Intracranial Recordings of the Human Orbitofrontal Cortical Activity during Self-Referential Episodic and Valenced Self-Judgments

We recorded directly from the orbital (oPFC) and ventromedial (vmPFC) subregions of the orbitofrontal cortex (OFC) in 22 (9 female, 13 male) epilepsy patients undergoing intracranial electroencephalography (iEEG) monitoring during an experimental task in which the participants judged the accuracy of self -referential autobiographical statements as well as valenced self -judgments (SJs). We found signi fi cantly increased high -frequency activity (HFA) in similar to 13% of oPFC sites (10/18 subjects) and 16% of vmPFC sites (4/12 subjects) during both of these self -referential thought processes, with the HFA power being modulated by the content of selfreferential stimuli. The location of these activated sites corresponded with the location of fMRI-identi fi ed limbic network. Furthermore, the onset of HFA in the vmPFC was signi fi cantly earlier than that in the oPFC in all patients with simultaneous recordings in both regions. In 11 patients with available depression scores from comprehensive neuropsychological assessments, we documented diminished HFA in the OFC during positive SJ trials among individuals with higher depression scores; responses during negative SJ trials were not related to the patients ' depression scores. Our fi ndings provide new temporal and anatomical information about the mode of engagement in two important subregions of the OFC during autobiographical memory and SJ conditions. Our fi ndings from the OFC support the hypothesis that diminished brain activity during positive self -evaluations, rather than heightened activity during negative self -evaluations, plays a key role in the pathophysiology of depression.