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.

NANO.PTML model for read-across prediction of nanosystems in neurosciences. computational model and experimental case of study.

Neurodegenerative diseases involve progressive neuronal death. Traditional treatments often struggle due to solubility, bioavailability, and crossing the Blood-Brain Barrier (BBB). Nanoparticles (NPs) in biomedical field are garnering growing attention as neurodegenerative disease drugs (NDDs) carrier to the central nervous system. Here, we introduced computational and experimental analysis. In the computational study, a specific IFPTML technique was used, which combined Information Fusion (IF) + Perturbation Theory (PT) + Machine Learning (ML) to select the most promising Nanoparticle Neuronal Disease Drug Delivery (N2D3) systems. For the application of IFPTML model in the nanoscience, NANO.PTML is used. IF-process was carried out between 4403 NDDs assays and 260 cytotoxicity NP assays conducting a dataset of 500,000 cases. The optimal IFPTML was the Decision Tree (DT) algorithm which shown satisfactory performance with specificity values of 96.4% and 96.2%, and sensitivity values of 79.3% and 75.7% in the training (375k/75%) and validation (125k/25%) set. Moreover, the DT model obtained Area Under Receiver Operating Characteristic (AUROC) scores of 0.97 and 0.96 in the training and validation series, highlighting its effectiveness in classification tasks. In the experimental part, two samples of NPs (Fe3O4_A and Fe3O4_B) were synthesized by thermal decomposition of an iron(III) oleate (FeOl) precursor and structurally characterized by different methods. Additionally, in order to make the as-synthesized hydrophobic NPs (Fe3O4_A and Fe3O4_B) soluble in water the amphiphilic CTAB (Cetyl Trimethyl Ammonium Bromide) molecule was employed. Therefore, to conduct a study with a wider range of NP system variants, an experimental illustrative simulation experiment was performed using the IFPTML-DT model. For this, a set of 500,000 prediction dataset was created. The outcome of this experiment highlighted certain NANO.PTML systems as promising candidates for further investigation. The NANO.PTML approach holds potential to accelerate experimental investigations and offer initial insights into various NP and NDDs compounds, serving as an efficient alternative to time-consuming trial-and-error procedures.

Neuroethology: Fear outside the box.

Behavioral neuroscience has successfully and in great detail deconstructed circuit mechanisms underlying fear behaviors using reductionist approaches. Recent research in more naturalistic settings now reveals additional higher-level organization, where hypothalamic circuits multiplex threat detection and fear memory updating to safely navigate complex environments.

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.

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.

Transitions in development - an interview with Ariel Waisman.

Ariel Waisman is a CONICET Junior Researcher in the Laboratory of Applied Research in Neurosciences at FLENI in Buenos Aires, Argentina. Ariel's group studies gene regulatory networks in human pluripotent stem cells to address mechanisms of development and cardiac differentiation, among other topics. We spoke to Ariel over Teams to learn more about his career path, the research interests in his group, and the challenges faced by researchers in Argentina and the Global South.

[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.

Pain neuroscience education improves post-traumatic stress disorder, disability, and pain self-efficacy in veterans and service members with chronic low back pain: Preliminary results from a randomized controlled trial with 12-month follow-up.

Post-traumatic stress disorder (PTSD) and chronic low back pain (CLBP) are frequently co-morbid. Some research suggests that PTSD and CLBP may share common neurobiological mechanisms related to stress. Traditional biomedical education may be ineffective for PTSD and CLBP, especially when co-morbid. The purpose of this study is to determine if pain neuroscience education (PNE) is more effective than traditional education in reducing PTSD, disability, pain, and maladaptive beliefs in patients with CLBP. Participants with CLBP and possible PTSD/PTSD-symptoms were recruited for this study. Participants were randomly allocated to a PNE group or a traditional education group. The intervention included 30 minutes of education followed by a standardized exercise program once a week for 4-weeks with a 4 and 8-week follow-up and healthcare utilization assessed at 12-months. Forty-eight participants consented for this research study with 39 allocated to treatment (PNE n = 18, traditional n = 21). PNE participants were more likely to achieve a clinically meaningful reduction in PTSD symptoms and disability at short-term follow-up. At 12-months, the PNE group utilized healthcare with 76% lower costs. In participants with CLBP, PNE may reduce hypervigilance toward pain and improve PTSD symptoms. Participants who received PNE were more confident body-tissues were safe to exercise. These beliefs about pain could contribute to a decrease in perceived disability and healthcare consumption for CLBP.

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.

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.