Abstract

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. We found significantly increased high-frequency activity (HFA) in about 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 self-referential stimuli. The location of these activated sites corresponded with the location of fMRI-identified limbic network. Furthermore, the onset of HFA in the vmPFC was significantly earlier than 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 activity in the OFC during positive self-judgment trials among individuals with higher depression scores; responses during negative self-judgment trials were not related to the patients' depression scores. Our findings provide new temporal and anatomical information about the mode of engagement in two important subregions of the OFC during autobiographical memory and self-judgment conditions. Our findings 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.Significance Statement In direct recordings from the human brain, we observed significant responses characterized by high-frequency activity, aka high gamma, in distinct populations of the orbital (oPFC) and ventromedial (vmPFC) regions of the orbitofrontal cortex (OFC) - corresponding to the location of the resting state limbic network and to a lesser extent default mode network - when human subjects were engaged in self-referential episodic memory retrieval and self-trait judgments. Notably, simultaneous recordings across the two OFC regions in the same individuals revealed earlier activations in vmPFC than oPFC, indicating that the two subregions are involved in different stages of self-referential thought processes. Lastly, in individuals with high depressive symptoms, the OFC responses were significantly reduced during positive self-judgments but not heightened during negative self-evaluations.

View details for DOI 10.1523/JNEUROSCI.1634-23.2024

View details for PubMedID 38316564