Ha ha! versus aha! a direct comparison of humor to nonhumorous insight for determining the neural correlates of mirth.

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.

Enhanced expression of matrix metalloproteinase-12 contributes to Npc1 deficiency-induced axonal degeneration.

Niemann-Pick type C (NPC) disease is a genetic disorder associated with intracellular cholesterol accumulation in the 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.

Needle type and the risk of post-lumbar puncture headache in the outpatient neurology clinic.

OBJECTIVE: Post-lumbar puncture headaches (PLPHs) are a common complication of diagnostic lumbar punctures (LPs) caused by a persistent leak of spinal fluid from the dural puncture site. We conducted a prospective study to determine risk factors associated with PLPHs in the neurology outpatient setting. METHODS: Clinical information from all diagnostic LPs performed at the Johns Hopkins Lumbar Puncture Clinic between September 2008 and June 2009 was reviewed. As standard of care, each patient was contacted by telephone by the attending physician within 2-5 days of having an LP to ascertain health status and the presence of PLPH. We performed multiple logistic regression analysis to evaluate the association between PLPH and needle type (traditional Quincke cutting needle 20 and 22 gauge, 20Q and 22Q, and Sprotte non-traumatic gauge 22 needle, 22S) adjusting for important variables such as traumatic LPs, number of attempts, positioning and volume of CSF drawn. RESULTS: The prevalence of PLPH was 32% with the popular gauge 20Q and 22Q needles compared to 19% with the 22S non-traumatic needle. Compared to the 20Q needle, the non-traumatic 22S needle was associated with 69% decreased odds of PLPH (adjusted OR: 0.31, 95% CI 0.12-0.82). In subset analysis, the odds of PLPH increased 4-fold when the 22Q needle was used compared to the 22S needle (adjusted OR=3.99, 95% CI 1.32-12.0). CONCLUSIONS: Our outpatient findings support the American Academy of Neurology recommendations to use smaller non-traumatic needles to reduce the risk of PLPH.