Neurophysiological Processes Research Articles

Foreign Contaminants Target Brain Health.

Neurodisease, caused by undesired substances, can lead to mental health conditions like depression, anxiety and neurocognitive problems like dementia. These substances can be referred to as contaminants that can cause damage, corruption, and infection or reduce brain functionality. Contaminants, whether conceptual or physical, have the ability to disrupt many processes. These observations motivate us to investigate contaminants and neurotoxicity collaboratively. This study investigates the link between pollutants and neuro-disease, examining transmission pathways and categorization. It also provides information on resources, causes, and challenges to minimize contamination risks. Contamination may cause various neuro-diseases, including Alzheimer's, Parkinson's, multi-system atrophy, Huntington's, autism spectrum disorder, psychiatric disorder, dementia, meningitis, encephalitis, schizophrenia, anxiety, and depression. The negative effects depend on the nature and extent of exposure. A comprehensive literature search was conducted using databases such as PubMed and Scopus, focusing on studies published till 2024. Studies were selected based on their examination of the relationship between environmental contaminants and brain health, emphasizing transmission pathways and the resulting neurological outcomes. Findings indicate that contaminants can penetrate the blood-brain barrier (BBB) via nasal, gut, and auditory routes, triggering harmful neurophysiological processes. This review highlights the urgent need for increased global awareness, policy interventions, and preventive measures to mitigate the long-term impacts of environmental contaminants on brain health, particularly in emerging nations.

Human cortical high-gamma power scales with movement rate in healthy participants and stroke survivors.

Motor cortical high-gamma oscillations (60-90Hz) occur at movement onset and are spatially focused over the contralateral primary motor cortex. Although high-gamma oscillations are widely recognized for their significance in human motor control, their precise function on a cortical level remains elusive. Importantly, their relevance in human stroke pathophysiology is unknown. Because motor deficits are fundamental determinants of symptom burden after stroke, understanding the neurophysiological processes of motor coding could be an important step in improving stroke rehabilitation. We recorded magnetoencephalography data during a thumb movement rate task in 14 chronic stroke survivors, 15 age-matched control participants and 29healthy young participants. Motor cortical high-gamma oscillations showed a strong relation with movement rate as trials with higher movement rate were associated with greater high-gamma power. Although stroke survivors showed reduced cortical high-gamma power, this reduction primarily reflected the scaling of high-gamma power with movement rate, yet after matching movement rate in stroke survivors and age-matched controls, the reduction of high-gamma power exceeded the effect of their decreased movement rate alone. Even though motor skill acquisition was evident in all three groups, it was not linked to high-gamma power. Our study quantifies high-gamma oscillations after stroke, revealing a reduction in movement-related high-gamma power. Moreover, we provide strong evidence for a pivotal role of motor cortical high-gamma oscillations in encoding movement rate. KEY POINTS: Neural oscillations in the high-gamma frequency range (60-90Hz) emerge in the human motor cortex during movement. The precise function of these oscillations in motor control remains unclear, and they have never been characterized in stroke survivors. In a magnetoencephalography study, we demonstrate that high-gamma oscillations in motor cortical areas scale with movement rate, and we further explore their temporal and spatial characteristics. Stroke survivors exhibit lower high-gamma power during movement than age-matched control participants, even after matching for movement rate. The results contribute to the understanding of the role of high-gamma oscillations in motor control and have important implications for neuromodulation in stroke rehabilitation.

Deciphering the role of neuropeptides as biomarkers for early diagnosis of Parkinson's disease.

Parkinson's disease (PD) is a neurological condition and is characterized by both motor and non-motor symptoms. Early diagnosis is essential for effective therapy and management; nevertheless, present diagnostic methods are frequently insufficient and primarily rely on clinical symptoms that appear later in the disease. Neuropeptides, such as alpha-synuclein (α-syn), Substance P (SP), neurotensin (Nts), Neuropeptide Y (NPY), and somatostatin (SST), exhibit significant potential as biomarkers for the early identification of Parkinson's disease (PD). The pathophysiology of Parkinson's disease is closely associated with the dysregulation of these neuropeptides, which are essential in many neurophysiological processes. Advancements in detection technologies, including the Enzyme-Linked Immunosorbent Assay (ELISA), have rendered it possible to precisely and sensitively quantify neuropeptides in a variety of bodily fluids, including blood, saliva, tears, urine, and cerebrospinal fluid (CSF). Studies show that PD patients have different amounts of neuropeptides in their biological fluids. These differences are correlated with the severity of the disease and help to distinguish PD patients apart from individuals with other neurodegenerative conditions. Despite being less investigated, Nts and SST are also involved in neuroprotection and dopaminergic transmission, they too hold significant characteristics as diagnostic biomarkers. This article highlights the possible use of neuropeptides as PD diagnostic biomarkers. Integrating neuropeptide biomarkers into normal diagnostic processes can substantially enhance early diagnosis. This enables early therapeutic interventions and improves outcomes for individuals with PD.

Mild hypohydration in healthy older adults increases pain-related brain activity without affecting pain perception: a single-blind study.

Understanding how hydration status influences pain perception is particularly important in older adults, as both dehydration and pain are prevalent in this population. Ten individuals (70 ± 4 yr) completed two randomized and counterbalanced trials. They were exposed to passive heat until they lost 1% body mass through sweat and urine (∼100 min), with the loss either unreplaced (sham infusion, HYPO) or fully replaced via 0.45% saline infusion (EUH). Nociceptive electrical stimulation was applied to the sural nerve 1) before heat exposure (baseline), 2) 60 min following hydration manipulation (R60, ∼160 min after baseline), 3) after mouth rinsing with water (MR, ∼170 min after baseline), and 4) following water ingestion (ING, ∼185 min after baseline). Pain-related event-related potentials were assessed using electroencephalography (EEG) at R60, MR, and ING. After hydration manipulation, body mass loss and plasma osmolality were greater, and plasma volumes were lower in HYPO than in EUH, although thirst did not differ between the conditions. There were no differences between the two conditions regarding pain intensity and unpleasantness. Still, EEG analyses revealed that the peak-to-peak amplitude of the pain-related N200-P300 potential (∼136-310 ms) was significantly greater in HYPO than in EUH (P = 0.036) and significantly greater in R60 compared with both MR (P = 0.01) and ING (P = 0.03), either with HYPO and EUH. These results suggest that mild hypohydration in healthy older adults may influence some neurophysiological processes related to nociception without significantly affecting pain perception.NEW & NOTEWORTHY This study reveals, for the first time, that mild hypohydration equivalent to ∼1% of body mass does not alter pain perception in healthy older adults when they are blinded to their hydration status, despite electroencephalography signals showing modulation of pain-related brain responses.

Voluntary blinks and eye-widenings, but not spontaneous blinks, facilitate perceptual alternation during continuous flash suppression.

The fact that blinks occur more often than necessary for ocular lubrication has led to the proposal that blinks are involved in altering some aspects of visual cognition. Previous studies have suggested that blinking can modulate the alternation of different visual interpretations of the same stimulus, that is, perceptual alternation in multistable perception. This study investigated whether and how different types of blinks, spontaneous and voluntary, interact with perceptual alternation in a multistable perception paradigm called continuous flash suppression. The results showed that voluntary blinking facilitated perceptual alternation, whereas spontaneous blinking did not. Moreover, voluntary eye-widening, as well as eyelid closing, facilitated perceptual alternation. Physical blackouts, which had timing and duration comparable to those of voluntary blinks, did not produce facilitatory effects. These findings suggest that the effects of voluntary eyelid movements are mediated by extraretinal processes and are consistent with previous findings that different types of blinks are at least partially mediated by different neurophysiological processes. Furthermore, perceptual alternation was also found to facilitate spontaneous blinking. These results indicate that eyelid movements and perceptual alternation interact reciprocally with each other.

Development of a Photoelectrochemical Microelectrode Using an Organic Probe for Monitoring Hydrogen Sulfide in Living Brains.

Hydrogen sulfide (H2S) is an important bioactive molecule that plays a significant role in various functions, particularly in the living brain, where it is closely linked to cognition, memory, and several neurological diseases. Consequently, developing effective detection methods for H2S is essential for studying brain functions and the underlying mechanisms of these diseases. This study aims to construct a novel photoelectrochemical (PEC) microelectrode Ti/TiO2@HSP for the quantitative monitoring of H2S levels in the living brain. The PEC microelectrode Ti/TiO2@HSP is formed by covalently bonding a specifically designed organic PEC probe HSP, which possesses a D-π-A structure, to the surface of TiO2 nanotubes generated via in situ anodic oxidation of titanium wire. The PEC probe HSP can effectively react with H2S and generate significant photocurrent response under long-wavelength excitation light (560 nm), thereby achieving quantitative detection of H2S. The sensor demonstrates high sensitivity and good selectivity. In vivo experiments utilizing the PEC microelectrode Ti/TiO2@HSP enable the monitoring of dynamic changes in H2S levels across various regions of the mouse brain. The findings reveal that in normal mice, the concentration of H2S in the hippocampus is significantly higher than in the striatum and cerebral cortex. Additionally, following propargylglycine drug stimulation, H2S concentrations in different brain regions were observed to decrease, with the most substantial reduction noted in the hippocampus. This suggests that cystathionine γ-lyase (CSE) is the primary enzyme responsible for H2S production in this area, while the striatum exhibits a less pronounced decrease in H2S concentration, indicating a reliance on alternative enzymatic pathways for H2S production. Therefore, this study not only successfully develops a high-performance H2S detection sensor but also provides new experimental tools and theoretical foundations for further exploring the roles of H2S in neurophysiological and pathological processes.

Motor learning promotes regionally-specific spindle-slow wave coupled cerebral memory reactivation

Sleep is essential for the optimal consolidation of newly acquired memories. This study examines the neurophysiological processes underlying memory consolidation during sleep, via reactivation. Here, we investigated the impact of slow wave - spindle (SW-SP) coupling on regionally-task-specific brain reactivations following motor sequence learning. Utilizing simultaneous EEG-fMRI during sleep, our findings revealed that memory reactivation occured time-locked to coupled SW-SP complexes, and specifically in areas critical for motor sequence learning. Notably, these reactivations were confined to the hemisphere actively involved in learning the task. This regional specificity highlights a precise and targeted neural mechanism, underscoring the crucial role of SW-SP coupling. In addition, we observed double-dissociation whereby primary sensory areas were recruited time-locked to uncoupled spindles; suggesting a role for uncoupled spindles in sleep maintenance. These findings advance our understanding the functional significance of SW-SP coupling for enhancing memory in a regionally-specific manner, that is functionally dissociable from uncoupled spindles.

Probing Neurophysiological Processes Related to Self-Referential Processing to Predict Improvement for Depressed Adolescents Receiving Cognitive Behavioral Therapy

BACKGROUNDCognitive Behavior Therapy (CBT) is a gold standard approach for treating major depressive disorder (MDD) among adolescents. However, nearly half of adolescents receiving CBT do not improve. In order to personalize treatment, it is essential to identify objective markers that predict treatment responsiveness. Toward addressing this aim, this study investigated neurophysiological processes related to self-referential processing that predicted CBT response among depressed, female adolescents. METHODSAt baseline, female adolescents ages 13-18-years-old (N=80) completed a comprehensive clinical assessment, and a self-referential encoding task was administered while electroencephalogram (EEG) data were recorded. Baseline EEG data were utilized to identify oscillatory differences between healthy (HC, n=38) and depressed (MDD, n=42) adolescents. Following the baseline assessment, depressed youth received up to 12-weeks of CBT. Baseline differences in EEG oscillations between healthy and depressed youth were used to guide CBT prediction analysis. Cluster-based event-related spectral perturbation analysis (ERSP) probed theta and alpha event-related synchronization/desynchronization (ERS/ERD) response to negative and positive words. RESULTSBaseline analyses showed that, relative to the healthy adolescents, depressed youth exhibited higher levels of frontal theta ERS and a greater posterior alpha ERD. Multilevel modeling identified primary neural pre-treatment predictors of treatment response: greater theta ERS in the right prefrontal cortex (PFC) after the onset of negative words and lower alpha ERD in both the right PFC and posterior cingulate cortex (PCC). ERS and ERD associations with treatment response remained significant, with baseline depressive and anxiety symptoms included as covariates in all analyses. CONCLUSIONSConsistent with prior research, results highlighted that relative to healthy youth, depressed adolescents are characterized by prominent theta synchronization and alpha desynchronization over PFC and PCC, respectively. Cluster-based ERSP analysis also identified key mechanisms underlying depression-related self-referential processing that predicted improved symptoms during the CBT course. Ultimately, a better characterization of the neural underpinnings of adolescent depression and its treatment may lead to more personalized interventions.

Human Neural Organoid Microphysiological Systems Show the Building Blocks Necessary for Basic Learning and Memory.

Brain Microphysiological Systems including neural organoids derived from human induced pluripotent stem cells offer a unique lens to study the intricate workings of the human brain. This paper investigates the foundational elements of learning and memory in neural organoids, also known as Organoid Intelligence by quantifying immediate early gene expression, synaptic plasticity, neuronal network dynamics, and criticality to demonstrate the utility of these organoids in basic science research. Neural organoids showed synapse formation, glutamatergic and GABAergic receptor expression, immediate early gene expression basally and evoked, functional connectivity, criticality, and synaptic plasticity in response to theta-burst stimulation. In addition, pharmacological interventions on GABAergic and glutamatergic receptors, and input specific theta-burst stimulation further shed light on the capacity of neural organoids to mirror synaptic modulation and short-term potentiation, demonstrating their potential as tools for studying neurophysiological and neurological processes and informing therapeutic strategies for diseases.

Differential effects of haloperidol on neural oscillations during wakefulness and sleep

The electrical activity of the brain, characterized by its frequency components, reflects a complex interplay between periodic (oscillatory) and aperiodic components. These components are associated with various neurophysiological processes, such as the excitation-inhibition balance (aperiodic activity) or interregional communication (oscillatory activity). However, we do not fully understand whether these components are truly independent or if different neuromodulators affect them in different ways. The dopaminergic system has a critical role for cognition and motivation, being a potential modulator of these power spectrum components. To improve our understanding of these questions, we investigated the differential effects of this system on these components using electrocorticogram recordings in cats, which show clear oscillations and aperiodic 1/f activity. Specifically, we focused on the effects of haloperidol (a D2 receptor antagonist) on oscillatory and aperiodic dynamics during wakefulness and sleep. By parameterizing the power spectrum into these two components, our findings reveal a robust modulation of oscillatory activity by the D2 receptor across the brain. Surprisingly, aperiodic activity was not significantly affected and exhibited inconsistent changes across the brain. This suggests a nuanced interplay between neuromodulation and the distinct components of brain oscillations, providing insights into the selective regulation of oscillatory dynamics in awake states.

Effects of lorazepam on saccadic eye movements - evidence from prosaccade and free viewing tasks.

Peak velocities of saccadic eye movements are reduced after benzodiazepine administration. Even though this is an established effect, past research has only examined it in horizontal prosaccade tasks. The spectrum of saccadic eye movements, however, is much larger. Therefore, we aimed to make a first attempt at filling this research gap by testing benzodiazepine effects on saccades under different experimental task conditions. 1mg lorazepam or placebo was administered (within-subjects, double-blind, in randomised order) to n = 30 healthy adults. Participants performed an extended version of the prosaccade task, including vertical saccade directions and different stimulus eccentricities, as well as a free viewing task. Results from the prosaccade task confirmed established effects of benzodiazepines as well as saccade direction on saccadic parameters but additionally showed that the drug effect on peak velocity was independent of saccade direction. Remarkably, in the free viewing task peak velocities as well as other saccade parameters were unaffected by lorazepam. Furthermore, exploration patterns during free viewing did not change under lorazepam. Overall, our findings further consolidate the peak velocity of prosaccades as a biomarker of sedation. Additionally, we suggest that sedative effects of low doses of benzodiazepines may be compensated in tasks that more closely resemble natural eye movement behaviour, possibly due to the lack of time constraints or via neurophysiological processes related to volition.

Mindfulness Training in High-Demand Cohorts Alters Resting-State Electroencephalography: An Exploratory Investigation of Individual Alpha Frequency, Aperiodic 1/f Activity, and Microstates

BackgroundMindfulness training (MT) programs have demonstrated utility as cognitive training tools, but there is little consensus on the neurophysiological processes that may underlie its benefits. It has been posited that intrinsic brain activity recorded at rest reflects the functional connectivity of large-scale brain networks and may provide insight into neuroplastic changes that support MT. In the current study, we indexed changes in several resting-state electroencephalography (EEG) parameters to investigate the neurophysiological underpinnings of MT. MethodsResting-state EEG data were collected from active-duty U.S. military personnel (N = 80) at 2 testing sessions: before (time [T] 1) and after (T2) engaging in an 8-week MT or active comparison intervention (positivity training). We examined longitudinal and/or groupwise differences in several EEG parameters through parameterization of power spectra (individual alpha frequency and 1/f activity) and microstate analysis. ResultsWhile no significant group × time differences were observed in individual alpha frequency, significant group × time effects were observed in several EEG parameters from T1 to T2. Compared with MT, positivity training was associated with a steepening of the 1/f slope and higher 1/f intercepts together with decreased duration and increased global field power of microstates. ConclusionsTaken together, these results suggest that the effects of interventions may be differentiated in resting-state brain activity in a sample of military personnel. Such findings provide insight into the neural underpinnings of MT-related brain changes, but more research is required to elucidate how these may relate to task-related neural and performance changes with MT and whether results generalize to other mindfulness interventions in alternative cohorts and contexts.

Correlation between compulsive behaviors and plastic changes in the dendritic spines of the prefrontal cortex and dorsolateral striatum of male rats

Obsessive-compulsive disorder (OCD) is a mental affliction characterized by compulsive behaviors often manifested in intrusive thoughts and repetitive actions. The quinpirole model has been used with rats to replicate compulsive behaviors and study the neurophysiological processes associated with this pathology. Several changes in the dendritic spines of the medial prefrontal cortex (mPFC) and dorsolateral striatum (DLS) have been related to the occurrence of compulsive behaviors. Dendritic spines regulate excitatory synaptic contacts, and their morphology is associated with various brain pathologies. The present study was designed to correlate the occurrence of compulsive behaviors (generated by administering the drug quinpirole) with the morphology of the different types of dendritic spines in the mPFC and DLS. A total of 18 male rats were used. Half were assigned to the experimental group, the other half to the control group. The former received injections of quinpirole, while the latter rats were injected with physiological saline solution, for 10 days in both cases. After the experimental treatment, the quinpirole rats exhibited all the parameters indicative of compulsive behavior and a significant correlation with the density of stubby and wide neckless spines in both the mPFC and DLS. Dendritic spines from both mPFC and DLS neurons showed plastic changes correlatively with the expression of compulsive behavior induced by quinpirole. Further studies are suggested to evaluate the involvement of glutamatergic neurotransmission in the neurobiology of OCD.

Mind and Brain: Experience in Developing Fundamental Theoretical Issues of the Hard Problem of Consciousness and Its Significance for Neuroscience

The article presents a retrospective analysis of the author’s 70-year contribution to philosophy and science, focusing primarily on the hard problem of consciousness – the relationship between mental phenomena and neurophysiological processes. The author traces his intellectual journey in addressing this fundamental challenge to natural scientific knowledge and presents his conceptual framework, initially developed in the early 1960s. The discussion examines the significant challenges faced in defending an information-based approach to consciousness, particularly during the notable debate with E.V. Ilyenkov and subsequent opposition from his followers who held considerable influence in philosophical circles. Despite ideological pressure and accusations of revisionism, the author successfully advanced his theoretical framework, publishing numerous books and articles that elaborate on his theoretical and methodological approaches to decoding neural correlates of subjective reality. Following the publication of an English-language article outlining his theoretical foundations in a leading international neuroscience journal in 2019, the author received extensive recognition, including invitations to keynote international conferences and join editorial boards of international journals. This response demonstrates the pressing need for theoretical and methodological developments in neuroscience and related disciplines, highlighting a deficit in fundamental theoretical frameworks capable of guiding and integrating empirical research. The article concludes by emphasizing the significance of the information paradigm and its derivative approaches for studying consciousness, mental processes, and genetic aspects of biological functions.

A Polymer Thick Film on an Organic Substrate Grid Electrode and an Open-Source Recording System for UHF MRI: An Imaging Study.

Electrocorticography (ECoG) is a critical tool in preclinical neuroscience research for studying global network activity. However, integrating ECoG with functional magnetic resonance imaging (fMRI) has posed challenges, due to metal electrode interference with imaging quality and heating around the metallic electrodes. Here, we introduce recent advancements in ECoG grid development that utilize a polymer-thick film on an organic substrate (PTFOS). PTFOS offers notable advantages over traditional ECoG grids. Firstly, it significantly reduces imaging artifacts, ensuring minimal interference with MR image quality when overlaying brain tissue with PTFOS grids. Secondly, during a 30-min fMRI acquisition, the temperature increase associated with PTFOS grids is remarkably low, measuring only 0.4 °C. These findings suggest that utilizing ECoG with PTFOS grids has the potential to enhance the safety and efficacy of neurosurgical procedures. By providing clearer imaging results and mitigating risk factors such as excessive heating during MRI scans, PTFOS-based ECoG grids represent a promising advancement in neurosurgical technology. Furthermore, we describe a cutting-edge open-source system designed for simultaneous electrophysiology and fMRI. This system stands out due to its exceptionally low input noise levels (<0.6 V peak-to-peak), robust electromagnetic compatibility (it is suitable for use in MRI environments up to 9.4 teslas), and the inclusion of user-programmable real-time signal-processing capabilities. The open-platform software is a key feature, enabling researchers to swiftly implement and customize real-time signal-processing algorithms to meet specific experimental needs. This innovative system has been successfully utilized in several rodent EEG/fMRI studies, particularly at magnetic field strengths of 4.7 and 9.4 teslas, focusing on the somatosensory system. These studies have allowed for detailed observation of neural activity and responses within this sensory system, providing insights that are critical for advancing our understanding of neurophysiological processes. The versatility and high performance of our system make it an invaluable tool for researchers aiming to integrate and analyze complex datasets from advanced imaging and electrophysiological recordings, ultimately enhancing the depth and scope of neuroscience research.

MEG Microstates: An Investigation of Underlying Brain Sources and Potential Neurophysiological Processes

Microstates are transient scalp configurations of brain activity measured by electroencephalography (EEG). The application of microstate analysis in magnetoencephalography (MEG) data remains challenging. In one MEG dataset (N = 113), we aimed to identify MEG microstates at rest, explore their brain sources, and relate them to changes in brain activity during open-eyes (ROE) or closed-eyes resting state (RCE) and an auditory Mismatch Negativity (MMN) task. In another dataset of simultaneously recorded EEG-MEG data (N = 21), we investigated the association between MEG and EEG microstates. Six MEG microstates (mMS) provided the best clustering of resting-state activity, each linked to different brain sources: mMS 1–2: left/right occipito-parietal; mMS 3: fronto-temporal; mMS 4: centro-medial; mMS 5–6: left/right fronto-parietal. Increases in occipital alpha power in RCE relative to ROE correlated with greater mMS 1–2 time coverage (τbs < 0.20, ps > .002), while the lateralization of deviance detection in MMN was associated with mMS 5–6 time coverage (τbs < 0.16, ps > .012). No temporal correlation was found between EEG and MEG microstates (ps > .05), despite some overlap in brain sources and global explained variance between mMS 2–3 and EEG microstates B-C (rs > 0.60, ps < .002). Hence, the MEG signal can be decomposed into microstates, but mMS brain activity clustering captures phenomena different from EEG microstates. Source reconstruction and task-related modulations link mMS to large-scale networks and localized activities. Thus, mMSs offer insights into brain dynamics and task-specific processes, complementing EEG microstates in studying physiological and dysfunctional brain activity.

Absence of BOLD adaptation in chronic fatigue syndrome revealed by task functional MRI.

Neurological symptoms are central to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), yet its underlying neurophysiological mechanisms remain elusive. We examined a neglected aspect of task-based functional MRI, focusing on how blood oxygenation level-dependent (BOLD) signals alter during cognitive tasks in ME/CFS. This prospective observational study utilised MRI scans on ME/CFS participants and healthy controls (HCs) with sedentary lifestyles (ACTRN12622001095752). Participants completed two blocks of a Symbol Digit Modalities Test, with 30 trials per block split into two sets. The fMRI signal changes between blocks and sets were compared within and between groups. Thirty-four ME/CFS participants (38 years ± 10; 27 women) and 34 HCs (38 ± 10; 27 women), were evaluated. In the second task block, ME/CFS participants exhibited increased activation in the right postcentral gyrus, contrasting with decreased activation in multiple regions in HCs. These results were further confirmed by significantly higher bilateral dynamic changes (2nd vs 1st set) in the motor, sensory and cognitive cortex in ME/CFS compared to HCs and significant correlations between those changes in the left primary motor cortex with fatigue severities. BOLD adaptation, potentially improving energy economy, was absent in ME/CFS, which may provide an underlying neurophysiological process in ME/CFS.

The pathophysiology of estrogen in perinatal depression: conceptual update.

Estrogen levels fall sharply after parturition and have long been considered an etiologic contributor to postpartum depression (PPD); however, no differences have been reported in plasma hormone concentrations in people who develop PPD. We examine the question: What is the current view of estrogen and the neurophysiologic processes it impacts in the development and treatment of PPD? A literature review of the role of estrogen on candidate hormonal and epigenetic systems in the peripartum period was performed, including landmark historical studies and recent publications on estrogen-related research. The authors reviewed these papers and participated in reaching consensus on a conceptual framework of estrogen activity within the complexity of pregnancy physiology to examine its potential role for driving novel interventions. Estrogen fluctuations must be conceptualized in the context of multiple dramatic and interacting changes inherent in pregnancy and after birth, including progesterone, corticosteroids, inflammation, circadian biology and psychosocial challenges. Individuals who develop PPD have increased sensitivity to epigenetic alteration at estrogen-responsive genes, and these changes are highly predictive of PPD. An effective estrogen-based treatment for PPD has yet to be found, but interventions focused on associated inflammation and circadian rhythms are promising. Our understanding of the biological basis of PPD, one of the most common morbidities of the perinatal period, is expanding beyond changes in gynecologic hormone concentrations to include their impact on other systems. This growing understanding of the many processes influencing PPD will allow for the development of novel prevention and treatment strategies.

Chromosome-contiguous genome for the Haecon-5 strain of Haemonchus contortus reveals marked genetic variability and enables the discovery of essential gene candidates

Millions of livestock animals worldwide are infected with the haematophagous barber’s pole worm, Haemonchus contortus, the aetiological agent of haemonchosis. Despite the major significance of this parasite worldwide and its widespread resistance to current treatments, the lack of a high-quality genome for the well-defined strain of this parasite from Australia, called Haecon-5, has constrained research in a number of areas including host-parasite interactions, drug discovery and population genetics. To enable research in these areas, we report here a chromosome-contiguous genome (∼280 Mb) for Haecon-5 with high-quality models for 19,234 protein-coding genes. Comparative genomic analyses show significant genomic similarity (synteny) with a UK strain of H. contortus, called MHco3(ISE).N1 (abbreviated as “ISE”), but we also discover marked differences in genomic structure/gene arrangements, distribution of nucleotide variability (single nucleotide polymorphisms (SNPs) and indels) and orthology between Haecon-5 and ISE. We used the genome and extensive transcriptomic resources for Haecon-5 to predict a subset of essential single-copy genes employing a “cross-species” machine learning (ML) approach using a range of features from nucleotide/protein sequences, protein orthology, subcellular localisation, single-cell RNA-seq and/or histone methylation data available for the model organisms Caenorhabditis elegans and Drosophila melanogaster. From a set of 1,464 conserved single copy genes, transcribed in key life-cycle stages of H. contortus, we identified 232 genes whose homologs have critical functions in C. elegans and/or D. melanogaster, and prioritised 10 of them for further characterisation; nine of the 10 genes likely play roles in neurophysiological processes, germline, hypodermis and/or respiration, and one is an unknown (orphan) gene for which no detailed functional information exists. Future studies of these genes/gene products are warranted to elucidate their roles in parasite biology, host-parasite interplay and/or disease. Clearly, the present Haecon-5 reference genome and associated resources now underpin a broad range of fundamental investigations of H. contortus and could assist in accelerating the discovery of novel intervention targets and drug candidates to combat haemonchosis.

Mitigating Traumatic Brain Injury: A Narrative Review of Supplementation and Dietary Protocols.

Traumatic brain injuries (TBIs) constitute a significant public health issue and a major source of disability and death in the United States and worldwide. TBIs are strongly associated with high morbidity and mortality rates, resulting in a host of negative health outcomes and long-term complications and placing a heavy financial burden on healthcare systems. One promising avenue for the prevention and treatment of brain injuries is the design of TBI-specific supplementation and dietary protocols centred around nutraceuticals and biochemical compounds whose mechanisms of action have been shown to interfere with, and potentially alleviate, some of the neurophysiological processes triggered by TBI. For example, evidence suggests that creatine monohydrate and omega-3 fatty acids (DHA and EPA) help decrease inflammation, reduce neural damage and maintain adequate energy supply to the brain following injury. Similarly, melatonin supplementation may improve some of the sleep disturbances often experienced post-TBI. The scope of this narrative review is to summarise the available literature on the neuroprotective effects of selected nutrients in the context of TBI-related outcomes and provide an evidence-based overview of supplementation and dietary protocols that may be considered in individuals affected by-or at high risk for-concussion and more severe head traumas. Prophylactic and/or therapeutic compounds under investigation include creatine monohydrate, omega-3 fatty acids, BCAAs, riboflavin, choline, magnesium, berry anthocyanins, Boswellia serrata, enzogenol, N-Acetylcysteine and melatonin. Results from this analysis are also placed in the context of assessing and addressing important health-related and physiological parameters in the peri-impact period such as premorbid nutrient and metabolic health status, blood glucose regulation and thermoregulation following injury, caffeine consumption and sleep behaviours. As clinical evidence in this research field is rapidly emerging, a comprehensive approach including appropriate nutritional interventions has the potential to mitigate some of the physical, neurological, and emotional damage inflicted by TBIs, promote timely and effective recovery, and inform policymakers in the development of prevention strategies.