Normal Brain Function Research Articles

MicroRNA signatures in neuroplasticity, neuroinflammation and neurotransmission in association with depression.

Depression is a multifactorial disorder that occurs mainly on account of the dysregulation of neuroplasticity, neurotransmission and neuroinflammation in the brain. In addition to environmental /lifestyle factors, the pathogenesis of disease has been associated with genetic and epigenetic factors that affect the reprogramming of normal brain function. MicroRNA (miRNAs), a type of non-coding RNAs, are emerging as significant players that play a vital role in the regulation of gene expression and have been extensively explored in neurodegenerative disorders. Recent studies have also shown the role of gut microbiota that forms a complex bidirectional network with gut brain axis, impacting neuroinflammation in case of Parkinson's disease and depression. Translating targeted miRNA-based therapies for the treatment of neurological disorders including depression, into clinical practice remains challenging due to the ineffective delivery of the therapeutic molecules and off-target effects of the specific miRNAs. This review provides significant insights into how miRNAs are emerging as vital players in the development of depression, especially the ones involved in three important processes including neuroplasticity, neurotransmission and neuroinflammation. In this review, the current status of miRNAs as biomarkers for therapeutic interventions in the case of depression has been discussed along with an overview of future perspectives, like use of nanotechnology and gene editing, keeping in view other multifactorial disorders where such interventions by mimics and inhibitors have already reached clinical trials. The challenges for targeting the specific miRNAs for therapeutic outcomes have also been highlighted.

Time-restricted eating for prevention of age-related vascular cognitive decline in older adults: A protocol for a single-arm open-label interventional trial.

Age-related cerebromicrovascular endothelial dysfunction underlies the initiation and progression of cognitive dysfunction and dementia, thus increasing the susceptibility of older adults to such conditions. Normal brain function requires dynamic adjustment of cerebral blood flow to meet the energetic demands of active neurons, which is achieved the homeostatic mechanism neurovascular coupling (NVC). In this context, therapeutical strategies aimed at rescuing or preserving NVC responses can delay the incidence or mitigate the severity of age-related cognitive dysfunction, and time-restricted eating (TRE) is a potential candidate for such a strategy. Studies have reported that TRE can improve cardiometabolic risk factors in older adults. However, the effect of TRE on cerebrovascular endothelial function remains unexplored. Thus, this protocol outlines the study procedures to test our hypothesis that a 6-month TRE regimen of 10-h eating window will improve NVC responses and endothelial function in community-dwelling older adults. This is a single-arm, open-label interventional trial. We aim to recruit 32 adults aged 55-80 years. Participants are instructed to maintain a TRE regimen of 10 h of free eating followed by 14 h of fasting for 6 months. Before and after fasting, participants are assessed for cognitive performance, peripheral micro- and macrovascular endothelial function, and NVC responses, as well as for several confounding factors, including body composition, dietary, and physical activity data. We expect that 6 months of TRE will improve NVC response and endothelial function in older adults compared with baseline, and that these improvements will be accompanied by improvements in cognitive performance. The study proposed herein will provide critical insight into a new potential therapeutical strategy for targeting age-related cognitive dysfunction. Ultimately, slowing down or alleviating cognitive decline will translate into improved quality of life and longer healthspan for aging adults. This study was prospectively registered at ClinicalTrials.gov (NCT06019195) on August 24, 2023.

Diffusion‐Based Causality‐Preserving Neural Network for Dementia Recognition

ABSTRACTAnalyzing large‐scale functional brain networks for brain disorders often relies on undirected correlations in activation signals between brain regions. While focusing on co‐occurring activations, this approach overlooks the potential for directionality inherent in brain connectivity. Established research indicates the causal nature of brain networks, suggesting that activation patterns co‐occur and potentially influence one another. To this end, we propose a novel dffusion vector auto‐regressive (Diff‐VAR) method, enabling the assessment of whole‐brain effective connectivity (EC) as a directed and weighted network by integrating the search objectives into the deep neural network model as learnable parameters. The EC learned by our method identifies widespread differences in flow of influence within the brain network for individuals with impaired brain function compared to those with normal brain function. Moreover, we introduce an adaptive smoothing mechanism to enhance the stability and reliability of inferred EC. We evaluated the results of our proposed method on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The model's performance is compared with existing correlation‐based and causality‐based methods. The results revealed that the brain networks constructed by our method achieve high classification accuracy and exhibit features consistent with physiological mechanisms. The code is available at https://github.com/SaqibMamoon/Diff‐VAR.

Effect of serum antioxidants on cognitive dysfunction in first-episode and drug-naïve patients with major depressive disorder.

Cognitive dysfunction is a persistent and difficult-to-treat symptom of major depressive disorder (MDD) and is receiving increasing attention. A balanced state of oxidative stress sustained by antioxidants is essential for normal functioning of brain, including learning capacity, emotional regulation, and cognitive function. The correlation between cognition and oxidative stress may also be altered in patients with mental disorders. This study aimed to explore the relationship between serum antioxidant levels and cognitive dysfunction in patients with MDD. We collected and matched cognitive performance data using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), serum antioxidants, and demographic and clinical characteristics of 105 first-episode drug-naïve patients with MDD and 53 healthy controls (HC) from February 2022 to October 2023, and then analyzed the differences between the two groups. HamiltonDepressionScale-17 and Young Mania Rating Scale (YMRS) were used to evaluate the clinical symptoms of the participants with MDD. Serum antioxidants, including albumin (ALB), uric acid (UA), and superoxide dismutase (SOD) were used to detect the level of oxidative stress in participants and its correlation with cognitive function. We then used a threshold for cognitive dysfunction of 1.5 standard deviations below the mean of the standard score to divide the participants with MDD into two groups to detect the relevant elements of the five different domains of cognitive dysfunction in MDD. ALB levels were significantly lower in the MDD group (p = 0.001) after adjusting for years of education. The performance in all five domains of cognitive function was significantly worse in the MDD group than in the HC group (p < 0.001). Speed of processing (SOP) in the MDD group correlated with ALB (r = 0.261, p = 0.008), and UA (r = 0.295, p = 0.002) levels. We also explored the correlation between the attention/vigilance (AV) domain and the UA (r = 0.239, p = 0.015). YMRS score was risk factor of impairment of SOP domain in patients with MDD. Yet UA was a protective factor against SOP impairment, with a 0.006-fold reduction in the risk of SOP impairment for each 1-unit increase in UA. As serum antioxidants, ALB and UA may serve as biomarkers of cognitive function in patients with MDD. Our findings contribute to the understanding of the potential ability of serum antioxidants to predict cognitive decline in patients with MDD.

Gene expression is associated with brain function of insomnia disorder, rather than brain structure

Previous research has found brain structural and functional abnormalities in patients with insomnia disorder (ID). However, the relationship between brain abnormalities in ID and brain gene expression is unclear. This study explored the relationship between gene expression and brain structural or functional abnormalities in ID, and we validated the reliability of the results with two independent datasets (discover dataset: healthy control (HC) = 129, ID = 264; validation dataset: HC = 160, ID = 115). Brain imaging results show that ID has abnormal resting-state spontaneous activity, regional homogeneity, and widespread gray matter volume reduction compared to HC. The association analysis results with gene expression further revealed that brain function abnormalities in ID were significantly associated with gene expression, but structural abnormalities were not. This study establishes a link between transcriptional changes and brain functional abnormalities in ID, revealing a genetic basis that may involve several biological pathways. Specifically, these pathways include hormonal regulation of the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in stress response and sleep regulation; ion transport across membranes, vital for neuronal communication; and inhibitory neuronal regulation, essential for maintaining normal brain function. Furthermore, the ID-related genes are enriched for brain tissue and cortical cells, emphasizing their relevance in understanding the biological underpinnings of ID.

Neural integration of egocentric and allocentric visual cues in the gaze system.

A fundamental question in neuroscience is how the brain integrates egocentric (body-centered) and allocentric (landmark-centered) visual cues, but for many years this question was ignored in sensorimotor studies. This changed in recent behavioral experiments, but the underlying physiology of ego / allocentric integration remained largely unstudied. The specific goal of this review is to explain how prefrontal neurons integrate eye-centered and landmark-centred visual codes for optimal gaze behavior. First, we briefly review the whole-brain / behavioral mechanisms for ego / allocentric integration in the human and summarize egocentric coding mechanisms in the primate gaze system. We then focus in more depth on cellular mechanisms for ego / allocentric coding in the frontal and supplementary eye fields. We first explain how prefrontal visual responses integrate eye-centered target and landmark codes to produce a transformation toward landmark-centered coordinates. Next, we describe what happens when a landmark shifts during the delay between seeing and acquiring a remembered target, initially resulting in independently co-existing ego / allocentric memory codes. We then describe how these codes are re-integrated in the motor burst for the gaze shift. Deep network simulations suggest that these properties emerge spontaneously for optimal gaze behavior. Finally, we synthesize these observations and relate them to normal brain function through a simplified conceptual model. Together, these results show that integration of visuospatial features continues well beyond visual cortex and suggests a general cellular mechanism for goal-directed visual behaviour.

Temporal attention fusion network with custom loss function for EEG–fNIRS classification

Objective.Methods that can detect brain activities accurately are crucial owing to the increasing prevalence of neurological disorders. In this context, a combination of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) offers a powerful approach to understanding normal and pathological brain functions, thereby overcoming the limitations of each modality, such as susceptibility to artifacts of EEG and limited temporal resolution of fNIRS. However, challenges such as class imbalance and inter-class variability within multisubject data hinder their full potential.Approach.To address this issue, we propose a novel temporal attention fusion network (TAFN) with a custom loss function. The TAFN model incorporates attention mechanisms to its long short-term memory and temporal convolutional layers to accurately capture spatial and temporal dependencies in the EEG-fNIRS data. The custom loss function combines class weights and asymmetric loss terms to ensure the precise classification of cognitive and motor intentions, along with addressing class imbalance issues.Main results.Rigorous testing demonstrated the exceptional cross-subject accuracy of the TAFN, exceeding 99% for cognitive tasks and 97% for motor imagery (MI) tasks. Additionally, the ability of the model to detect subtle differences in epilepsy was analyzed using scalp topography in MI tasks.Significance.This study presents a technique that outperforms traditional methods for detecting high-precision brain activity with subtle differences in the associated patterns. This makes it a promising tool for applications such as epilepsy and seizure detection, in which discerning subtle pattern differences is of paramount importance.

Intravascular delivery of an ultraflexible neural electrode array for recordings of cortical spiking activity

Although intracranial neural electrodes have significantly contributed to both fundamental research and clinical treatment of neurological diseases, their implantation requires invasive surgery to open craniotomies, which can introduce brain damage and disrupt normal brain functions. Recent emergence of endovascular neural devices offers minimally invasive approaches for neural recording and stimulation. However, existing endovascular neural devices are unable to resolve single-unit activity in large animal models or human patients, impeding a broader application as neural interfaces in clinical practice. Here, we present the ultraflexible implantable neural electrode as an intravascular device (uFINE-I) for recording brain activity at single-unit resolution. We successfully implanted uFINE-Is into the sheep occipital lobe by penetrating through the confluence of sinuses and recorded both local field potentials (LFPs) and multi-channel single-unit spiking activity under spontaneous and visually evoked conditions. Imaging and histological analysis revealed minimal tissue damage and immune response. The uFINE-I provides a practical solution for achieving high-resolution neural recording with minimal invasiveness and can be readily transferred to clinical settings for future neural interface applications such as brain-machine interfaces (BMIs) and the treatment of neurological diseases.

Assessment of brain function during stunning and killing of channel catfish (Ictalurus punctatus)

Measurement of brain activity is a reliable method to determine loss of consciousness during the slaughter of terrestrial farm animals. In fish, the ability to obtain an electroencephalogram (EEG), even in unrestrained individuals, has enabled the assessment and optimization of stunning and killing methods in aquaculture. This study evaluated the effect of percussive and in-water electrical stunning in channel catfish (Ictalurus punctatus) using the loss of visual evoked responses (VERs) as indicator of loss of consciousness. Our results show that percussive stunning with a fish bonker effectively caused permanent disruption of normal brain function when applied correctly. However, there is a risk of mis-stuns, with 20 % of the catfish showing temporarily or permanently responsiveness after stunning (i.e. presence of VERs). Exposure to an electric field strength of 13 Vrms cm−1 and a current density of 1.3 Arms dm−2 for 1 s caused immediate but, in contrast to successful percussive stunning, transient loss of VERs. Extending the exposure time to 10 s using the same electrical parameters did not affect recovery based on VERs, nor did increasing the field strength to 24 Vrms cm−1 and a current density to 2.1 Arms dm−2 using a 10 s exposure time. The recovery time was also unaffected by post-stun placement of fish in air or water. However, a 10 s shock with an electric field of 24 Vrms cm−1 and a current density of 2.1 Arms dm−2 immediately followed by decapitation, prevented recovery in 70 % of the catfish with the remaining 30 % experiencing temporary recovery (i.e. presence of VERs) for a few minutes. Our findings show that different stunning methods offer distinct advantages and limitations. Modifying the slaughter protocol in commercial catfish production, considering these methods, could significantly enhance the welfare of channel catfish during slaughter.

TGF-β Signaling in Microglia: A Key Regulator of Development, Homeostasis and Reactivity.

Microglia, the resident immune cells of the central nervous system (CNS), are crucial for normal brain development and function. They become reactive in response to brain injury and disease, a process known as microglial reactivity. This reactivity, along with microglial homeostasis, is tightly regulated by the local microenvironment and interactions with surrounding cells. The TGF-β signaling pathway plays an essential role in this regulation. Recent genetic studies employing microglia-specific manipulation of the TGF-β signaling pathway have shed light on its significance in microglial development, homeostasis and reactivity. This review provides an updated overview of how TGF-β signaling modulates microglial function and reactivity, contributing to our understanding of microglial biology in health and disease.

In Case You Haven't Heard…

Keeping your brain sharp as you age has a lot to do with your heart — and the younger you start taking better care of it, the better — according to a new scientific statement published by the American Heart Association (AHA), CNN Health reported Oct. 10. “Dementia is commonly seen as an incurable and relentless disease that cannot be prevented,” said Fernando Testai, M.D., Ph.D., a professor of neurology and rehabilitation at the University of Illinois College of Medicine in Chicago, in a statement. “Evidence shows, however, that adopting a healthy lifestyle and identifying and treating vascular risk factors early may help preserve normal brain function and reduce the burden of Alzheimer's disease and other related dementias,” said Testai, who chaired the statement writing group. Nearly 130 million adults in the United States have some form of heart disease, according to the AHA. The disease also takes a toll on the brain. The narrowing of arteries that occurs with coronary heart disease and high blood pressure can reduce blood flow and cause damage to the small blood vessels in the brain, resulting in cognitive impairment, the AHA said. High blood pressure and Type 2 diabetes can also reduce blood flow to the brain and increase inflammation, leading to cognitive decline and dementia. Having coronary heart disease raises the risk of future dementia by 27% compared with people without heart disease, the AHA statement said.

The Dysregulation of the Glymphatic System in Patients with Psychosis Spectrum Disorders Minimally Exposed to Antipsychotics: La dérégulation du système glymphatique en présence de troubles psychotiques chez des patients peu exposés à des antipsychotiques.

The pathophysiological mechanisms influencing psychosis spectrum disorders are largely unknown. The glymphatic system, which is a brain waste clearance pathway, has recently been implicated in its pathophysiology and has also been shown to be disrupted in various neurodegenerative and vascular diseases. Initial studies examining the glymphatic system in psychosis spectrum disorders have reported disruptions, but the findings have been confounded by medication effects as they included antipsychotic-treated patients. In this study, we used diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) as a technique to measure the functionality of the glymphatic system in a sample of antipsychotic-minimally exposed patients with psychosis spectrum disorders and healthy controls. The study included 13 antipsychotic-minimally exposed (2 weeks antipsychotic exposure in the past 3 months/lifetime) patients with psychosis spectrum disorders and 114 healthy controls. We quantified water diffusion metrics along the x-, y-, and z-axes in both projection and association fibres to derive the DTI-ALPS index, a proxy for glymphatic activity. Between-group differences were analyzed using two-way ANCOVA controlling for age and sex. Partial correlations were used to assess the association between the ALPS index and clinical variables. Analyses revealed that antipsychotic-minimally exposed psychosis spectrum disorder patients had a lower DTI-ALPS index value than healthy controls in both hemispheres and the whole brain (all P < 0.005). Significant differences were also observed between the x and y projections/associations between patients and healthy controls (P < 0.001). Furthermore, we did not find any significant correlations (all P > 0.05) between the DTI-ALPS index with age, body mass index, symptomatology, and metabolic parameters. This study shows that the glymphatic system is dysregulated in antipsychotic-minimally exposed patients with psychosis spectrum disorders. Understanding the mechanisms that influence the glymphatic system may help to understand the pathophysiology of psychosis spectrum disorders as proper waste clearance is needed for normal brain functioning.

White matter engagement in brain networks assessed by integration of functional and structural connectivity

Current models of brain networks may potentially be improved by integrating our knowledge of structural connections, within and between circuits, with metrics of functional interactions between network nodes. The former may be obtained from diffusion MRI of white matter (WM), while the latter may be derived by measuring correlations between resting state BOLD signals from pairs of gray matter (GM) regions. From inspection of diffusion MRI data, it is clear that each WM voxel within a 3D image array may be traversed by multiple WM structural tracts, each of which connects a pair of GM nodes. We hypothesized that by appropriately weighting and then integrating the functional connectivity of each such connected pair, the overall engagement of any WM voxel in brain functions could be evaluated. This model introduces a structural constraint to earlier studies of WM engagement and addresses some limitations of previous efforts to relate structure and function. Using concepts derived from graph theory, we obtained spatial maps of WM engagement which highlight WM regions critical for efficient communications across the brain. The distributions of WM engagement are highly reproducible across subjects and depict a notable interdependence between the distribution of GM activities and the detailed organization of WM. Additionally, we provide evidence that the engagement varies over time and shows significant differences between genders. These findings suggest the potential of WM engagement as a measure of the integrity of normal brain functions and as a biomarker for neurological and cognitive disorders.

Glial cells undergo rapid changes following acute chemogenetic manipulation of cortical layer 5 projection neurons

Bidirectional communication between neurons and glial cells is crucial to establishing and maintaining normal brain function. Some of these interactions are activity-dependent, yet it remains largely unexplored how acute changes in neuronal activity affect glial-to-neuron and neuron-to-glial dynamics. Here, we use excitatory and inhibitory designer receptors exclusively activated by designer drugs (DREADD) to study the effects of acute chemogenetic manipulations of a subpopulation of layer 5 cortical projection and dentate gyrus neurons in adult (Rbp4Cre) mouse brains. We show that acute chemogenetic neuronal activation reduces synaptic density, and increases microglia and astrocyte reactivity, but does not affect parvalbumin (PV+) neurons, only perineuronal nets (PNN). Conversely, acute silencing increases synaptic density and decreases glial reactivity. We show fast glial response upon clozapine-N-oxide (CNO) administration in cortical and subcortical regions. Together, our work provides evidence of fast, activity-dependent, bidirectional interactions between neurons and glial cells.

Unveiling the interplay of MAPK/NF-κB/MLKL axis in brain health: Omega-3 as a promising candidates against copper neurotoxicity

Excessive intake of copper (Cu) may lead to increased inflammatory responses in brain, which can cause damage to neurons and glial cells, thereby affecting normal brain function. Omega-3 (ω-3) is a common dietary supplement, particularly rich in DHA in the brain, known for its anti-inflammatory properties and its role in lipid balance regulation and structural maintenance. Here, ω-3 is supplemented to Cu-exposed chickens to assess its neuroprotection in vivo and in vitro. Pathologically, ω-3 significantly alleviated structural and functional abnormalities in brain under excess Cu, including barrier disruption, neuronal shrinkage necroptosis and increased release of inflammatory factors such as IL-1β. The molecular docking analyses unveiled high enrichment values of inflammation and MAPK pathway, with IL-1β gene enrichment the highest value. Mechanistically, DHA stabilized the active site of IL-1β, thereby reducing the activation of NF-κB signal and phosphorylation of MAPK/MLKL cascades, ultimately mitigating Cu-induced inflammatory effects. These mechanisms elucidate the action mode of Cu neurotoxicity from aspect of MAPK/NF-κB/MLKL axis and the promising neuroprotection of ω-3.

A Study to Assess the Effectiveness of Structured Teaching Programme on Knowledge regarding Cardio Pulmonary Resuscitation among Higher Secondary School Students in Selected Schools, Aizawl, Mizoram

Background: Cardio pulmonary resuscitation is a process of oxygenating heart, lung through external cardiac massage and artificial respiration until the definite medical treatment can restore the normal functioning of heart, lung and brain. Cardio pulmonary resuscitation (CPR) is a lifesaving technique that is useful in many emergencies in which someone's breathing or heartbeat has stopped. The purpose of this study is to assess the knowledge and effectiveness of Structured Teaching Programme regarding cardio pulmonary resuscitation among higher secondary school students. Methods: The research design used in the study was one group pre-test post-test design, in which stratified random sampling technique was used to select 100 students of Govt. Chaltlang Higher Secondary School. Self-Structured Knowledge Questionnaires was used to collect the Data. Post test was conducted after 7 days using the same self-structured knowledge questionnaires used for the pre- test. Results: The mean difference between the pre - test and post- test knowledge score was found to be 12.29 with t-value=-24.82, &amp; p value =0.05 which indicates that indicates that Structured Teaching Programme regarding cardio pulmonary resuscitation was effective. Thus, the research Hypothesis H 1 is accepted. Conclusion: The overall findings of the study suggested that Structured Teaching Programme on Cardio pulmonary resuscitation was significantly effective in improving the knowledge of students regarding Cardio pulmonary resuscitation technique.

Development and evaluation of an EMP course to teach fMRI technology and brain science in handwriting for university nursing students

In traditional nursing education, brain science is often limited to physiology, anatomy, and pathology, with little emphasis on advanced diagnostic tools like fMRI or the brain’s functional processes, such as language learning and handwriting. This study developed an English for Medical Purposes (EMP) course to teach university nursing students about fMRI technology and brain science related to handwriting, highlighting the importance of interprofessional education. The study aimed to (a) assess the course’s effectiveness in enhancing students’ knowledge in fMRI, brain science, and handwriting; and (b) evaluate the students’ satisfaction and perceptions toward the course. A single-group quasi-experimental design with pre/post-tests involved 49 nursing students. Data were collected using the Brain Science Related Knowledge Test (BSKT), assignments, and a Course Satisfaction Questionnaire (CSQ). Results showed significant improvements in students’ knowledge of fMRI and brain science in handwriting, with high assignment scores and overall course satisfaction. Students also reported increased awareness of reading professional English journals and learned about fMRI safety issues. This pioneering EMP course effectively introduced nursing students to fMRI technology and brain science in handwriting, potentially enhancing their understanding of normal brain function and its contrast with brain injury cases.

The epigenetic modification of DNA methylation in neurological diseases.

Methylation, a key epigenetic modification, is essential for regulating gene expression and protein function without altering the DNA sequence, contributing to various biological processes, including gene transcription, embryonic development, and cellular functions. Methylation encompasses DNA methylation, RNA methylation and histone modification. Recent research indicates that DNA methylation is vital for establishing and maintaining normal brain functions by modulating the high-order structure of DNA. Alterations in the patterns of DNA methylation can exert significant impacts on both gene expression and cellular function, playing a role in the development of numerous diseases, such as neurological disorders, cardiovascular diseases as well as cancer. Our current understanding of the etiology of neurological diseases emphasizes a multifaceted process that includes neurodegenerative, neuroinflammatory, and neurovascular events. Epigenetic modifications, especially DNA methylation, are fundamental in the control of gene expression and are critical in the onset and progression of neurological disorders. Furthermore, we comprehensively overview the role and mechanism of DNA methylation in in various biological processes and gene regulation in neurological diseases. Understanding the mechanisms and dynamics of DNA methylation in neural development can provide valuable insights into human biology and potentially lead to novel therapies for various neurological diseases.

From gut to brain: unveiling probiotic effects through a neuroimaging perspective-A systematic review of randomized controlled trials.

The gut-brain axis, a bidirectional communication network between the gastrointestinal system and the brain, significantly influences mental health and behavior. Probiotics, live microorganisms conferring health benefits, have garnered attention for their potential to modulate this axis. However, their effects on brain function through gut microbiota modulation remain controversial. This systematic review examines the effects of probiotics on brain activity and functioning, focusing on randomized controlled trials using both resting-state and task-based functional magnetic resonance imaging (fMRI) methodologies. Studies investigating probiotic effects on brain activity in healthy individuals and clinical populations (i.e., major depressive disorder and irritable bowel syndrome) were identified. In healthy individuals, task-based fMRI studies indicated that probiotics modulate brain activity related to emotional regulation and cognitive processing, particularly in high-order areas such as the amygdala, precuneus, and orbitofrontal cortex. Resting-state fMRI studies revealed changes in connectivity patterns, such as increased activation in the Salience Network and reduced activity in the Default Mode Network. In clinical populations, task-based fMRI studies showed that probiotics could normalize brain function in patients with major depressive disorder and irritable bowel syndrome. Resting-state fMRI studies further suggested improved connectivity in mood-regulating networks, specifically in the subcallosal cortex, amygdala and hippocampus. Despite promising findings, methodological variability and limited sample sizes emphasize the need for rigorous, longitudinal research to clarify the beneficial effects of probiotics on the gut-brain axis and mental health.

Isoflurane Titration Improves Detection of Hippocampal Lactate by 1H-MRS

Abstract Lactate has increasingly been recognized as both an important fuel source and signaling molecule within the brain. Alterations in brain lactate levels are associated with various neurological diseases. Thus, there is great interest in the in vivo detection and measurement of cerebral lactate levels in animals used for investigation of normal brain function and models of disease. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive technique used to measure lactate and other metabolites within the brain. However, lactate can be difficult to detect with conventional 1H-MRS due to its low abundance and spectral overlap with lipids. In addition, volatile anesthetics used during image acquisition increase lactate production, potentially masking any subtle physiological changes in lactate levels. Here we made use of a transgenic mouse model in which expression of lactate dehydrogenase A (Ldha), the rate-limiting enzyme of lactate production, was induced within cortical and hippocampal neurons. Unexpectedly, 1H-MRS analysis under typical isoflurane-induced anesthesia of 4% induction followed by 1.6-2% maintenance, revealed no significant elevation of hippocampal lactate levels in neuronal Ldha induction mice compared to control mice. In contrast, 1H-MRS analysis using an isoflurane titration protocol in which mice were sequentially exposed to 1.6%, 2%, then finally 3% isoflurane, revealed significantly higher hippocampal lactate levels in Ldha transgenic mice compared to controls. In addition, significantly fewer mice were required to detect differences in lactate levels using the isoflurane titration protocol compared to conventional isoflurane-induced anesthesia. Our findings highlight the importance of controlling for the effects of anesthesia when detecting changes in hippocampal lactate levels in vivo and offer a novel protocol for enhanced cerebral lactate detection.