While humor typically involves a surprising discovery, not all discoveries are perceived as humorous or lead to a feeling of mirth. Is there a difference in the neural signature of humorous versus nonhumorous discovery? Subjects viewed drawings that were uninterpretable until a caption was presented that provided either: 1) a nonhumorous interpretation (or insight) of an object from an unusual or partial view (UV) or 2) a humorous interpretation (HU) of the image achieved by linking remote and unexpected concepts. fMRI activation elicited by the UV captions was a subset of that elicited by the humorous HU captions, with only the latter showing activity in the temporal poles and temporo-occipital junction (linking remote concepts), and medial prefrontal cortex (unexpected reward). Mirth may be a consequence of the linking of remote ideas producing high-and unexpected-activation in association and classical reward areas. We suggest that this process is mediated by opioid activity as part of a system rewarding attention to novel information.

No abstract

Niemann-Pick type C (NPC) disease is a genetic disorder associated with intracellular cholesterol accumulation in brain and other organs, and neurodegeneration is generally believed to be the fatal cause of the disease. In view of the emerging role of matrix metalloproteinase-12 (MMP-12) in neuronal injury, we investigated its expression and potential roles in axonal degeneration in Npc1−/− mouse brain. Microarray and quantitative real-time reversed transcription PCR analysis indicated a marked increase in MMP-12 mRNA levels in cerebellum of 3 week-old Npc1−/− mice, as compared to wild-type littermates. Western blots showed that the ratio of mature MMP-12 over pro-MMP-12 was significantly increased in cerebellum of Npc1−/−, as compared to wild-type mice. Immunohistochemical studies confirmed that MMP-12 expression was increased, especially in the cell bodies of Purkinje neurons in Npc1−/− mice. Neuritic growth was significantly reduced by Npc1 siRNA knockdown in nerve growth factor-differentiated PC-12 cells, and this effect was completely reversed by treatment with an MMP-12 specific inhibitor. Furthermore, in vivo experiments showed that chronic treatment with the MMP-12 inhibitor ameliorated Npc1 deficiency-induced axonal pathology in the striatum. Our results indicate that abnormal neuronal expression of MMP-12 may contribute to axonal degeneration in NPC disease, thus providing a potential novel target for treatment.

No abstract