MnDRIVE Neuromodulation Research Fellowship Recipients

Neuromodulation Graduate Fellows

A novel thalamostriatal circuit for treatment of attentional disorders

Louisa Kuper, Department of Neuroscience

Mentor: Benjamin Saunders, Ph.D., Department of Neuroscience

Many disorders, including addiction, schizophrenia, ADHD, and OCD involve inappropriate reactivity to cues in the environment. Potential neuromodulatory targets for these conditions must be thoroughly tested and understood before making their way to patient care. In this project, Louisa Kuper will make use of brain circuit manipulation and recording techniques in rodent models to investigate a promising thalamostriatal target involved in the control of cue-directed attention. This work will lay the groundwork for new neuromodulation intervention strategies.

Cognitive Control-Informed Application for Optimizing Deep Brain Stimulation in Psychiatric Disorders for Enhanced Patient Care

Sumedh Sopan Nagrale, Department of Biomedical Engineering

Mentor: Alik Widge, M.D., Ph.D., Department of Psychiatry and Behavioral Sciences

This study seeks to make deep brain stimulation programming better for psychiatric disorders by using a more reliable measure than relying only on how patients feel. We're trying out different methods to see which ones work best at finding the right settings. In the end, we want to create a tool for doctors to use when programming deep brain stimulation, based on what we learn from this research.

Optogenetic Dissection of Striatal Deep Brain Stimulation

Elizabeth Sachse, Department of Neuroscience

Mentor: Alik Widge, M.D., Ph.D., Department of Psychiatry and Behavioral Sciences

Ellie investigates the physiological mechanism by which deep brain stimulation (DBS) improves psychiatric illnesses. Colleagues in her lab previously developed a rat model of human ventral internal capsule/ventral striatum DBS by delivering high-frequency electrical stimulation to a particular area of the rat brain while they performed a task that engages cognitive control. Rats exhibit the same behavioral effects of DBS as do humans, which makes this a powerful animal model to use to figure out how DBS works. With this, Ellie is developing an optogenetic paradigm to deliver high-frequency light stimulation to specific, separate, neural components and figure out which ones drive DBS's behavioral effects. This work is important because we do not know how DBS works in humans, for example, if it acts on axons that make up the internal capsule or local cell bodies. With this knowledge, we could improve surgical targeting in DBS patients and improve therapeutic efficacy.

Personalized Deep Brain Electrical Stimulation in Refractory Epilepsy Subjects using Percept PC Local Field Potential and Empatica Watch Wearable Biomarker Feedback

Zachary Sanger, Department of Biomedical Engineering

Mentor: Tay Netoff, Ph.D., Department of Biomedical Engineering

Zach Sanger’s research project aims to personalize deep brain stimulation (DBS) therapy for subjects whose epilepsy symptoms cannot be managed by medication or surgical resection. By utilizing the Medtronic Percept device’s ability to simultaneously stimulate and record, neural response to different DBS stimulation parameters can be captured in real time in the clinic and at home. Integration of Empatica watch wearable biomarker feedback such as heart rate, sleep detection, and accelerometer data may provide rich supplemental data of subject state to utilize with neural response for assessment of therapy. We will investigate Percept recorded anterior nucleus of the thalamus local field potentials and Empatica wearable data as feasible quantitative metrics for assessing stimulation therapy and seizure event tracking and/or forecasting.

Deep Brain Stimulation for Obsessive-Compulsive Disorder: Identifying Pathway Activation Patterns for Improving Cognitive Control

Karianne Sretavan Wong, Department of Neuroscience

Mentor: Matthew Johnson, Ph.D., Department of Biomedical Engineering

Karianne Sretavan Wong’s research aims to identify how deep brain stimulation (DBS) parameters and white matter pathway activation in the ventral anterior limb of the internal capsule results in cognitive control improvements for patients with severe obsessive-compulsive disorder (OCD). This project’s findings will be the first to translate the use of patient-specific computational models into the psychiatric space for OCD patients to inform clinicians about which white matter pathways to target and how to optimize stimulation settings for cognitive control improvements.

Neuromodulation Postdoctoral Fellows

Optimizing the stimulation location for intermittent burst deep brain stimulation in Parkinsonian nonhuman primates

Sana Amoozegar, Ph.D., Department of Neurology

Mentor: Jing Wang, Ph.D., Department of Neurology

Dr. Amoozegar’s study focuses on the intermittent burst DBS (ibDBS) pattern for Parkinson’s disease (PD). Her study aims to identify the optimal stimulation location of ibDBS in the STN and the GPi regions and investigate the relationship between the optimal stimulation location and GPe neuronal responses in the NHP models of PD. Her research endeavors will further develop this novel burst stimulation for treating PD and move it one step forward toward translating this into clinical use. Once shown effective, the burst DBS can largely reduce the duration of stimulation while maintaining a level of motor improvement the same with, if not better than, the traditional DBS therapy. This can lead to a lower chance of side effects caused by DBS and reduced battery consumption leading to less exposure to the risks associated with surgical battery replacement or frequency battery recharge. Ultimately, this novel DBS approach has the potential to further improve the clinical outcome of DBS therapy and the quality of life for PD patients

Optogenetic Modulation of the Projections from the Paraventricular Thalamus to the Nucleus Accumbens in Compulsive Alcohol Drinking

Meredith Bauer, Ph.D., Department of Neuroscience

Mentor: Jocelyn Richard, Ph.D., Department of Neuroscience

Dr. Bauer’s project aims to identify a neural circuit that causes alcohol drinking despite negative consequences, a defining feature of alcohol use disorder. By using optogenetics to manipulate the neural projections from the paraventricular nucleus of the thalamus to the nucleus accumbens, we hope to reduce alcohol drinking in the presence of negative consequences. Identification of a neural circuit that can reduce alcohol drinking despite known negative consequences is the first step to discovering a novel therapeutic treatment for alcohol use disorder. The long-term outcomes of Dr. Bauer’s neuromodulation research may lead to both the prevention and treatment of alcohol use disorder.

A novel method for modulation of cognitive functions using traveling wave transcranial alternating current stimulation

Sangjun Lee, Ph.D., Department of Biomedical Engineering

Mentor: Alexander Opitz, Ph.D., Department of Biomedical Engineering

Dr. Lee’s project aims to investigate the effects of a novel noninvasive brain stimulation technique called traveling wave transcranial alternating current stimulation (twtACS) on human cognitive functions and brain dynamics. His research will allow for unraveling the mechanisms underlying traveling waves during cognition and will establish a new technological development in the treatment of cognitive impairment.

Multiregional neural population effects of directional DBS

Yuxiao Ning, Ph.D., Department of Neurology

Mentor: Jerrold Vitek, M.D., Ph.D., Department of Neurology

Dr. Ning’s project aims to understand the therapeutic mechanisms of directional DBS for improving clinical outcomes in Parkinson’s disease (PD) patients. By simultaneously recording neural activity across multiple regions forming critical circuitry to PD under different DBS settings, as well as analyzing these large neural datasets using cutting-edge machine learning techniques, this project will provide insights hardly discovered by traditional methods. The insights from this project will have an immediate impact on DBS planning and programming approaches, ultimately improving the quality of life for individuals living with PD.

Development of Personalized, Reliable, Generalizable, and Valid Targeting Neuromarker in Neuromodulation for Addiction

Ghazaleh Soleimani, MSc, Ph.D., Department of Psychiatry & Behavioral Sciences

Mentors: Kelvin Lim, M.D., Department of Psychiatry & Behavioral Sciences

Hamed Ekhtiari, M.D., Ph.D., Department of Psychiatry & Behavioral Sciences

Ghazaleh Soleimani is a postdoctoral associate collaborating with Hamed Ekhtiari, Alex Opitz, and Kelvin O. Lim. Her research interests include the development of optimized brain stimulation protocols informed by brain mapping tools. She aims to understand how transcranial electrical and magnetic stimulation affects neural and behavioral outcomes. Utilizing MRI neuroimaging, EEG data, signal processing, and machine learning techniques, she investigates the relationship between stimulation-induced electric fields and changes in brain functions and behaviors. Her research is directed toward creating personalized brain stimulation protocols and refining stimulation parameters for individuals with substance use disorders (SUD). Ghazaleh is developing an innovative approach to improving neuromodulation targeting strategies and developing new treatments for SUD, using multimodal neuroimaging. Her work builds upon resting state fMRI and drug cue reactivity data to identify targeting neuromarkers in the fronto-limbic network for addiction treatment. Her project will utilize new multimodal neuroimaging data, including high-quality structural, resting-state, and task-based fMRI data from multiple groups of participants with different SUDs, including test-retest data. Connectome-based predictive modeling using machine learning methods will also be applied to predict individual behavior (craving) from brain connectivity. This pipeline provides a unique opportunity to develop, validate, and test the reliability and generalizability of targeting neuromarkers in independent samples with SUDs. The ultimate goal is to integrate these insights into developing a precise, individualized MRI-guided TMS protocol targeting the fronto-limbic circuit, a known predictor of relapse in SUDs.

Neuromodulation Clinical Fellow

Dual mechanisms of deep-brain stimulation (DBS) to enhance cognitive control in treatment-resistant mental illnesses

Jaejoong Kim, M.D., Ph.D., Department of Psychiatry and Behavioral Sciences

Mentor: Alik Widge, M.D., Ph.D., Department of Psychiatry and Behavioral Sciences

Patients with severe mental illnesses, such as treatment-resistant depression and OCD, suffer from decreased brain’s ability to control their unwanted thoughts and behaviors and the current treatment options to recover this ability are inefficient. Dr. Kim’s research aims to identify what brain pathways we should stimulate using deep brain stimulation (DBS) to help patients with recovering their brain’s ability to control their thoughts and behaviors, which is called cognitive control. This will provide a better understanding of how we should stimulate our brain to enhance cognitive control, which will potentially lead to a development of DBS algorithms that can benefit the cognitive control of treatment-resistant mental illnesses.