The Journal of neuroscience : the official journal of the Society for Neuroscience
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Risky decision making on the Iowa Gambling Task (IGT) has been observed in several psychiatric disorders, including substance abuse, schizophrenia, and pathological gambling. Such deficits are often attributed to impaired processing within the orbitofrontal cortex (OFC) because patients with damage to this area or to the amygdala, which is strongly interconnected with the OFC, can likewise show enhanced choice of high-risk options. However, whether damage to the OFC or amygdala impairs subjects' ability to learn the task, or actually affects the decision-making process itself, is currently unclear. ⋯ In contrast, lesions of the BLA, but not the OFC, made after the task had been acquired increased risky choice. These results suggest that, although both regions contribute to the development of appropriate choice behavior under risk, the BLA maintains a more fundamental role in guiding these decisions. The maladaptive choice pattern observed on the IGT in patients with OFC lesions could therefore partially reflect a learning deficit, whereas amygdala damage may give rise to a more robust decision-making impairment.
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Several lines of evidence suggest a major role of the trigeminovascular system in the pathogenesis of migraine. Using functional magnetic resonance imaging (fMRI), we compared brain responses during trigeminal pain processing in migraine patients with those of healthy control subjects. The main finding is that the activity of the spinal trigeminal nuclei in response to nociceptive stimulation showed a cycling behavior over the migraine interval. ⋯ Migraine patients scanned during the acute spontaneous migraine attack showed significantly lower signal intensities in the trigeminal nuclei compared with controls, demonstrating activity levels similar to interictal patients. Additionally we found-for the first time using fMRI-that migraineurs showed a significant increase in activation of dorsal parts of the pons, previously coined "migraine generator." Unlike the dorsal pons activation usually linked to migraine attacks, the gradient-like activity following nociceptive stimulation in the spinal trigeminal neurons likely reflects a raise in susceptibility of the brain to generate the next attack, as these areas increase their activity long before headache starts. This oscillating behavior may be a key player in the generation of migraine headache, whereas attack-specific pons activations are most likely a secondary event.
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Phosphinositide 3-kinase (PI3K), Akt, and their downstream kinase, mammalian target of rapamycin (mTOR), are implicated in neural plasticity. The functional linkages of this signaling cascade in spinal dorsal horn and their role in inflammatory hyperalgesia have not been elucidated. ⋯ Intrathecal injection of Substance P activated this cascade (increased phosphorylation) and resulted in hyperalgesia, both of which effects were blocked by intrathecal wortmannin and rapamycin. Together, these findings reveal that afferent inputs trigged by peripheral inflammation initiate spinal activation of PI3K-Akt-mTOR signaling pathway, a component of which participates in neuronal circuits of facilitated pain processing.
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Simulation models of expression recognition contend that to understand another's facial expressions, individuals map the perceived expression onto the same sensorimotor representations that are active during the experience of the perceived emotion. To investigate this view, the present study examines facial expression and identity recognition abilities in a rare group of participants who show facilitated sensorimotor simulation (mirror-touch synesthetes). ⋯ Mirror-touch synesthetes outperformed nonsynesthetic participants on measures of facial expression recognition, but not on control measures of face memory or facial identity perception. These findings imply a role for sensorimotor simulation processes in the recognition of facial affect, but not facial identity.
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With aging, multiple Ca(2+)-associated electrophysiological processes exhibit increased magnitude in hippocampal pyramidal neurons, including the Ca(2+)-dependent slow afterhyperpolarization (sAHP), L-type voltage-gated Ca(2+) channel (L-VGCC) activity, Ca(2+)-induced Ca(2+) release (CICR) from ryanodine receptors (RyRs), and Ca(2+) transients. This pattern of Ca(2+) dysregulation correlates with reduced neuronal excitability/plasticity and impaired learning/memory and has been proposed to contribute to unhealthy brain aging and Alzheimer's disease. However, little is known about the underlying molecular mechanisms. ⋯ Rapamycin, which displaces FKBP1b from RyRs in myocytes, similarly enhanced VGCC current and the sAHP and also increased CICR. Moreover, FKBP1b knockdown in vivo was associated with upregulation of RyR2 and mTOR protein expression. Thus, disruption of FKBP1b recapitulated much of the Ca(2+)-dysregulation aging phenotype in young rat hippocampus, supporting a novel hypothesis that declining FKBP function plays a major role in unhealthy brain aging.