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Optogenetics is a powerful technique that allows target-specific spatiotemporal manipulation of neuronal activity for dissection of neural circuits and therapeutic interventions. Recent advances in wireless optogenetics technologies have enabled investigation of brain circuits in more natural conditions by releasing animals from tethered optical fibers. However, current wireless implants, which are largely based on battery-powered or battery-free designs, still limit the full potential of in vivo optogenetics in freely moving animals by requiring intermittent battery replacement or a special, bulky wireless power transfer system for continuous device operation, respectively. To address these limitations, here we present a wirelessly rechargeable, fully implantable, soft optoelectronic system that can be remotely and selectively controlled using a smartphone. Combining advantageous features of both battery-powered and battery-free designs, this device system enables seamless full implantation into animals, reliable ubiquitous operation, and intervention-free wireless charging, all of which are desired for chronic in vivo optogenetics. Successful demonstration of the unique capabilities of this device in freely behaving rats forecasts its broad and practical utilities in various neuroscience research and clinical applications., Although wireless optogenetic technologies enable brain circuit investigation in freely moving animals, existing devices have limited their full potential, requiring special power setups. Here, the authors report fully implantable optogenetic systems that allow intervention-free wireless charging and controls for operation in any environment.

This chapter provides a broad overview of the major findings in the neuroscience of navigation to date. It focuses on two issues: how specialized spatial cells located throughout the brain represent an organism's location in and movement through an environment and the roles of different brain areas and neural networks involved in accomplishing navigational tasks. Much of early neuroscience research has been guided by the principle of localization of function in which particular mental processes or representations are linked to specific brain areas. In the study of navigation, this led to a strong focus on the identification of the neural systems underlying egocentric representations and those responsible for allo‐centric representations. The chapter concludes with a discussion of the limitations of the work conducted to date and the challenges for the field in understanding how the brain accomplishes large‐scale navigation in natural environments.

Ion activities are tightly associated with brain physiology, such as intracranial cell membrane potential, neural activity and neuropathology. Thus, monitoring the ion levels in the brain is of great significance in neuroscience research. Recently, nanosensors have emerged as powerful tools for monitoring brain ion levels and dynamics. With controllable structures and functions, nanosensors have been intensively used for monitoring neural activity and cell function and can be used in disease diagnosis. Here, we summarize the recent advances in the design and application of ion level nanosensors at different physiological levels, aiming to draw a connection of the interrelated intracranial ion activities. Furthermore, perspectives on the rationally designed ion level nanosensors in understanding the brain functions are highlighted.

Implantable neural devices are the most widely applied tools in neuroscience research as well as neuroprosthetics to record neural signal activities at single‐neuron and sub‐millisecond resolution. However, lack of mechanical compatibility between the traditional rigid probes and brain tissues causes neuroinflammatory responses and deteriorate recorded signal quality. Decreasing the cross‐sectional area while improving flexibility of the probes can significantly enhance the chronic stability of neural interfaces. Additionally, magnetic resonance imaging (MRI) compatibility is another issue that should be addressed for the development of future implantable devices. Herein, current advancement in developing the chronically stable implantable neural devices is highlighted, with a emphasis on making use of the sophisticated materials and structural design concepts.

Recent advances in cancer neuroscience necessitate the systematic analysis of neural influences in cancer as potential therapeutic targets in oncology. Here, we outline recommendations for future preclinical and translational research in this field.

Interest in deciphering the fundamental mechanisms and processes of the human mind represents a central driving force in modern neuroscience research. Activities in support of this goal rely on advanced methodologies and engineering systems that are capable of interrogating and stimulating neural pathways, from single cells in small networks to interconnections that span the entire brain. Recent research establishes the foundations for a broad range of creative neurotechnologies that enable unique modes of operation in this context. This review focuses on those systems with proven utility in animal model studies and with levels of technical maturity that suggest a potential for broad deployment to the neuroscience community in the relatively near future. We include a brief summary of existing and emerging neuroscience techniques, as background for a primary focus on device technologies that address associated opportunities in electrical, optical and microfluidic neural interfaces, some with multimodal capabilities. Examples of the use of these technologies in recent neuroscience studies illustrate their practical value. The vibrancy of the engineering science associated with these platforms, the interdisciplinary nature of this field of research and its relevance to grand challenges in the treatment of neurological disorders motivate continued growth of this area of study.

Emotionally significant experiences tend to be well remembered in learning Mathematics in the classroom. Recent advances in neuroscientific methods have led to an increased understanding of the neural mechanisms underlying emotions in learning mathematics. The aim of this research is to use neuroscience research perspectives in classroom setting involving students’ emotion in learning Mathematics and its relationship with memory. Therefore, this research examined how students’ emotions in learning Mathematics and its relationship with their memory using mixed–method design. Data from survey (n= 644) and interview informants (n= 6) indicated positive emotions (enjoyment, hope, pride) negative emotions (shame, anger, boredom, anxiety) and memory. Students who accurately identified positive emotions indicated they were more likely to learn Mathematics compared to negative emotions, and findings indicated a strong, positive correlation between positive emotions and memory. Qualitative findings indicated that students who are more likely prefer positive emotions in learning could lead to better memory compared to negative emotions. Moreover, interview data showed that memory performance in Mathematics increased when teacher has embedded positive emotions through the use of humor in teaching, inspiring student with positive words and engaging student in classroom. This study supports neuroscience research findings that positive emotions influence students' memory in learning mathematics. Thus, this study provides insight for teachers to emphasize the importance of positive emotions in learning mathematics as well as reduce negative emotions.

Research driven solely by curiosity and the desire to understand fundamental principles of brain function. The freedom to address important questions with bold, sometimes risky experiments. A platform for open scientific exchange and discussions at highest academic level to provide new impulses to the field. And a growing number of scientists who share the passion for neuroscience and who join forces to tackle some of the big mysteries that surround the brain. These visions together with the deep conviction that basic research is the fundament needed for any progress in applied science motivated Dr. Armin Schram to create the foundation that carries his name. They are also the ideals that the foundation still pursues, and to date, 26 research proposals designed by individual researchers or small teams have been, or are, supported in this spirit. Here, we introduce the reader to the individual scientists who were awarded grants by the Schram Foundation over the years, highlight some of the many discoveries made in the course of their studies and list some of the key publications that arose from this work.

Purpose of Review Review of US medical and recreational marijuana laws (MML and RML), their effects on cannabis potency, prevalence of non-medical cannabis use and cannabis use disorder (CUD) in adolescents and adults, and implications for neuroscience research, given what is known about the relationship of cannabis to neurocognitive impairments and underlying brain functioning. Recent Findings Cannabis potency may be increasing faster in states with MML or RML than in other states. MML and RML have not impacted prevalence in adolescents but have consistently been shown to increase rates of adult non-medical use and CUD. Summary Recent neurocognitive or neuroimaging studies may be more impacted by cannabis than studies conducted when MML and RML were less common. Neurocognitive or neuroimaging studies conducted in MML or RML states should carefully test potential participants for recent cannabis use. More research is needed on cannabis and cognition in medical marijuana patients.

The formation of the nervous system and its striking complexity is a remarkable feat of development. C. elegans served as a unique model to dissect the molecular events in neurodevelopment, from its early visionaries to the current booming neuroscience community. Soon after being introduced as a model, C. elegans was mapped at the level of genes, cells, and synapses, providing the first metazoan with a complete cell lineage, sequenced genome, and connectome. Here, I summarize mechanisms underlying C. elegans neurodevelopment, from the generation and diversification of neural components to their navigation and connectivity. I point out recent noteworthy findings in the fields of glia biology, sex dimorphism and plasticity in neurodevelopment, highlighting how current research connects back to the pioneering studies by Brenner, Sulston and colleagues. Multifaceted investigations in model organisms, connecting genes to cell function and behavior, expand our mechanistic understanding of neurodevelopment while allowing us to formulate emerging questions for future discoveries.

Optical control of neural ensemble activity is crucial for understanding brain function and disease, yet no technology can achieve optogenetic control of very large numbers of neurons at extremely fast rate over a large volume. State-of-the-art multiphoton holographic optogenetics requires high power illumination that only addresses relatively small populations of neurons in parallel. Conversely, one-photon holographic techniques can stimulate more neurons with 2-3 orders lower power, but with a trade-off between resolution and addressable volume. Perhaps most problematically, two-photon holographic optogenetic systems are extremely expensive and sophisticated which has precluded their broader adoption in the neuroscience community. To address this technical gap, we introduce a new one-photon light sculpting technique, Three- Dimensional Multi-site random Access Photostimulation (3D-MAP), that overcomes these limitations by modulating light dynamically, both in the spatial and in the angular domain at multi-kHz rates. We use 3D-MAP to interrogate neural circuits in 3D and demonstrate simultaneous photostimulation and imaging of dozens of user-selected neurons in the intact mouse brain in vivo with high spatiotemporal resolution. 3D-MAP could be broadly adopted for high-throughput all-optical interrogation of brain circuits owing to its powerful combination of scale, speed, simplicity, and cost.

Recent years have seen a substantial increase in the amount of research concerning sex/gender differences in the human brain. In this chapter, we review and synthesize some key research findings concerning sex/gender differences in brain structure, brain function, and structural/functional connectivity. In light of the findings, we concluded that although sex/gender differences in the brain exist at multiple levels, results in some areas are inconsistent, partly because the large inter- and intra-individual variability within each sex/gender has not been sufficiently considered. Consequently, neuroscience research should routinely include both men and women. Moreover, concepts referring to “male brain”, “female brain” or “sexual dimorphism” are outdate and incorrect, and therefore should be avoided in the neuroscientific literature. Finally, neuroscientists with a focus on sex/gender difference should adopt a psychobiosocial approach whenever possible, because structural and functional differences in the brains of men and women will never be fully understood, if psychological, biological and environmental/social factors are not routinely taken into account in combination.

Background: Veterans with chronic spinal cord injury usually have various comorbidities. They are, therefore, visited by different doctors and use different medications. It is necessary to monitor the health of these veterans. One of the important issues in this regard is the attention to drug interactions. The purpose of this study was to investigate the drugs used and their interactions.Methods: This descriptive study of the cross-sectional studies was carried out retrospectively in 2015 under the Shefa Neuroscience Research Center’s supervision, examining the medical records of veterans with spinal cord injury participating in the health screening program at Khatam Alanbiya hospital in Tehran. Demographic data, comorbidities, used drugs, and the level of involvement collected. According to the FDA, drug interactions among the drugs used for each patient has evaluated and classified into three severe, moderate, and weak groups. SPSS v. 21 analyzed data.Results: The study population consisted of 404 men, ranging in age from 41 to 74, with a mean of 51.6 ± 6.4 years. One hundred forty-two of them (35.1%) had a complete injury, and 262 veterans (64.8%) had an incomplete injury. Only 17 veterans (4.2%) had no drug interactions. The number of drug interactions varied from 1 to 38, with an average of 5.9 ± 12.8 interactions per patient. The total number of interactions was 2856, of which 32.5% were weak, 55.3% moderate, and 12.2% severe, with a 95% confidence interval. Among the severe drug interactions in the study, the highest number belonged to the antidepressant drugs.Conclusion: This study highlights the necessity of developing a strategy for investigating and preventing drug interactions in veterans with chronic spinal cord injury. It has recommended that physicians pay more attention to other medications used by the patient and prescribe as little as possible of the drug and the drug with the least number of interactions.

How fundamentally different do people generally think men and women are? Gender essentialism refers to beliefs that women and men have distinct, innate, and fixed biological essences that differentiate them from each other. Exposure to popularized neuroscience research may shape such views. We examined whether exposure to scientific evidence for gender differences or similarities in the brain affects beliefs about gender essentialism, and indirectly shapes sexism and justification of gender inequality, using samples from Turkey. Study 1 (n = 414 undergraduates) showed that exposure to evidence on brain similarities led to lower gender essentialist beliefs, which, in turn, negatively predicted sexism and justification of gender inequality. Unexpectedly, exposure to evidence on gender differences did not lead to an increase in gender essentialist beliefs. Although men scored higher than women on all measures, the indirect effects were significant for both men and women. In Study 2 (n = 119 online community respondents), we found indirect effects of exposure to evidence of brain similarities on justification of gender inequality. We discuss the implications of our findings for challenging gender essentialist views among students and the general public through exposure to research on gender similarities and increased critical thinking about scientific research evidence.

Individuals of African ancestry have been starkly underrepresented in the pursuit of personalized medicine for brain illnesses. The African Ancestry Neuroscience Research Initiative will seek to generate much-needed brain gene and protein expression profiles for people of African ancestry.

Recent advances in the study of political attitudes and behavior have incorporated neurobiological methods to elucidate the basic affective and cognitive processes that support political decisions. This review integrates perspectives in political neuroscience research and focuses on the neurobiological bases of system justification — the motivation to regard the existing social system as legitimate and desirable. Neuroscientific evidence indicates that system justification and propensity to engage in political protest are associated with interindividual differences in amygdala structure. This suggests the possibility that our inclinations to protect versus protest the status quo are linked to our biological responses. Much of the promise of using neuroscience approaches in this interdisciplinary work lies in future investigations to help clarify outstanding questions about the palliative function of system justification and the neurocognitive bases of political participation.

SummaryWe review basic science research on neural mechanisms underlying emotional processing in individuals of differing socioeconomic status (SES). We summarise SES differences in response to positive and negative stimuli in limbic and cortical regions associated with emotion and emotion regulation. We discuss the possible relevance of neuroscience to understanding the link between mental health and SES. We hope to provide insights into future neuroscience research on the etiology and pathophysiology of mental disorders relating to SES.

The Golgi method gave birth to modern neuroscience. The Nauta method, developed in a novel Army think tank at the Walter Reed Army Medical Center, was the next major breakthrough before neuroscience emerged as a separate discipline. Dr. Walle Nauta's (1916-1994) method allowed for the first time the ability to trace interneuronal connections accurately to their termination. The think tank, created by Dr. David Rioch (1900-1985), provided a unique intellectual environment for interdisciplinary neuroscience research, the first of its kind. Rioch hired exceptional senior faculty and recruited outstanding young investigators who were drafted into the Army, typically after finishing their M.D.s or Ph.D.s, and were interested in brain research. Many of these young investigators went on to illustrious careers in neuroscience. I worked with Walle Nauta at a time when the technique was first being applied to nonmammalian vertebrate brains. Along with other Army draftees, I was encouraged to pursue my own research interests. This led me on a quest to understand interspecific variability of connections in relation to evolution and ontogeny of the brain. By 1980, I had found that the variability of all known connections could be explained by a theory to the effect that new structures such as the neocortex were not formed by one system invading another and mingling, as Clarence Luther Herrick (1858-1904) had proposed, but by selective proliferation and differentiation sometimes involving the select loss of connections to reduce cross-modality interference as in the case of the parcellation and differentiation of cortical areas. The resulting parcellation theory predicts that elements of a primordial neocortex existed from the beginning of vertebrate evolution and did not originate by an invasion of nonolfactory modalities into the olfactory lobe, as commonly believed before the introduction of the Nauta method. This theory would not have been created if it were not for the brilliant environment that was Walter Reed in the 1960s.

Collecting comprehensive data sets of the same subject has become a standard in neuroscience research and uncovering multivariate relationships among collected data sets have gained significant attentions in recent years. Canonical correlation analysis (CCA) is one of the powerful multivariate tools to jointly investigate relationships among multiple data sets, which can uncover disease or environmental effects in various modalities simultaneously and characterize changes during development, aging, and disease progressions comprehensively. In the past 10 years, despite an increasing number of studies have utilized CCA in multivariate analysis, simple conventional CCA dominates these applications. Multiple CCA‐variant techniques have been proposed to improve the model performance; however, the complicated multivariate formulations and not well‐known capabilities have delayed their wide applications. Therefore, in this study, a comprehensive review of CCA and its variant techniques is provided. Detailed technical formulation with analytical and numerical solutions, current applications in neuroscience research, and advantages and limitations of each CCA‐related technique are discussed. Finally, a general guideline in how to select the most appropriate CCA‐related technique based on the properties of available data sets and particularly targeted neuroscience questions is provided., Neuroscience applications of canonical correlation analysis (CCA) and its variants are systematically reviewed from a technical perspective. Detailed formulations, analytical and numerical solutions, current applications, and advantages and limitations of CCA and its variants are discussed. A general guideline to select the most appropriate CCA‐related technique is provided.

Exposure to stress during early life affects subsequent behaviors and increases the vulnerability to adult pathologies, a phenomenon that has been well documented in humans and rodents. In this study, we introduce a chronic unpredictable stress protocol adapted to young zebrafish, which is an increasingly popular vertebrate model in neuroscience research. We exposed zebrafish to a series of intermittent and unpredictable mild stressors from day 10 to 17 post-fertilization. The stressed fish showed a reduced exploration of a novel environment one day post-stress and an increased responsiveness to dark-light transition two days post-stress, indicative of heightened anxiety-related behaviors. The stress-induced decrease in exploration lasted for at least three days and returned to control levels within one week. Moreover, stressed fish were on average 8% smaller than their control siblings two days post-stress and returned to control levels within one week. All together, our results demonstrate that young zebrafish exposed to chronic unpredictable stress develop growth and behavioral alterations akin to those observed in rodent models.

The Iseult project is a French-German initiative focused on very high magnetic-field molecular imaging. The project includes a Whole Body 11.7 T MRI magnet installed at Neurospin, a neuroscience research center operating at CEA Saclay since November 2006. After 7 years of fabrication at Belfort by GE Power (Ex Alstom), the Iseult magnet was delivered to CEA in June 2017, its connection with the cryoplant and all the ancillary equipment was completed in October 2018. After 4 months of cooldown and another 4 months of tests, the Iseult magnet reached its nominal field of 11.72 T without any quench for the first time, on July 18th. This paper deals with the magnet connection at Neurospin with the cryoplant and with the electrical and control systems. Finally, the paper will present the magnet commissioning data, from the cooling phase to the step-by-step energization up to the nominal current.

Dendrites have always fascinated researchers: from the artistic drawings by Ramon y Cajal to the beautiful recordings of today, neuroscientists have been striving to unravel the mysteries of these structures. Theoretical work in the 1960s predicted important dendritic effects on neuronal processing, establishing computational modelling as a powerful technique for their investigation. Since then, modelling of dendrites has been instrumental in driving neuroscience research in a targeted manner, providing experimentally testable predictions that range from the subcellular level to the systems level, and their relevance extends to fields beyond neuroscience, such as machine learning and artificial intelligence. Validation of modelling predictions often requires - and drives - new technological advances, thus closing the loop with theory-driven experimentation that moves the field forward. This Review features the most important, to our understanding, contributions of modelling of dendritic computations, including those pending experimental verification, and highlights studies of successful interactions between the modelling and experimental neuroscience communities.

Canines, which exhibit similar emotional and social processing to humans, are becoming one of the preferred animal models for neuroscience research. Beagles are the most common laboratory canine, thanks to their moderate size, docile nature, and strong immunity. However, there is currently no MRI brain template for the purebred Beagle, which hinders their use in studies involving neuroimaging. Here, we present the Beagle Brain Template (BBT), which consists of high-resolution in vivo T1-weighted and T2-weighted templates, as well as a myelin template, generated from purebred Beagles. We also present a normalized pipeline for mapping individual structure images onto the BBT space. The BBT shows low variation in the tissue probability map and provides descriptive statistics with smaller variability of brain tissue volumes and brain sizes than that of existing templates. This high-resolution purebred canine brain template lays the foundation for future studies aimed at in vivo analyses of the brain structure and function of the Beagle dogs.

Biobanking plays an important role between clinical practice and translational research. In addition to the traditional biomolecular-based biobanks, there is a growing interest in establishing living biobanks, including organoid biobanks that can collect and store viable and functional tissues and proliferative cell types for long periods of time. An organoid is a three-dimensional cell complex derived by self-organization of small tissue blocks or stem cells, which can recapitulate the phenotypic and genetic characteristics of targeted human organs. Publications on brain organoids have increased recently, and several types of brain organoids have been reported to model normal and abnormal neural development, as well as different neurodegenerative diseases, neuropsychiatric disorders, and other neural conditions. Based on the current status of research, more exploration on brain organoids is needed, through technical advancements, to improve the reproducibility and scalability, as well as to decrease the diversity. Moreover, given their natural characteristics, more attention to ethical considerations is needed, considering the extent of maturation and complexity of brain organoids. Living biobanks that are engaged in collecting categories of brain organoids possessing different genetic backgrounds, and with spatial and temporal characteristics, will eventually contribute to the understanding of neural conditions and ultimately facilitate innovative treatment development.

Kainic acid is a marine natural product and extremely useful for neuroscience research. A number of years ago, a preliminary account of its tritiation was reported and based on decades of experience with it, updated technical details about its tritium labelling as well as storage, stability and repurification are described.

The human brain is a social organ. Whatever an educator’s instructional goals or lesson plans, students’ brains experience the classroom first and foremost as a social system. Neuroscience research...

Recent neuroscience research provides evidence on how decision making systems can be implemented in cortical networks of human brains. In this paper we investigate the possibility of developing a biophysically-realistic decision making model based on the asynchronous recurrent network with attractors and binary neurons. Success of our approach suggests that decision making is a network phenomenon and biologically plausible performance of the model does not rely on neuron activation dynamics of the leaky integrate-and-fire neurons. Results presented here provide supplementary evidence that the postulates formulated by recent empirical research are indeed essential for the implementation of decision making system into neuronal networks.

Objectives: To review the dynamics of neuroscience research in the Kingdom of Saudi Arabia (KSA) from 2013-2018. Methods: Subject category of Neuroscience was selected in the SciVal feature of Scopus database, which includes all relevant categories of the field limiting it to Saudi Arabia. Results: Saudi Arabia is ranked 39th in publishing neuroscientific research worldwide. The number of yearly published articles has increased from 123 to 332 during the time period between 2013 and 2018. King Saud University & King Abdul Aziz University & their corresponding regions namely Western and Central regions are the major contributors to publications. Neuroscientists working in Saudi Arabia have collaboration with scientists from all over the world. The top 10 preferred journals are all international. In subcategories of neuroscience, developmental neuroscience seems the one that needs attention. Conclusion: Neuroscience research is on the rise in KSA. Older and well-established institutions like King Saud University & King Abdul Aziz University have taken lead in publishing neuroscientific research. International collaboration in all subfields of neuroscience is substantial. Eastern Southern and Northern regions and developmental neuroscience require more focus and funding.

Monkeys are a premier model organism for neuroscience research. Activity in the central nervous systems of monkeys can be recorded and manipulated while they perform complex perceptual, motor, or cognitive tasks. Conventional techniques for manipulating neural activity in monkeys are too coarse to address many of the outstanding questions in primate neuroscience, but optogenetics holds the promise to overcome this hurdle. In this article, we review the progress that has been made in primate optogenetics over the past 5 years. We emphasize the use of gene regulatory sequences in viral vectors to target specific neuronal types, and we present data on vectors that we engineered to target parvalbumin-expressing neurons. We conclude with a discussion of the utility of optogenetics for treating sensorimotor hearing loss and Parkinson’s disease, areas of translational neuroscience in which monkeys provide unique leverage for basic science and medicine.

Pharmacology and optogenetics are widely used in neuroscience research to study the central and peripheral nervous systems. While both approaches allow for sophisticated studies of neural circuitry, continued advances are, in part, hampered by technology limitations associated with requirements for physical tethers that connect external equipment to rigid probes inserted into delicate regions of the brain. The results can lead to tissue damage and alterations in behavioral tasks and natural movements, with additional difficulties in use for studies that involve social interactions and/or motions in complex 3-dimensional environments. These disadvantages are particularly pronounced in research that demands combined optogenetic and pharmacological functions in a single experiment. Here, we present a lightweight, wireless, battery-free injectable microsystem that combines soft microfluidic and microscale inorganic light-emitting diode probes for programmable pharmacology and optogenetics, designed to offer the features of drug refillability and adjustable flow rates, together with programmable control over the temporal profiles. The technology has potential for large-scale manufacturing and broad distribution to the neuroscience community, with capabilities in targeting specific neuronal populations in freely moving animals. In addition, the same platform can easily be adapted for a wide range of other types of passive or active electronic functions, including electrical stimulation.

Strongly affecting human and animal physiology, sounds and vibration are critical environmental factors whose complex role in behavioral and brain functions necessitates further clinical and experimental studies. Zebrafish are a promising model organism for neuroscience research, including probing the contribution of auditory and vibration stimuli to neurobehavioral processes. Here, we summarize mounting evidence on the role of sound and vibration in zebrafish behavior and brain function, and outline future directions of translational research in this field. With the growing environmental exposure to noise and vibration, we call for more active use of zebrafish models for probing neurobehavioral and bioenvironmental consequences of acute and long-term exposure to sounds and vibration in complex biological systems.

Summary In basic neuroscience research, data are often clustered or collected with repeated measures, hence correlated. The most widely used methods such as t test and ANOVA do not take data dependence into account and thus are often misused. This Primer introduces linear and generalized mixed-effects models that consider data dependence and provides clear instruction on how to recognize when they are needed and how to apply them. The appropriate use of mixed-effects models will help researchers improve their experimental design and will lead to data analyses with greater validity and higher reproducibility of the experimental findings.

After over seven decades of neuroscience research, it is now well established that γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. In this paper dedicated to Krešimir Krnjević (1927–2021), a pioneer and leader in neuroscience, we briefly highlight the fundamental contributions he made in identifying GABA as an inhibitory neurotransmitter in the brain and our personal interactions with him. Of note, between 1972 and 1978 Dr. Krnjević was a highly reputed Chief Editor of the Canadian Journal of Physiology and Pharmacology.

Implantable neural interfaces are important tools to accelerate neuroscience research and translate clinical neurotechnologies. The promise of a bidirectional communication link between the nervous system of humans and computers is compelling, yet important materials challenges must be first addressed to improve the reliability of implantable neural interfaces. This perspective highlights recent progress and challenges related to arguably two of the most common failure modes for implantable neural interfaces: (1) compromised barrier layers and packaging leading to failure of electronic components; (2) encapsulation and rejection of the implant due to injurious tissue-biomaterials interactions, which erode the quality and bandwidth of signals across the biology-technology interface. Innovative materials and device design concepts could address these failure modes to improve device performance and broaden the translational prospects of neural interfaces. A brief overview of contemporary neural interfaces is presented and followed by recent progress in chemistry, materials, and fabrication techniques to improve in vivo reliability, including novel barrier materials and harmonizing the various incongruences of the tissue-device interface. Challenges and opportunities related to the clinical translation of neural interfaces are also discussed.

Autism spectrum disorder (ASD) is a specific brain disease that causes communication impairments and restricted interests. Functional connectivity analysis methodology is widely used in neuroscience research and shows much potential in discriminating ASD patients from healthy controls. However, due to heterogeneity of ASD patients, the performance of conventional functional connectivity classification methods is relatively poor. Graph neural network is an effective graph representation method to model structured data like functional connectivity. In this paper, we proposed a functional graph discriminative network (FGDN) for ASD classification. On the basis of pre-built graph templates, the proposed FGDN is able to effectively distinguish ASD patient from health controls. Moreover, we studied the size of training set for effective training, inter-site predictions, and discriminative brain regions. Discriminative brain regions were determined by the proposed model to investigate its applicability and biomarkers for ASD identification. For functional connectivity classification and analysis, FGDN is not only an effective tool for ASD identification but also a potential technique in neuroscience research.

Decades of research have informed our understanding of how stress impacts the brain to perturb behavior. However, stress during development has received specific attention as this occurs during a sensitive period for scaffolding lifelong socio-emotional behavior. In this review, we focus the developmental neurobiology of stress-related pathology during infancy and focus on one of the many important variables that can switch outcomes from adaptive to maladaptive outcome: caregiver presence during infants’ exposure to chronic stress. While this review relies heavily on rodent neuroscience research, we frequently connect this work with the human behavioral and brain literature to facilitate translation. Bowlby’s Attachment Theory is used as a guiding framework in order to understand how early care quality impacts caregiver regulation of the infant to produce lasting outcomes on mental health.

Characterization of the interwoven complexities of early cortical thickness development has been an ongoing undertaking in neuroscience research. Longitudinal studies of Non-Human Primates (NHP) offer unique advantages to categorizing the diverse patterns of cortical growth trajectories. Here, we used latent growth models to characterize the trajectories of typical cortical thickness development in Japanese macaques at each cortical surface vertex (i.e. grayordinate). Cortical thickness from 4 to 36 months showed regional specific linear and non-linear trajectories and distinct maturation timing across the cortex. Intriguingly, we revealed a “accumulation/ablation phenomenon” of cortical maturation where the most profound development changes in cortical thickness occur in the accumulation or ablation zones surrounding the focal points (i.e., a center of a delineated regions where cortical thickness is thickest or thinnest) throughout the brain. We further examined maternal diet and inflammation in the context of these typical brain trajectories and known network architecture. A well-controlled NHP model of a maternal “Western-style” diet was used alongside measures of inflammatory cytokine interleukin-6 (IL-6) in the mothers during gestation. We observed that these accumulation and ablation zones of variable change might be most susceptible to environmental effects. The maternal factors, diet and inflammation during pregnancy were distinctively associated with different aspects of offspring cortical development reflected in regions related to distinctive functional networks. Our findings characterize the versatile intricacies of typical cortical thickness development and highlight how the maternal environment plays a role in offspring cortical development.

Understanding capacity is a crucial benchmark to manage the continent’s knowledge resources Understanding capacity is a crucial benchmark to manage the continent’s knowledge resources

Movies, audio stories, and virtual reality are increasingly used as stimuli for functional brain imaging. Such naturalistic paradigms are in sharp contrast to the tradition of experimental reductionism in neuroscience research. Being complex, dynamic, and diverse, naturalistic stimuli set up a more ecologically relevant condition and induce highly reproducible brain responses across a wide range of spatiotemporal scales. Here, we review recent technical advances and scientific findings on imaging the brain under naturalistic stimuli. Then we elaborate on the premise of using naturalistic paradigms for multi-scale, multi-modal, and high-throughput functional characterization of the human brain. We further highlight the growing potential of using deep learning models to infer neural information processing from brain responses to naturalistic stimuli. Lastly, we advocate large-scale collaborations to combine brain imaging and recording data across experiments, subjects, and labs that use the same set of naturalistic stimuli.

Leslie Iversen, a giant of modern neuropharmacology, died peacefully on July 30, 2020, after a lifetime of leading transformational discoveries in the biochemical pharmacology of catecholamines. He was suffering from Parkinson’s disease, a pathology that resides fundamentally in a loss of dopamine in brain centers regulating locomotion. For a man who made transformational discoveries on catecholamines, it was an ironic turn of events. Leslie Iversen ( Right ) at the NCPU laboratory with A.C.C. Reprinted from ref. 7. Copyright (2020), with permission from Elsevier. Leslie Iversen punting on the river Cam, with William F. Ganong as a passenger. Iversen’s major contributions to his field of science, as well as his awards and recognitions, have been amply documented, their magnitude reflected in his election as a Fellow of the Royal Society and an international member of the National Academy of Sciences, as well as being awarded the highest-ranking order of the British Empire Award: Commander of the Order of the British Empire for his services to pharmacology. Leslie Iversen led a scientific life with a stellar trajectory at Cambridge University, the Medical Research Council (MRC), Merck, Sharp & Dohme Neuroscience Research Centre, and as Visiting Professor of Pharmacology at the University of Oxford. Who was Leslie Iversen? Despite all of these accolades and titles, to friends and close colleagues he was known as “Les.” Les was an extraordinarily intelligent individual with a particular talent for identifying which were the important and most significant problems in neuropharmacology and in the neurosciences. He married an equally intelligent person, Susan Kibble (later known as Susan Iversen), whom he met during his undergraduate years at Cambridge. The Les–Sue relationship, besides being a happy marriage, was also a mutually enriching interaction. Sue benefited from Les’s discoveries in neuroactive molecules and his wide repertoire of illustrious visiting scientists, … [↵][1]1Email: claudio.cuello{at}mcgill.ca. [1]: #xref-corresp-1-1

Anxiety is the most prevalent brain disorder and a common cause of human disability. Animal models are critical for understanding anxiety pathogenesis and its pharmacotherapy. The zebrafish (Danio rerio) is increasingly utilized as a powerful model organism in anxiety research and anxiolytic drug screening. High similarity between human, rodent and zebrafish molecular targets implies shared signaling pathways involved in anxiety pathogenesis. However, mounting evidence shows that zebrafish behavior can be modulated by drugs beyond conventional anxiolytics or anxiogenics. Furthermore, these effects may differ from human and/or rodent responses, as such 'unconventional' drugs may affect zebrafish behavior despite having no such profiles (or exerting opposite effects) in humans or rodents. Here, we discuss the effects of several putative unconventional anxiotropic drugs (aspirin, lysergic acid diethylamide (LSD), nicotine, naloxone and naltrexone) and their potential mechanisms of action in zebrafish. Emphasizing the growing utility of zebrafish models in CNS drug discovery, such unconventional anxiety pharmacology may provide important, evolutionarily relevant insights into complex regulation of anxiety in biological systems. Albeit seemingly complicating direct translation from zebrafish into clinical phenotypes, this knowledge may instead foster the development of novel CNS drugs, eventually facilitating innovative treatment of patients based on novel 'unconventional' targets identified in fish models.

Neural mass models are among the most popular mathematical models of brain activity, since they enable the rapid simulation of large-scale networks involving different neural types at a spatial scale compatible with electrophysiological experiments (e.g. local field potentials). However, establishing neural mass model (NMM) equations associated with specific neuronal network architectures can be tedious and is an error-prone process, restricting their use to scientists who are familiar with mathematics. In order to overcome this challenge, we have developed a user-friendly software that enables a user to construct rapidly, under the form of a graph, a neuronal network with its populations and connectivity patterns. The resulting graph is then automatically translated into the corresponding set of differential equations, which can be solved and displayed within the same software environment. The software is proposed as open access, and should assist in offering the possibility for a wider audience of scientists to develop NMM corresponding to their specific neuroscience research questions.

Environmental endocrine-disrupting chemicals (EDCs), a type of exogenous organic pollutants, are ubiquitous in natural aquatic environments. Therefor, this review focused on the use of the zebrafish as a model to explore the effect of different EDCs on behavior, as well as the molecular mechanisms that drive these effects. Furthermore, our study summarizes the current knowledge on the neuromodulatory effects of different EDCs in zebrafish. This study also reviews the current state of zebrafish behavior research, in addition to the potential mechanisms of single and mixed pollutant-driven behavioral dysregulation at the molecular level, as well as the applications of zebrafish behavior experiments for neuroscience research. This review broadens our understanding of the influence of EDCs on zebrafish behavior and provides guidance for future research.

The common marmoset ( Callithrix jacchus), a small New World primate, is receiving substantial attention in the neuroscience and biomedical science fields because its anatomical features, functional and behavioral characteristics, and reproductive features and its amenability to available genetic modification technologies make it an attractive experimental subject. In this review, I outline the progress of marmoset neuroscience research and summarize both the current status (opportunities and limitations) of and the future perspectives on the application of marmosets in neuroscience and disease modeling.