Neuroscience
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Frontal areas are thought to be the coordinators of working memory processes by controlling other brain areas reflected by oscillatory activities like frontal-midline theta (4-7 Hz). With aging substantial changes can be observed in the frontal brain areas, presumably leading to age-associated changes in cortical correlates of cognitive functioning. The present study aimed to test whether altered frontal-midline theta dynamics during working memory maintenance may underlie the capacity deficits observed in older adults. 33-channel EEG was recorded in young (18-26 years, N=20) and old (60-71 years, N=16) adults during the retention period of a visual delayed match-to-sample task, in which they had to maintain arrays of 3 or 5 colored squares. ⋯ Old participants showed reduced frontal theta activity during both tasks compared to the young group. In the young memory maintenance-related frontal-midline theta activity was shown to be sensitive both to the increased memory demands and to efficient subsequent memory performance, whereas the old adults showed no such task-related difference in the frontal theta activity. The decrease of frontal-midline theta activity in the old group indicates that cerebral aging may alter the cortical circuitries of theta dynamics, thereby leading to age-associated decline of working memory maintenance function.
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Physical activity influences inflammation, and both affect brain structure and Alzheimer's disease (AD) risk. We hypothesized that older adults with greater reported physical activity intensity and lower serum levels of the inflammatory marker tumor necrosis factor α (TNFα) would have larger regional brain volumes on subsequent magnetic resonance imaging (MRI) scans. In 43 cognitively intact older adults (79.3±4.8 years) and 39 patients with AD (81.9±5.1 years at the time of MRI) participating in the Cardiovascular Health Study, we examined year-1 reported physical activity intensity, year-5 blood serum TNFα measures, and year-9 volumetric brain MRI scans. ⋯ When considered together, more intense physical activity intensity and lower serum TNFα were both associated with greater total brain volume on follow-up MRI scans. TNFα, but not physical activity, was associated with regional volumes of the inferior parietal lobule, a region previously associated with inflammation in AD patients. Physical activity and TNFα may independently influence brain structure in older adults.
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Task execution almost always occurs in the context of reward-seeking or punishment-avoiding behavior. As such, ongoing task-monitoring systems are influenced by reward anticipation systems. In turn, when a task has been executed either successfully or unsuccessfully, future iterations of that task will be re-titrated on the basis of the task outcome. ⋯ Rather, ERP measures suggested that only the magnitude of actual reward or loss was now processed. Reward and task-monitoring processes are clearly dissociable, but interact across very fast timescales to update reward predictions as information about task success or failure is accrued. Careful delineation of these processes will be useful in future investigations in clinical groups where such processes are suspected of having gone awry.
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Aspirin-triggered Lipoxin A4 (ATL), as a Lipoxin A4 (LXA4) epimer, is endogenously produced by aspirin-acetylated cycloxygenase-2 (COX-2) and plays a vital role in endogenous anti-inflammation via the LXA4 receptor (ALX). Recent investigations have indicated that spinal neuroinflammation and the activation of the Janus Kinase 2 (JAK2)/Signal Transducers and Transcription Activators 3 (STAT3) signaling pathway are involved in neuropathic pain states. However, the effect of ATL on neuroinflammation and JAK2/STAT3 signaling in chronic constriction injury (CCI)-induced neuropathic pain in rats has not been well-studied. ⋯ Blockade of JAK2-STAT3 signaling with intrathecal administration of the JAK2 inhibitor AG490 or the STAT3 inhibitor S3I-201 clearly reduced mechanical allodynia and the upregulation of pro-inflammatory cytokines in CCI rats. Interestingly, inhibition of JAK2/STAT3 signaling via ATL or the specific signaling inhibitor (AG49, S3I-201) further promoted the increased expression of suppressor of cytokine signaling 3 (SOCS3) mRNA in the spinal cord induced by CCI surgery. Taken together, our results suggested that the analgesic effect of ATL was mediated by inhibiting spinal JAK2/STAT3 signaling and hence the spinal neuroinflammation in CCI rats.
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Fragile X mental retardation protein (FMRP) binds select mRNAs, functions in intracellular transport of these mRNAs and represses their translation. FMRP is highly expressed in neurons and lack of FMRP has been shown to result in dendritic dysmorphology and altered synaptic function. FMRP is known to interact with mRNAs for the Kv3.1b potassium channel which is required for neurons to fire action potentials at high rates with remarkable temporal precision. ⋯ To examine this hypothesis, we have studied normal human brainstem tissue with immunohistochemical techniques and confocal microscopy. Our results demonstrate that FMRP is widely expressed in cell bodies and dendritic arbors of neurons in the human cochlear nucleus and superior olivary complex and also that coincidence detector neurons of the medial superior olive colocalization of FMRP and Kv3.1b. We interpret these observations to suggest that the lower auditory brainstem is a potential site of dysfunction in FXS.