The human brain: Medicine's last frontier.

Exploring magneto-electric nanoparticles (MENPs): a platform for implanted deep brain stimulation

During the past 2 decades, the elucidation of susceptibility and causative genes for Alzheimer disease as well as proteins involved in the pathogenic process has greatly facilitated the development of genetically altered mouse models. These models have played a major role in defining critical disease-related mechanisms and in evaluating novel therapeutic approaches, with many treatments currently in clinical trial owing their origins to studies initially performed in mice. This review discusses the utility of transgenic mice as a research tool and their contributions to our understanding of Alzheimer disease.

Noninvasive brain modulation (NBM) is such a stimulation technique that uses electric or magnetic fields to non-intrusively stimulate the central nervous system (CNS). Common NBM modalities include transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). TMS usually uses pulsed fields of 1–4 Tesla in intensity with duration less than a millisecond to stimulate brain. Such strong field is sufficient to directly evoke action potentials in relevant neural tissue, which is referred as to suprathreshold field. Unlike TMS, tDCS delivers weak constant current of 0.5–2 mA in intensity to stimulate human cortex by means of a pair of electrode pads placed on the scalp. Such weak stimulus is unable to excite neural tissue to initiate action potentials, which is referred as to subthreshold fields. Nowadays, NBM has become a promising option for the treatment, diagnosis, and rehabilitation of a number of neurologic or psychiatric disorders in clinics, such as, epilepsy, schizophrenia, Alzheimer’s disease, depression, Parkinson’s disease, stroke, as well as pain syndromes. What is more, it is also a common tool used to study brain physiology and function, which has great potentials in exploring cognitive, emotion, memory, attention, learning, perception, language, and plasticity. As a noninvasive method of intervening brain activities, the NBM technique has significantly promoted the developments of cognitive science, neurophysiology, neurology and psychiatry in recent years. Although NBM has been widely and successfully applied in clinics and basic researches, it is still largely unknown how it interacts with CNS and modulates brain function. Such insufficient understanding of the potential mechanisms underlying NBM would delay the design of more effective stimulator as well as limit the development and optimization of stimulation protocols. One common principle for NBM techniques is that they modulate neural activity and ultimately behavior through the generation of extracellular electric fields around the interested brain tissue. According to this principle, two key problems should be considered when we are probing how NBM participates in brain activity and function. One is to determine the characteristics of extracellular fields generated in the brain tissue during stimulation. The common method for addressing this problem is finite element analysis. The other one is to investigate how this induced field modulates neural activity to alter brain function and ultimately behavior. The focus of recent researches associated with this problem is to identify the spiking behaviors of neural system stimulated by electric fields as well as to explore the biophysical basis for their generation. In this paper, we first introduce the application status of NBM in neuroscience and clinics. Then, we review the main findings on the neuromodulation effects of electric field, including electrophysiological experiment and computational modeling simulation. Finally, we raise several key issues that need to be addressed in the future.

Neuroimaging is a powerful and innovative tool for studying the pathology of psychiatric and neurological diseases and, more recently, for studying the drugs used in their treatment. Technological advances in imaging have made it possible to noninvasively extract information from the human brain regarding a drug's mechanism and site of action. Until now, our understanding of human brain pharmacology has depended primarily on indirect assessments or models derived from animal studies. However, the advent of multiple techniques for human brain imaging allows researchers to focus directly on human pharmacology and brain function. In this review article, our PET studies on the histaminergic neuron system were presented as an example. We have developed and used the PET techniques for 10 years in order to examine the H1 receptors in the living human brain. This review outlines available PET techniques and examines how these various methods have already been applied to the drug development process and neuropharmacology in the living human brain.

Epigenetic regulation is a level of transcriptional regulation that occurs in addition to the genetic programming found in biological systems. In the brain, the epigenetic machinery gives the system an opportunity to adapt to a given environment to help not only the individual but also the species survive and expand. However, such a regulatory system has risks, as mutations resulting from epigenetic regulation can cause severe neurological or psychiatric disorders. Here, we review the most recent findings regarding the epigenetic mechanisms that control the activitydependent gene transcription leading to synaptic plasticity and brain function and the defects in these mechanisms that lead to neurological disorders. A search was carried out systematically, searching all relevant publications up to June 2017, using the PubMed search engine. The following keywords were used: “activity induced epigenetic,” “gene transcription,” and “neurological disorders.” Awide range of studies focused on the roles of epigenetics in transgenerational inheritance, neural differentiation, neural circuit assembly and brain diseases. Thirty-one articles focused specifically on activity-induced epigenetic modifications that regulated gene transcription and memory formation and consolidation. Activity-dependent epigenetic mechanisms of gene expression regulation contribute to basic neuronal physiology, and defects were associated with an elevated risk for brain disorders.

Electrolytes Disturbances and Seizures

Hundreds of proteins determine the function of synapses, and synapses define the neuronal circuits that subserve myriad brain, cognitive, and behavioral functions. It is thus necessary to precisely manipulate specific proteins at specific sub-cellular locations and times to elucidate the roles of particular proteins and synapses in brain function. We developed PHOtochemically TArgeting Chimeras (PHOTACs) as a strategy to optically degrade specific proteins with high spatial and temporal precision. PHOTACs are small molecules that, upon wavelength-selective illumination, catalyze ubiquitylation and degradation of target proteins through endogenous proteasomes. Here, we describe the design and chemical properties of a PHOTAC that targets Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα), which is abundant and crucial for the baseline synaptic function of excitatory neurons. We validate the PHOTAC strategy, showing that the CaMKIIα-PHOTAC is effective in mouse brain tissue. Light activation of CaMKIIα-PHOTAC removed CaMKIIα from regions of the mouse hippocampus only within 25 μm of the illuminated brain surface. The optically controlled degradation decreases synaptic function within minutes of light activation, measured by the light-initiated attenuation of evoked field excitatory postsynaptic potential (fEPSP) responses to physiological stimulation. The PHOTACs methodology should be broadly applicable to other key proteins implicated in synaptic function, especially for evaluating their precise roles in the maintenance of long-term potentiation and memory within subcellular dendritic domains.

Advanced computational models and simulations to unravel the complexities of brain function have known a growing interest in recent years in the field of neurosciences, driven by significant technological progress in computing platforms. Multicompartment models, which capture the detailed morphological and functional properties of neural circuits, represent a significant advancement in this area providing more biological coherence than single compartment modeling. These models serve as a cornerstone for exploring the neural basis of sensory processing, learning paradigms, adaptive behaviors, and neurological disorders. Yet, the high complexity of these models presents a challenge for their real-time implementation, which is essential for exploring alternative therapies for neurological disorders such as electroceutics that rely on biohybrid interaction. Here, we present an accessible, user-friendly, and real-time emulator for multicompartment Hodgkin-Huxley neurons on SoC FPGA. Our system enables real-time emulation of multicompartment neurons while emphasizing cost-efficiency, flexibility, and ease of use. We showcase an implementation utilizing a technology that remains underrepresented in the current literature for this specific application. We anticipate that our system will contribute to the enhancement of computation platforms by presenting an alternative architecture for multicompartment computation. Additionally, it constitutes a step toward developing neuromorphic-based neuroprostheses for bioelectrical therapeutics through an embedded real-time platform running at a similar timescale to biological networks.

Background. Over-stimulation of the purinergic P2X7 receptor may bring about cellular dysfunction and injury in settings of neurodegeneration, chronic inflammation, as well as in psychiatric and cardiovascular diseases. Here we speculate how P2X7 receptor over-activation may lead to the co-occurrence of neurological and psychiatric disorders with cardiovascular disorders. Presentation. We hypothesize that proinflammatory cytokines, in particular interleukin-1β, are key players in the pathophysiology of neurological, psychiatric, and cardiovascular diseases. Critically, this premise is based on a role for the P2X7 receptor in triggering a rise in these cytokines. Given the broad distribution of P2X7 receptors in nervous, immune, and vascular tissue cells, this receptor is proposed as central in linking the nervous, immune, and cardiovascular systems. Testing. Investigate, retrospectively, whether a bidirectional link can be established between illnesses with a proinflammatory component (e.g., inflammatory and chronic neuropathic pain) and cardiovascular disease, for example, hypertension, and whether patients treated with anti-inflammatory drugs have a lower incidence of disease complications. Positive outcome would indicate a prospective study to evaluate therapeutic efficacy of P2X7 receptor antagonists. Implications. It should be stressed that sufficient direct evidence does not exist at present supporting our hypothesis. However, a positive outcome would encourage the further development of P2X7 receptor antagonists and their application to limit the co-occurrence of neurological, psychiatric, and cardiovascular disorders.

Jim Beauregard, a clinical neuropsychologist specializing in geriatric neuropsychology, from his clinical experience in geropsychiatry and as a postgraduate teacher in the areas of Biological Bases of Behavior, Ethics, Aging, and Educational Neuroscience, offers us this interesting work, which boldly delves into the field of neuroethics. Is it necessary to establish an ethical framework in the context of the dizzying advances that are being observed in the field of neuroscience? What ethical challenges do the new possibilities of intervention on the human brain, its functioning, and the alteration of its capacities pose? Can biomedical research intervene without limits in the cognitive functions of the human brain, at the beginning or end of life, in vegetative or minimally conscious states? What relationship should be established between brain, mind, and personal identity? How would interventions on the human brain affect personal dignity?

Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, and Neuroimaging Advancing the Field of Neurology.

INTRODUCTION AND AIM OF WORK One of the key factors shaping human health is diet. It serves as the foundation for the functioning of cells, organs, and the entire body. Properly chosen food has an impact, among other things, on the functioning of the immune, digestive, and cardiovascular systems. MATERIALS AND METHODS The objective of this study is to analyze the changes in the functioning of the cardiovascular, digestive, and immune systems through the application of different dietary approaches. For this purpose, an original questionnaire was developed. The questionnaire was distributed via social media (Telegram platform) in August 2023 among the population of Ukraine. RESULTS We collected a total of 94 surveys, with an average participant age of 26 years. A similar number of participants indicated consuming meals 3 times, 4 times, or 5 times a day. These were 23 individuals (24.47%), 25 individuals (26.6%), and 21 individuals (22.3%) respectively. The analysis of correlations revealed a negative correlation between the frequency of meal consumption and the frequency of infections (r = -0.21, p = 0.035). A significant relationship was also observed between body weight and the frequency of meal consumption (r = 0.34, p < 0.001). However, no significant relationship was found between following a special diet and body weight (p > 0.05). CONCLUSIONS The collected results suggest a connection between dietary habits and the frequency of infections as well as body weight. Interestingly, this relationship was related specifically to the frequency of meal consumption and was not linked to the intake of specific food groups. The obtained results highlight the significance of regular meal consumption in maintaining a healthy body weight and reducing the frequency of infections.

The midline thalamus is critical for flexible cognition, memory, and stress regulation in humans and its dysfunction is associated with several neurological and psychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. Despite the pervasive role of the midline thalamus in cognition and disease, there is a limited understanding of its function in humans, likely due to the absence of a rigorous noninvasive neuroimaging methodology to identify its location. Here, we introduce a new method for identifying the midline thalamus in vivo using probabilistic tractography and k-means clustering with diffusion weighted imaging data. This approach clusters thalamic voxels based on data-driven cortical and subcortical connectivity profiles and then segments the midline thalamus according to anatomical connectivity tracer studies in rodents and macaques. Results from two different diffusion weighted imaging sets, including adult data (22-35years) from the Human Connectome Project (n = 127) and adolescent data (9-14years) collected at Florida International University (n = 34) showed that this approach reliably classifies midline thalamic clusters. As expected, these clusters were most evident along the dorsal/ventral extent of the third ventricle and were primarily connected to the agranular medial prefrontal cortex (e.g., anterior cingulate cortex), nucleus accumbens, and medial temporal lobe regions. The midline thalamus was then bisected based on a human brain atlas into a dorsal midline thalamic cluster (paraventricular and paratenial nuclei) and a ventral midline thalamic cluster (rhomboid and reuniens nuclei). This anatomical connectivity-based identification of the midline thalamus offers the opportunity for necessary investigation of this region in vivo in the human brain and how it relates to cognitive functions in humans, and to psychiatric and neurological disorders.

Adult neurogenesis: implications for psychiatry

Post-mortem analysis of CNS tissue was the gold-standard in the diagnosis of neurologic and psychiatric diseases in former times. This resulted in the storage of hundreds of thousands of precisely catalogued brain tissue specimens at our institute. As a first approach towards using these specimens for modern reanalysis, we identified 62 patients with clinical definite or probable Amyotrophic Lateral Sclerosis (ALS). After diagnostic verification, we successfully established modified methods for the isolation of genomic DNA from formalin-fixed, paraffin-embedded (FFPE) CNS tissue from glass object carriers. Despite the strong grade of DNA degradation and fragmentation, we were able to detect a variety of single nucleotide polymorphisms (SNP) which were shown to be significantly associated with ALS in recent genome-wide association studies (GWAS). 11 SNPs seem to show potential significant association in our patient sample compared to 123 neurologically healthy controls with 3 SNPs bearing p-values < 0.01. However, call rates differed to a considerable degree given the low quality of the preserved nucleic acids. Additionally, we work on standardized methods for the isolation and detection of small non-coding RNAs to take advantage of the easily accessable brain tissue. Our MPI-P historic brain bank offers unique opportunities not only for the verification but also for the discovery of new biomarkers in psychiatric or neurologic diseases.