Proposal for a Mechanistic Disease Conceptualization in Clinical Neurosciences: The Neural Network Components (NNC) Model.

ABSTRACT: Clinical neurosciences, and psychiatry specifically, have been challenged by the lack of a comprehensive and practical framework that explains the core mechanistic processes of variable psychiatric presentations. Current conceptualization and classification of psychiatric presentations are primarily centered on a non-biologically based clinical descriptive approach. Despite various attempts, advances in neuroscience research have not led to an improved conceptualization or mechanistic classification of psychiatric disorders. This perspective article proposes a new-work-in-progress-framework for conceptualizing psychiatric presentations based on neural network components (NNC). This framework could guide the development of mechanistic disease classification, improve understanding of underpinning pathology, and provide specific intervention targets. This model also has the potential to dissolve artificial barriers between the fields of psychiatry and neurology.

Engram Studies: A Call for Historical, Philosophical, and Sociological Approaches.

In this chapter, we identify three distinct avenues of research on the philosophical, historical, and sociopolitical dimensions of engram research. First, we single out the need to refine philosophical understandings of memory within neuroscientific research on the engram. Specifically, we question the place of constructivist and preservationist philosophical claims on memory in the formulation of the engram concept and its operationalization in contemporary neuroscience research. Second, we delve into the received historiography of the engram claiming its disappearance after Richard Semon's (1859-1918) coinage of the concept. Differently from this view, we underline that Semon's legacy is still largely undocumented: Unknown are the ways the engram circulated within studies of organic memory as well as the role Semon's ideas had in specific national contexts of research in neurosciences. Finally, another research gap on the engram concerns a socio-anthropological documentation of the factual and normative resources this research offers to think about memory in healthcare and society. Representations of memory in this research, experimental strategies of intervention into the engram, as well as their translational potential for neurodegenerative (e.g., Alzheimer's disease) and psychiatric (e.g., post-traumatic stress disorder) conditions have not yet received scrutiny notwithstanding their obvious social and political relevance.All these knowledge gaps combined call for a strong commitment towards interdisciplinarity to align the ambitions of a foundational neuroscience of the engram with a socially responsible circulation of this knowledge. What role can the facts, metaphors, and interventional strategies of engram research play in the wider society? With what implications for philosophical questions at the foundation of memory, which have accompanied its study from antiquity? And what can neuro- and social scientists do jointly to shape the social and political framings of engram research?

If Engrams Are the Answer, What Is the Question?

Engram labelling and manipulation methodologies are now a staple of contemporary neuroscientific practice, giving the impression that the physical basis of engrams has been discovered. Despite enormous progress, engrams have not been clearly identified, and it is unclear what they should look like. There is an epistemic bias in engram neuroscience toward characterizing biological changes while neglecting the development of theory. However, the tools of engram biology are exciting precisely because they are not just an incremental step forward in understanding the mechanisms of plasticity and learning but because they can be leveraged to inform theory on one of the fundamental mysteries in neuroscience-how and in what format the brain stores information. We do not propose such a theory here, as we first require an appreciation for what is lacking. We outline a selection of issues in four sections from theoretical biology and philosophy that engram biology and systems neuroscience generally should engage with in order to construct useful future theoretical frameworks. Specifically, what is it that engrams are supposed to explain? How do the different building blocks of the brain-wide engram come together? What exactly are these component parts? And what information do they carry, if they carry anything at all? Asking these questions is not purely the privilege of philosophy but a key to informing scientific hypotheses that make the most of the experimental tools at our disposal. The risk for not engaging with these issues is high. Without a theory of what engrams are, what they do, and the wider computational processes they fit into, we may never know when they have been found.

Internal world models in humans, animals, and AI.

How do brains-biological or artificial-respond and adapt to an ever-changing environment? In a recent meeting, experts from various fields of neuroscience and artificial intelligence met to discuss internal world models in brains and machines, arguing for an interdisciplinary approach to gain deeper insights into the underlying mechanisms.

The effects of a prehabilitation programme based on therapeutic exercise, back care education, and pain neuroscience education in patients scheduled for lumbar radiculopathy surgery: A study protocol for a randomised controlled trial.

The aim of this present clinical trial is to evaluate the effectiveness of a multicomponent prehabilitation programme administered through educational videos versus another programme based on written exercise recommendations, in patients scheduled for lumbar radiculopathy surgery. This study will be a multicentre, controlled, randomised, parallel clinical trial. One hundred participants undergoing lumbar radiculopathy surgery who meet the established inclusion criteria will be recruited at different Spanish hospitals. The experimental group will follow a 4-week prehabilitation programme combining therapeutic exercise, back care education, and pain neuroscience education delivered through videos designed for consumption at home. The control group will be provided with written instructions to perform therapeutic exercises during the same prehabilitation time period. The primary outcome of the study will be disability, assessed using the Spanish version of the Oswestry Disability Index. The secondary outcomes will be pain perception, health-related quality of life, fear avoidance, kinesiophobia, catastrophising, anxiety, depression, physical activity, and the treatment satisfaction of the patients. This study will provide evidence for the effectiveness of a home-based multicomponent prehabilitation programme that addresses some already identified barriers to patient attendance in face-to-face programmes. Understanding the medium and long-term effects of pre-surgery lumbar muscle training and pain neuroscience education administered via instructional videos watched by patients at home, will help improve the design of prehabilitation programmes in this population while also improving the cost-effectiveness of such interventions.

Anesthetized animal experiments for neuroscience research.

Brain research has progressed with anesthetized animal experiments for a long time. Recent progress in research techniques allows us to measure neuronal activity in awake animals combined with behavioral tasks. The trends became more prominent in the last decade. This new research style triggers the paradigm shift in the research of brain science, and new insights into brain function have been revealed. It is reasonable to consider that awake animal experiments are more ideal for understanding naturalistic brain function than anesthetized ones. However, the anesthetized animal experiment still has advantages in some experiments. To take advantage of the anesthetized animal experiments, it is important to understand the mechanism of anesthesia and carefully handle the obtained data. In this minireview, we will shortly summarize the molecular mechanism of anesthesia in animal experiments, a recent understanding of the neuronal activities in a sensory system in the anesthetized animal brain, and consider the advantages and disadvantages of the anesthetized and awake animal experiments. This discussion will help us to use both research conditions in the proper manner.

Stress, working memory, and academic performance: a neuroscience perspective.

The relationship between stress and working memory (WM) is crucial in determining students' academic performance, but the interaction between these factors is not yet fully understood. WM is a key cognitive function that is important for learning academic skills, such as reading, comprehension, problem-solving, and math. Stress may negatively affect cognition, including WM, via various mechanisms; these include the deleterious effect of glucocorticoids and catecholamines on the structure and function of brain regions that are key for WM, such as the prefrontal cortex and hippocampus. This review explores the mechanisms underlying how stress impacts WM and how it can decrease academic performance. It highlights the importance of implementing effective stress-management strategies to protect WM function and improve academic performance.

From developmental neuroscience to policy: A novel framework based on participatory research.

Insights from developmental neuroscience are not always translated to actionable policy decisions. In this review, we explore the potential of bridging the gap between developmental neuroscience and policy through youth participatory research approaches. As the current generation of adolescents lives in an increasingly complex and rapidly changing society, their lived experiences are crucial for both research and policy. Moreover, their active involvement holds significant promise, given their heightened creativity and need to contribute. We therefore advocate for a transdisciplinary framework that fosters collaboration between developmental scientists, adolescents, and policy makers in addressing complex societal challenges. We highlight the added value of adolescents' lived experiences in relation to two pressing societal issues affecting adolescents' mental health: performance pressure and social inequality. By integrating firsthand lived experiences with insights from developmental neuroscience, we provide a foundation for progress in informed policy decisions.

Large-scale neurophysiology and single-cell profiling in human neuroscience.

Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.

Hyperscanning literature after two decades of neuroscientific research: A scientometric review.

Hyperscanning, a neuroimaging approach introduced in 2002 for simultaneously recording the brain activity of multiple participants, has significantly contributed to our understanding of social interactions. Nevertheless, the existing literature requires systematic organization to advance our knowledge. This study, after two decades of hyperscanning research, aims to identify the primary thematic domains and the most influential documents in the field. We conducted a scientometric analysis to examine co-citation patterns quantitatively, using a sample of 548 documents retrieved from Scopus and their 32,022 cited references. Our analysis revealed ten major thematic domains in hyperscanning research, with the most impactful document authored by Czeszumski and colleagues in 2020. Notably, while hyperscanning was initially developed for functional magnetic resonance imaging (fMRI), our findings indicate a substantial influence of research conducted using electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). The introduction of fNIRS and advancements in EEG methods have enabled the implementation of more ecologically valid experiments for investigating social interactions. The study also highlights the need for more research that combines multi-brain neural stimulation with neuroimaging techniques to understand the causal role played by interpersonal neural synchrony in social interactions.

[The role and responsibility of clinical neuroscience in brain-computer interface clinical research].

Brain-computer interface (BCI) constructs the direct communication between human brain and external devices, which has been extensively applied in clinical research of the diagnosis and treatment of nervous system diseases, and plays a crucial role in functional evaluation, communication control, reconstruction, rehabilitation training, and neural regulation. This paper summarizes the different forms of BCI technology, the progress of clinical research on BCI for neurological diseases, and the importance of developing appropriate clinical trial standards and ethical norms. Further emphasis is placed on the interpretation of the scope of BCI clinical research in neurological diseases, the ethical principles of BCI clinical research in neurological diseases, and the key points of BCI clinical research implementation and management summarized in the Chinese expert Consensus on the implementation and management of BCI clinical research in Neurological diseases. Finally, the role and responsibility of clinical neuroscience in BCI clinical trials are put forward, emphasizing interdisciplinary cooperation in clinical research to better promote the clinical transformation of BCI technology.

Neurosteroids and their Therapeutic Potential: Remembering the Contribution of Dr. Sabina Luchetti, Netherlands Institute for Neuroscience, Amsterdam, Netherlands.

This article traces the career of Dr. Sabina Luchetti (1969-2021), a noted physician (medical doctor, specialized in Neurology at Tor Vergata University of Rome, Italy), a dedicated neuroscientist (Ph.D. in Neuroscience at Tor Vergata University and IRCCS Santa Lucia of Rome), and a member of a renowned Netherlands group (senior researcher at Professor Swaab Laboratory of the Netherlands Institute for Neuroscience, Amsterdam, Netherlands), working in the field of brain function and diseases. She is particularly involved in the study of natural compounds, such as neurosteroids and their biosynthetic pathways in neurodegenerative and neuroinflammation- related disorders, working on post-mortem human brains. This editorial outlines Dr. Luchetti's wide range of interests, discloses her superior fund of knowledge, and recollects her humanitarian spirit, all of which contribute to creating a great sense of belonging to any group of researchers whom she worked with. The impact of Dr. Luchetti's work will continue to be felt for many years. From the bench to the bedside, her work has indirectly contributed to shedding light on the neurosteroids' potential therapeutic effects, considering that neurosteroids and their analogues (some of which are over-the-counter) are now used to treat depression, epilepsy, and substance abuse disorders. Moreover, the potential therapeutic effects of allopregnanolone with respect to its capability to promote neuroregeneration and neuroprotection are a promising basis for future treatment of neurodegenerative diseases.

Social neuroscience: Primate research goes wireless.

A new study leads the way to a more ethical and ethologically meaningful way of investigating brain functions of complex behaviors in social animals.