Neuroscience
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The effects of muscle fatigue are known to be altered in older adults, and age-related changes in the brain are likely to be a contributing factor. However, the neural mechanisms underlying these changes are not known. The aim of the current study was to use transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) to investigate age-related changes in cortical excitability with muscle fatigue. ⋯ For TMS-EEG, the amplitude of the P30 and P180 potentials were unaffected by fatigue in older participants (P > 0.05). In contrast, the amplitude of the N45 potential in older adults was significantly reduced both during (positive cluster: mean voltage difference = 0.7 µV, P < 0.005; negative cluster: mean voltage difference = 0.9 µV, P < 0.0005) and after (mean voltage difference = 0.5 µV, P < 0.005) fatiguing exercise, whereas this response was absent in young participants. These results suggest that performance of maximal intermittent isometric exercise in old but not young adults is associated with modulation of cortical inhibition likely mediated by activation of gamma-aminobutyric acid type A receptors.
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The role of the dopamine D2 receptor (D2R) in regulating appetitive behavior continues to be controversial. Earlier literature suggests that reduced D2R signaling diminishes motivated behavior while more recent theories suggest that reduced D2R, as has been putatively observed in obesity, facilitates compulsive appetitive behavior and promotes overeating. Using a homecage foraging paradigm with mice, we revisit classic neuroleptic pharmacological studies from the 1970s that led to the 'extinction mimicry' hypothesis: that dopamine blockade reduces reinforcement leading to an extinction-like reduction in a learned, motivated behavior. ⋯ The selective knockouts exhibit no change in sucrose preference or sucrose reinforcement. These data suggest that striatal D2R regulates effort in response to costs, mediating cost sensitivity and behavioral thrift. In the context of obesity, these data suggest that reduced D2R is more likely to diminish effort and behavioral energy expenditure rather than increase appetitive motivation and consumption, possibly contributing to reduced physical activity commonly observed in obesity.
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High gamma activity (HGA) of verbal-memory encoding using invasive-electroencephalogram has laid the foundation for numerous studies testing the integrity of memory in diseased populations. Yet, the functional connectivity characteristics of networks subserving these memory linkages remains uncertain. ⋯ The HGA-memory network comprised regions from both the cognitive control and primary processing networks, validating that effective verbal-memory encoding requires integrating brain functions, and is not dominated by a central cognitive core. Our results demonstrate a tonic intrinsic set of functional connectivity, which provides the necessary conditions for effective, phasic, task-dependent memory encoding.
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In several tauopathies such as Alzheimer's disease (AD), an increased incidence of seizures is observed. Tau, one of the major proteins implicated in AD pathology, is an important regulator of neural network excitability and might participate in the underlying epileptic cascade. However, the mechanisms underlying this relationship are not fully elucidated. ⋯ Also, age-related differences in susceptibility could be demonstrated for both genotypes. Identification and targeting of secondary diseases such as epilepsy, which aggravate dementia and lead to earlier institutionalization, is key. This study finds that tau pathology itself is sufficient to alter seizure susceptibility in a rodent model, indicating that the disease process is crucial in the emergence of epilepsy in patients with tauopathy.
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Endolymphatic hydrops is associated with low-frequency sensorineural hearing loss, with a large body of research dedicated to examining its putative causal role in low-frequency hearing loss. Investigations have been thwarted by the fact that hearing loss is measured in intact ears, but gold standard assessments of endolymphatic hydrops are made postmortem only; and that no objective low-frequency hearing measure has existed. Yet the association of endolymphatic hydrops with low-frequency hearing loss is so strong that it has been established as one of the important defining features for Ménière's disease, rendering it critical to detect endolymphatic hydrops early, regardless of whether it serves a causal role or is the result of other disease mechanisms. ⋯ The ANOW detected low-frequency hearing loss with perfect sensitivity and specificity in all ears after endolymphatic hydrops developed, where there was a strong linear relationship between degree of endolymphatic hydrops and severity of low-frequency hearing loss. Further, histological data demonstrated that endolymphatic hydrops is seen first in the high-frequency cochlear base, though the ANOW demonstrated that dysfunction begins in the low-frequency apical cochlear half. The results lay the groundwork for future investigations of the causal role of endolymphatic hydrops in low-frequency hearing loss.