Frontal hypoactivation and alterations in the reward-system during humor processing in patients with schizophrenia spectrum disorders.

Humor is a ubiquitous human ability with important implications for both social and emotional functioning. Patients with neuropsychiatric disorders, such as schizophrenia, experience difficulties in the comprehension and appreciation of humor. However, the specific neural mechanisms underlying these deficits are unknown. In the current study, we sought to elucidate the neural correlates of humor processing in patients with schizophrenia spectrum disorders (SSD). Functional Magnetic Resonance Imaging (fMRI) was used in thirty-one patients with SSD and a control group, performing a humor processing paradigm. Both regional brain activation and parametric modulation of brain responses via subjective funniness ratings were collected during the scanning procedure. On a neural level, large overlaps in fronto-temporal brain activation was found in both groups. However, patients compared to healthy control subjects showed attenuated responses in frontal brain regions, including the anterior cingulate cortex, medial prefrontal cortex (mPFC), superior frontal gyrus and middle frontal gyrus, as well as in the striatum (i.e. caudate nucleus, putamen). Furthermore, parametric modulation of subjective funniness ratings resulted in attenuated responses in the mPFC, bilateral insula, and left hippocampus. Analysis of functional connectivity revealed alterations in mPFC-caudate nucleus coupling in patients with SSD, which might reflect impairments in reward-related processing. Notably, alterations in mPFC-caudate nucleus coupling in patients were significantly associated to subjective funniness ratings. Our results extend previous findings demonstrating the relevance of frontal hypoactivation for humor processing impairments in patients with SSD and first point towards alterations in humor appreciation processes.