Dr. Charles Lewis

Medical School
Twin Cities
Project Title: 
Brain Physiology, Neuroimaging, and Behavior

This group's research aims to better understand the relationship between brain functioning, symptoms of depression, and suicidal thoughts and behaviors during the teenage years, when the brain is developing and changing rapidly. The researchers use a number of different techniques to measure how the brain’s functions change when a person is experiencing depression as well as suicidal thoughts and urges. The goal of the research is to develop improved ways of assessing depression and suicidal thoughts and behaviors in teens, and ultimately to develop improved treatments that reduce risks and improve mental health for adolescents.

This particular project studies the neural underpinnings of impulsivity in adolescent suicidal behavior (SB). Suicide is the second leading cause of death in adolescence, and rates of adolescent SB are increasing. However, its neurobiology remains poorly understood, and treatments specifically targeting SB are lacking. SB in adolescents is a critical public health problem that demands urgent attention, particularly with research that will rapidly translate knowledge to clinical applications. Negative urgency, a component of impulsivity, is the tendency to act rashly in the context of negative emotion. It has been found to be increased among youth with SB and attempts, and has been linked to impaired inhibition of limbic circuitry by the dorsolateral prefrontal cortex (DLPFC), yet precise mechanisms are unclear. Transcranial magnetic stimulation (TMS) permits noninvasive quantification of DLPFC functions such as cortical inhibition (CI), the process by which cortical interneurons regulate the activity of other circuits. Previous research indicates that adolescents with lifetime SB have reduced CI in the motor cortex that distinguishes them from non-suicidal youth. However, DLPFC CI has not been measured in adolescents with SB, nor is it clear how CI relates to cognitive and emotional systems implicated in SB, such as negative urgency. In order to study CI-related mechanisms of negative urgency in the DLPFC, simultaneous TMS and electroencephalography (TMS-EEG) is required. These researchers will conduct a longitudinal study of inhibitory physiology and negative urgency in 40 depressed adolescents with suicidal ideation (but no SB) and 40 depressed adolescents with SB. The study will utilize neuronavigated TMS-EEG, measured from an individualized target determined by task-based functional MRI, as well as self-report measures of negative urgency to test hypotheses that dysregulated CI is associated with negative urgency, that DLPFC CI is deficient in adolescents with SB, and that CI deficits correlate longitudinally with changes in negative urgency and newly emergent SB. The long-term goal is to utilize data gathered in this project to design a large-scale longitudinal study assessing neural and behavioral risk factors for developing SB, as well as trials of neuromodulatory treatments that will reduce the transition from suicidal thoughts to behaviors by targeting alterations in CI and negative urgency.


Project Investigators

Erik Lee
Dr. Charles Lewis
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