Arij D

- Research Program Mentor

Bio

Project ideas

Biology of Parkinson’s Disease : Pathogenesis and Pathophysiology

Parkinson's disease is a multisystem neurodegenerative and progressive disorder that affects the nervous system and the parts of the body controlled by the nerves. In this project, I explore the molecular, cellular and network pathways that are connected to the neurology and neuroscience of Parkinson’s disease, cover a wide range of subjects and unravel the complex relationships between genetics, molecular biology, pharmaceutical chemistry, neurobiology, imaging, assessments, and treatment regimens. Initially, I will cover foundational topics and then goes relatively in depth in covering the classical and cutting-edge research on the mechanisms that have been discovered to play a role in Parkinson's pathology.

An Explainable Web-Based Diagnostic System for Alzheimer’s Disease Using XRAI and Deep Learning on Brain MRI

Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by cognitive decline and memory loss. Despite advancements in AI-driven neuroimaging analysis for AD detection, clinical deployment remains limited due to challenges in model interpretability and usability. Explainable AI (XAI) frameworks such as XRAI offer potential to bridge this gap by providing clinically meaningful visualizations of model decision-making. Methods: This study developed a comprehensive, clinically deployable AI system for AD severity classification using 2D brain MRI data. Three deep learning architectures MobileNet-V3 Large, EfficientNet-B4, and ResNet-50 were trained on an augmented Kaggle dataset (33,984 images across four AD severity clas-ses). The models were evaluated on both augmented and original datasets, with inte-grated XRAI explainability providing region-based attribution maps. A web-based clinical interface was built using Gradio to deliver real-time predictions and visual ex-planations. Results: MobileNet-V3 achieved the highest accuracy (99.18% on the augmented test set; 99.47% on the original dataset), while using the fewest parameters (4.2M), confirming its efficiency and suitability for clinical use. XRAI visualizations aligned with known neuroanatomical patterns of AD progression, enhancing clinical interpretability. The web interface delivered sub-20 second inference with high classi-fication confidence across all AD severity levels, successfully supporting real-world diagnostic workflows. Conclusion: This research presents the first systematic integra-tion of XRAI into AD severity classification using MRI and deep learning. The Mo-bileNet-V3-based system offers high accuracy, computational efficiency, and inter-pretability through a user-friendly clinical interface. These contributions demonstrate a practical pathway toward real-world adoption of explainable AI for early and accu-rate Alzheimer’s disease detection.

Olfactory Stimulation and Cognition: Natural Scents as Neuroprotective Agents in Alzheimer’s Disease

Alzheimer’s disease is a prevalent neurodegenerative disease with cognitive decline and memory impairment. Though currently there is no definitive cure, non-invasive interventions such as aromatherapy may offer a promising complementary approach to retard the onset and soothe the symptoms. Olfactory stimulation of essential oils plays a role in slowing AD progression. Essential oils, such as lavender, rosemary, and bergamot, influence brain function by modulating neurotransmitters, including GABA, serotonin, and acetylcholine, reducing neuroinflammation, and promoting neuroplasticity. The uniqueness of olfactory pathways, bypassing the thalamus and directly connecting with the hippocampus and the limbic system, allows for constant and effective modulation of memory and emotion. The link with critical brain regions offers potential for improving cognition and enhancing mood. Furthermore, phytoncides, volatile organic compounds released by plants in the forest environment, act as an alternative natural intervention that influences the olfactory system. While the research is promising, challenges such as safety issues and a lack of sufficient data demonstrate the need for future research. Overall, aromatherapy is an accessible, cost-effective, and non-invasive intervention for enhancing brain health, reducing stress, and supporting cognitive function in Alzheimer’s patients.

Leveraging CRISPR Cas-9 Technology for Modelling and Treating Huntington’s Disease

Huntington’s Disease is a rare neurodegenerative disease characterized by psychiatric and motor disturbances, cognitive decline, sleep disturbances, and weight loss. The disease is caused by a dominantly inherited mutation in exon 1 of the Huntingtin (HTT) gene, characterized by excess CAG repeats. This mutation results in the accumulation of a toxic, misfolded protein, which leads to neuronal dysfunction and death. As with most neurodegenerative diseases, HD has no cure; however, due to its root genetic cause, scientists have recently begun exploring gene-editing tools, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas-9, as a means to manipulate DNA and generate models of HD in vitro and in vivo. While the research within this topic is still in its developmental phases, findings from various studies have shown great potential for this technology. This paper aims to collate the main studies that have used CRISPR technology in order to model HD and uncover its potential pathways for treatment. In studies where CRISPR was used to model HD in vitro, researchers found that the genetic mutation of extended CAG repeats could be contracted without disrupting the rest of the allele. By modelling HD in vivo, researchers were able to gain a deeper understanding of HD and observe phenotypic changes resulting from different lengths of CAG repeats, finding that even a 20-30% decrease in CAG repeats could lead to significant symptom alleviation. Thus, these findings highlight the potential CRISPR Cas-9 holds in the treatment of neurodegenerative diseases such as Huntington’s Disease.

Beyond genetics: The role of lipid dysregulation, sex, and age in the underlying pathogenesis of ALS

i. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with heterogeneous progression and poorly defined prognostic biomarkers. Altered lipid metabolism has been implicated in ALS pathogenesis, but its clinical relevance remains unclear. Despite decades of investigation, the etiology, pathophysiological mechanisms, and disease progression of ALS remain notoriously difficult to understand. Genetic mutations have been demonstrated to be responsible for 70% of familial ALS, and a significant proportion of sporadic ALS cases (though the exact percentage is not specified). This underscores the significance of genetic factors in the development of ALS. In response to these challenges, this review aims to provides a comprehensive and up-to-date overview of key advances in ALS research, with a particular focus on lipid metabolism in the brain, evidence of lipid metabolism in ALS, the epidemiology of sex differences in ALS, and hormonal factors involved in sex differences. This work aims to serve as a valuable reference, offering a concise and integrated foundation for understanding this complex and devastating disease.

Diet-driven epigenetic modifications in Alzheimer’s Disease

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide, currently ranking as the sixth leading cause of death in the United States. Despite decades of research, the precise etiology and disease-modifying treatment strategies for AD remain elusive, largely due to the multifactorial nature of the disease involving both genetic predispositions and environmental influences. With increasing life expectancy, the global prevalence of AD continues to rise, particularly in developed nations. Among emerging areas of investigation, epigenetic mechanisms - such as DNA methylation and histone modifications - have gained significant attention for their role in AD pathogenesis. Environmental factors, including diet, have been shown to influence epigenetic regulation. By understanding the interactions between diet, epigenetics, and neuropathology, this review aims to explore related strategies for the prevention and management of AD.

The impact of environmental factors on Alzheimer’s Disease

While age and genetics are well-established risk factors in Alzheimer’s disease (AD), growing evidence highlights the significant influence of environmental and lifestyle factors in its onset and progression. This review synthesizes current findings on a variety of external contributors to AD pathology, with a particular focus on environmental exposures such as air pollutants (e.g. PM 2.5 and nitrogen dioxide), pesticides, heavy metals (e.g. lead, cadmium and aluminum) and electromagnetic fields. Furthermore, it examines the role of lifestyle factors such as sleep disruption and dietary patterns. A persistent theme throughout the reviewed literature is the conversion of these diverse factors on common pathological mechanisms, including oxidative stress, neuroinflammation, and abnormal protein aggregation in the brain. By examining the current research, this review highlights the importance of identifying and mitigating modifiable risk factors as a critical strategy in the prevention and management of Alzheimer’s disease.

The role of oxidative stress in the pathogenesis and progression of Multiple Sclerosis

Multiple Sclerosis (MS) is a neurodegenerative disease characterized by demyelination and neurological dysfunction. While the precise etiology of MS remains unclear, accumulating evidence points to oxidative stress as a central player in its pathogenesis and progression. This review explores the multifaceted role of oxidative stress in MS, including its contribution to immune system dysregulation, mitochondrial dysfunction, and damage to myelin and axonal structures. We discuss how oxidative stress may influence disease progression and therapeutic resistance. Understanding the mechanistic role of oxidative stress in MS may offer valuable insights for the development of more effective, targeted interventions to slow disease progression and improve patient outcomes.

Altered Intrinsic Properties of Hippocampal Pyramidal Neurons in a Mouse Model of Parkinson’s Disease

Parkinson’s disease (PD), though classically defined by its motor symptoms, is increasingly recognized for its profound cognitive deficits, which often arise early and substantially impact patients’ quality of life. Recent evidence suggests that the hippocampus, particularly its pyramidal neuron populations, may play a critical role in the non-motor manifestations of PD. However, the biophysical underpinnings of hippocampal dysfunction in PD remain largely unexplored at the single-cell level. This study investigated the intrinsic properties (IPs) of hippocampal pyramidal neurons in the MitoPark mouse model of PD using whole-cell patch-clamp electrophysiology and comprehensive spike feature analysis. Compared to healthy controls, PD neurons exhibited significantly higher spike frequencies, shortened first spike delays, elevated and more variable spike thresholds, and pronounced reductions in action potential (AP) peak, amplitude, and width. In addition, afterhyperpolarization (AHP) amplitude was markedly increased, while its time to peak was shortened, indicating a shift toward deeper but briefer post-spike hyperpolarization. Joint feature analysis revealed that these neurons not only shift in the means of individual properties, but also occupy an altered region of multidimensional parameter space, characterized by changed variability and the breakdown of normal physiological correlations. These electrophysiological alterations are consistent with dysregulation of sodium and potassium channel function, which may underlie the enhanced excitability and impaired firing precision observed in PD neurons. Our findings provide new mechanistic insight into the cellular basis of cognitive deficits in PD, and suggest that ion channel dysfunction represents a promising therapeutic target for early intervention. Future work integrating pharmacological and genetic manipulation of specific channel subtypes will be critical to disentangle the molecular drivers of these changes and to develop disease-modifying treatments targeting hippocampal circuit function in PD.

Investigating neuroprotective compounds in Parkinson’s Disease: Efficacy and mechanisms of action

Parkinson’s disease is a motor neuron disease that affects roughly 8.5 million people globally. It is characterised by several motor and nonmotor symptoms of varying intensities. Parkinson’s is caused by various genetic and environmental risk factors that contribute to its pathology. Hallmarks of Parkinson’s include aggregates of misfolded 𝛼-synuclein known as Lewy bodies and the selective death of dopaminergic neurons from the substantia nigra pars compacta. There are many mechanisms that contribute to neuronal death implicated in Parkinson’s, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, excitotoxicity, and iron accumulation. Unfortunately, there is neither a cure nor any disease-modifying treatment for Parkinson’s yet. All existing therapies offer solely symptomatic relief, offering no means to slow or stop the progression of neurodegeneration. A promising candidate for disease-modifying therapies is neuroprotective compounds. There are many categories of neuroprotective agents on the basis of the neurodegenerative injuries they target. This review looks specifically at mitochondrial protectors, antioxidants, anti-inflammatory agents, neurotrophic factors, and iron chelators, exploring their mechanisms of action. Specific compounds have achieved success in preventing neuronal loss and improving motor handicaps in both in vitro and in vivo models of Parkinson’s disease, and some have even reached the clinical trial stage. Although many challenges lie ahead in terms of developing safe and effective therapies, on-going research surrounding methods of delivery and innovative disease models are likely to accelerate this process. This review outlines the key mechanisms of neuronal death in Parkinson’s, the neuroprotective agents to combat them, as well as challenges and limitations involved in the evaluation of novel drugs.

Enhancing Alzheimer’s disease diagnostics: advances in non-invasive biomarker tests

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by severe cognitive decline that progressively leads to dementia over time. This disease heavily affects the patient’s quality of life and often proving fatal. The progression of AD varies in different people, with survival time after diagnosis ranging from 4 to 8 years, with pathogenesis potentially starting a decade before symptom onset. Therefore, it is important to diagnose this disease early on in its pathogenesis to preserve patients’ quality of life with therapies and help the patient and their caretakers plan ahead for the future. However, the hallmark biomarkers of AD are proteotoxic proteins that mostly occur within the central nervous system, therefore current diagnosis methods such as cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), and positron emission tomography (PET) are invasive. Furthermore, they are expensive and can cost around several thousand dollars in the United States, making them unavailable to many people. Moreover, this disease may be caused by environmental factors, making it difficult to simply use genetic testing for diagnosis. These problems may discourage patients from getting diagnosed. Therefore, non-invasive and inexpensive methods in AD diagnosis are needed to improve and encourage diagnosis. This review summarizes non-invasive biomarkers that are currently being researched.

Temperature Induced Codimension-One and Codimension-Two Bifurcations in Hodgkin-Huxley Neurons

Temperature fluctuations can have detrimental effects on the firing pattern and electrical activity of biological neurons, eliciting diverse responses depending on the neuronal cell types and the underlying ion channels exhibited. Using the classical Hodgkin-Huxley (HH) model, we performed a comprehensive dynamical systems analysis to determine how temperature fluctuations alter neuronal excitability, spike morphology, and bifurcation structure. We first relied on experimentally-derived temperature coefficients, or Q10 values, associated with gating kinetics and conductances, and examined codimension-1 and codimension-2 bifurcations across a range of temperatures and standard HH parameters governing the intrinsic properties (firing frequency, spike amplitude, spike width, afterhyperpolarization (AHP), time-to-peak AHP, etc…) of the model HH neuron. Our analysis revealed that increasing temperature accelerates gating dynamics, leading to narrower and higher-frequency spikes but reduced amplitudes, and ultimately to a loss of sustained firing via temperature-induced depolarization block. We identified generalized Hopf (Bautin) bifurcations as critical boundaries beyond which the system becomes strictly monostable. Extending the model to independently scale sodium activation, sodium inactivation, and potassium activation kinetics showed that excitability is particularly sensitive to potassium gating dynamics. Our findings provide a quantitative framework for understanding temperature modulations of neuronal activity, highlighting how temperature reshapes the excitability landscape, unveiling the intricate interplays between the activation/inactivation kinetics of ion channels, and identifying key parameters governing temperature robustness in neuronal models.

Computational Neuroscience Meets Down Syndrome: Bridging Molecular, Cellular, and Network Mechanisms

Trisomy 21 is the cause of Down syndrome (DS) and results in a wide range of neurobiological and cognitive impairments. This paper reviews the genetic, cellular, and network mechanisms underlying DS and explores the integration of computational models with neurobiological research to improve the understanding of DS’s phenotypic manifestations. This review discusses findings about DS’s gene overexpression, cellular alterations, structural brain changes, and manifestations. Additionally, it highlights computational models' roles in bridging the gap between neurobiological data and phenotypic manifestations. Despite significant advancements, there are many unknowns about DS, and computational models offer valuable insights into these complex interactions, guiding future research and the development of targeted interventions. This review highlights the importance of integrating computational approaches to enhance today’s understanding of DS and improve outcomes for affected individuals.

A Computational Model of the Dopaminergic and Pharmacological Modulations in the Subthalamopallidal Network of the Basal Ganglia

The basal ganglia, a large region comprising multiple complex subcortical nucleic areas interconnected in circuit systems, is crucial for regulating motor control, cognition, and reward processing. One such important system, the subthalamopallidal network, involves three specific cerebral areas: the globus pallidus, the subthalamic nucleus, and the dopaminergic substantia nigra pars compacta. This study focuses on computationally modeling the three components of the subthalamopallidal network to elucidate the neuron interactions and dopaminergic modulations of the substantia pars compacta and to highlight the effects of altering ion channel properties in the network. Simulations of substantia nigra pars compacta excitation on the network showed the importance of regulating firing and activity levels to maintain structured behavior throughout the other areas in the network. Manipulations of T-type low voltage-activated calcium channels and other ion properties revealed an important role of the T-type channel in regulating neuron firing throughout the network, suggesting potential pharmacological targets for neurodegenerative disorders like Parkinson’s disease. Despite alterations to many ion channels and the introduction of gradual neuronal dysfunction, the network showed robust tendencies. These findings contribute to understanding neural mechanisms in basal ganglia circuits and offer insights into the neurobiology and interactions between ion channels, individual neurons themselves, and whole networks communicating together in the human brain.

Understanding the Relationship Between Music and Neurodegenerative Diseases

Although it is speculated that music predates language, our understanding of the complicated and vast neural processes of music in the brain remains limited, especially concerning its effect on neurodegeneration. Music has a mainly positive effect on our mental well-being, a statement that is generally true for the average listener. However, the underlying mechanisms and reasons for this impact continue to be vague. This paper explores questions of “how” music impacts the development of neurodegenerative diseases and touches upon important questions of “why” understanding music on a neural basis is important. This paper argues that the fundamental qualities of music, namely melody, harmony, and rhythm, engage the brain’s predictive models, thereby activating its emotional and psychological perception; cognitive learning and memory; and physiological action. Consequently, this engagement activates all associated brain regions, leading to improvement in brain diseases that may lack activation in some of these regions. The attempt to understand music through a neural lens might seem counterproductive. After all, to advance our knowledge means to diminish the sense of novelty and amazement music is first viewed with. Historically, the tools used to analyze the brain were inadequate for finding meaningful conclusions about music’s relation with the brain. However, with the advent of advanced neuroimaging techniques such as fMRI and EEG, it has become clear that exploring music can help uncover deeper secrets about human emotions and mental health.

Illuminating the Depths: The Neurobiology of Bioluminescence in Marine Life

Bioluminescence, the phenomenon of light production by living organisms through chemical reactions, illuminates the ocean’s depths much like stars adorn the night sky. This review explores the physiological control mechanisms behind marine bioluminescence across diverse taxa including Echinodermata, Cnidaria, Ctenophora, Arthropoda, Annelida, and Chordata. Organisms employ two main light-producing systems—luciferase-luciferin and photoprotein—housed in structures ranging from simple photocytes to complex photophores. Neurological and hormonal regulation finely tunes bioluminescent displays, which are crucial for understanding adaptive strategies of marine organisms and ecosystem health assessments. Despite advancements, gaps in electrophysiological and neurotransmitter studies persist, particularly in deep-sea species. Future research opportunities lie in developing noninvasive techniques for prolonged physiological studies, broadening comparative neurobiology across species, and elucidating neurotransmitter roles. Understanding these mechanisms not only unveils evolutionary adaptations but also informs bioengineering and conservation efforts, underscoring the enduring scientific interest and ecological significance of bioluminescence.

Integrating Real-Time EEG Feedback with VR Systems: A Holistic Study in Neuroadaptive Interfaces

Background: Virtual Reality (VR) technology has great impact across various fields. Electroencephalography (EEG) feedback, on the other hand, measures brain activity and offers insights into cognitive and emotional states. Combining VR and real-time EEG feedback has become a popular area of research and creates adaptive, personalized systems that respond to the user’s brain activity. Objectives: This review aims to introduce neuroadaptive interfaces and provide an overview of the current state of research on integrating EEG feedback with VR technology. It seeks to explore the applications of EEG-VR systems, especially in therapeutic settings. The review identifies and examines key studies demonstrating the use of EEG-VR systems in neurological rehabilitation. Methods: The review involved a search of the official database of the National Institute of Health(NIH) and the Institute of Electrical and Electronics Engineers(IEEE). 38 papers were selected. The procedure and significance of EEG-VR are analyzed in detail using these papers. Results: EEG-VR systems have been shown to have a wide range of applications in modern medical settings. For example, it enhances pain management and improves neurosurgical practice in the treatment of mental health conditions. As demonstrated in the case studies, neuroadaptive interfaces adapt in real-time based on the user’s brain activity, providing a highly personalized and individualized experience and treatment.

The interplay between the amygdala and the hippocampus in the emotional processing of music and memories

For the human brain to analyze and understand music, there is a brilliant and meticulous symphony that orchestrates our ability to perceive a compilation of sounds as music. Starting as variations in air pressure received by the pinna at the outer ear, musical sounds are transmitted via the ossicles in the middle ear to the cochlea of the inner ear that harbor our sensory hair cells, which due to their mechanotransduction capabilities, transform the mechanical forces into electrical signaling that is then picked by the spiral ganglions transmitting the auditory message to various areas and pathways in the brain. While this cascade of events holds for every sound that enters our ears, why and how does music affect us? Why do specific songs trigger happiness while others unleash sad memories, and yet other songs bring relaxation or send shivers down our spines? In this work, we review the involvement of two major brain nuclei, the amygdala and the hippocampus, in the emotional processing of music. Among their many roles in the brain, these two nuclei had been shown to be heavily involved in enhancing emotional music memories and the euphoric response to music, interacting with one another to form long-lasting memories. This review gives an elaborate overview of the intricate interplay between the amygdala and the hippocampal neurons in the generation of the neural encoding of musical memories and their associated emotions.

The Link Between Depression and Neurodegeneration in Alzheimer’s Disease

Alzheimer’s Disease (AD) is often feared as a disease of losing memories, but what if depression could predict its arrival before memory loss proceeds? Affecting approximately 46.8 million people worldwide, Alzheimer’s is a progressive neurodegenerative disorder, one of the main causes of mortality and morbidity, especially among the elderly population (Sáiz-Vázquez et al., 2021). AD is the most prevalent type of dementia, accounting for 60 - 70% of all cases globally. It affects more than 50 million individuals worldwide, with incidence rising steadily due to global population aging. At the neuropathological level, AD is defined by two hallmark features: the extracellular aggregation of amyloid-beta (Aβ) plaques and the intracellular accumulation of hyperphosphorylated tau protein in the form of neurofibrillary tangles (NFTs). These protein aggregates are the main causes governing synaptic dysfunction, neuroinflammation, and widespread neuronal loss, particularly in regions essential for memory and cognition, such as the hippocampus and cerebral cortex. Despite decades of research, the precise mechanisms that drive AD pathogenesis remain shrouded in mystery, and there is currently no disease-modifying therapy.

Epigenetic downregulations of the Vitamin D receptor gene in Multiple Sclerosis

Multiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS) (Huang et al. 2017). Recent studies suggest that vitamin D deficiencies have risen as a central risk factor. The vitamin D receptor (VDR) is known to modulate immune tolerance to inflammatory responses in the CNS, which is correlated to MS susceptibility (Ao et al. 2021). Although high vitamin D levels provide capability for VDR activation, there are alternative factors that can accelerate MS development. This includes epigenetic mechanisms in the suppression of the VDR. Such epigenetic mechanisms, DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), are recognised as regulators of VDR activity (Gasperini et al. 2023). For example, a silencing of VDR activity is noticed in patients with methylation in the promoter regions of the VDR. In a similar fashion, suppressive histone modifications leave VDR in a depressive state, allowing pro-inflammatory responses to activate. Additionally, ncRNAs, specifically microRNAs, directly silence VDR levels in MS patients. These interconnections found in epigenetic mechanisms in VDR downregulations and MS pathogenesis highlights how the VDR engenders conditions that prohibit inflammatory responses to weaken the CNS. This review serves to clarify the association between VDR downregulations and MS pathogenesis with emphasis on epigenetic control of VDR activity. By comprehensively analyzing epigenetic mechanisms in MS intervention, there are newfound opportunities for targeted epigenetic modulation as a therapeutic and preventive measure of MS.

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