Hypo- and hyper-activation in frontotemporal lobe during humor processing in patients with first episode schizophrenia

Background: Patients with schizophrenia present difficulties in humor recognition and appreciation, but the neural mechanism of these deficits remains unclear. This study aimed to elucidate neural substrates underlying humor processing in patients with first episode schizophrenia (FES).

Methods: This study recruited 40 patients with FES (illness duration ≤ 4 years) and 31 healthy controls matching for age, gender and education level. Participants completed a fMRI verbal humor processing paradigm comprising 96 stories, half for funny punch-line condition and the other half for unfunny condition. Participants were required to judge whether the story was funny or not. Signal detection theory (SDT) analysis was used to calculate d' and β values which represented sensitivity and inner criteria for humor signals respectively. The funny-unfunny contrast was analyzed to identify the brain regions related with humor processing. d' and β values were put into the imaging regression analysis.

Results: Patients with FES showed significantly lower hit rate and sensitivity of humor signals (d'). At the neural level, patients with FES hypo-activated in ventral medial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) while hyper-activated in middle temporal gyrus (MTG) and superior temporal gyrus (STG) compared to controls. In addition, activity in vmPFC and ACC was positively associated with d' and β values, while activity in STG was positively associated with β values in the clinical group.

Conclusions: Patients with FES exhibited decreased sensitivity to humor signals. Hypo-activation in frontal regions and hyper-activation in temporal regions were associated with the humor processing deficits.