Neuroscience
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Hypoxic-ischemic encephalopathy (HIE) in neonates can lead to severe long-term disabilities including cerebral palsy and brain injury. The small molecule P7C3-A20 has been shown to exert neuroprotective effects in various disorders such as ischemic stroke and neurodegenerative diseases. However, it is unclear whether P7C3-A20 has therapeutic potential for the treatment of HIE, and the relationship between P7C3-A20 and neuronal apoptosis is unknown. ⋯ In HI model rats, treatment with 5 or 10 mg/kg P7C3-A20 reduced infarct volume; reversed cell loss in the cortex and hippocampus and improved motor function without causing neurotoxicity. The neuroprotective effects were abrogated by treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results demonstrate that P7C3-A20 exerts neuroprotection by activating PI3K/protein kinase B/glycogen synthase kinase 3β signaling and can potentially be used to prevent brain injury in neonates following HIE.
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Sodium tanshinone IIA sulfonate (STS) can protect against brain damage induced by stroke. However, the neural protection mechanism of STS remains unclear. We investigated whether STS performs its protective function by suppressing autophagy and inflammatory activity during brain injury. ⋯ STS treatment reduced neuroinflammation, as assessed by the infiltration of macrophages and neutrophils, corresponding with reduced numbers of macrophages, T cells, and B cells in ischemia/reperfusion (I/R) brains. In addition, STS treatment also attenuated the upregulation of autophagy associated proteins, such as LC3-II, Beclin-1 and Sirt 6, which was induced by MCAO. These results demonstrated that STS can provide remarkable protection against ischemic stroke, possibly via the inhibition of autophagy and inflammatory activity.
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Randomized Controlled Trial
Exploring the effects of an acute dose of antipsychotic medication on motivation-mediated BOLD activity using fMRI and a perceptual decision-making task.
The left inferior frontal gyrus and the bilateral ventral striatum are thought to be involved in motivation-mediated decision-making. Antipsychotics may influence this relationship, and atypical antipsychotics improve secondary negative symptoms in schizophrenia, such as loss of motivation, although the acute effects of pharmacological medication on motivation are not fully understood. In this single-blinded, randomized controlled trial, 49 healthy volunteers were randomized into three groups to receive a single dose of haloperidol, aripiprazole or placebo. ⋯ No robust between-group differences in brain activity in the left inferior frontal gyrus or the bilateral ventral striatum were found. Overall, we found no robust evidence for an effect of either aripiprazole or haloperidol on motivationally mediated behavior. An interesting pattern of correlations possibly related to pharmacologically induced alterations in the dopamine system was observed, although findings remain inconclusive and must be replicated in larger samples.
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As we listen to everyday sounds, auditory perception is heavily shaped by interactions between acoustic attributes such as pitch, timbre and intensity; though it is not clear how such interactions affect judgments of acoustic salience in dynamic soundscapes. Salience perception is believed to rely on an internal brain model that tracks the evolution of acoustic characteristics of a scene and flags events that do not fit this model as salient. The current study explores how the interdependency between attributes of dynamic scenes affects the neural representation of this internal model and shapes encoding of salient events. ⋯ Salient notes embedded in these scenes deviate from the melody's statistical distribution along pitch, timbre and/or intensity. Recordings of brain responses to salient notes reveal that neural power in response to the melodic rhythm as well as cross-trial phase alignment in the theta band are modulated by degree of salience of the notes, estimated across all acoustic attributes given their probabilistic context. These neural nonlinear effects across attributes strongly parallel behavioral nonlinear interactions observed in perceptual judgments of auditory salience using similar dynamic melodies; suggesting a neural underpinning of nonlinear interactions that underlie salience perception.
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Previous studies have shown that aging is associated with changes in decision behavior. However, the neural mechanisms that underpin such age differences are inadequately understood. In this study, we aim to characterize the optimal neural model underlying a dynamic decision making task in both young and older adults, and further examine the age differences from the perspective of effective connectivity. ⋯ The dynamic causal modeling analysis, with the coupling between the ventromedial prefrontal cortex (VMPFC), dorsolateral prefrontal cortex (DLPFC) and anterior insula (AI) that were identified in our task-related activation and psychophysiological interaction analysis, was performed to address the best fitting neural model and characterize age differences. Although both age groups adopted the same optimal model with bidirectional connection between the VMPFC and DLPFC, older adults exhibited up-regulation in several connections and among which the increased modulatory effect of AI-to-VMPFC subserving their decision quality. Our finding suggests that older adults might utilize different neural strategy via compensation to counteract the impact of advanced age in risk taking process.