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Contains fulltext : 291020.pdf (Publisher’s version ) (Open Access) Memory, one of the hallmarks of human cognition, can be modified when humans voluntarily modulate neural population activity using neurofeedback. However, it is currently unknown whether neurofeedback can influence the integration of memories, and whether memory is facilitated or impaired after such neural perturbation. In this study, participants memorized objects while we provided them with abstract neurofeedback based on their brain activity patterns in the ventral visual stream. This neurofeedback created an implicit face or house context in the brain while memorizing the objects. The results revealed that participants created associations between each memorized object and its implicit context solely due to the neurofeedback manipulation. Our findings shed light onto how memory formation can be influenced by synthetic memory tags with neurofeedback and advance our understanding of mnemonic processing. 10 p.

Introduction Overpopulation and industrial growth result in an increase in air pollution, mainly due to suspended particulate matter and the formation of ozone. Repeated exposure to low doses of ozone, such as on a day with high air pollution levels, results in a state of chronic oxidative stress, causing the loss of dendritic spines, alterations in cerebral plasticity and in learning and memory mechanisms, and neuronal death and a loss of brain repair capacity. This has a direct impact on human health, increasing the incidence of chronic and degenerative diseases. Development We performed a search of the PubMed, Scopus, and Google Scholar databases for original articles and reviews published between 2000 and 2018 and addressing the main consequences of ozone exposure on synaptic plasticity, information processing in cognitive processes, and the alterations that may lead to the development of neurodegenerative diseases. Conclusions This review describes one of the pathophysiological mechanisms of the effect of repeated exposure to low doses of ozone, which causes loss of synaptic plasticity by producing a state of chronic oxidative stress. This brain function is key to both information processing and the generation of structural changes in neuronal populations. We also address the effect of chronic ozone exposure on brain tissue and the close relationship between ozone pollution and the appearance and progression of neurodegenerative diseases.

Human brain networks undergo pronounced changes during development. The emergence of highly connected hub regions that can support integrated brain function is central to this maturational process, with these areas undergoing a particularly protracted period of development that extends into adulthood. The location of cortical network hubs emerges early but connections to and from hubs continue to strengthen throughout childhood and adolescence. Patterns of functional coupling in cortical association hubs are immature and incomplete at birth, but gradually strengthen during development. Early establishment of hub connectivity may provide a stable substrate that is refined by changes in tissue organization and microstructure, resulting in the emergence of complex functional dynamics by adulthood.

Advances in our understanding of brain function, along with the development of neural interfaces that allow for the monitoring and activation of neurons, have paved the way for brain-machine interfaces (BMIs), which harness neural signals to reanimate the limbs via electrical activation of the muscles or to control extracorporeal devices, thereby bypassing the muscles and senses altogether. BMIs consist of reading out motor intent from the neuronal responses monitored in motor regions of the brain and executing intended movements with bionic limbs, reanimated limbs, or exoskeletons. BMIs also allow for the restoration of the sense of touch by electrically activating neurons in somatosensory regions of the brain, thereby evoking vivid tactile sensations and conveying feedback about object interactions. In this review, we discuss the neural mechanisms of motor control and somatosensation in able-bodied individuals and describe approaches to use neuronal responses as control signals for movement restoration and to activate residual sensory pathways to restore touch. Although the focus of the review is on intracortical approaches, we also describe alternative signal sources for control and noninvasive strategies for sensory restoration.

INTRODUCTION: Lateralization in brain function has been associated with age and sex in previous work; however, there has been less focus on lateralization of functional networks during development. AIM: We aim to examine laterality in typical development; a clearer understanding of how and to what extent functional brain networks are lateralized in typical development may eventually prove to hold predictive information in psychopathology. MATERIAL AND METHODS: In this study, we examine the lateralization of resting-state networks assessed with a group-independent component analysis using resting-state functional magnetic resonance imaging from a large cohort consisting of 774 children, ages 6–10 years. This is an extension of our previous work on normal aging in adults, where we now assess whether there are similar patterns in children. RESULTS: Unlike the results from our study of healthy aging in adults, which showed a decrease in laterality with increasing age, in this study we found both decreases and increases in lateralization in multiple networks with development. For example, auditory and sensorimotor regions had greater bilateral connectivity with development, whereas regions including the dorsolateral frontal cortex (Brodmann area left 9 and left 46) showed an increase in left lateralization with development. CONCLUSION: Our findings support a complex, nonlinear association between laterality and age in school-age children, a time when brain function and structure are developing rapidly. We also found brain networks in which laterality was significantly associated with sex, handedness, and intelligence quotient, but we did not find any significant association with behavioral scores. IMPACT STATEMENT: Lateralization in brain function has been associated with age and sex in several previous studies; however, there has been less focus on lateralization of functional networks during development. A clearer understanding of how and to what extent functional brain networks are lateralized in typical development may eventually prove to hold predictive information in psychopathology. In this study, we examine the lateralization of resting-state networks assessed with a group-independent component analysis using resting-state functional magnetic resonance imaging from a large cohort consisting of 774 children, ages 6–10 years.

Background: Functional magnetic resonance imaging (fMRI) is a brain imaging technique that provides detailed insights into brain function and its disruption in various brain disorders. The data-driven analysis of fMRI brain activity maps involves several postprocessing steps, the first of which is identifying whether the estimated brain network maps capture signals of interest, for example, intrinsic connectivity networks (ICNs), or artifacts. This is followed by linking the ICNs to standardized anatomical and functional parcellations. Optionally, as in the study of functional network connectivity (FNC), rearranging the connectivity graph is also necessary to facilitate interpretation. Methods: Here we develop a novel and efficient method (Autolabeler) for implementing and integrating all of these processes in a fully automated manner. The Autolabeler method is pretrained on a cross-validated elastic-net regularized general linear model from the noisecloud toolbox to separate neuroscientifically meaningful ICNs from artifacts. It is capable of automatically labeling activity maps with labels from several well-known anatomical and functional parcellations. Subsequently, this method also maximizes the modularity within functional domains to generate a more systematically structured FNC matrix for post hoc network analyses. Results: Results show that our pretrained model achieves 86% accuracy at classifying ICNs from artifacts in an independent validation data set. The automatic anatomical and functional labels also have a high degree of similarity with manual labels selected by human raters. Discussion: At a time of ever-increasing rates of generating brain imaging data and analyzing brain activity, the proposed Autolabeler method is intended to automate such analyses for faster and more reproducible research. IMPACT STATEMENT: Our proposed method is capable of implementing and integrating some of the crucial tasks in functional magnetic resonance imaging (fMRI) studies. It is the first to incorporate such tasks without the need for expert intervention. We develop an open-source toolbox for the proposed method that can function as stand-alone software and additionally provides seamless integration with the widely used group independent component analysis for fMRI toolbox (GIFT). This integration can aid investigators to conduct fMRI studies in an end-to-end automated manner.

Background: The olfactory system is affected very early in Alzheimer’s disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI), an early stage of AD. Objective: The aim of this randomized, prospective, controlled, blinded study was to evaluate whether olfactory training (OT) may have an effect on olfactory function, cognitive impairment, and brain activation in MCI patients after a 4-month period of frequent short-term exposure to various odors. Methods: A total of 38 MCI outpatients were randomly assigned to OT or a control training condition, which were performed twice a day for 4 months. Olfactory testing, comprehensive neuropsychological assessment, and a passive odor perception task based on magnetic resonance imaging were performed before and after training. Results: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. Additionally, OT exhibited a positive effect on frontal lobe activation (left middle frontal gyrus and orbital-frontal cortex) but exhibited no effect on grey matter volume. Moreover, the change of olfactory scores was positively associated with the change of frontal activation. Conclusion: OT was found to have a limited effect on olfaction and cognition in patients with MCI compared to a non-OT condition but increased their functional response to odors in frontal area.

Engineering of cellular biomolecules is an emerging landscape presenting creative therapeutic opportunities. Recently, several strategies such as biomimetic materials, drug-releasing scaffolds, stem cells, and dynamic culture systems have been developed to improve specific biological functions, however, have been confounded with fundamental and technical roadblocks. Rapidly emerging investigations on the bioengineering prospects of mammalian ribonucleic acid (RNA) is expected to result in significant biomedical advances. More specifically, the current trend focuses on devising non-coding (nc) RNAs as therapeutic candidates for complex neurological diseases. Given the pleiotropic and regulatory role, ncRNAs such as microRNAs and long non-coding RNAs are deemed as attractive therapeutic candidates. Currently, the list of non-coding RNAs in mammals is evolving, which presents the plethora of hidden possibilities including their scope in biomedicine. Herein, we critically review on the emerging repertoire of ncRNAs in neurological diseases such as Alzheimer’s disease, Parkinson’s disease, neuroinflammation and drug abuse disorders. Importantly, we present the advances in engineering of ncRNAs to improve their biocompatibility and therapeutic feasibility as well as provide key insights into the applications of bioengineered non-coding RNAs that are investigated for neurological diseases., GRAPHICAL ABSTRACT

Introduction: Monitoring of brain function using continuous electroencephalography (aEEG/cEEG) is an essential tool in the standard care of the term infant, and its use is growing in the premature infant as a biomarker of lesion and brain maturity. However, the placing of the electrodes is a great challenge, particularly in the extremely premature infant, which often discourages neuromonitoring. The aim of this study is to assess the different electrodes available, to select the one that best suits the peculiarities of the extremely premature infant, and evaluate its applicability in clinical practice. Population and methods: With the aim of designing a neuromonitoring study protocol using aEEG/cEEG in

Changes in cognition, affect, and brain function combine to promote a shift in the nature of mentation in older adulthood, favoring exploitation of prior knowledge over exploratory search as the starting point for thought and action. Age-related exploitation biases result from the accumulation of prior knowledge, reduced cognitive control, and a shift toward affective goals. These are accompanied by changes in cortical networks, as well as attention and reward circuits. By incorporating these factors into a unified account, the exploration-to-exploitation shift offers an integrative model of cognitive, affective, and brain aging. Here, we review evidence for this model, identify determinants and consequences, and survey the challenges and opportunities posed by an exploitation-biased mental mode in later life.

Background and purpose Multiple sclerosis (MS) is a chronic inflammatory disease causing a wide range of symptoms including motor and cognitive impairment, fatigue and pain. Over the last two decades, non-invasive brain stimulation, especially transcranial direct current stimulation (tDCS), has increasingly been used to modulate brain function in various physiological and pathological conditions. However, its experimental applications for people with MS were noted only as recently as 2010 and have been growing since then. The efficacy for use in people with MS remains questionable with the results of existing studies being largely conflicting. Hence, the aim of this review is to paint a picture of the current state of tDCS in MS research grounded on studies applying tDCS that have been done to date. Methods A keyword search was performed to retrieve articles from the earliest article identified until 14 February 2021 using a combination of the groups (1) ‘multiple sclerosis’, ‘MS’ and ‘encephalomyelitis’ and (2) ‘tDCS’ and ‘transcranial direct current stimulation’. Results The analysis of the 30 articles included in this review underlined inconsistent effects of tDCS on the motor symptoms of MS based on small sample sizes. However, tDCS showed promising benefits in ameliorating fatigue, pain and cognitive symptoms. Conclusion Transcranial direct current stimulation is attractive as a non-drug approach in ameliorating MS symptoms, where other treatment options remain limited. The development of protocols tailored to the individual's own neuroanatomy using high definition tDCS and the introduction of network mapping in the experimental designs might help to overcome the variability between studies.

Cdk5 is a proline-directed serine/threonine protein kinase that governs a variety of cellular processes in neurons, the dysregulation of which compromises normal brain function. The mechanisms underlying the modulation of Cdk5, its modes of action, and its effects on the nervous system have been a great focus in the field for nearly three decades. In this review, we provide an overview of the discovery and regulation of Cdk5, highlighting recent findings revealing its role in neuronal/synaptic functions, circadian clocks, DNA damage, cell cycle reentry, mitochondrial dysfunction, as well as its non-neuronal functions under physiological and pathological conditions. Moreover, we discuss evidence underscoring aberrant Cdk5 activity as a common theme observed in many neurodegenerative diseases.

Background High-positioned and/or superoposteriorly directed anterior communicating artery aneurysms can be treated by direct clipping using the pterional (fronto-temporo-sphenoidal) approach. This procedure, however, requires stronger retraction of the frontal lobe. Hence, preservation of the prominent frontal bridging veins (FBVs) draining into the sphenoparietal sinus (SPS) remains a significant challenge in preventing postoperative venous congestion. Methods We developed a technique to release the tension on the FBVs by pulling them together with the SPS epidurally. In 2 patients, who had presented with high-positioned and/or superoposteriorly directed anterior communicating artery aneurysms, we peeled off the arachnoid surrounding the FBVs and detached it from the brain surface. We further released the veins by moving them posteriorly, together with the SPS epidurally. Results Using this technique, we established a wide corridor through a more lateral transsylvian trajectory with effective posterior retraction of the frontal lobe and were successful in clipping and obliterating the aneurysms. Conclusions Open clipping of unruptured intracranial aneurysms requires accuracy to preserve higher brain function. Our technique was successful in both patients, and preserving the FBVs could be useful in the treatment of such aneurysms.

Sleep is essential for brain function in a surprisingly diverse set of ways. In the short term, lack of sleep leads to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. This review article discusses recent advances in understanding how sleep maintains the physiological health of the brain, via interconnected systems of neuronal activity and fluid flow. The neural dynamics that appear during sleep are intrinsically coupled to its consequences for blood flow, cerebrospinal fluid dynamics, and waste clearance. Recognizing these linked causes and consequences of sleep has shed new light on why sleep is important for such disparate aspects of brain function.

Newborn care has witnessed significant improvements in survival, but ongoing concerns persist about neurodevelopmental outcome. Protecting the newborn brain is the focus of neurocritical care in the intensive care unit. Brain-focused care places emphasis on clinical practices supporting neurodevelopment in conjunction with early detection, diagnosis, and treatment of brain injury. Technology now facilitates continuous cot-side monitoring of brain function. Neuromonitoring techniques in neonatal intensive care units include the use of electroencephalography (EEG) or amplitude-integrated EEG (aEEG) and near-infrared spectroscopy. This article aims to provide an introduction to EEG, which is appropriate for neonatal healthcare professionals.

Traumatic brain injury (TBI) is a common neurological condition that results from an external force altering normal brain function, whether temporarily or permanently. A concussion is one type of TBI. TBIs vary greatly in severity, which concomitantly creates tremendous variability in their manifestation. The fingerprint of TBI is damage to the frontal areas of the brain, which, with sufficient magnitude, results in impairment of a person's ability to regulate cognition, emotion, and behavior. These consequences of TBI make recognition in the context of treating behavioral health conditions of utmost importance. TBI not only causes behavioral health problems but also produces associated deficits that can undermine the effectiveness of treatment for a behavioral health condition. This overview delineates key characteristics of TBI and describes its association with behavioral health conditions. Mechanisms underlying the relationship between TBI and behavioral health are presented, and a series of recommendations for professionals are proposed. This article is intended to raise awareness about TBI and simultaneously introduce key concepts for accommodating the effects of TBI in behavioral health care.

Congenital Zika Syndrome (CZS) is characterized by changes in cranial morphology associated with heterogeneous neurological manifestations and cognitive and behavioral impairments. In this syndrome, longitudinal neuroimaging could help clinicians to predict developmental trajectories of children and tailor treatment plans accordingly. However, regularly acquiring magnetic resonance imaging (MRI) has several shortcomings besides cost, particularly those associated with childrens' clinical presentation as sensitivity to environmental stimuli. The indirect monitoring of local neural activity by non-invasive functional near-infrared spectroscopy (fNIRS) technique can be a useful alternative for longitudinally accessing the brain function in children with CZS. In order to provide a common framework for advancing longitudinal neuroimaging assessment, we propose a principled guideline for fNIRS acquisition and analyses in children with neurodevelopmental disorders. Based on our experience on collecting fNIRS data in children with CZS we emphasize the methodological challenges, such as clinical characteristics of the sample, desensitization, movement artifacts and environment control, as well as suggestions for tackling such challenges. Finally, metrics based on fNIRS can be associated with established clinical metrics, thereby opening possibilities for exploring this tool as a long-term predictor when assessing the effectiveness of treatments aimed at children with severe neurodevelopmental disorders.

The functions of the brain and heart, which are the two main supporting organs of human life, are closely linked. Numerous studies have expounded the mechanisms of the brain-heart axis and its related clinical applications. However, the effect of heart disease on brain function, defined as the heart-brain axis, is less studied even though cognitive dysfunction after heart disease is one of its most frequently reported manifestations. Hypoperfusion caused by heart failure appears to be an important risk factor for cognitive decline. Blood perfusion, the immune response, and oxidative stress are the possible main mechanisms of cognitive dysfunction, indicating that the blood-brain barrier, glial cells, and amyloid-β may play active roles in these mechanisms. Clinicians should pay more attention to the cognitive function of patients with heart disease, especially those with heart failure. In addition, further research elucidating the associated mechanisms would help discover new therapeutic targets to intervene in the process of cognitive dysfunction after heart disease. This review discusses cognitive dysfunction in relation to heart disease and its potential mechanisms.

Internet gaming addiction (IGD) is a common disease in teenagers which usually reflects the abnormalities in brain function or structure. Several computational models have been applied to investigate the characteristic of IGD brain networks, for instance, the conception of brain controllability. The primary objective of this study was to explore the relationship between brain controllability and IGD related clinical behaviour. A sample of 101 subjects, including 49 IGD patients and 52 normal controls, were recruited to undergo MR T1 and DTI scanning. Specifically, the MR images were used to generate the white matter connectivity matrix and the morphometry similarity network. The morphometry similarity network was then divided into several communities using modular decomposition. After, average controllability, modal controllability and synchronizability were calculated through measuring the adjacency matrix. The results indicated that the IGD group had greater synchronizability and modal controllability compared to that of the control group, and different morphological-based brain communities had different controllability properties. Furthermore, the addiction demonstrated the mediating effects between nodal or modular brain controllability as well as anxiety. In conclusion, brain controllability could be a potential biomarker of IGD.

Astrocytes are known to play many important roles in brain function. However, research underscoring the extent to which astrocytes modulate neuronal activity is still underway. Here we review the latest evidence regarding the contribution of astrocytes to neuronal oscillations across the brain, with a specific focus on how astrocytes respond to changes in brain state (e.g., sleep, arousal, stress). We then discuss the general mechanisms by which astrocytes signal to neurons to modulate neuronal activity, ultimately driving changes in behavior, followed by a discussion of how astrocytes contribute to respiratory rhythms in the medulla. Finally, we contemplate the possibility that brain stem astrocytes could modulate brainwide oscillations by communicating the status of oxygenation to higher cortical areas.

The ability to spatially resolve the cellular architecture of human cortical cell types over informative areas is essential to understanding brain function. We combined in situ sequencing gene expression data and single-nucleus RNA-sequencing cell type definitions to spatially map cells in sections of the human cortex via probabilistic cell typing. We mapped and classified a total of 59,816 cells into all 75 previously defined subtypes to create a first spatial atlas of human cortical cells in their native position, their abundances and genetic signatures. We also examined the precise within- and across-layer distributions of all the cell types and provide a resource for the cell atlas community. The abundances and locations presented here could serve as a reference for further studies, that include human brain tissues and disease applications at the cell type level., Langseth et al. present cell type maps of human cortical tissue sections and show an efficient and robust workflow to accurately resolve anatomical organization of human brain tissue.

Objectives Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival. Design Clinical case control study followed by translational laboratory study. Setting Research institution. Patients/subjects Adult cardiac arrest patients and male Sprague-Dawley rats. Interventions Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle. Measurements and main results We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect. Conclusions Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.

Somnolence during brain function mapping is one of the factors that inhibit the accomplishment of the goals of awake craniotomy. We examined the effect of anesthesia depth measured by bispectral index (BIS) during pre-awake phase on somnolence during brain function mapping and also explored the factors associated with somnolence. We examined the association between BIS values during pre-awake phase and somnolence during the first 30 min of brain function mapping in 55 patients who underwent awake craniotomy at Kyoto University Hospital from 2015 to 2018. The pre-awake BIS value was defined as the mean BIS value for 60 min before the removal of the airway. Somnolence during brain function mapping was the primary outcome, defined as either of the following conditions: inability to follow up, disorientation, or inability to assess speech function. Additionally, we compared patient or perioperative variables between patients with/without somnolence. Somnolence occurred in 14 patients (25.5%), of which 6 patients (10.9%) were unable to complete brain function mapping. There was no significant difference in the pre-awake BIS value between patients with/without somnolence (median: 46 vs. 49, P = 0.192). Somnolence was not significantly associated with age, gender, and the number of preoperative anticonvulsive drugs, but patients with somnolence had a significantly lower preoperative Western Aphasia Battery (WAB) aphasia quotient score (median 93.8 vs. 98.6, P = 0.011). We did not find an association between pre-awake BIS value and somnolence during brain function mapping. Somnolence likely occurs in patients with a low preoperative WAB aphasia quotient score.

Background: Modifications in brain function remain relatively unexplored in progressive multiple sclerosis (PMS), despite their potential to provide new insights into the pathophysiology of the disease at this stage. Objectives: To characterize the dynamics of functional networks at rest in patients with PMS, and the relation with clinical disability. Methods: Thirty-two patients with PMS underwent clinical and cognitive assessment. The dynamic properties of functional networks, retrieved from transient brain activity, were obtained from patients and 25 healthy controls (HCs). Sixteen HCs and 19 patients underwent a 1-year follow-up (FU) clinical and imaging assessment. Differences in the dynamic metrics between groups, their longitudinal changes, and the correlation with clinical disability were explored. Results: PMS patients, compared to HCs, showed a reduced dynamic functional activation of the anterior default mode network (aDMN) and a decrease in its opposite-signed co-activation with the executive control network (ECN), at baseline and FU. Processing speed and visuo-spatial memory negatively correlated to aDMN dynamic activity. The anti-couplings between aDMN and auditory/sensory-motor network, temporal-pole/amygdala, or salience networks were differently associated with separate cognitive domains. Conclusion: Patients with PMS presented an altered aDMN functional recruitment and anti-correlation with ECN. The aDMN dynamic functional activity and interaction with other networks explained cognitive disability.

A large body of research has indicated that bilingualism - through continual practice in language control - may impact cognitive functions, as well as relevant aspects of brain function and structure. The present review aimed to bring together findings on the relationship between bilingualism and domain-general cognitive functions from a neural perspective. The final sample included 210 studies, covering findings regarding neural responses to bilingual language control and/or domain-general cognitive tasks, as well as findings regarding effects of bilingualism on non-task-related brain function and brain structure. The evidence indicates that a) bilingual language control likely entails neural mechanisms responsible for domain-general cognitive functions; b) bilingual experiences impact neural responses to domain-general cognitive functions; and c) bilingual experiences impact non-task-related brain function (both resting-state and metabolic function) as well as aspects of brain structure (both macrostructure and microstructure), each of which may in turn impact mental processes, including domain-general cognitive functions. Such functional and structural neuroplasticity associated with bilingualism may contribute to both cognitive and neural reserves, producing benefits across the lifespan.

The human gut microbiome influence on brain function and mental health is an emerging area of intensive research. Animal and human research indicates adolescence as a sensitive period when the gut-brain axis is fine-tuned, where dietary interventions to change the microbiome may have long-lasting consequences for mental health. This study reports a systematic review and meta-analysis of microbiota-targeted (psychobiotics) interventions on anxiety in youth, with discussion of a consultation on the acceptability of psychobiotic interventions for mental health management amongst youth with lived experience. Six databases were searched for controlled trials in human samples (age range: 10–24 years) seeking to reduce anxiety. Post intervention outcomes were extracted as standard mean differences (SMDs) and pooled based on a random-effects model. 5416 studies were identified: 14 eligible for systematic review and 10 eligible for meta-analysis (total of 324 experimental and 293 control subjects). The meta-analysis found heterogeneity I2 was 12% and the pooled SMD was −0.03 (95% CI: −0.21, 0.14), indicating an absence of effect. One study presented with low bias risk, 5 with high, and 4 with uncertain risk. Accounting for risk, sensitivities analysis revealed a SMD of −0.16 (95% CI: −0.38, 0.07), indicative of minimal efficacy of psychobiotics for anxiety treatment in humans. There is currently limited evidence for use of psychobiotics to treat anxiety in youth. However, future progress will require a multidisciplinary research approach, which gives priority to specifying mechanisms in the human models, providing causal understanding, and addressing the wider context, and would be welcomed by anxious youths.

In this study, the effects of a 12-week exercise program combining aerobic and resistance training on high-fat diet-induced obese Sprague Dawley (SD) rats after the injection of beta-amyloid into the cerebral ventricle were investigated. Changes in physical fitness, cognitive function, blood levels of beta-amyloid and metabolic factors, and protein expressions of neurotrophic factors related to brain function such as BDNF (brain-derived neurotrophic factor) in the quadriceps femoris, hippocampus, and cerebral cortex were analyzed. The subjects were thirty-two 10-week-old SD rats (DBL Co., Ltd., Seoul, Korea). The rats were randomized into four groups: β-Non-Ex group (n = 8) with induced obesity and βA25-35 injection into the cerebral ventricle through stereotactic biopsy; β-Ex group (n = 8) with induced obesity, βA25-35 injection, and exercise; S-Non-Ex group (n = 8) with an injection of saline in lieu of βA25-35 as the control; and S-Ex group (n = 8) with saline injection and exercise. The 12-week exercise program combined aerobic training and resistance training. As for protein expressions of the factors related to brain function, the combined exercise program was shown to have a clear effect on activating the following factors: PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), FNDC5 (fibronectin type III domain-containing protein 5), and BDNF in the quadriceps femoris; TrkB (Tropomyosin receptor kinase B), FNDC5, and BDNF in the hippocampus; PGC-1α, FNDC5, and BDNF in the cerebral cortex. The protein expression of β-amyloid in the cerebral cortex was significantly lower in the β-Ex group than in the β-Non-Ex group (p < 0.05). The 12-week intervention with the combined exercise program of aerobic and resistance training was shown to improve cardiopulmonary function, muscular endurance, and short-term memory. The results demonstrate a set of positive effects of the combined exercise program, which were presumed to have arisen mainly due to its alleviating effect on β-amyloid plaques, the main cause of reduced brain function, as well as the promotion of protein expressions of PGC-1α, FNDC5, and BDNF in the quadriceps femoris, hippocampus, and cerebral cortex.

Background The acute changes in brain function in newborn infants undergoing ET remain unclear. This study aimed to determine whether fully automated simultaneous peripheral arteriovenous ET would influence the brain function. Methods A retrospective analysis was conducted on the clinical data of 39 neonates with hyperbilirubinemia who received ET. Seventeen patients were in the encephalopathy group, and the other 22 patients were in the non-encephalopathy group. Changes in amplitude-integrated electroencephalogram (aEEG) during ETs were analyzed, including background activities, sleep-wake cycling (SWC), and seizures. Before and after the ET, routine blood test parameters, electrolytes, blood glucose, and blood gas parameters were measured. Results After ETs, there were no significant changes in the levels of pH, PaO2, PaCO2, lactate, and red blood cells, while the levels of total bilirubin, indirect bilirubin, blood potassium, blood sodium, serum calcium, while blood cells, and platelets were significantly lower and the level of blood glucose was significantly higher compared to those before therapy. There was no significant difference in the changes of electroencephalographic activities during ETs, including background activities, SWC, and seizures. However, there were significant differences in suppressions on background activities, while there were no significant statistical differences in SWC or seizures between the 2 groups. Conclusion Fully automated simultaneous peripheral arteriovenous ET is safe and efficient without significant influence on the disorder of the internal environment and electroencephalographic activities after ET in neonates. However, background activities are more significantly depressed in infants of bilirubin encephalopathy than infants of non-encephalopathy during ET.

Inflammation is associated with both lower and higher activity in brain regions that process rewarding stimuli. How can both low and high sensitivity to rewards be associated with higher inflammation? We propose that one potential mechanism underlying these apparently conflicting findings pertains to how people pursue goals in their environment. This prediction is based on evidence that both an inability to disengage from unattainable goals and low interest in and pursuit of important life goals are associated with poor health outcomes, including inflammation. Accordingly, this study examined the relationship between reward-related brain function and peripheral inflammation among individuals with different levels of ambitious goal-striving tendencies. Eighty-three participants completed an ambitious goal-striving tendency measure, an fMRI Monetary Incentive Delay task assessing orbitofrontal cortex (OFC) and nucleus accumbens (NAc) activation during reward anticipation and outcome, and a venous blood draw to assess the inflammatory biomarkers interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and C-reactive protein, from which we computed an inflammation composite score. We observed a reward anticipation by goal-striving interaction on inflammation, such that high OFC and NAc activation to reward anticipation (but not outcome) were associated with more inflammation, among high goal-striving individuals. By contrast, low NAc activation during reward anticipation (but not outcome) was associated with more inflammation, among low goal-striving individuals. The current study provides further evidence that both blunted and elevated reward function can be associated with inflammation. It also highlights the role that goal-striving tendencies may play in moderating the relationship between neural reward anticipation and inflammation.

The complexity and variability of human brain activity, such as quantified from Functional Magnetic Resonance Imaging (fMRI) time series, have been widely studied as potential markers of healthy and pathological states. However, the extent to which fMRI temporal features exhibit stable markers of inter-individual differences in brain function across healthy young adults is currently an open question. In this study, we draw upon two widely used time-series measures—a nonlinear complexity measure (sample entropy; SampEn) and a spectral measure of low-frequency content (fALFF)—to capture dynamic properties of resting-state fMRI in a large sample of young adults from the Human Connectome Project. We observe that these two measures are closely related, and that both generate reproducible patterns across brain regions over four different fMRI runs, with intra-class correlations of up to 0.8. Moreover, we find that both metrics can uniquely differentiate subjects with high identification rates (ca. 89%). Canonical correlation analysis revealed a significant relationship between multivariate brain temporal features and behavioral measures. Overall, these findings suggest that regional profiles of fMRI temporal characteristics may provide stable markers of individual differences, and motivate future studies to further probe relationships between fMRI time series metrics and behavior.

The World Health Organization (WHO) has declared that neurodegenerative diseases will be the biggest health issues of the twenty-first century. Among these, Alzheimer's and Parkinson's diseases can be considered as the most acute incurable neurological diseases. Researchers are studying and developing a new treatment approach that uses nanotechnology to diagnosis and treatment neurodegenerative diseases. This treatment strategy will be used to regress neurodegenerative diseases such as Alzheimer's disease. Alzheimer's disease (AD) is one of the most common forms of reduced brain function, which causes many devastating complications. Current neurodegenerative diseases treatment protocols only help to treat symptoms nevertheless with nanotechnology approaches, can regress nerve cells apoptosis, reduce inflammation, and improve brain drug delivery. In this paper, new nanotechnology methods such as nanobodies, nano-antibodies, and lipid nanoparticles have been investigated. Correspondingly blood-brain barrier drug delivery improvement methods have been suggested.

Individual variability exists in both brain function and behavioral performance. However, changes in individual variability in brain functional connectivity and capability across adult development and aging have not yet been clearly examined. Based on resting-state functional magnetic resonance imaging data from a large cohort of participants (543 adults, aged 18–88 years), brain functional connectivity was analyzed to characterize the spatial distribution and differences in individual variability across the adult lifespan. Results showed high individual variability in the association cortex over the adult lifespan, whereas individual variability in the primary cortex was comparably lower in the initial stage but increased with age. Individual variability was also negatively correlated with the strength/number of short-, medium-, and long-range functional connections in the brain, with long-range connections playing a more critical role in increasing global individual variability in the aging brain. More importantly, in regard to specific brain regions, individual variability in the motor cortex was significantly correlated with differences in motor capability. Overall, we identified specific patterns of individual variability in brain functional structure during the adult lifespan and demonstrated that functional variability in the brain can reflect behavioral performance. These findings advance our understanding of the underlying principles of the aging brain across the adult lifespan and suggest how to characterize degenerating behavioral capability using imaging biomarkers.

l-theanine (γ-glutamylethylamide), an amino acid in green tea, has been shown to affect brain functions by relieving stress disorders, improving mood, and maintaining normal sleep. However, the cognitive functions for which theanine is effective are unclear. This study aimed to clarify which cognitive functions are positively affected by intake of l-theanine. A double-blind, randomized, placebo-controlled study was conducted. The subjects were Japanese men and women aged 50-69 years. Mini Mental State Examination-Japanese version score was 24 or higher. Cognitrax was used as a test battery for cognitive function. Evaluations were performed before the intervention, after a single dose of l-theanine, and after 12 weeks of regular intake. The single dose of l-theanine reduced the reaction time to attention tasks (Stroop test, Part 1), and it increased the number of correct answers and decreased the number of omission errors in working memory tasks (4-Part continuous performance test, Part 4). In conclusion, our study indicated that l-theanine may contribute to improving attention, thus enhancing working memory and executive functions. Clinical Trial No.: UMIN000033812.

Fluorescence imaging techniques play a pivotal role in our understanding of the nervous system. The emergence of various super-resolution microscopy methods and specialized fluorescent probes enables direct insight into neuronal structure and protein arrangements in cellular subcompartments with so far unmatched resolution. Super-resolving visualization techniques in neurons unveil a novel understanding of cytoskeletal composition, distribution, motility, and signaling of membrane proteins, subsynaptic structure and function, and neuron-glia interaction. Well-defined molecular targets in autoimmune and neurodegenerative disease models provide excellent starting points for in-depth investigation of disease pathophysiology using novel and innovative imaging methodology. Application of super-resolution microscopy in human brain samples and for testing clinical biomarkers is still in its infancy but opens new opportunities for translational research in neurology and neuroscience. In this review, we describe how super-resolving microscopy has improved our understanding of neuronal and brain function and dysfunction in the last two decades.

Sustaining neuronal proteostasis during the course of our life is a central aspect required for brain function. The dynamic nature of synaptic composition and abundance is a requisite to drive cognitive and motor processes involving a tight control of many aspects of protein biosynthesis and degradation. Through the concerted action of specialized stress sensors, the proteostasis network monitors and limits the accumulation of damaged, misfolded, or aggregated proteins. These stress pathways signal to the cytosol and nucleus to reprogram gene expression, enabling adaptive programs to recover cell function. During aging, the activity of the proteostasis network declines, which may increase the risk of accumulating abnormal protein aggregates, a hallmark of most neurodegenerative diseases. Here, I discuss emerging concepts illustrating the functional significance of adaptive signaling pathways to normal brain physiology and their contribution to age-related disorders. Pharmacological and gene therapy strategies to intervene and boost proteostasis are expected to extend brain healthspan and ameliorate disease states.

Background: The optimisation of learning has long been a focus of scientific research, particularly in relation to improving psychological treatment and recovery of brain function. Previously, partial N-methyl-D-aspartate agonists have been shown to augment reward learning, procedural learning and psychological therapy, but many studies also report no impact of these compounds on the same processes. Aims: Here we investigate whether administration of an N-methyl-D-aspartate partial agonist (D-cycloserine) modulates a previously unexplored process – tactile perceptual learning. Further, we use a longitudinal design to investigate whether N-methyl-D-aspartate-related learning effects vary with time, thereby providing a potentially simple explanation for apparent mixed effects in previous research. Methods: Thirty-four volunteers were randomised to receive one dose of 250 mg D-cycloserine or placebo 2 h before tactile sensitivity training. Tactile perception was measured using psychophysical methods before and after training, and 24/48 h later. Results: The placebo group showed immediate within-day tactile perception gains, but no further improvements between-days. In contrast, tactile perception remained at baseline on day one in the D-cycloserine group (no within-day learning), but showed significant overnight gains on day two. Both groups were equivalent in tactile perception by the final testing – indicating N-methyl-D-aspartate effects changed the timing, but not the overall amount of tactile learning. Conclusions: In sum, we provide first evidence for modulation of perceptual learning by administration of a partial N-methyl-D-aspartate agonist. Resolving how the effects of such compounds become apparent over time will assist the optimisation of testing schedules, and may help resolve discrepancies across the learning and cognition domains.

To reveal whether neurodevelopmental outcome of infants after epilepsy surgery can be quantitatively assessed by electroencephalography (EEG) functional connectivity analysis.We enrolled 13 infants with posterior quadrant dysplasia aged2 years who were treated using posterior quadrantectomy and 21 age-matched infants. EEG was performed both before and one year after surgery. Developmental quotient (DQ) was assessed both before and 3 years after surgery. The phase lag index (PLI) of three different pairs of electrodes in the nonsurgical hemisphere, i.e., the anterior short distance (ASD), posterior short distance (PSD), and long distance (LD) pairs, were calculated as indices of brain connectivity. The relationship between the PLI and DQ was evaluated.Overall, 77% infants experienced seizure freedom after surgery. The beta- and gamma- range PLI of PSD pairs increased preoperatively. All these pairs normalized postoperatively. Simple linear regression analysis revealed a significant relationship between the postoperative DQ and the postoperative beta-band PLI of ASD pairs.Preoperative abnormal hyper-connectivity was normalized to the control level after surgery. The postoperative hyperconnectivity was associated with long-term neurodevelopmental improvement.PLI quantifies neurodevelopmental improvements after posterior quadrantectomy.

Multiregional communication is important to understanding the brain mechanisms supporting complex behaviors. Work in animals and human subjects shows that multiregional communication plays significant roles in cognitive function and is associated with neurological and neuropsychiatric disorders of brain function. Recent experimental advances enable empirical tests of the mechanisms of multiregional communication. Recent mechanistic insights into brain network function also suggest new therapies to treat disordered brain networks. Here, we discuss how to use the concept of communication channel modulation can help define and constrain what we mean by multiregional communication. We discuss behavioral and neurophysiological evidence for multiregional channels modulation. We then consider the role of causal manipulations and their implications for developing novel therapies based on multiregional communication.

Single-cell transcriptomic approaches are revolutionizing neuroscience. Integrating this wealth of data with morphology and physiology, for the comprehensive study of neuronal biology, requires multiplexing gene expression data with complementary techniques. To meet this need, multiple groups in parallel have developed “Patch-seq,” a modification of whole-cell patch-clamp protocols that enables mRNA sequencing of cell contents after electrophysiological recordings from individual neurons and morphologic reconstruction of the same cells. In this review, we first outline the critical technical developments that enabled robust Patch-seq experimental efforts and analytical solutions to interpret the rich multimodal data generated. We then review recent applications of Patch-seq that address novel and long-standing questions in neuroscience. These include the following: (1) targeted study of specific neuronal populations based on their anatomic location, functional properties, lineage, or a combination of these factors; (2) the compilation and integration of multimodal cell type atlases; and (3) the investigation of the molecular basis of morphologic and functional diversity. Finally, we highlight potential opportunities for further technical development and lines of research that may benefit from implementing the Patch-seq technique. As a multimodal approach at the intersection of molecular neurobiology and physiology, Patch-seq is uniquely positioned to directly link gene expression to brain function.

Background and aim Jointly analyzing structural and functional brain networks enables a better understanding of pathological underpinnings of irritable bowel syndrome (IBS). Multiplex network analysis provides a novel framework to study complex networks consisting of different types of connectivity patterns in multimodal data. Methods In the present work, we integrated functional and structural networks to a multiplex network. Then, the multiplex metrics and the inner-layer/inter-layer hub nodes were investigated through 34 patients with IBS and 33 healthy controls. Results Significantly differential multiplex degree in both left and right parts of calcarine was found, and meanwhile, IBS patients lost inner-layer hub properties in these regions. In addition, the left fusiform was no longer practicing as an inner-layer hub node, while the right median cingulate acted as a new inner-layer hub node in the IBS patients. Besides, the right calcarine, which lost its inner-layer hub identity, became a new inter-layer hub node, and the multiplex degree of the left hippocampus, which lost its inter-layer hub identity in IBS patients, was significantly positively correlated with the IBS Symptom Severity Score scores. Conclusions Inner-layer hub nodes of multiplex networks were preferentially vulnerable, and some inner-layer hub nodes would convert into inter-layer hub nodes in IBS patients. Besides, the inter-layer hub nodes might be influenced by IBS severity and therefore converted to general nodes.

Background Regarding an important effects of physical exercise on brain function in elders, the aim of this study was to examine the effects of strength and endurance exercise on brain neurobiological factors in older men. Methods Thirty older men volunteered to participate in this study and were randomly assigned to strength, endurance and control groups. The subjects in strength group performed two circuits of resistance exercise (6 exercises with 10 repetition of 65–70% of one repetition maximum), while endurance group performed 30 min running with 65–70% of maximal heart rate. Blood was obtained pre and post-exercise to determine changes in serum BDNF, IGF-1 and platelets. Results After exercise, both the strength and endurance groups showed significant increases in serum BDNF and IGF-1 concentrations and platelets at post-exercise and in comparison to control group (p Conclusion Our findings indicate that both the strength and endurance interventions are effective in elevating BDNF, IGF-1, and platelets, without significant differences between them.

The autonomic nervous system governs the body's multifaceted internal adaptation to diverse changes in the external environment, a role more complex than is accessible to the methods—and data scales—hitherto used to illuminate its operation. Here we apply generative graphical modelling to large-scale multimodal neuroimaging data encompassing normal and abnormal states to derive a comprehensive hierarchical representation of the autonomic brain. We demonstrate that whereas conventional structural and functional maps identify regions jointly modulated by parasympathetic and sympathetic systems, only graphical analysis discriminates between them, revealing the cardinal roles of the autonomic system to be mediated by high-level distributed interactions. We provide a novel representation of the autonomic system—a multidimensional, generative network—that renders its richness tractable within future models of its function in health and disease.

Electroencephalography (EEG) is the reference tool for the analysis of brain function, reflecting normal and pathological neuronal network activity. During the neonatal period, EEG patterns evolve weekly, according to gestational age. The first analytical criteria for the various maturational stages and standardized neonatal EEG terminology were published by a group of French neurophysiologists training in Paris (France) in 1999. These criteria, defined from analog EEG, were completed in 2010 with digital EEG analysis. Since then, this work has continued, aided by the technical progress in EEG acquisition, the improvement of knowledge on the maturating processes of neuronal networks, and the evolution of critical care. In this review, we present an exhaustive and didactic overview of EEG characteristics from extremely premature to full-term infants. This update is based on the scientific literature, enhanced by the study of normal EEGs of extremely premature infants by our group of neurophysiologists. For educational purposes, particular attention has been paid to illustrations using new digital tools.

Consistent cerebral blood flow (CBF) is fundamental to brain function. Cerebral autoregulation ensures CBF stability. Chronic hypertension can lead to disrupted cerebral autoregulation in older people, potentially leading to blood pressure levels interfering with CBF. This study tested whether low BP and AHD use are associated with contemporaneous low CBF, and whether longitudinal change in BP is associated with change in CBF, using arterial spin labelling (ASL) MRI, in a prospective longitudinal cohort of 186 community-dwelling older individuals with hypertension (77 ± 3 years, 53% female), 125 (67%) of whom with 3-year follow-up. Diastolic blood pressure, systolic blood pressure, mean arterial pressure, and pulse pressure were assessed as blood pressure parameters. As additional cerebrovascular marker, we evaluated the ASL signal spatial coefficient of variation (ASL SCoV), a measure of ASL signal heterogeneity that may reflect cerebrovascular health. We found no associations between any of the blood pressure measures and concurrent CBF nor between changes in blood pressure measures and CBF over three-year follow-up. Antihypertensive use was associated with lower grey matter CBF (−5.49 ml/100 g/min, 95%CI = −10.7|−0.27, p = 0.04) and higher ASL SCoV (0.32 SD, 95%CI = 0.12|0.52, p = 0.002). These results warrant future research on the potential relations between antihypertensive use and cerebral perfusion.