Projects | MnDRIVE Brain Conditions

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

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.

Postdoctoral Fellow: Sana Amoozegar, Ph.D., Neurology

Mentor: Jing Wang, Ph.D., Neurology

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

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.

Postdoctoral Fellow: Meredith Bauer Ph.D., Neuroscience

Mentor: Jocelyn Richard, Ph.D., Neuroscience

Modulating Anxiety by Selective Disruption of Hippocampal Sharp Waves

According to a recent survey conducted in December 2022 by the National Center for Health Statistics, a quarter of Minnesotans (23.9%) reported experiencing symptoms of anxiety. For those receiving treatment, benzodiazepines are commonly prescribed despite their association with many harmful side effects including memory loss, dependency, and withdrawal. From 2019-2020, the number of deaths from benzodiazepine overdoses in Minnesota increased by 70%, underscoring the dangers of this class of drug. As this number increases, so does the urgency for effective and innovative treatment options.

Dr. Damphousse's project aims to examine how anxiety-related events could be disrupted through neuromodulation applied to a specific brain region as these events occur, potentially enabling more selective and efficient treatment options than those currently available. By understanding the neural mechanisms underlying anxiety and targeting these mechanisms for therapeutic intervention, findings from this project may offer an alternative way forward in making treatment of anxiety easier and safer.

Graduate Fellow: Chelsey Damphousse, Ph.D., Neuroscience

Mentor: David Redish, Ph.D., Neuroscience

Interrogating the synaptic mechanisms of deep brain stimulation with single-synapse resolution during motor behavior

Thalamic deep brain stimulation (DBS) is a therapy that can effectively treat a range of brain disorders, although there are still challenges with long-term treatment efficacy and side-effects. Computational models suggest that the therapeutic effects of thalamic DBS are the result of neurotransmitter depletion at thalamocortical synapses in the motor cortex, however direct measurement of synaptic function in vivo is lacking.

Jacob Gable's project will explore the development of new methods to characterize how thalamic DBS directly influences neurotransmitter release at thalamocortical synapses during motor behavior. Understanding the synaptic mechanisms of thalamic DBS may inform the development of improved treatments and quality of life for individuals that are afflicted by a range of brain disorders as well as advance the next generation of neuromodulation technology.

Graduate Fellow: Jacob Gable, Neuroscience

Mentor: Aaron Kerlin, Ph.D., Neuroscience

Evaluating precision functional mapping for improved clinical efficacy of real-time transcranial magnetic stimulation (TMS)

Stroke affects approximately 2.7% of the United States population. In Minnesota, more than 5% of all deaths are caused by a stroke. Fortunately, Minnesota is ranked the 11th lowest for stroke mortality rates; however, that means more people are living with stroke-related symptoms like aphasia and hemiplegia, which decrease their quality of life. By improving TMS therapies for stroke, we are helping Minnesotans improve their recovery.

Zachary Haigh's functional mapping research will reveal precise targeting methods for transcranial magnetic stimulation (TMS) based on functional MRI (fMRI) and electroencephalography (EEG). His research will allow for accurate targeting of specific functional networks during therapeutic use of TMS and will improve the efficacy of therapeutic TMS for a variety of stroke-related symptoms including motor, speech, and cognitive deficits.

Graduate Fellow: Zachary Haigh, Biomedical Engineering

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

Pharmacological enhancement of optogenetic neuromodulation to correct substance use disorder-related dysfunction of striatal neurocircuitry

Substance misuse is an especially prevalent problem in Minnesota, where 13.66% of all deaths from 2008 to 2017 were caused by drugs or alcohol. The state’s significant funding for research, rehab centers, and education about substance abuse reflects the gravity of the matter. Our research on new treatments for substance use disorders has the potential to reduce the prevalence of drug abuse, which would greatly benefit Minnesotans struggling with SUDs and relieve the public burden of SUD-related costs on Minnesotan taxpayers.

Filip Hanak’s preclinical research on pharmacological enhancement of neuromodulation in the Nucleus Accumbens will lead to improved treatments for patients suffering from substance use disorders. In addition to clinical applications, the proposed research will result in fundamental science discoveries about neural circuitry in the Nucleus Accumbens.

Graduate Fellow: Filip Hanak, Neuroscience

Mentor: Patrick Rothwell, Ph.D., Neuroscience

A Multi-Modal Neuromodulation Approach to Enhancing Speech Perception in Noise

Scientific findings of this study will be disseminated to the community of hearing scientists and Minnesota-based audiologists through conferences for hearing healthcare and research professionals. The timely communication between the research team and the local research and healthcare community is vital to raise awareness of the unmet needs in the current hearing healthcare system. It will also draw the attention of Minnesota-based audiologists and hearing technology companies to incorporate neuromodulation approaches into their day-to-day practice, which will potentially benefit 20% of Minnesota citizens who have hearing loss.

Dr. He's study focuses on developing techniques and devices that can potentially benefit a large population of hearing-impaired adults in terms of improving their general hearing health and speech perception in noise. By adopting the paired stimulation paradigm successfully demonstrated in animals, Dr. He’s team will be the first to show whether human hearing can benefit from a similar non-invasive paradigm. This study will provide a foundational understanding of principles for the safe and effective use of multimodal neuromodulation in humans. The knowledge gained from this research will shed light on the role of neuroplasticity in auditory rehabilitation and have important implications for neuromodulation-mediated language learning and cognition, tinnitus, and hyperacusis.

Postdoctoral Fellow: Yuan He, Ph.D., Biomedical Engineering and Otolaryngology

Mentor: Hubert Lim, Ph.D., Biomedical Engineering and Otolaryngology

Neural Mechanisms of Closed-loop Phase-locked Transcranial Magnetic Stimulation

Approximately 226,000 adults have a serious mental illness in Minnesota, and major depressive disorder (MDD) remains one of the leading causes of disability with a rising diagnosis rate (8-10). Aside from representing a significant mental health problem, MDD leads to a growing economic burden in Minnesota, estimated at $3.8 billion in 2018. The application of emerging neuromodulation technologies holds promise in increasing treatment efficacy for depression and thus potentially addressing the mental health challenges and economic cost faced by citizens in Minnesota.

Güldamla Kalender's research aims to develop a personalized transcranial magnetic stimulation (TMS) protocol that delivers stimulation timed to a certain phase of an endogenous brain rhythm and explores the utility of physiologically informed neuromodulation in psychiatric disorders. Carrying this phase-dependent approach into TMS for neuropsychiatric disorders may enhance the TMS-induced neuroplasticity and lead to the optimization of its therapeutic effects, which would be beneficial both in developing a theoretical understanding of clinically relevant neuroplasticity and in providing direction for clinicians to maximize the benefit of neuromodulation techniques.

Graduate Fellow: Güldamla Kalender, Psychiatry and Behavioral Sciences

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

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

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.

Clinical Fellow: Jaejoong Kim, M.D., Ph.D., Psychiatry & Behavioral Sciences

Mentor: Alik Widge, M.D., Ph.D., Psychiatry & Behavioral Sciences

Neural mechanisms of impaired axial muscle coupling during turns in people with Parkinson’s disease and freezing of gait

Minnesota has a larger than average population of people living with Parkinson’s Disease (13,400 currently, greater than 28 other US states). This population is at a high risk of experiencing a fall due to postural instability, gait disturbances and freezing of gait, which can often lead to further severe injury including hip fractures, traumatic brain injuries, prolonged loss of functional mobility, and even death. Falls also contribute significantly to the $61 billion spent in healthcare in Minnesota annually (as of 2020) This project will contribute improved understanding of the underlying neural control of trunk muscles in this population, with the goal to translate this knowledge to improved treatments for postural instability and a reduction in the number of falls and fall-related consequences for Minnesotans.

Callen Maupin's project will lead to an increased understanding of the neural mechanisms contributing to impaired turning. The findings from these experiments can be translated into new approaches to improve trunk muscle control, such as physical therapy interventions that target axial muscles and the sequencing of leg and trunk coupling during turns, or the use of novel vestibular training interventions to improve the modulation of vestibulospinal pathways.

Graduate Fellow: Callen Maupin, Neurology

Mentor: Colum MacKinnon, Ph.D., Neurology

State-dependent effects of prefrontal transcranial magnetic stimulation

Mental illnesses have a significant social and economic impact on the state of Minnesota. The findings from this research may be used to inform and improve current brain stimulation protocols in clinics. As such, this project can directly lead to improved health outcomes and reduce the social and economic costs of mental illness to the citizens of Minnesota. By offering directions to make neuromodulation techniques more effective and reliable, the findings of this project may help optimize medical device capabilities in the treatment of psychiatric disorders. Given the prominence of Minnesota’s medical device sector, this can have a direct positive impact on Minnesota’s economy.

Dr. McInnes' research aims to explore conditions which enhance the effectiveness of electromagnetic brain stimulation on brain function. He will examine whether the benefits of brain stimulation on mental functioning can be enhanced if patients are actively engaging the target brain networks whilst receiving brain stimulation. This will lead to a better understanding of how brain stimulation improves brain function, as well as provide directions to clinicians regarding how they can better utilize brain stimulation as a more effective and reliable treatment for mental illness.

Postdoctoral Fellow: Aaron McInnes, Ph.D., Psychiatry and Behavioral Sciences

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

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

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.

Graduate Fellow: Zachary Sanger, Biomedical Engineering

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

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

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.

Postdoctoral Fellow: Ghazaleh Soleimani, MSc, Ph.D., Psychiatry and Behavioral Sciences

Mentors: Kelvin Lim, M.D., Ph.D., Psychiatry and Behavioral Sciences

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

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

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.

Graduate Fellow: Karianne Sretavan Wong, Neuroscience

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

Multi-Method Identification of Neural Correlates of Symptom Improvement in Combined Transcranial Direct Current Stimulation-Mindful Breathing Treatment for Depressed Adolescents

The prevalence of depression in Minnesota is consistently higher than that of other states. Of particular concern, adolescent depression is 50% higher in Minnesota when compared to the national average, and depression is the second most common mental health diagnosis among the student population at the University of Minnesota - Twin Cities. Existing interventions, including tDCS, have largely failed to adequately treat depressive symptoms in the majority of patients, especially those with more severe depression. This project aims to better understand the neural mechanisms underlying tDCS-related treatment outcomes in order to better optimize the treatment selection process. The results will help clinicians determine which patients would benefit the most from tDCS as a treatment for depression,
expediting the treatment process for Minnesotans.

Marvin Yan’s research will leverage brain imaging and neuromodulation technology to elucidate neurobiological correlates of suicide risk and depression. His project will identify patterns of neural activity that are associated with the reduction of depressive symptoms in those that received active vs. sham tDCS in addition to mindful breathing training. His research will test whether a novel data analytic technique that identifies causal connections in the brain provides unique information above and beyond traditional analytic approaches. His research work signifies an initial step towards refining the adaptation of causal discovery analysis for use with neuroimaging and neuromodulation data to make clinically-relevant decisions. The results will help clinicians determine which patients would benefit the most from tDCS as a treatment for depression, expediting the treatment process.

Graduate Fellow: Marvin Yan, Psychiatry and Behavioral Sciences

Mentor: Kathryn Cullen, M.D., Psychiatry and Behavioral Sciences