Advanced Brain Function Research Articles

Introducing BRAINOER: The Behavioral Research and Interdisciplinary Neuroscience Open Educational Repository.

Foundational textbooks for neuroscience courses can be cost-prohibitive for students and may omit recent advances in the field. Therefore, an Open Educational Resource (OER) repository was curated using existing OER materials for use in behavioral neuroscience and physiology courses. The Behavioral Research and Interdisciplinary Neuroscience Open Educational Repository (BRAINOER) contains 9 modules that include the following foundational topics: (1) The Brain and Nervous System, (2) Neurons, (3) The Endocrine System, (4) Neurotransmitters and Psychopharmacology, (5) Motor Processing, (6) Advanced Brain Functions, (7) Sensation and Perception, (8) Genetics and Evolution, (9) Research, Design, and Methods. Each module contains learning objectives in a checklist format, and modules are divided into basic and advanced content where appropriate. Because the repository is divided into content modules, the materials can be used as a full-curriculum or assigned on a module-by-module basis.

Deciphering brain cellular and behavioral mechanisms: Insights from single-cell and spatial RNA sequencing.

The brain is a complex computing system composed of a multitude of interacting neurons. The computational outputs of this system determine the behavior and perception of every individual. Each brain cell expresses thousands of genes that dictate the cell's function and physiological properties. Therefore, deciphering the molecular expression of each cell is of great significance for understanding its characteristics and role in brain function. Additionally, the positional information of each cell can provide crucial insights into their involvement in local brain circuits. In this review, we briefly overview the principles of single-cell RNA sequencing and spatial transcriptomics, the potential issues and challenges in their data processing, and their applications in brain research. We further outline several promising directions in neuroscience that could be integrated with single-cell RNA sequencing, including neurodevelopment, the identification of novel brain microstructures, cognition and behavior, neuronal cell positioning, molecules and cells related to advanced brain functions, sleep-wake cycles/circadian rhythms, and computational modeling of brain function. We believe that the deep integration of these directions with single-cell and spatial RNA sequencing can contribute significantly to understanding the roles of individual cells or cell types in these specific functions, thereby making important contributions to addressing critical questions in those fields. This article is categorized under: RNA Evolution and Genomics > Computational Analyses of RNA RNA in Disease and Development > RNA in Development RNA in Disease and Development > RNA in Disease.

Knowledge atlas of white matter microstructure: a bibliometric analysis.

White matter microstructure is valued for being an indicator of neural network integrity, which plays an indispensable role in the execution of advanced brain functions. Although the number of publications has increased in the past 10 years, no comprehensive analysis has yet been conducted of this field. Therefore, this study aimed to identify the research hotspots and trends in research on white matter microstructure using a bibliometric analysis of the related literature published from 2013 to 2022. VOSviewer and CiteSpace were used to objectively analyze the research articles concerning white matter microstructure, which were retrieved from the Web of Science Core Collection (WoSCC). A total of 5,806 publications were obtained, with the number of published articles increasing annually over the past decade. The United States, China, the United Kingdom, and Canada maintained the top positions worldwide and had strong cooperative relationships. The top institution and journal were Harvard Medical School and Neuroimage, respectively. Alexander Leemans, Marek Kubicki, and Martha E Shenton were the most productive authors. Thematic keywords mainly included "diffusion tensor imaging" (DTI), "white matter integrity", and "connectivity". The keyword analysis revealed that DTI has a critical role in detecting white matter microstructure integrity and that fractional anisotropy is the main parameter in the assessment process. Keyword burst detection identified four research hotspots: movement, distortion correction, voxelwise analysis, and fixel-based analysis. This bibliometric analysis provided a systematic understanding of the research on white matter microstructure and identified the current frontiers. This may help clinicians and researchers comprehensively identify hotspots and trends in this field.

Epigenetic and transcriptional landscapes during cerebral cortex development in a microcephaly mouse model

The cerebral cortex is a pivotal structure integral to advanced brain functions within the mammalian central nervous system. DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development. However, it remains unclear whether abnormal cerebral cortex development, such as microcephaly, could rescale the epigenetic landscape, potentially contributing to dysregulated gene expression during brain development. In this study, we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type (WT) mice and Mcph1 knockout (Mcph1-del) mice with severe microcephaly. Intriguingly, we discover a global reduction of 5′-hydroxymethylcytosine (5hmC) level, primarily in TET1-binding regions, in Mcph1-del mice compared to WT mice during juvenile and adult stages. Notably, genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions. Additionally, genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage. These findings reveal that aberrant cerebral cortex development in the early stages profoundly alters the epigenetic regulation program, which provides unique insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.

JS05.6.A CONTINUOUS DYNAMIC MAPPING OF LANGUAGE FUNCTION AND COGNITIVE CONTROL AND SPATIAL CORRELATION TO WHITE MATTER TRACTS USING INTRAOPERATIVE MRI TRACTOGRAPHY

Abstract BACKGROUND Subcortical mapping of white matter tracts (WMTs) subserving complex processes as movement, language and cognition is critical in glioma surgery. Continuous dynamic mapping (CDM) is an indispensable tool for mapping of the corticospinal tract (CST). There is, however, no widespread method for CDM of more advanced brain functions. MATERIAL AND METHODS Patients undergoing awake craniotomy for diffuse gliomas at the Oslo University Hospital with the use of neuronavigation, diffusion tensor imaging (DTI) and CDM coupled with structured evaluation as well as intraoperative magnetic resonance imaging (iMRI) were included in a retrospective analysis. Subcortical CDM was conducted when resection became close to the arcuate fasciculus (AF) and the frontal aslant tract (FAT) with clinical testing using language paradigms and Stroop task. The current was delivered through a monopolar suction probe applying a modified Taniguchi technique with short train of pulses. The spatial relationship between the stimulation response and the examined tracts was determined by measuring the shortest distance between the resection cavity and the relevant white matter tracts (WMTs) using iMRI DTI. RESULTS Twenty IDH-mutant and eight IDH wild type gliomas operated 2021-2023 were included in the analysis. Subcortical CDM of the AF and the FAT proved to be amenable as both language function and the ability to perform Stroop test were affected when the stimulation site gradually became close (< 1 cm) to the examined tracts. Positive stimulation response was verified by repeat challenge. The stimulation intensity was thereafter reduced in a stepwise fashion when there was a consistent hesitation in the patient’s response. Resection was continued until the tumor border was reached and not beyond the threshold of 3mA. The threshold of stimulation intensity correlated to the minimal distance from the resection cavity to the delineated WMTs. We did not observe any seizure activity induced by CDM. CONCLUSION We have experienced subcortical CDM to be a safe and reliable method, where distance to identified WMT appear to be correlated to the applied stimulation intensity.

Proteomic Analysis Reveals That Mitochondria Dominate the Hippocampal Hypoxic Response in Mice.

Hypoxic stress occurs in various physiological and pathological states, such as aging, disease, or high-altitude exposure, all of which pose a challenge to many organs in the body, necessitating adaptation. However, the exact mechanisms by which hypoxia affects advanced brain function (learning and memory skills in particular) remain unclear. In this study, we investigated the effects of hypoxic stress on hippocampal function. Specifically, we studied the effects of the dysfunction of mitochondrial oxidative phosphorylation using global proteomics. First, we found that hypoxic stress impaired cognitive and motor abilities, whereas it caused no substantial changes in the brain morphology or structure of mice. Second, bioinformatics analysis indicated that hypoxia affected the expression of 516 proteins, of which 71.1% were upregulated and 28.5% were downregulated. We demonstrated that mitochondrial function was altered and manifested as a decrease in NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 expression, accompanied by increased reactive oxygen species generation, resulting in further neuronal injury. These results may provide some new insights into how hypoxic stress alters hippocampal function via the dysfunction of mitochondrial oxidative phosphorylation.

M6A Modification in Mammalian Nervous System Development, Functions, Disorders, and Injuries.

N6-methyladenosine (m6A) modification, as the most prevalent internal modification on mRNA, has been implicated in many biological processes through regulating mRNA metabolism. Given that m6A modification is highly enriched in the mammalian brain, this dynamic modification provides a crucial new layer of epitranscriptomic regulation of the nervous system. Here, in this review, we summarize the recent progress on studies of m6A modification in the mammalian nervous system ranging from neuronal development to basic and advanced brain functions. We also highlight the detailed underlying mechanisms in each process mediated by m6A writers, erasers, and readers. Besides, the involvement of dysregulated m6A modification in neurological disorders and injuries is discussed as well.

The Benefits of Handwriting Class Notes: Neuroanatomy, Mindfulness, and Anecdotal Evidence Supporting Handwritten Notes

Students who take notes by hand are more likely to process the content by summarizing or paraphrasing the material to maximize understanding and recall compared to those who use a keyboard for note taking. The benefits of handwriting notes can be seen not only in student performance but also in the brain itself as measured by high density encephalograms (HD-EEG), which indicate that proficiency in handwriting is associated with advanced brain function. Proficient handwriting is strongly correlated with the quality of writing, the ability to read, the ability to spell, and the ability to compose written documents, all of which are beneficial to students at all grade levels. This article examines the benefits of taking notes in class, the computer versus handwriting for note taking, and the neuroanatomy of the regions of the brain that are triggered by the process of taking handwritten notes. Anecdotal evidence of the value of note taking in class is offered and the role that mindfulness can play in the process of handwriting and reviewing class notes is examined.

A functional assembly framework based on implementable neurobionic material.

Neurobionic material is an emerging field in material and translational science. For material design, much focus has already been transferred from von Neumann architecture to the neuromorphic framework. As it is impractical to reconstruct the real neural tissue solely from materials, it is necessary to develop a feasible neurobionics framework to realize advanced brain function. In this study, we proposed a mathematical neurobionic material model, and attempted to explore advanced function only by simple and feasible structures. Here an equivalent simplified framework was used to describe the dynamics expressed in an equation set, while in vivo study was performed to verify simulation results. In neural tissue, the output of neurobionic material was characterized by spike frequency, and the stability is based on the excitatory/inhibitory proportion. Spike frequency in mathematical neurobionic material model can spontaneously meet the solution of a nonlinear equation set. Assembly can also evolve into a certain distribution under different stimulations, closely related to decision making. Short‐term memory can be formed by coupling neurobionic material assemblies. In vivo experiments further confirmed predictions in our mathematical neurobionic material model. The property of this neural biomimetic material model demonstrates its intrinsic neuromorphic computational ability, which should offer promises for implementable neurobionic device design.

A Study on the Gaze Range Calculation Method During an Actual Car Driving Using Eyeball Angle and Head Angle Information.

Car operation requires advanced brain function. Currently, evaluation of the motor vehicle driving ability of people with higher brain dysfunction is medically unknown and there are few evaluation criteria. The increase in accidents by elderly drivers is a social problem in Japan, and a method to evaluate whether elderly people can drive a car is needed. Under these circumstances, a system to evaluate brain dysfunction and driving ability of elderly people is needed. Gaze estimation research is a rapidly developing field. In this paper, we propose the gaze calculation method by eye and head angles. We used the eye tracking device (TalkEyeLite) made by Takei Scientific Instruments Cooperation. For our image processing technique, we estimated the head angle using the template matching method. By using the eye tracking device and the head angle estimate, we built a system that can be used during actual on-road car operation. In order to evaluate our proposed method, we tested the system on Japanese drivers during on-road driving evaluations at a driving school. The subjects were one instructor of the car driving school and eight general drivers (three 40–50 years old and five people over 60 years old). We compared the gaze range of the eight general subjects and the instructor. As a result, we confirmed that one male in his 40s and one elderly driver had narrower gaze ranges.

Kenyon Cell Subtypes/Populations in the Honeybee Mushroom Bodies: Possible Function Based on Their Gene Expression Profiles, Differentiation, Possible Evolution, and Application of Genome Editing.

Mushroom bodies (MBs), a higher-order center in the honeybee brain, comprise some subtypes/populations of interneurons termed as Kenyon cells (KCs), which are distinguished by their cell body size and location in the MBs, as well as their gene expression profiles. Although the role of MBs in learning ability has been studied extensively in the honeybee, the roles of each KC subtype and their evolution in hymenopteran insects remain mostly unknown. This mini-review describes recent progress in the analysis of gene/protein expression profiles and possible functions of KC subtypes/populations in the honeybee. Especially, the discovery of novel KC subtypes/populations, the “middle-type KCs” and “KC population expressing FoxP,” necessitated a redefinition of the KC subtype/population. Analysis of the effects of inhibiting gene function in a KC subtype-preferential manner revealed the function of the gene product as well as of the KC subtype where it is expressed. Genes expressed in a KC subtype/population-preferential manner can be used to trace the differentiation of KC subtypes during the honeybee ontogeny and the possible evolution of KC subtypes in hymenopteran insects. Current findings suggest that the three KC subtypes are unique characteristics to the aculeate hymenopteran insects. Finally, prospects regarding future application of genome editing for the study of KC subtype functions in the honeybee are described. Genes expressed in a KC subtype-preferential manner can be good candidate target genes for genome editing, because they are likely related to highly advanced brain functions and some of them are dispensable for normal development and sexual maturation in honeybees.

Constant light environment suppresses maturation and reduces complexity of new born neuron processes in the hippocampus and caudal nidopallium of a diurnal corvid: Implication for impairment of the learning and cognitive performance.

Periodic day-night environment shapes the temporal pattern in the behaviour and physiology (e.g. 24-h activity-rest and sleep-wake cycles) and the advanced brain function, such as learning, memory and decision making. In a previous study, we showed the abolition of 24-h rhythm in the activity-rest pattern, and an attenuated cognitive performance in diurnal Indian house crows (Corvus splendens) under constant light (no-night; LL) environment. Present study extended this, and investigated LL-induced effects on the neurogenesis (birth, maturation and neurite complexity of new born neurons) in the hippocampus and caudal nidopallium, the brain regions directly associated with learning and cognition in birds. We performed immunohistochemistry of doublecortin (DCX; a neurogenesis marker) and tyrosine hydroxylase (TH, a key enzyme of the dopamine biosynthesis) in the brain section containing hippocampus or caudal nidopallium of Indian house crows exposed for 2 weeks to LL, with controls maintained under 12L:12D. As expected, crows showed arrhythmicity with a significantly reduced rest period in the 24-h activity-rest pattern, and a decreased cognitive performance when tested for the spatial and pattern association learning tasks under LL. Importantly, there was a significant decrease in DCX-immunoreactive (ir) cells and, as shown by Sholl analysis, in the complexity of DCX-ir neurites in both, the hippocampus and caudal nidopallium of crows under LL, as compared to those under 12L:12D. The anatomical proximity of DCX-ir neurons with TH-ir fibers suggested a functional association of the new born hippocampal and caudal nidopallial neurons with the learning, and perhaps cognition in Indian house crows. These results give insights into possible impact of the loss of night on brain health and functions in an emerging ecosystem in which other diurnal species including humans may be inadvertently exposed to an illuminated night, such as in an overly lighted metropolitan urban habitat.

Effect of no-night light environment on behaviour, learning performance and personality in zebra finches

A periodic day–night environment is critical for daily behavioural patterns and advanced brain functions such as learning and cognition in animals. We investigated whether a no-night light environment would impair these functions in parent and F1 and F2 zebra finches, Taeniopygia guttata . Particularly, we examined song acquisition as a measure of learning, tested cognitive performance with reference to spatial and colour association tasks, and assessed personality with respect to an exploratory trait, first in the parent (P) and subsequently in F1 and F2 birds born and raised under 12:12 h light:dark or constant light (hence no-night, LL) environments. Daily patterns in activity and singing were monitored as circadian response indicators. After initial decay, the rhythmic patterns in daily activity and singing were restored after several weeks in the majority of P and F1 birds under LL; F2 birds displayed robust circadian rhythms in both behavioural patterns under LL. Further, LL decreased participation and performance in cognitive tests and reduced exploratory behaviour in birds from all generations. Overall, we found negative effects of the LL environment on daily behavioural patterns, advanced brain functions (i.e. learning and cognition) and personality in zebra finches when adult and in subsequent generations. These results give insights into the possible impact on animals of night-time illumination such as in an overly lit urban habitat.

Production of Knockout Mutants by CRISPR/Cas9 in the European Honeybee, Apis mellifera L.

The European honeybee (Apis mellifera L.) is used as a model organism in studies of the molecular and neural mechanisms underlying social behaviors and/or advanced brain functions. The entire honeybee genome has been sequenced, which has further advanced molecular biologic studies of the honeybee. Functions of genes of interest, however, remain largely to be elucidated in the honeybee due to the lack of effective reverse genetic methods. Moreover, genetically modified honeybees must be maintained under restricted laboratory conditions due to legal restrictions, further complicating the application of reverse genetics to this species. Here we applied CRISPR/Cas9 to the honeybee to develop an effective reverse genetic method. We targeted major royal jelly protein 1 (mrjp1) for genome editing, because this gene is predominantly expressed in adult workers and its mutation is not expected to affect normal development. By injecting sgRNA and Cas9 mRNA into 57 fertilized embryos collected within 3 h after oviposition, we successfully created six queens, one of which produced genome-edited male offspring. Of the 161 males produced, genotyping demonstrated that the genome was edited in 20 males. All of the processes necessary for producing these genome-edited queens and males were performed in the laboratory. Therefore, we developed essential techniques to create knockout honeybees by CRISPR/Cas9. Our findings also suggested that mrjp1 is dispensable for normal male development, at least till the pupal stage. This new technology could pave the way for future functional analyses of candidate genes involved in honeybee social behaviors.

Differential activation and tyrosine hydroxylase distribution in the hippocampal, pallial and midbrain brain regions in response to cognitive performance in Indian house crows exposed to abrupt light environment

Disruption of the cyclic feature of the day-night environment can cause negative effects on daily activity and advanced brain functions such as learning, memory and decision-making behaviour. These functions in songbirds, including corvids, involve the hippocampus, pallium and midbrain, as revealed by ZENK (a neuronal activation marker) and tyrosine hydroxylase (TH) expressions. TH is rate-limiting marker enzyme of the biosynthesis of dopamine, widely implicated in learning and memory. Here, we measured ZENK and TH immunoreactivity in the hippocampal, pallial and midbrain regions in response to cognitive performance (learning-memory retrieval) tests in Indian house crows (Corvus splendens) exposed to constant light environment (LL) with controls on 12h light:12h darkness. Along with the decay of circadian rhythm in activity behaviour, LL caused a significant decline in the cognitive performance. There was also a decrease under LL in the activity of neurons in the hippocampus, medial and central caudal nidopallium, and hyperpallium apicale, which are widely distributed with TH-immunoreactive fibres. Further, under LL, TH- immunoreactive neurons were reduced in number in midbrain dopamine synthesis sites, the venteral tegmental area (VTA) and substantia nigra (SN), with a negative correlation of co-localized ZENK/TH- immunoreactive cells on errors during the association tasks. These results show decreased activity of learning and memory neural systems, and underscore the role of dopamine in reduced cognitive performance of diurnal corvids with disrupted circadian rhythms under an abrupt light environment.

脑研究的重要机遇: 开展胶质细胞调控大脑高级功能的研究

Exploring the secrets of the brain has long been a dream of neuroscientists. Our brains consist of neurons and glial cells, which comprise approximately 10% and 90% of total brain cells, respectively. During the past century, neurons have been regarded as the leading brain cells responsible for advanced brain functions such as learning and memory, whereas glial cells have been believed to be supporting brain cells providing supportive, nutritional, protective, and clearing contributions to neurons. However, recent studies have revealed novel functions of astroglial cells, the major subtype of glial cells. This review will discuss recent in vitro evidence showing the direct modula-tion of neuronal synaptic transmission by astroglial cells, evaluate the importance of astroglial regulation of sleep, analyze our recent in vivo data published in the 2012 March issue of Cell demonstrating direct regulation of working memory by astroglial cells, and comment on their scientific inspiration: we are now witnessing a crucial time in neuroscience research history in which mankind is starting to explore the active regulation of advanced brain functions by glial cells.

The Urbilaterian genes implicated to underlie the evolution of advanced brain functions

The Urbilaterian genes implicated to underlie the evolution of advanced brain functions

Juvenile zebra finches can use multiple strategies to learn the same song.

Does the ontogeny of vocal imitation follow a set program that, given a target sound, unfolds in a predictable manner, or is it more like problem solving, with many possible solutions? We report that juvenile male zebra finches, Taeniopygia guttata, can master their imitation of the same song in various ways; these developmental trajectories are sensitive to the social setting in which the bird grows up. A variety of vocal developmental trajectories have also been described in infants. Are these many ways to learn unique to the vocal domain or a hallmark of advanced brain function?

Developmental neurotoxicity of dioxin and its related compounds.

This manuscript reviewed the neurotoxicity of dioxins and related compounds with an emphasis on maternal exposure. The brain during developmental period is thought to be highly sensitive to dioxin and its related compounds that affect a broad range of brain functions from the advanced brain function to the reproduction-controlling function, even at low doses. It is suggested that dioxins exhibit endocrine-disrupting action on the gonadal and thyroid hormone axes, as well as the 'neural-disrupting action' on neural transmission and neural network formation. From behavioral toxicological studies as well as studies on the underlying mechanisms of dioxins' toxicity, dioxins affect some specific functions in particular regions or cells of the brain at critical windows during the developmental period.