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Neuroscience and Neurobiology

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Full-Text Articles in Engineering

Data Preprocessing And Machine Learning For Intracranial Electroencephalography, Mauricio Cespedes Tenorio Jul 2024

Data Preprocessing And Machine Learning For Intracranial Electroencephalography, Mauricio Cespedes Tenorio

Electronic Thesis and Dissertation Repository

This thesis serves to address the problem of non-standardized preprocessing of intracranial electroencephalography (iEEG) recordings by implementing a software workflow that compiles some of the most common steps followed for the preparation of this type of data. This workflow improves the consistency, replicability, and ease of use of iEEG preprocessing, facilitating the replication and extension of previous studies and the combination of separately preprocessed inter-institutional datasets. Automatic detection of artifacts for iEEG data was also explored as a potential step to include in the preprocessing workflow. Despite training the models with cross-institutional data, poor performance was observed when tested on …


Embracing The Irreplaceable: The Role Of Neurodiversity In Cultivating Human-Ai Symbiosis In Education, Piper Hutson Jun 2024

Embracing The Irreplaceable: The Role Of Neurodiversity In Cultivating Human-Ai Symbiosis In Education, Piper Hutson

International Journal of Emerging and Disruptive Innovation in Education : VISIONARIUM

This study investigates the indispensable role of human skills—such as empathy, ethical judgment, and nuanced understanding—in the development and application of artificial intelligence (AI) within higher education, highlighting the unique contributions of neurodivergent perspectives in creating a symbiotic human-AI relationship. Drawing upon research that evidences the superior performance of diverse teams in creativity and innovation, the paper argues for the integration of neurodiversity into AI development as a means to address the philosophy of 'fearing the Other,' thereby mitigating biases and fostering ethical AI interactions. The technology sector's adoption of Diversity, Equity, and Inclusion (DEI) programs, including biopsychosocial interventions and …


Facilitation In Pattern Motion Perception Of Self-Operated Stimuli Explained By Adaptive Contrast Normalization, Fulvio Missoni, Francesca Peveri, Andrea Canessa, Giulia Sedda, Vittorio Sanguineti, Silvio P. Sabatini May 2024

Facilitation In Pattern Motion Perception Of Self-Operated Stimuli Explained By Adaptive Contrast Normalization, Fulvio Missoni, Francesca Peveri, Andrea Canessa, Giulia Sedda, Vittorio Sanguineti, Silvio P. Sabatini

MODVIS Workshop

Movement can affect the way we make sense of complex visual information. To investigate this issue, we designed an experiment to assess changes of plaid motion perception threshold after a period of sensorimotor contingency experience. We found that movement training facilitates combination of elementary motion cues into a global motion percept. No changes in perceptual thresholds are observed in a passive visual condition. A Bayesian model suggested a reduction, after training, of the cross-talk between two gratings with unbalanced contrasts in corresponding sensory channels. To test plausible neural mechanisms for active reduction of cross-talk in cortical representation of complex visual …


Explaining The Staircase Gelb Illusion, Simultaneous Contrast, And Perceptual Fading Of Stabilized Images With A Neural Model Driven By Fixational Eye Movements, Michael E. Rudd May 2024

Explaining The Staircase Gelb Illusion, Simultaneous Contrast, And Perceptual Fading Of Stabilized Images With A Neural Model Driven By Fixational Eye Movements, Michael E. Rudd

MODVIS Workshop

A neural model of lightness computation driven by fixational eye movements is described and used to simulate various lightness phenomenon, including the Staircase Gelb illusion and its variants, simultaneous contrast, the Chevreul illusion, and perceptual fading of stabilized images. The model provides a precise account of the lightness matches from several experiments, with an overall error of only 1.5%. In the model, spatial maps of transient ON and OFF cell activations—produced as the eyes traverse the visual scene—are sorted by eye movement direction in visual cortex. At a subsequent processing stage, the activations within these maps are summed across space …


Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed May 2024

Biophysical Model Of Retraction Motor Neurons And Their Modification By Operant Conditioning, Maria Rasheed

Dissertations & Theses (Open Access)

Operant conditioning (OC) is a form of associative learning in which an animal modifies its behavior based on the consequences that follow that behavior. Despite its ubiquity, the underlying mechanisms of OC are poorly understood. Insights into the mechanisms of OC can be obtained by studying Aplysia feeding behavior as it can be modified by OC. This behavior is mediated by a central pattern generator (CPG) network in the buccal ganglia that contains a relatively small number of neurons. This CPG generates rhythmic motor patterns (BMPs) that move food into the gut by closing a tongue-like structure (i.e., radula) during …


Faa Medical Reform, Dana Rose Apr 2024

Faa Medical Reform, Dana Rose

Honors Projects

This project investigates the challenges and implications of obtaining medical certification for pilots with a history of childhood misdiagnoses, focusing on Attention-Deficit/Hyperactivity Disorder (ADHD). Misdiagnoses in childhood can lead to significant obstacles in the aviation industry's medical certification process, posing unique hurdles for aspiring pilots. The study examines the current FAA guidelines and procedures for medical certification, particularly the evaluation requirements for individuals with ADHD. It also explores common challenges faced by pilots, the effects of childhood misdiagnoses on their eligibility, and the impact of the FAA's ADHD evaluation process.

Through interviews with Aviation Medical Examiners (AMEs), this project identifies …


Effects Of Energy Drink Additives On Crayfish Metabolism, Katherine Paltz Jan 2024

Effects Of Energy Drink Additives On Crayfish Metabolism, Katherine Paltz

Williams Honors College, Honors Research Projects

The effects of caffeine and additives commonly found in energy drinks were tested on crayfish to record changes, if any, in their metabolism. Three experimental groups were studied: 1. Caffeine; 2. Caffeine + Glucuronolactone; 3.) Caffeine + Glucuronolactone + Taurine. Caffeine is a common stimulant used to improve mental awareness, headaches, memory, and athletic performance. Glucuronolactone is connected with cardiovascular issues and aggressive behavior. Taurine is said to improve mood and focus. The experiment was performed at two different caffeine levels: 600mg and 1200mg for an initial 1 hour of exposure and 10 hours after exposure used as a pseudo-baseline. …


Improving Peripheral Nerve Regeneration Through Rehabilitation And Biomaterial-Based Drug Delivery Strategies, Yunfan Kong Aug 2023

Improving Peripheral Nerve Regeneration Through Rehabilitation And Biomaterial-Based Drug Delivery Strategies, Yunfan Kong

Theses & Dissertations

Peripheral nerve injury (PNI) is a common problem worldwide, with trauma being a common cause. PNI can lead to loss of sensory and motor functions, chronic neuropathic pain, and mental health issues, significantly impacting patients' family life, work, and social situation. Recent studies revealed that beyond the topical injury site at peripheral nerves, PNIs can also induce dysfunctions in the central nervous system (CNS) by causing maladaptive plasticity, which will result in exaggeration and exacerbation of the pathological condition caused by primary injuries. The common therapy strategies for PNI treatment are using sutures, nerve autografts or conduits in cases requiring …


Methods To Study Activity Dependent Protein Synthesis In Autism Spectrum Disorder, Megan Webb, Karin F K Ejendal, Tamara L. Kinzer-Ursem Jul 2023

Methods To Study Activity Dependent Protein Synthesis In Autism Spectrum Disorder, Megan Webb, Karin F K Ejendal, Tamara L. Kinzer-Ursem

Discovery Undergraduate Interdisciplinary Research Internship

It is estimated by the World Health Organization that 1 in 100 children have autism spectrum disorder (ASD), a condition characterized by neurological differences that may impact a person’s learning or behavior. Clinically, ASD symptoms are alleviated with behavioral or pharmacological therapies, however, not all patients respond to these interventions. Deep brain stimulation (DBS) is a promising treatment of Parkinson’s disease that could also be effective in treating ASD. SynGAP1 is a protein involved in neuronal action that is crucial for regulating synaptic plasticity. Mutations in the SYNGAP1 gene causing haploinsufficiency can result in the manifestation of ASD symptoms. This …


Multiple Ways To Implement And Infer Sentience, Nicolas Rouleau, Michael Levin Jul 2023

Multiple Ways To Implement And Infer Sentience, Nicolas Rouleau, Michael Levin

Animal Sentience

Segundo-Ortin & Calvo’s (S&C’s) thorough review of “plant neurobiology” presents evidence supporting the possibility of plant sentience. They make a compelling case that plants anticipate, assess risk, cooperate, mimic, and pursue goals, as do their animal counterparts. S&C point out that there is a double standard: behavioural patterns associated with subjective experiences in humans are considered valid for inferring cognition in non-human animals but not in diverse other systems including plants. We argue that cognitive functions, including sentience, can potentially be achieved by very different systems and their disparate substrates. We offer some context from the basal cognition literature and …


Neural Correlates Of Post-Traumatic Brain Injury (Tbi) Attention Deficits In Children, Meng Cao May 2023

Neural Correlates Of Post-Traumatic Brain Injury (Tbi) Attention Deficits In Children, Meng Cao

Dissertations

Traumatic brain injury (TBI) in children is a major public health concern worldwide. Attention deficits are among the most common neurocognitive and behavioral consequences in children post-TBI which have significant negative impacts on their educational and social outcomes and compromise the quality of their lives. However, there is a paucity of evidence to guide the optimal treatment strategies of attention deficit related symptoms in children post-TBI due to the lack of understanding regarding its neurobiological substrate. Thus, it is critical to understand the neural mechanisms associated with TBI-induced attention deficits in children so that more refined and tailored strategies can …


Extracting Edges In Space And Time During Visual Fixations, Lynn Schmittwilken, Marianne Maertens May 2023

Extracting Edges In Space And Time During Visual Fixations, Lynn Schmittwilken, Marianne Maertens

MODVIS Workshop

No abstract provided.


Optical Perturbation Of Protein Kinase A Activity Via Photoactivatable Inhibitor Peptides, Peter Chen May 2023

Optical Perturbation Of Protein Kinase A Activity Via Photoactivatable Inhibitor Peptides, Peter Chen

McKelvey School of Engineering Theses & Dissertations

Protein Kinase A (PKA) plays important roles in diverse biological processes such as sleep, long term memory, and synaptic plasticity. In addition, PKA also acts as an integrator of neuromodulator signaling though G protein-coupled receptor activation. However, despite genetic knockout and pharmacological inhibition experiments that demonstrate the importance of PKA, it is unclear where, when, or how PKA plays these roles in cellular physiology and behavior. In order to better understand the function of PKA in these processes, and how neuromodulator signaling drives complex behavioral changes, there exists a need for a method to selectively activate/inactivate PKA with high spatial …


Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik May 2023

Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik

McKelvey School of Engineering Theses & Dissertations

ABSTRACT OF THE THESIS Preparing Non-Human Primates to Study Hand-Eye Coordination in Frontal Eye Fields (FEF) During Delayed Movement Task by Juliusz Cydzik Master of Science in Biomedical Engineering Washington University in St. Louis, 2023 Professor Lawrence Snyder, Chair Hand-eye coordination enables humans and non-human primates to use their hands and eyes to perform various tasks. We are interested in coordination at the systems level, where saccades and reaches are encoded. The parietal reach region (PRR), situated at the posterior end of the intraparietal sulcus (IPS) and overlapping portions of the medial intraparietal area (MIP) and V6a, is commonly attributed …


Vi Energy-Efficient Memristor-Based Neuromorphic Computing Circuits And Systems For Radiation Detection Applications, Jorge Iván Canales Verdial May 2023

Vi Energy-Efficient Memristor-Based Neuromorphic Computing Circuits And Systems For Radiation Detection Applications, Jorge Iván Canales Verdial

Electrical and Computer Engineering ETDs

Radionuclide spectroscopic sensor data is analyzed with minimal power consumption through the use of neuromorphic computing architectures. Memristor crossbars are harnessed as the computational substrate in this non-conventional computing platform and integrated with CMOS-based neurons to mimic the computational dynamics observed in the mammalian brain’s visual cortex. Functional prototypes using spiking sparse locally competitive approximations are presented. The architectures are evaluated for classification accuracy and energy efficiency. The proposed systems achieve a 90% true positive accuracy with a high-resolution detector and 86% with a low-resolution detector.


Consolidated Chamber Design And Protocol For Olfactory Conditioning Assay With Drosophila Melanogaster, Sasha Bronovitskiy, Andres Castillo, Michael Yan, Fang Ju Lin May 2023

Consolidated Chamber Design And Protocol For Olfactory Conditioning Assay With Drosophila Melanogaster, Sasha Bronovitskiy, Andres Castillo, Michael Yan, Fang Ju Lin

Journal of the South Carolina Academy of Science

The olfactory conditioning assay is widely used in Alzheimer’s disease research to quantify learning and memory in Drosophila melanogaster. The assay tests ability to recall an aversive conditioned stimulus of scent paired with electrical shock when presented a choice between shock-associated and unrelated scents. The T-maze, a commonly used apparatus for olfactory conditioning assays, employs an elevator mechanism to transfer live flies from the shock-delivering training chamber to the scent selection point. This elevator mechanism is known to cause fly casualty. T-mazes are not commercially available and often difficult to reproduce. Other existing variations of olfactory conditioning apparatuses use …


Do Plants Have The Cognitive Complexity For Sentience?, Ricard V. Solé May 2023

Do Plants Have The Cognitive Complexity For Sentience?, Ricard V. Solé

Animal Sentience

Are plants sentient? Like other aspects of the cognitive potential of plants, this is a controversial issue, often driven by analogies and seldom supported on solid theoretical grounds. Sentience is understood in cognitive sciences as the capacity to feel. I suggest that because of plants’ evolved adaptations to morphological plasticity, sessile nature and ecological constraints, they are unlikely to have the requisite cognitive complexity for sentience.


Multi-View Contrastive Learning For Unsupervised Domain Adaptation In Brain-Computer Interfaces, Sepehr Asgarian Mar 2023

Multi-View Contrastive Learning For Unsupervised Domain Adaptation In Brain-Computer Interfaces, Sepehr Asgarian

Electronic Thesis and Dissertation Repository

Electroencephalography (EEG) has been widely used to record electromagnetic fields for motor imagery (MI)-based brain-computer interfaces (BCIs). However, collecting MI signals is often time-consuming and challenging to classify due to the inter-subject variability of EEG signals. To address these issues, we propose a novel framework MACNet, which stands for Multi-view Adversarial Contrastive Network. MACNet employs a contrastive learning approach to learn spatial and temporal features in two views, using Riemannian and Euclidean encoders. By jointly extracting underlying features and learning domain-invariant representations in both source and target features, MACNet improves the alignment and accuracy. In addition, we propose a domain …


Computational Mechanisms Of Face Perception, Jinge Wang Jan 2023

Computational Mechanisms Of Face Perception, Jinge Wang

Graduate Theses, Dissertations, and Problem Reports

The intertwined history of artificial intelligence and neuroscience has significantly impacted their development, with AI arising from and evolving alongside neuroscience. The remarkable performance of deep learning has inspired neuroscientists to investigate and utilize artificial neural networks as computational models to address biological issues. Studying the brain and its operational mechanisms can greatly enhance our understanding of neural networks, which has crucial implications for developing efficient AI algorithms. Many of the advanced perceptual and cognitive skills of biological systems are now possible to achieve through artificial intelligence systems, which is transforming our knowledge of brain function. Thus, the need for …


Eeg-Based Spanish Language Proficiency Classification: An Eeg Power Spectrum And Cross-Spectrum Analysis, Blaise Xavier O'Mara, Skyler Baumer Jan 2023

Eeg-Based Spanish Language Proficiency Classification: An Eeg Power Spectrum And Cross-Spectrum Analysis, Blaise Xavier O'Mara, Skyler Baumer

Honors Theses and Capstones

Second language proficiency may be predicted with electrophysiological techniques. In a machine learning application, this electrophysiological data may be used for language instructors and language students to assess their language learning. This study identifies how electroencephalogram (EEG) power spectrum and cross spectrum data of the brain cortex relates to Spanish second language (L2) proficiency of 20 Spanish language students of varying proficiency levels at the University of New Hampshire. The two metrics for assessing cortical power and processing were event-related desynchronization (ERD)—a measure of relative change in power—of the alpha (8-12 Hz) brain frequency band, and alpha and beta (13-30Hz) …


Tdcs Effects On Synaptic Plasticity And Motor Skill Learning, Forouzan Vasheghani Farahani Jan 2023

Tdcs Effects On Synaptic Plasticity And Motor Skill Learning, Forouzan Vasheghani Farahani

Dissertations and Theses

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that involves the application of low-intensity constant current to the brain through electrodes placed on the scalp. Its potential to enhance brain function and treat brain-related disorders has led to its increasing popularity due to its safety, simplicity, and affordability. However, its effectiveness remains a topic of debate.


Improving The Stimulation Selectivity In The Human Cochlea By Strategic Selection Of The Current Return Electrode, Ozan Cakmak Dec 2022

Improving The Stimulation Selectivity In The Human Cochlea By Strategic Selection Of The Current Return Electrode, Ozan Cakmak

Dissertations

The hearing quality provided by cochlear implants are poorly predicted by computer simulations. A realistic cochlear anatomy is crucial for the accuracy of predictions. In this study, the standard multipolar stimulation paradigms are revisited and Rattay’s Activating Function is evaluated in a finite element model of a realistic cochlear geometry that is based on µ-CT images and a commercial lead. The stimulation thresholds across the cochlear fibers were investigated for monopolar, bipolar, tripolar, and a novel (distant) bipolar electrode configuration using an active compartmental nerve model based on Schwartz-Eikhof-Frijns membrane dynamics. The results suggest that skipping of the stimulation point …


Deciphering The Firing Patterns Of Hippocampal Neurons During Sharp-Wave Ripples, Kourosh Maboudi Ashmankamachali Dec 2022

Deciphering The Firing Patterns Of Hippocampal Neurons During Sharp-Wave Ripples, Kourosh Maboudi Ashmankamachali

Theses and Dissertations

The hippocampus is essential for learning and memory. Neurons in the rat hippocampus selectively fire when the animal is at specific locations - place fields - within an environment. Place fields corresponding to such place cells tile the entire environment, forming a stable spatial map supporting navigation and planning. Remarkably, the same place cells reactivate together outside of their place fields and in coincidence with sharp-wave ripples (SWRs) - dominant electrical field oscillations (150-250 Hz) in the hippocampus. These offline SWR events frequently occur during quiet wake periods in the middle of exploration and the follow-up slow-wave sleep and are …


Sensorimotor Content Of Multi-Unit Activity In The Paramedian Lobule Of The Cerebellum, Esma Cetinkaya Aug 2022

Sensorimotor Content Of Multi-Unit Activity In The Paramedian Lobule Of The Cerebellum, Esma Cetinkaya

Dissertations

Based on Center for Disease Control and Prevention report 2016, around 39.5 million people in the United States suffer from motor disabilities. These disabilities are due to traumatic conditions like traumatic brain injury (TBI), neurological diseases such as amyotrophic lateral sclerosis (ALS), or congenital conditions. One of the approaches for restoring the lost motor function is to extract the volitional information from the central nervous system (CNS) and control a mechanical device that can replace the function of a paralyzed limb through systems called Brain-Computer Interfaces (BCI).

One of the major challenges being faced in BCIs and also in general …


Development Of Noninvasive Biomarkers For Cervical Spondylotic Myelopathy, Dinal Jayasekera Aug 2022

Development Of Noninvasive Biomarkers For Cervical Spondylotic Myelopathy, Dinal Jayasekera

McKelvey School of Engineering Theses & Dissertations

Cervical spondylotic myelopathy (CSM) represents the most common cause of chronic spinal cord injury (SCI) in adults. Many patients with symptomatic CSM will experience a decline in neurological function and consequently undergo surgical decompression. Unfortunately, surgeons are unable to adequately counsel patients about the benefits of surgery because the natural history of disease and outcome after decompression vary widely among patients. This can hinder the decision-making capacity of patients and physicians. Therefore, we require additional tools to help guide therapy and counsel patients with CSM. Noninvasive biomarkers present valuable potential as predictors of a patient’s recovery in the long term. …


Noninvasive Neuromodulation Via Ultrasonic Activation Of Endogenous And Exogenous Ion Channels, Yaoheng Yang Aug 2022

Noninvasive Neuromodulation Via Ultrasonic Activation Of Endogenous And Exogenous Ion Channels, Yaoheng Yang

McKelvey School of Engineering Theses & Dissertations

Neuromodulation technology is key to understanding brain function and treating brain diseases. Conventional neuromodulation technologies, such as direct current stimulation, transcranial magnetic stimulation, and optogenetics, predominately rely on electromagnetic waves. However, the fundamental physical law  the tradeoff-relationship between penetration and spatial resolution, limits their transcranial penetration within the superficial cortex layer. To overcome this challenge, electrodes or optical fibers need to be surgically implanted into the brain to modulate specific brain regions. Different from electromagnetic waves, ultrasound, as a mechanical wave, can non-invasively penetrate through the intact skull to reach deep brain regions with millimeter spatial focus. Ultrasound has …


Behavioral And Histological Inflammatory Analysis Of A Single, Mild Traumatic Brain Injury And Repeated Subconcussive Brain Injury Using A Rodent Model., Anna Marie Clay Aug 2022

Behavioral And Histological Inflammatory Analysis Of A Single, Mild Traumatic Brain Injury And Repeated Subconcussive Brain Injury Using A Rodent Model., Anna Marie Clay

Theses and Dissertations

Subconcussive (SC) impacts have become a growing concern within the neuroscience community regarding the immediate and long-lasting effects of sports-related injuries. While a single low-level impact, i.e., a subconcussion, may not cause cerebral perturbations, it has been increasingly recognized that repeated SC exposure can induce deleterious effects. Therefore, determining the lower limits of systematic perturbation resulting from multiple SC impacts is of critical importance in expanding our understanding of cerebral vulnerability and recovery. Currently, there is a lack of correlation between a mild traumatic brain injury (mTBI) and repeated SC impacts with respect to injury biomechanics. Moreover, the cumulative threshold …


Effect Of Dorsal Quadrant Or Ventral Quadrant Spinal Cord Injury On Gait Features During Locomotion., Anya Nicole Trell Aug 2022

Effect Of Dorsal Quadrant Or Ventral Quadrant Spinal Cord Injury On Gait Features During Locomotion., Anya Nicole Trell

Electronic Theses and Dissertations

In the Unites States, approximately 1.5 million people currently have a spinal cord injury and suffer permanent sensory and motor loss due to the disruption of the spinal cord. Due to the significant morbidity, it is vital to understand the functional impact of disrupting neural descending pathways that modulate spinal neurons involved in intermuscular coordination critical for gait behaviors. Tasks that are more difficult require additional input from these neural pathways; therefore, fourteen feline subjects were familiarized with level overground locomotion and stair descent gait tasks. After collection of baseline kinematic data, the subjects received either a dorsal or ventral …


One-Stage Blind Source Separation Via A Sparse Autoencoder Framework, Jason Anthony Dabin May 2022

One-Stage Blind Source Separation Via A Sparse Autoencoder Framework, Jason Anthony Dabin

Dissertations

Blind source separation (BSS) is the process of recovering individual source transmissions from a received mixture of co-channel signals without a priori knowledge of the channel mixing matrix or transmitted source signals. The received co-channel composite signal is considered to be captured across an antenna array or sensor network and is assumed to contain sparse transmissions, as users are active and inactive aperiodically over time. An unsupervised machine learning approach using an artificial feedforward neural network sparse autoencoder with one hidden layer is formulated for blindly recovering the channel matrix and source activity of co-channel transmissions. The BSS sparse autoencoder …


Assessing Structural And Functional Brain Alterations And Work-Related Fatigue In Non-Hyposmic And Hyposmic Covid-19 Survivors, Rakibul Hafiz May 2022

Assessing Structural And Functional Brain Alterations And Work-Related Fatigue In Non-Hyposmic And Hyposmic Covid-19 Survivors, Rakibul Hafiz

Dissertations

In the year 2019, life began to change at the advent of a global pandemic caused by the novel coronavirus. Mask mandates and mass vaccinations have mitigated the effects significantly, yet cases keep rising with new variants, especially, in densely populated countries, like India. Recent neuroimaging evidence shows the virus can attack the central nervous system (CNS). However, exactly which brain regions undergo structural and functional changes remain largely unknown. Many patients experience 'loss of/reduced sense of smell' (i.e., hyposmic) and an alarming number of survivors develop persistent symptoms ('long-COVID') for several months after initial infection. Fatigue is the most …