Neuroscience
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The frequency of intrusive saccades during maintenance of active visual fixation has been used as a measure of sustained visual attention in studies of healthy subjects as well as of neuropsychiatric patient populations. In this study, the mechanism that generates intrusive saccades during active visual fixation was investigated in a population of young healthy men performing three sustained fixation tasks (fixation to a visual target, fixation to a visual target with visual distracters, and fixation straight ahead in the dark). Markov Chain modeling of inter-saccade intervals (ISIs) was utilized. ⋯ Accordingly, the system of intrusive saccade generation may operate in two "attractor" states, one in which intrusive saccades occur at short consecutive ISIs and another in which intrusive saccades occur at long consecutive ISIs. These states might correspond to two distinct states of the attention system, one of low focused - high distractibility and another of high focused - low distractibility, such as those proposed in the adaptive gain theory for the control of attention by the noradrenergic system in the brain. To the authors knowledge, this is the first time that Markov Chain modeling has been applied to the analysis of the ISIs of intrusive saccades.
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Spinocerebellar ataxia type-3 (SCA-3) is a rare disease but it is the most frequent type within the autosomal dominant inherited ataxias. The disease lacks an effective treatment to alleviate major symptoms and to modify disease progression. Our recent findings that endocannabinoid receptors and enzymes are significantly altered in the post-mortem cerebellum of patients affected by autosomal-dominant hereditary ataxias suggest that targeting the endocannabinoid signaling system may be a promising therapeutic option. ⋯ We also measured the levels of endocannabinoid lipids and found reductions in anandamide and oleoylethanolamide in the brainstem. These changes correlated with an increase in the FAAH enzyme in the brainstem, which also occurred in some cerebellar areas, whereas other endocannabinoid-related enzymes were not altered. Collectively, our results in SCA-3 mutant mice confirm a possible dysregulation in the endocannabinoid system in the most important brain structures affected in this type of ataxia, suggesting that a pharmacological manipulation addressed to correct these changes could be a promising option in SCA-3.
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Compared to isometric activities, the neural basis of fatigue induced by repetitive tasks has been scarcely studied. Recently, we showed that during short-lasting repetitive tasks at the maximal possible rate (finger tapping for 10 and 30s), tapping rate and maximal voluntary contraction (MVC) force decrease at the end of finger tapping. We also observed larger silent periods (SP) induced by transcranial magnetic stimulation during MVC post finger tapping. ⋯ While indices of excitability increased initially in both tasks, they decreased with the isometric task only when the task was prolonged to 30s. We suggest that the inability to maintain increased levels of spinal excitability during task execution is a neurophysiological mark of fatigue. Our results suggest that the origin of fatigue induced by brief and fast repetitive tasks is not spinal.
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Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). ⋯ These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart.
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Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid's impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. ⋯ Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health.