Projects | MnDRIVE Brain Conditions

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.

Postdoctoral 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., Department of Biomedical Engineering and Otolaryngology

Mentors: 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.

Postdoctoral Fellow: Güldamla Kalender, Psychiatry and Behavioral Sciences

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

Postdoctoral 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.

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

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

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.

Postdoctoral Fellow: Marvin Yan, Psychiatry and Behavioral Sciences

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