Ep. 1: Integrative Physiological Responses to Exercise-Heat Stress: Sex as a Biological Variable

September 7, 2023

In the kickoff episode of the 2023 Neurophysiology Series, Dr. Nisha Charkoudian, Chief of the Thermal & Mountain Medicine Division at the US Army Research Institute of Environmental Medicine, examines how the autonomic nervous system coordinates body temperature and blood pressure regulation during exercise and heat exposure. She explains why the combined demands of exercise-heat stress create competing regulatory pressures, producing familiar symptoms such as lightheadedness and dizziness in the heat. Charkoudian highlights the substantial influence of female reproductive hormones on the autonomic pathways controlling both thermoregulation and blood pressure, with implications for athletes and military personnel.

Key Highlights

• The autonomic nervous system regulates both body temperature and blood pressure in humans, and integrating these responses becomes considerably more complex during exercise or high environmental temperature exposure, with lightheadedness and dizziness in the heat serving as a common manifestation of that regulatory conflict.
• Female reproductive hormones exert significant influence over the autonomic regulatory pathways controlling thermoregulation and blood pressure, making sex a biological variable that must be accounted for in exercise-heat stress research rather than treated as a source of noise.
• Evidence suggests women hold some advantages in adaptive responses to heat stress while men appear advantaged in other domains, and considerable work remains to define these differences and translate them into guidance for athletic and military populations.

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Ep. 2: Autonomic Regulation of Metabolic and Cardiovascular Functions in Health and Disease

September 13, 2023

Dr. Kamal Rahmouni, Professor of Neuroscience and Pharmacology at the University of Iowa, examines the autonomic neurocircuitry that governs energy homeostasis and cardiovascular function, and the molecular mechanisms controlling sympathetic and parasympathetic activity within it. Drawing on a multidisciplinary approach spanning basic cellular systems, genetic models, and physiological techniques including multifiber direct nerve recording, his research traces the neuroendocrine pathways underlying energy imbalance and cardiovascular disorders. Rahmouni connects molecular-level signaling to whole-organism outcomes to clarify how autonomic dysregulation contributes to metabolic and cardiovascular disease.

Key Highlights

• Energy homeostasis and cardiovascular function share overlapping autonomic neurocircuitry, and defining that circuitry is a prerequisite for understanding how sympathetic and parasympathetic activity is controlled at the molecular level.
• Multifiber direct nerve recording, combined with genetic models and cellular systems, allows sympathetic and parasympathetic output to be measured directly rather than inferred, linking discrete molecular signals to measurable autonomic activity.
• Neuroendocrine pathways connecting the brain to peripheral tissues underlie both energy imbalance and cardiovascular disorders, positioning autonomic dysregulation as a shared mechanism across metabolic and cardiovascular disease rather than two separate problems.

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Ep. 3: New Horizons: Gonadotropin-Releasing Hormone and Cognition

‍September 20, 2023

Dr. Vincent Prevot, Research Director and Laboratory Head in Development and Plasticity of the Neuroendocrine Brain at Lille Neuroscience & Cognition, Inserm, traces the gonadotropin-releasing hormone system from its first postnatal activation, known as minipuberty, through its later reproductive and non-reproductive functions. Recent studies indicate that GnRH-producing neurons contribute not only to puberty and fertility via the hypothalamic-pituitary-gonadal axis but also to postnatal brain maturation, odor discrimination, and adult cognition. Prevot presents evidence that restoring pulsatile GnRH improves olfactory and cognitive deficits in Down syndrome and preclinical Alzheimer's models, while cautioning that long-term continuous, non-physiological GnRH administration carries risks in certain disorders. Sponsored by iPRECIO Micro Infusion Pumps.

Key Highlights

• Pulsatile GnRH secretion is essential for activating and maintaining the hypothalamic-pituitary-gonadal axis that governs pubertal onset and fertility, and minipuberty, the first postnatal activation of this system, appears to shape brain development well beyond reproduction.
• GnRH-producing neurons are implicated in postnatal brain maturation, odor discrimination, and adult cognition, and restoring physiological pulsatile GnRH levels improved olfactory and cognitive alterations in Down syndrome and in preclinical models of Alzheimer's disease.
• The pulsatile pattern matters as much as the hormone itself, since long-term continuous non-physiological GnRH administration carries risks in certain disorders, while properly pulsatile GnRH therapy may hold therapeutic potential for neurodevelopmental cognitive disorders and pathological aging in the elderly.

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Ep. 4: Impact of Sleep and Circadian Disruption on Human Health and Disease Risk

September 27, 2023

Dr. Josiane Broussard, Associate Professor in the Department of Health and Exercise Science at Colorado State University and in the Division of Endocrinology, Metabolism and Diabetes at the University of Colorado Anschutz Medical Campus, examines how sleep loss and circadian misalignment affect cardiovascular function and metabolic health. As a clinical and translational scientist, she reviews recent studies on the effects of sleep disruption on insulin resistance and metabolism, connecting experimental findings to disease risk in the general population. Broussard closes with potential countermeasures for situations where sleep and circadian disruption cannot be avoided, such as shift work.

Key Highlights

• Sleep and circadian rhythms are directly linked to cardiovascular function and metabolic health, making disruption of either a modifiable contributor to disease risk rather than a lifestyle inconvenience.
• Recent clinical and translational studies demonstrate that sleep disruption impairs insulin sensitivity and alters metabolism, establishing measurable physiological pathways from inadequate or misaligned sleep to metabolic disease.
• When sleep and circadian disruption are unavoidable, as in shift work and other around-the-clock occupations, targeted countermeasures may help offset the metabolic and cardiovascular consequences.

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Ep. 5: Evaluation of Novel Therapies Using Spontaneous Seizure Models

October 4, 2023

Dr. Cameron Metcalf, Research Assistant Professor of Pharmacology & Toxicology and Associate Director of the Anticonvulsant Drug Development Program at the University of Utah, joined by Katrina Irey, Kaha Sales Specialist at ADInstruments, reviews the technical requirements and advantages of spontaneous seizure models for epilepsy therapy development. As the Contract Site for the NINDS Epilepsy Therapy Screening Program, the ADD Program has moved beyond traditional single-administration evoked seizure screens toward more etiologically relevant spontaneous seizure models, validated by testing FDA-approved antiseizure drugs. Metcalf addresses the practical challenges of running 24/7 video-EEG across multiple animals and the blinded study design that supports preclinical compound profiling. Sponsored by ADInstruments.

Key Highlights

• Traditional anticonvulsant screening has relied on single administration in evoked seizure models, while spontaneous seizure models offer greater etiological relevance to human epilepsy at the cost of substantially more demanding data collection.
• Spontaneous seizure screening requires 24/7 video-EEG systems capable of recording multiple animals simultaneously using both tethered and radio-telemetry setups, with larger group sizes needed to achieve statistical power for the program's endpoints.
• The ADD Program validated its spontaneous seizure models by screening FDA-approved antiseizure drugs first, establishing benchmarks against which novel compounds can be compared, with all studies including blinded video-EEG review to guard against interpretation bias.

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Ep. 6: Implantable Circuit-Specific Treatments for Autonomic Dysfunction

October 11, 2023

Dr. Aaron Phillips, Associate Professor of Physiology and Pharmacology at the University of Calgary, presents his research on the neural mechanisms underlying hemodynamic stability and how those mechanisms break down after neurological injury. Drawing on preclinical models of neurological injury alongside novel tools for identifying the causes of hemodynamic instability, he develops mechanistic insights aimed at clinical translation. Phillips also explores the potential of circuit-specific neurostimulation as a treatment for hemodynamic instability following neurological injury.

Key Highlights

• Hemodynamic stability depends on specific neural circuits, and understanding how the nervous and cardiovascular systems interact is a prerequisite for identifying why blood pressure regulation fails after neurological injury.
• Preclinical models of neurological injury paired with novel investigative tools allow the causes of hemodynamic instability to be isolated mechanistically rather than described only at the level of clinical symptoms.
• Circuit-specific neurostimulation delivered through implantable devices offers a targeted therapeutic route for hemodynamic instability after neurological injury, addressing the underlying autonomic circuitry rather than managing blood pressure pharmacologically.

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Ep. 7: From Models to Heartbeats: Computational Design of Vagus Nerve Stimulation for Cardiac Health

October 18, 2023

Dr. Max Haberbusch, Postdoctoral Associate at the Center for Medical Physics and Biomedical Engineering at the Medical University of Vienna, and Dr. Esra Neufeld, Associate Director and Head of Computational Life Sciences at the IT'IS Foundation in Zurich, trace the computational design of vagus nerve stimulation for restoring closed-loop cardiac rhythm control in heart transplant patients. They describe how the European NeuHeart consortium leveraged infrastructure from the NIH SPARC program, which funds over 100 research teams mapping the autonomic peripheral nervous system and maintains platforms for FAIR data sharing and reproducible modeling. The presentation covers hybrid electromagnetic and electrophysiological modeling of neural interfaces, an experimentally validated model of cardiovascular regulation, and the integration of both within a closed-loop control framework aimed at generating in silico regulatory evidence for safety and efficacy trials. Sponsored by the SPARC Data and Resource Centre.

Key Highlights

• Hybrid electromagnetic and electrophysiological modeling of neural interfaces enables model-based optimization of stimulation selectivity and maximization of neural sensing information content, allowing device parameters to be tuned computationally before implantation.
• A comprehensive and experimentally validated model of cardiovascular regulation was integrated with the independently developed neural interface model inside a generic closed-loop control framework, demonstrating how separately built models can be combined into a single predictive system.
• In silico regulatory evidence generated from these integrated models offers a path to assess safety and efficacy computationally, with the SPARC infrastructure and the freely accessible o2S2PARC platform supporting reproducible simulation of nerve electrophysiology and its interaction with organ physiology.

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Ep. 8: Systemic and Intraspinal Pathology and Repair After Spinal Cord Injury in Rodents

October 25, 2023

Dr. Dana McTigue, Professor of Neuroscience and Associate Dean at Ohio State University, traces two decades of work on glial repair after spinal cord injury and the unexpected systemic pathology her lab uncovered along the way. Her research shows that oligodendrocyte progenitor cells robustly divide and differentiate into myelin-generating oligodendrocytes after injury, a process that continues in mice for at least six months, indicating the adult spinal cord remains highly dynamic long after the initial insult. While investigating iron as a regulator of these progenitor responses, McTigue's lab found the liver to be pathological after SCI, leading to the discovery that injury rapidly induces non-alcoholic steatohepatitis, insulin resistance, and hyperlipidemia. Sponsored by ALZET.

Key Highlights

• Oligodendrocyte progenitor cells continue dividing and differentiating into oligodendrocytes that generate new myelin for at least six months after spinal cord injury in mice, demonstrating that the adult spinal cord remains highly dynamic well beyond the acute injury window.
• Because the spinal cord innervates the entire body at and below the neck, spinal cord injury damages not only neural tissue but every organ below the injury level, making systemic pathology intrinsic to the condition rather than an incidental complication.
• Investigating iron, which is essential for myelination, led to the discovery that SCI causes rapid non-alcoholic steatohepatitis alongside insulin resistance and hyperlipidemia, features typically associated with metabolic syndrome and obesity and prominent in clinical SCI, with current work aimed at relieving that metabolic pathology.

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Ep. 9: Unveiling the Primate Brain: Advanced Insights through Ultra-Dense Electrophysiology

November 1, 2023

Dr. Kari Hoffman, Associate Professor of Psychological Sciences, Dr. André Bastos, Assistant Professor of Psychology, and Dr. Thilo Womelsdorf, Professor of Psychology and head of the Attention Circuits Control lab, all of Vanderbilt University, present complementary approaches to recording neural activity across interconnected brain regions in non-human primates. Hoffman describes wireless recordings with Deep Array probes that resolve layer-specific oscillatory currents and track neural circuit characteristics across learning, while Bastos applies Multi-Area, high-Density, Laminar Neurophysiology (MaDeLaNe) to examine how visual processing is modulated along the cortical hierarchy. Womelsdorf uses dense laminar sampling of spiking activity during attentional shifting tasks to map inter-areal correlations and the direction of information flow, particularly how the prefrontal cortex dynamically couples to other regions. Sponsored by Diagnostic Biochips.

Key Highlights

• Deep Array probes enable wireless recording that identifies layer-specific oscillatory currents and allows neural circuit characteristics to be monitored over the course of learning, combining local microcircuit resolution with the ability to track change across time in macaques.
• Traditional neurophysiological methods restrict researchers to a few areas per task, obscuring how networks contribute to neural computation, while MaDeLaNe approaches permit high-resolution recording from entire networks in alert animals performing behavioral tasks.
• Dense laminar sampling of spiking activity during attentional shifting tasks reveals inter-areal correlations and the direction of information flow, opening a network-wide window into higher cognitive function and clarifying how the prefrontal cortex connects dynamically to other brain regions.

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Ep. 10: Cellular Brain Repair for Parkinson's Disease: Is the Answer in the (Biomaterial) Matrix?

November 8, 2023

Dr. Eilís Dowd, Professor of Pharmacology & Therapeutics at the University of Galway, presents data showing that dopaminergic cell replacement in the Parkinsonian rodent brain improves substantially when neurons are transplanted within a neurotrophin-enriched collagen hydrogel. Cell-based repair aims to replace the nigrostriatal dopaminergic neurons lost to Parkinson's disease, but the approach has long been limited by poor transplant survival and maturation in situ. Dowd's work identifies three mechanisms by which the hydrogel helps, and argues that the clinical transplant field should incorporate biomaterials into future trials to improve therapeutic efficacy for patients.

Key Highlights

• Cell-based brain repair for Parkinson's disease replaces degenerated nigrostriatal dopaminergic neurons through transplantation of healthy neurons, but poor transplant survival and maturation in situ have long limited the efficacy of this approach.
• A neurotrophin-enriched collagen hydrogel benefits transplanted neurons in three ways, providing a physical scaffold for cell-matrix adhesion, acting as a neurotrophin reservoir for sustained exposure after transplantation, and shielding the graft from the host innate immune response.
• Together these mechanisms produce a dramatic improvement in transplant survival and maturation in the Parkinsonian brain, supporting the case for incorporating biomaterials into future clinical transplantation trials rather than transplanting cells alone.

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Ep. 11: Measuring Neuronal Activity and Vascular Physiology in the Human Brain Using High-Resolution Functional Magnetic Resonance Imaging

December 6, 2023

Dr. Jonathan Polimeni, Associate Investigator at the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital and Associate Professor of Radiology at Harvard Medical School, examines how vascular anatomy and physiology shape the hemodynamic signals that fMRI measures, and how far the technique's neuronal specificity can be pushed. Because all current fMRI methods track blood flow, volume, and oxygenation rather than neuronal activity directly, indirectness has long been viewed as the method's fundamental limitation. Polimeni argues that recent microscopy evidence showing the brain's smallest vessels respond with far greater spatial and temporal precision than previously believed implies fMRI has an intrinsically high biological resolution, one that sufficiently high imaging resolution could exploit.

Key Highlights

• Every fMRI technique in use measures brain function indirectly by tracking blood flow, volume, and oxygenation changes that accompany neuronal activity, a dependence long treated as the method's defining constraint.
• Microscopy studies showing that the brain's smallest blood vessels respond to neuronal activity with much greater spatial and temporal precision than previously assumed indicate the biological resolution of fMRI is intrinsically high, making neuronally specific information extractable at sufficiently high imaging resolution.
• Because cerebral vascular architecture reflects brain structure and function across spatial scales, and because modern fMRI is also used to measure the cerebrovascular physiology impaired in many neurological disorders, a deeper understanding of the fMRI signal advances the study of the brain in both health and disease.

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Ep. 12: Compensatory Mechanisms in Parkinson's Disease

January 17, 2024

Professor Bastiaan Bloem, neurologist in the Department of Neurology at Radboud University Medical Centre in Nijmegen, argues that the clinical phenotype of Parkinson's disease is shaped not only by substantia nigra neurodegeneration and the resulting nigrostriatal circuit changes but also by two complementary forms of compensation. The first is adaptive cerebral plasticity, in which intact areas such as the cerebral cortex take over functions originally controlled by the basal ganglia, a process Bloem discusses promoting through exercise. The second is behavioral adaptation, illustrated with video material showing how people living with Parkinson's disease self-invent a wide range of strategies to overcome both motor and non-motor deficits.

Key Highlights

• Substantia nigra neurodegeneration and downstream nigrostriatal circuitry changes account for much of Parkinson's pathophysiology, but they do not fully explain the clinical phenotype, which is substantially colored by compensatory processes.
• Adaptive cerebral plasticity allows intact brain regions including the cerebral cortex to support functions originally governed by the basal ganglia, and this plasticity can be actively promoted through exercise.
• Compensatory behaviors are largely self-invented by people living with Parkinson's disease and are increasingly adopted by physiotherapists as deliberate therapeutic tools, with video evidence demonstrating a remarkable capacity to work around both motor and non-motor deficits.

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Ep. 13: Organoid Meets Microelectrode Array (MEA) - Accelerating Drug Discovery and Development

January 23, 2024

Dr. Sven Schönecker, Global Product Manager for Multielectrode Arrays at Multi Channel Systems, a Harvard Bioscience company, and Sara Mirsadeghi, MSc, a PhD student and research assistant at the University of Texas at San Antonio's Neuroscience, Developmental and Regenerative Biology program, explored how 3D Mesh MEA technology is advancing the study of brain organoids. Schönecker outlined the evolution from 2D electrodes to the MEA2100 system's 3D Mesh MEA platform, highlighting its role in supporting the 3Rs (replace, reduce, refine) of animal research, while Mirsadeghi discussed her work recording electrophysiological activity from organoids derived from healthy donors and patients with congenital epilepsy using standard MEAs, 3D-MEAs, and the newer Mesh-MEAs. Together they addressed how growing organoids directly around Mesh MEA electrodes offers a more true-to-life system for monitoring neural network formation and manipulating synaptic plasticity in mature brain organoids. Sponsored by Harvard Bioscience, Inc.

Key Highlights

• The 3D Mesh MEA platform builds on the well-established MEA2100 system from Multi Channel Systems to offer a more true-to-life electrophysiological recording environment for brain organoids compared with traditional 2D electrode arrays.
• Sara Mirsadeghi's research applies standard MEAs, 3D-MEAs, and Mesh-MEAs to compare the electrophysiological properties of brain organoids derived from healthy donors against those derived from patients with congenital epilepsy.
• Growing organoids around Mesh MEA electrodes helps overcome a central challenge in the brain organoid field, monitoring neural network formation and manipulating synaptic plasticity in mature organoids, moving the field closer to a functional brain-on-chip model.

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Ep. 14: Updates in Chronic Traumatic Encephalopathy (CTE)

January 31, 2024

Dr. Ann McKee, Professor and Director of the Neuropathology Core in the Department of Neurology and Pathology at Boston University, traces the emergence of chronic traumatic encephalopathy (CTE) as a distinct disease over the past two decades, with hundreds of individuals diagnosed at postmortem examination since 2003. She explains that CTE has been identified in amateur and professional athletes, military service members, and individuals exposed to head banging, interpersonal violence, and poorly controlled epilepsy, and describes the disease's pathognomonic lesion, a perivascular accumulation of neuronal phosphorylated tau (p-tau) at the depths of the cortical sulci, whose molecular structural configuration is distinct from the tau changes seen in aging, Alzheimer's disease, or any other tauopathy.

Key Highlights

• Since 2003, hundreds of individuals have been diagnosed with chronic traumatic encephalopathy at postmortem examination, reflecting its emergence as a distinct, recognized disease over the past 20 years.
• CTE has been documented in amateur and professional athletes, military service members, and individuals exposed to head banging, interpersonal violence, and poorly controlled epilepsy, indicating a broad range of at-risk populations.
• The disease is defined by a pathognomonic lesion, perivascular accumulation of neuronal phosphorylated tau (p-tau) at the depths of the cortical sulci, featuring a distinctive molecular structural configuration of p-tau fibrils unlike that seen in aging, Alzheimer's disease, or any other tauopathy