stimulation parameters remained stable over time. Simultaneous stimulation via multiple electrodes was associated with a significant reduction in thresholds (P < 0.001, ANOVA) and evoked discriminable phosphene percepts, allowing the blind participant to identify some letters and recognize object boundaries. CONCLUSIONS: Our results demonstrate the safety and efficacy of chronic intracortical microstimulation via a large number of electrodes in human visual cortex, showing its high potential for restoring functional vision in the blind. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02983370. FUNDING: The Spanish Ministerio de Ciencia Innovación y Universidades, the Generalitat Valenciana (Spain), the Europan Union’s Horizon 2020 programme, the Bidons Egara Research Chair of the University Miguel Hernández (Spain), and the John Moran Eye Center of the University of Utah.

Neuroscience and its findings have deep personal and cultural meaning, so the implications of brain science raise new flavors of ethical issues not covered by traditional bioethics. The field of neuroethics bridges this gap, addressing and responding to the ethical, legal, and social issues intimately related to the evolving landscape of neuroscience. Neuroethical concerns have registered at the highest levels of government. In 2018, an interdisciplinary global neuroethics group working with leading scientists from the International Brain Initiative, a consortium of seven large-scale national-level brain research projects around the globe, published “Neuroethics Questions to Guide Ethical Research in the International Brain Initiatives.” The document provides guiding questions to consider throughout the lifecycle of neuroscience research. These questions tackle issues such as identity, morality, cross-cultural differences, privacy, and potential stakeholder involvement in ethical decision-making. In our work with the International Brain Initiative, we noted the important role that the private sector will play in translating and scaling neuroscience for society. We also noticed a gap in communication and collaboration between government, academia and the private sector. These guiding questions were largely co-created with policy makers and academics, so it was unclear how these issues might be received by neuro-entrepreneurs and neuro-industry. We hoped to identify not only common concerns, but also a common language for discussing neuroethical issues with stakeholders outside of government and academia. We used empirical ethics methods to assess the perceived value and attitudes of neuro-entrepreneurs toward neuroethical issues and whether or not these issues align with the process of neuro-innovation. We conducted one-on-one structured interviews with 21 neuro-entrepreneurs in the private sector and used two independent reviewers to analyze for themes. From this preliminary research, we identified key neuroethical themes and processual pain points of neurotech entrepreneurs throughout the innovation process. We also provide a preliminary neuroethics needs assessment for neuro-industry and suggest avenues through which neuroethicists can work with neurotech leadership to build an ethically aligned future. Overall, we hope to raise awareness and provide actionable steps toward advancing and accelerating societally impactful neuroscience.

This study aims to identify correlations between the directions of the hand movements and the brain signals recorded from the brain surface using electrocorticography (ECoG). We suppose that the coding of the hand movement direction occurs in the motor cortex and could be detected with ECoG. Using representational similarity analysis (RSA) and the cosine tuning assumption we confirmed that indeed, there is a significant concordance between the brain signals and the hand movement directions. And the main areas of the brain responsible for this have been identified.

A nature-inspired bioengineering methodology is presented. The methodology includes (1) identifying a set of “bottom-up” normative models or fundamental mechanisms by which nature builds tissues and organs from progenitor cells during development, (2) recapitulating these bottom-up developmental processes in vitro by using stem cells to grow tissue and organ-like structures, called organoids, and (3) implementing “top-down” technologies that provide specific supportive niches for growing structures at each developmental level. Also presented, is a systematic nature-inspired solution framework that applies universal concepts in natural development to inform designs for organ repair. This organizational framework, which integrates developmental models, recapitulation of development in vitro, and engineered niches is illustrated by considering repair of two body organs: the retina and spinal cord, respectively. The former repair involves transplanting a retinal patch grown in vitro on a synthetic sheet, while the latter uses implanted stem cells to promote growth of relay circuits in the injured human spinal cord or activity-based neurotechnology.

Recovering arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control practically limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury using spinal cord stimulation. Our neural interface leverages the functional organization of the dorsal roots to convey artificial excitation via electrical stimulation to relevant spinal segments at appropriate movement phases. Stimulation bursts, triggered by intracortical signals produced sustained arm movements enabling monkeys with arm paralysis to perform an unconstrained, three-dimensional reach-and-grasp task. Stimulation specifically improved strength, task performances and movement quality. Electrophysiology suggested that artificial recruitment of the sensory afferents was synergistically integrated with spared descending inputs and spinal reflexes to produce coordinated movements. The efficacy and reliability of our approach hold realistic promises of clinical translation.

This chapter introduces the importance of contextual and cultural interaction with neuroscience, neurotechnology, artificial intelligence and neuroethics. It presents the relevance of this interplay, since it will partly shape perceptions about the development, use and regulation of these advanced tools and techniques, as well as the need to analyze the possible neuroethical, legal, social and cultural implications and concerns. It then exposes how these contextually and culturally shaped perceptions could help to understand the global neurotechnological gap and the global legal/ethical gap. Responsible innovation from developer countries (mainly high-income countries) is also discussed, as well as the proposal for a responsible acquisition of novel neuroscience, neurotechnology and artificial intelligence from consumer countries (mainly low and middle-income countries) to promote responsible, pertinent and responsive development of policymaking.

Neuroscience lies at the heart of a wide range of novel scientific and technological advances, from neurotechnology to computing and the cognitive sciences. Observing and studying the human brain allows glimpses into the most valuable resource resulting from evolution: the human mind. However abundant and widely available, neuroscience research data are knowledge and resource intensive to acquire and maintain, demanding a high level of skill and expertise to be produced, accessed and applied. As in all complex knowledge domains, reasoning with neuroscience relies on implicit metacognitive processes, and metacognition relies on high level cognitive models. This paper proposes a System Level Knowledge Representation schema as an abstraction for neuroscience data aimed at supporting explicit metacognition as well as knowledge organisation, understandability and to ease the cognitive load of processing systems neuroscience data.