Proceedings of the National Academy of Sciences of the United States of America
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Humans often accept the status quo when faced with conflicting choice alternatives. However, it is unknown how neural pathways connecting cognition with action modulate this status quo acceptance. Here we developed a visual detection task in which subjects tended to favor the default when making difficult, but not easy, decisions. ⋯ Analysis of effective connectivity showed that inferior frontal cortex, a region more active for difficult decisions, exerted an enhanced modulatory influence on the STN during switches away from the status quo. These data suggest that the neural circuits required to initiate controlled, nondefault actions are similar to those previously shown to mediate outright response suppression. We conclude that specific prefrontal-basal ganglia dynamics are involved in rejecting the default, a mechanism that may be important in a range of difficult choice scenarios.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2010
Pain perception is altered by a nucleotide polymorphism in SCN9A.
The gene SCN9A is responsible for three human pain disorders. Nonsense mutations cause a complete absence of pain, whereas activating mutations cause severe episodic pain in paroxysmal extreme pain disorder and primary erythermalgia. This led us to investigate whether single nucleotide polymorphisms (SNPs) in SCN9A were associated with differing pain perception in the general population. ⋯ Finally, we genotyped 186 healthy females characterized by their responses to a diverse set of noxious stimuli. The A allele of rs6746030 was associated with an altered pain threshold and the effect mediated through C-fiber activation. We conclude that individuals experience differing amounts of pain, per nociceptive stimulus, on the basis of their SCN9A rs6746030 genotype.
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Proc. Natl. Acad. Sci. U.S.A. · Mar 2010
Multicenter StudyToward discovery science of human brain function.
Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. ⋯ These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/.
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Sensory-selective local anesthesia has long been a key goal in local anesthetic development. For example, it allows women to be pain-free during labor without compromising their ability to push. ⋯ Sensory selectivity was imparted to varying degrees by cationic, neutral, and anionic surfactants, and also was achieved with another lidocaine derivative, QX-222. Simultaneous injection of OTAB at a s.c. injection site remote from the sciatic nerve did not result in prolonged sensory-specific nerve blockade from QX-314, suggesting that the observed effect is due to a local interaction between the surfactant and the lidocaine derivative, not a systemic effect.