University of California, San Francisco
The purpose of this study is to understand how the orbitofrontal cortex (OFC), a region at the front of the brain, guides decisions about whether to pursue a possible reward when doing so also carries a risk of loss, and how this process is altered in depression. People with depression are often less motivated by rewards and more sensitive to potential losses, leading them to avoid situations that others would approach. The OFC is thought to play a central role in these "approach or avoid" decisions, but how it normally does so, and what goes wrong in depression, is not well understood. This study asks two questions: (1) How does activity in different parts of the OFC signal the decision to approach or avoid? (2) Does this activity differ in people with depression in a way that explains a bias toward avoidance? We hypothesize that the medial OFC (toward the middle of the brain) signals approach, the lateral OFC (toward the side of the brain) signals avoidance, and that in depression the medial OFC signal is weakened, tipping decisions toward avoidance. Participants are adults who are hospitalized with stereo-EEG (sEEG) electrodes already placed in the brain by their medical team, either to locate the source of seizures in epilepsy or as part of a separate clinical trial for treatment-resistant depression. The electrodes are placed for clinical reasons only, not for this study. During their hospital stay, participants complete a short, game-like computer task (about 20 minutes per session) in which they repeatedly choose whether to approach or avoid options that offer different chances of reward and loss. Their choices and reaction times are recorded along with brain activity from the existing electrodes, and participants rate their mood before each session. The researchers will compare OFC activity during approach versus avoid decisions, use mathematical models of decision-making to measure how strongly each participant weighs rewards and losses, and compare participants with and without depression. No drugs, devices, or brain stimulation are given as part of this study. The findings are intended to guide the development of more targeted brain-stimulation treatments for treatment-resistant depression.
Inclusion Criteria: All participants: * 18 years of age or older * Implanted with stereo-EEG (sEEG) depth electrodes, including at least one electrode in the orbitofrontal cortex (OFC) * Able to read, write, and provide informed consent Depressed cohort: * Enrolled in the PRESIDIO trial (NCT04004169) of deep brain stimulation for treatment-resistant depression and undergoing inpatient sEEG monitoring as part of that trial * Meets DSM-5 criteria for major depressive disorder (single episode of at least 2 years' duration, or recurrent), without psychotic features, confirmed by structured cli…
A computerized, gamified approach-avoidance decision-making task built in the Unity game engine and presented on a laptop at the bedside during inpatient sEEG monitoring. On each trial, the participant views a virtual corridor containing a reward offer (0-7 treasure chests) and a punishment offer (0-4 bombs) and indicates by button press whether to approach the corridor, with probabilistic gain and loss outcomes, or avoid it, with a neutral outcome. Reward and punishment magnitudes are varied in pseudorandomized order across 220 trials per session (\~20 minutes). Choices and reaction times are recorded and synchronized with intracranial neural recordings at millisecond precision. The task serves as an experimental probe of the neural and behavioral mechanisms of approach-avoidance decision-making; it is not a treatment, and no therapeutic effect is expected. Task code is openly available (github.com/cstarkweather).