JoVE Neuroscience is a multidisciplinary section devoted to investigations of the structure, function, physiology, and pathophysiology of the brain and nervous system. Included methodologies range from molecular and cellular level studies to full central and peripheral neural systems. Potential treatment platforms and surgical techniques for neurological diseases and disorders are also presented in this section.

Neuroscience

JoVE Medicine serves as a connection between basic research and clinical applications. Articles may present medical procedures, case studies or clinical trial methodologies. Included studies are often modeled towards predictive, preventative, personalized, and practical approaches to treatment of disease. The goal of research methodologies in this section is to improve overall patient care and prognosis.

Medicine

JoVE Immunology and Infection includes content from a variety of fields working toward a shared initiative of improving global health. Techniques evaluating the biological response to pathogens from the molecular to organismal level are presented as well as therapeutic agents and their efficacy in treating disease.

Immunology and Infection

JoVE Genetics publishes video articles demonstrating experimental approaches to investigate gene function and regulation. This includes methods to study gene expression, mutagenesis, epigenetics, genetic determinants of development, genetic disorders, population genetics and evolution.

Genetics

JoVE Environment is dedicated to research methodologies that address environmental concerns and seek to better understand Earth's ecosystem.  Special consideration is given to experimental methodologies that assess society’s impact on the environment, suggest solutions for protecting Earth’s resources, and develop sustainable fuel sources. Moving towards an environmentally conscious planet is a collaborative effort with contributions from both life and physical scientists.

Environment

JoVE Engineering encompasses a broad range of experimental and instrumental techniques utilized in physics research. Investigations in this area strive to address and answer a broad range of scientific questions, such as device mechanisms and efficiencies, using physical tools. This approach often requires a combination of specialties, and research in this area tends to be interdisciplinary with contributions from mechanical, electrical, and chemical engineers.

Engineering

JoVE Developmental Biology publishes research methodologies in the field of developmental biology. This includes methods that are used to study biological development in vitro and in vivo at the molecular, cellular, tissue, organ and whole organism levels.

Developmental Biology

JoVE Chemistry surveys a broad scope of chemical disciplines. This collection includes fundamental and applied research that investigates molecular interactions, properties, and structure spanning in the following core divisions: analytical, organic, organometallic, inorganic, bioinorganic, and biochemistry. This section also includes the design and preparation of materials and small molecules for advanced or unique applications.

Chemistry

JoVE Cancer Research illustrates experimental approaches in biomedical research and clinical practice aimed at understanding, detecting, treating and preventing cancer. The video articles in this section demonstrate methods to study the cellular and molecular mechanisms of cancer, animal models of cancer research, development of new therapies and diagnostics, tumor imaging, chemical and radiation treatments, surgical procedures and improvements in therapy. These video articles offer researchers and clinical practitioners an efficient way to learn the technologies and experimental methods in cancer research.

Cancer Research

JoVE Biology welcomes all general biology research methodologies. Content in this section canvases all fields of cell, molecular, and organismal biology, ranging from new applications of standard techniques to novel approaches aimed at understanding the functions of life and living organisms. This diverse section includes, but is not limited to, techniques in physical biology, cellular biochemistry, genetics, physiology, systems biology and a combination of eukaryotic and prokaryotic model systems.

Biology

JoVE Bioengineering merges both physical and life sciences to understand and predict biological processes. Applying physical science tools to life science questions allow for the discovery of better technologies to measure, diagnose, and clinically treat disease.

Bioengineering

JoVE Biochemistry publishes experiments that investigate the structure, function, and interactions of biological molecules. The video articles in this section demonstrate methods to study nucleic acids, proteins, carbohydrates and lipids as well as enzyme function, protein folding, molecular interactions and biochemical reactions.

Biochemistry

JoVE Behavior documents observational and experimental techniques that seek to understand human and animal behavior. Work in this field includes analysis of genetic causes and physiological responses to internal or external stimuli as well as the implicated brain regions.

Behavior

The default mode network (DMN) is a central, large-scale brain network implicated in a range of cognitive functions and neuropsychiatric disorders, such as major depressive disorder (MDD). Studying the DMN&#39;s complex dynamics in animal models provides invaluable insights into its function in both healthy and pathological states. However, performing stable, long-term, large-scale electrophysiological recordings from the multiple deep and distributed nodes of the DMN in awake, behaving mice remains a significant challenge.
Here, a novel two-phase surgical protocol is presented to create a large (4 mm &#215; 7.6 mm), durable, and resealable cranial window in mice. The procedure is designed to preserve the integrity of the dura mater, which is paramount for long-term brain health and recording stability.
This window enables simultaneous, repeated, longitudinal recordings from over 1,000 electrodes by combining surface-level micro-electrocorticography (&#181;ECoG) with two high-density intracranial electrode probes, providing unprecedented access to the DMN. This technique provides a robust platform for multi-modal, multi-scale interrogation of network-wide electrophysiological dynamics over several weeks, opening new avenues for investigating the neuroplastic changes underlying the pathophysiology of brain disorders and for evaluating the chronic effects of novel therapeutics.

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Surgical Protocol for a Large, Resealable Cranial Window Enabling Longitudinal, Multi-Modal Electrophysiology Recordings of Mouse Default Mode Network

The default mode network (DMN) is a central, large-scale brain network implicated in a range of cognitive functions and neuropsychiatric disorders, such ...

The objective of this study was to assess oxidative phosphorylation (OXPHOS) function in cultured cells using defined substrate&#8211;inhibitor combinations while retaining cellular structure and cytosolic context lost in isolated mitochondrial preparations. Because intact cells are poorly permeable to several Krebs cycle intermediates, direct assessment of substrate-supported respiration through specific electron transport chain (ETC) entry points is limited. To overcome this, we applied digitonin-mediated selective plasma membrane permeabilization and performed extracellular flux analyzer&#8211;based coupling and electron flow assays in BE(2)-C neuroblastoma cells. To determine cell-type dependence, digitonin was empirically titrated in HEK293 cells and primary rat dorsal root ganglion (DRG) neurons using succinate + rotenone to isolate Complex II&#8211;IV&#8211;driven respiration.
Succinate-supported respiration with Complex I inhibition showed increased Complex II&#8211;IV&#8211;driven oxygen (O&#8322;) consumption in permeabilized compared with non-permeabilized cells, consistent with improved access of a membrane-impermeant substrate to mitochondria. In contrast, respiration supported by substrates that enter via endogenous transport pathways (e.g., pyruvate/malate) showed smaller differences between conditions. Using this platform to test muscarinic ligands, we observed agonist- versus antagonist-associated differences in O&#8322; consumption in the coupling assay, whereas the electron flow assay revealed minimal ligand-associated effects under the tested conditions. These findings indicate that detectable ligand effects were more prominent at the level of coupling-defined respiratory states than maximal electron transfer capacity. Overall, selective permeabilization expands substrate accessibility in cultured-cell bioenergetic assays and enables analysis of pharmacologic modulation of mitochondrial respiration.

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Cholinergic Ligand&#8211;dependent Modulation of Oxidative Phosphorylation Coupling in Digitonin-permeabilized BE(2)-C Neuroblastoma Cells

The objective of this study was to assess oxidative phosphorylation (OXPHOS) function in cultured cells using defined substrate&#8211;inhibitor ...

Improving the outcomes of transcranial magnetic stimulation (TMS) therapy for treatment-resistant depression may be achieved by personalizing the targeting of the dorsolateral prefrontal cortex (DLPFC) and providing precise dose delivery. We recently reported the initial clinical outcomes of an open-label study using a robotically delivered functional magnetic resonance imaging (fMRI) guided, personalized TMS therapy in treatment-resistant depression. Here, we describe the protocol used in the clinical implementation of personalized TMS for treatment-resistant depression. This protocol has been clinically implemented since November 2021. Patients with treatment-resistant depression are assessed and consented for TMS therapy. Eligible patients undertake an anatomical and 15 min eyes-open, resting-state MRI. Anatomical and functional data are uploaded to a cloud-based platform to calculate the optimal TMS target within the left dorsolateral prefrontal cortex (DLPFC) via an established approach. The output of this processing pipeline identifies brain clusters characterized by the strongest anticorrelation between fMRI signals in the subgenual cingulate cortex (SGC) and DLPFC. The TMS target is refined based on individual anatomy (e.g., gyrus position) and the size of targeted cortical cluster(s). A scalp entry point for the target is calculated via neuronavigation software. Neuronavigation is used to guide a TMS coil mounted to a robotic arm, enabling precise and consistent stimulation within and across sessions. Patients undertake daily TMS sessions over 4-6 weeks using intermittent theta-burst stimulation at 120% resting motor threshold. Symptom response is assessed 2 weeks after treatment completion. This protocol demonstrates the resources and workflow required for robotically delivered fMRI-guided personalized TMS for treatment-resistant depression.

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Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Treatment-Resistant Depression

Improving the outcomes of transcranial magnetic stimulation (TMS) therapy for treatment-resistant depression may be achieved by personalizing the ...

Studying brachial plexus birth injuries (BPBI) has been challenging due to heterogeneous clinical presentations and limited reliable animal models. To that end, we have developed a surgical protocol that reproducibly induces a pan-plexal neonatal brachial plexus injury in 5-day-old Sprague-Dawley rat pups. In this article, step-by-step instructions are provided for approaching the brachial plexus in a rat pup. The technique was performed on 15 Sprague Dawley rat pups. Using a dorsal approach under operative microscopy, a 5 mm dorsal incision was made starting at the base of the skull towards the level of C7-T1 vertebral transition. Blunt dissection is carried down to the trapezius muscle, followed by dissection through the underlying rhomboid and levator scapulae muscles. After identifying anatomical landmarks such as the spine and the scapula, the superior angle of the scapula was gently retracted to visualize the brachial plexus. The brachial plexus was localized and cauterized, evidenced by observable twitches in the upper extremity. To prevent nerve regeneration, a small block of an absorbable gelatin sponge was placed between the proximal and distal ends of the injured nerves. This procedure was successfully performed on all 15 rat pups with 87% survival. Postoperative and at sacrifice, all surviving rats demonstrated complete pan-plexal injuries, validating this model as effective and reproducible for research in brachial plexus birth injuries.

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Development of a Neonatal Rat Model for Brachial Plexus Birth Injury

Studying brachial plexus birth injuries (BPBI) has been challenging due to heterogeneous clinical presentations and limited reliable animal models. To ...

In the ride-hailing industry, effective service recovery strategies following service failures are crucial for passenger satisfaction and platform reputation. However, how the combination of agent type and language style influences passenger satisfaction and the underlying neural mechanisms remains unclear. This study designed an event-related potentials (ERPs) experiment to investigate how two key factors in post-failure remediation -- service agent type and language style -- affect passenger satisfaction and its neural correlates. A 2 (Agent Type: Human/AI) &#215; 2 (Language Style: Humorous/Rational) within-subjects design was employed. Using E-Prime software, participants were presented with five pre-selected, common ride-hailing service failure scenarios. Each scenario was followed by a standardized voucher compensation offer delivered by an agent, with the agent type and language style systematically varied across trials. The procedure involved simultaneous recording of 64-channel electroencephalographic (EEG) signals and collection of behavioral satisfaction ratings. Behavioral data indicated higher satisfaction ratings for human agent and the humorous language style. ERPs results revealed more negative N2 and feedback-related negativity (FRN) amplitudes elicited by the rational language style, whereas human agents and the rational style elicited more positive P300 amplitudes. This study details the standardized preparation of experimental stimuli, precise timing control of the experimental procedure, EEG recording preparation based on the International 10-20 system, and the complete methodological pipeline from data acquisition to preprocessing. This protocol offers high temporal resolution and good reproducibility. It is suitable for research in consumer neuroscience, human-computer interaction, and service management that requires precise quantification of the temporal dynamics underlying social cognition and decision-making processes.

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Humor or Rationality? The Neural Mechanisms of How Agent Type and Language Style Influence Satisfaction with Ride-Hailing Service Failure Recovery

In the ride-hailing industry, effective service recovery strategies following service failures are crucial for passenger satisfaction and platform ...

Early childhood (3 to 5 years of age) is a period marked by significant changes in the brain. This development underlies age-related improvements in several domains - including language, memory, and socioemotional skills. However, assessing brain structure and function during this period using MRI poses several challenges. For example, difficulty remaining still, maintaining attention for long periods and non-compliance in performing behavioral responses in the scanner are particularly prevalent issues. Technological advances in neuroimaging techniques over the past decade have significantly improved success rates for pediatric neuroimaging studies. For example, shorter scan durations and real-time monitoring and correction of motion during scanning have proven especially valuable in acquiring reliable data. However, developmental researchers must still be creative to adequately prepare young participants for the scanning environment and, subsequently, ensure the data acquired can be used to address the questions of interest. The success of these sessions has become paramount with the onset of large, multi-site consortium studies, such as the HEALthy Child and Brain Development study, which seek to track normative and atypical brain development across the first years of life. To this end, the current report provides a pediatric neuroimaging protocol to improve young children&#39;s scanning experience and developmental neuroimaging data quality results from four neuroimaging studies conducted in a single laboratory over the past 11 years. These results provide an indication of expected scan preparation time, total scan duration, and success rates for structural and functional scans in young children when using this protocol.

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Scanning Dos and Don'ts: Using Magnetic Resonance Imaging in Awake Children Aged 3 to 5 Years to Assess Brain Structure and Function

Early childhood (3 to 5 years of age) is a period marked by significant changes in the brain. This development underlies age-related improvements in ...

Motor imagery-brain-computer interfaces (MI-BCIs) have demonstrated significant potential for neurorehabilitation and cognitive neuroscience. However, a standardized and reproducible MI-EEG workflow for configurable spatial-temporal-frequency feature analysis remains limited, and many pipelines require complex configuration and parameter tuning with limited interpretability, hindering practical deployment and generalization. To address these challenges, an STFEEG-Tool was developed to provide a user-friendly, standardized, and interpretable workflow for EEG decoding in MI paradigms. STFEEG-Tool enables fine-grained configuration of temporal, frequency-band, and spatial segmentation, allowing the extraction of multiscale MI features. The toolbox integrates multiple feature extraction algorithms, including common spatial patterns (CSP) and divergence-based CSP (div-CSP), along with various classifiers, such as support vector machines (SVMs), Ridge Regression Classifier, and Lasso Classifier. A dynamic time-frequency scalp topographical map is provided to summarize spatial patterns across time-frequency segments and support interpretation of decoding results. Overall, STFEEG-Tool serves as a reproducible and extensible platform for fine-grained MI-EEG analysis, facilitating the translation of fine-grained decoding pipelines into practical, user-oriented applications.

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STFEEG-Tool: A Spatial-Temporal-Frequency EEG Analysis Tool for Motor Imagery Brain-Computer Interfaces

Motor imagery-brain-computer interfaces (MI-BCIs) have demonstrated significant potential for neurorehabilitation and cognitive neuroscience. However, a ...

Navigated transcranial magnetic stimulation (nTMS) is based on the integration of individual brain imaging data to determine the precise positioning of the stimulation coil, thus enabling anatomically guided stimulation of cortical targets. The interest of neuronavigation systems is well recognized in the optimization of coil positioning during repetitive TMS (rTMS) treatments. Furthermore, nTMS is increasingly applied for functional mapping of brain regions in different applications, such as the identification and delineation of eloquent motor and language areas before tumor resection. Besides its usefulness in optimizing neurosurgical procedures, nTMS mapping can also be a tool for monitoring cortical plasticity and quantifying the integrity of the motor system in various neurological diseases. This methodological paper presents a standardized protocol for motor mapping using nTMS, in combination with diffusion tensor imaging (DTI)-based reconstruction of the corticospinal tract (CST). This approach allows for precise delineation of eloquent motor cortical regions and their subcortical projections, and the detection of functional reorganizations in patients with adjacent lesions. When integrated into presurgical planning, this method provides guidance for individualized surgical strategies aimed at maximizing lesion resection while preserving motor function. The protocol presented here is reproducible, clinically applicable, and suitable for integration into routine workflows. It constitutes a promising tool for neuroplasticity research and rehabilitation planning.

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A Standardized Protocol for Functional Motor Mapping Using Navigated Transcranial Magnetic Stimulation

Navigated transcranial magnetic stimulation (nTMS) is based on the integration of individual brain imaging data to determine the precise positioning of ...

Intrathecal (IT) administration of central nervous system (CNS)-targeted therapeutics offers a minimally invasive route for direct drug delivery into the cerebrospinal fluid (CSF), facilitating enhanced specificity and target engagement. While IT catheterization is standard for sustained delivery in rats, its application in mice is limited by anatomical constraints and elevated risk of procedure-related complications, including spinal injury and infection. To overcome these limitations, we employed an acute needle puncture technique for IT drug delivery in adult mice, providing a reproducible and less invasive alternative compatible with single or repeated dosing regimens. In a transgenic mouse model of amyotrophic lateral sclerosis (ALS) harboring the SOD1-G93A mutation, we achieved efficient IT delivery of antisense oligonucleotides (ASOs) targeting the SOD1 gene. This approach effectively downregulated mutant SOD1 expression and significantly ameliorated the disease phenotype, as demonstrated by electrophysiological and biomarker assessments. These results validate both the IT delivery method and the therapeutic efficacy, with outcomes comparable to intracerebroventricular (ICV) administration. Most importantly, the technique mirrors procedures used in human clinical studies, offering strong translational relevance and utility in preclinical evaluation of CNS-directed interventions. Although technical expertise is required to ensure consistency and avoid off-target effects, this IT delivery strategy represents a robust, reproducible, and clinically relevant methodology for advancing therapeutic development in small animal models.

lumbar-intrathecal-injection-sod1-asos-for-precise-cns-targeting

Lumbar Intrathecal Injection of SOD1-ASOs for Precise CNS Targeting and Predictive Efficacy in Human SOD1-G93A ALS Mice

Intrathecal (IT) administration of central nervous system (CNS)-targeted therapeutics offers a minimally invasive route for direct drug delivery into the ...

Increasing interest in using newborn piglets as a study model for neonatal development and pathology has raised the need for a brain matrix to accurately acquire histological sections. However, the fast growth of the newborn brain limits the utility of commercially available matrices to a narrow developmental window. Therefore, an adjustable brain matrix construction method was developed. First, a glass container was placed on wet ice, and a layer of 4% agarose gel was laid at the bottom. Next, a formalin-fixed brain was placed on this layer and embedded with 4% agarose gel. After the gel solidified, the gel above the brain was carefully removed, and the brain was extracted. The cavity was filled with 4% agarose gel with 2% Indian Ink. After solidification, the gel block was removed and sliced into the desired thickness (2 mm or 5 mm) and orientation (coronal or sagittal) to print the brain templates on scale paper. The templates were copied to a series of transparent acrylic plates (2 mm or 5 mm thickness) and cut out accordingly on a band saw. Finally, the plates were assembled and secured with three sets of bolts and nuts through predrilled alignment holes to build a customized brain matrix. Construction of both coronal and sagittal matrices is illustrated for a neonatal day 5 piglet brain with steps of 2 mm and a coronal matrix for postnatal day 32-38 brains with steps of 5 mm. By adding or removing proper acrylic plates, the matrix was adjusted to adapt to the various sizes of piglet brains. Thus, a simple, cost-effective method to customize brain matrices for varied sizes of large animals is introduced to the neurological research community.

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Fabrication of an Expandable Brain Matrix Customizable Across Developmental Stages

Increasing interest in using newborn piglets as a study model for neonatal development and pathology has raised the need for a brain matrix to accurately ...

Journal - Neuroscience