Novel invasive neurostimulation stimulation strategies through neurosurgical interventions are emerging as a promising therapeutical strategy for major depressive disorder. These have been applied mostly to the anterior cingulate cortex, but other limbic brain regions have shown promise as anatomical targets for new neurostimulation strategies. The researchers seek to study neural activity in limbic brain areas implicated in decision behavior and mood regulation to identify novel targets for treatment through electrical stimulation. To do this, the study team will record local field potentials (LFPs) from the orbitofrontal cortex, hippocampus and amygdala of epilepsy participants undergoing invasive monitoring (intracranial encephalography, iEEG) during choice behavior. Leveraging the high co-morbidity of depression and intractable epilepsy (33-50%), neural responses will be compared to reward across depression status to identify abnormal responses in depression. Finally, the researchers will use these as biomarkers to guide development of neurostimulation strategies for the treatment of depression.

Participants (n=24) will complete a decision-making task in which participants will make decisions under uncertainty and seek to maximize rewards. The researchers will assess behavioral (risk attitudes) and neural (LFP) responses using a combination of intracranial recordings and computational modeling. A subset of patients will complete the game a second time under electrical stimulation of pre-identified anatomical targets in orbitofrontal cortex, hippocampus or amygdala. In addition, patients' depression status will be assessed through questionnaires (BDI-II and HDSA). Finally, the researchers will examine whether electrical stimulation results in behavioral or mood modulation.

Inclusion Criteria:

- The study will follow clinical criteria for epilepsy patient recruitment for invasive monitoring. As a results, individuals of adults of all ages are expected to be included in this study.

Exclusion Criteria:

• Adults over 80 years of age will be excluded as per concerns of cognitive decline.
• Children under 18 will be excluded from the study since the maturation of frontal lobes continues through adolescence and significant differences in frontal lobe functioning between children younger than 18 and adults are often observed.

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Beginning 3 months and ending 5 years following article publication.

Researchers who provide a methodologically sound proposal. Any purpose. Proposals should be directed to ignacio.saez@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be included in the URL field below).