Biology subjects

Brothers, T.

Publications and source records attributed to Brothers, T..

4 recordsLinked to original sources

bioRxiv2025

Aging reveals divergent responses of AgRP/NPY neurons to diet in male and female mice.

ObjectivesNeurons coexpressing Agouti-related peptide (AgRP) and Neuropeptide Y (NPY) are an essential component of an interoceptive circuit regulating hunger and metabolism. Their activity is closely linked to metabolic state and their output is sensitive to diet-induced plasticity, which may influence the development of obesity and associated metabolic diseases. However, most studies use young male mice, even though obesity and its comorbidities are sensitive to both biological sex and aging, leaving a significant gap in our understanding of the role of these neurons in females and in older animals. Our goal was to begin to address this gap by investigating the effects of diet and age on AgRP/NPY neuronal activity in female mice in both early adulthood and midlife. MethodsFemale transgenic NPY-GFP mice aged 8 - 32 weeks were fed either a standard control chow diet or a high-fat, high-sugar diet (HFD) for 8 - 24 weeks and brain slice patch clamp electrophysiology was used to measure the response of AgRP/NPY neurons. ResultsWe found that in young, lean female mice, the baseline firing rate of AgRP/NPY neurons is significantly elevated compared to age-matched males, thus the impact of HFD on the output of these neurons is blunted relative to control. However, in the baseline firing rate of neurons from lean middle-aged female mice is significantly lower, resulting in a greater relative impact of HFD on AgRP/NPY neuronal output, the development of neuronal leptin resistance, and significant weight gain. ConclusionsBoth sex and age significantly impact the function and modulation of AgRP/NPY neurons, emphasizing the need to include these biological variables in experimental design. HighlightsO_LIMale and female mice exhibit sex-dependent responses to a high-fat diet, with female mice requiring twice as long to develop an overt obese phenotype. C_LIO_LIAgRP/NPY neurons in young, lean female mice have significantly higher activity than those from male mice. C_LIO_LIAging female mice develop obesity and altered function and leptin sensitivity of AgRP/NPY neurons. C_LIO_LIThe hypothalamic glial response to high-fat diet is influenced by sex - age interactions. C_LI

neuroscience↗

bioRxiv2021

Dynamic predictive coding across the left fronto-temporal language hierarchy: Evidence from MEG, EEG and fMRI

We used MEG and ERPs to track the time-course and localization of evoked activity produced by expected, unexpected plausible and implausible words during incremental language comprehension. We interpret the full pattern of evoked responses and functional connectivity within a hierarchical predictive coding framework in which evoked activity reflects residual information (error) that is passed up and down the cortical hierarchy. Between 300-500ms, the three conditions produced progressively larger responses within left temporal cortex (lexico-semantic prediction error), while implausible inputs produced a selectively enhanced response within left inferior frontal cortex (event-level prediction error). Between 600-1000ms, unexpected plausible words activated left inferior frontal and middle temporal cortices (feedback activity that induced top-down shifts of event-level and lexico-semantic representations), while highly implausible inputs activated posterior fusiform and medial temporal cortices, supporting orthographic reanalysis and new learning. Therefore, predictive coding may provide a unifying theory that links language comprehension to other domains of cognition.

neuroscience↗

bioRxiv2021

Domain-general conflict monitoring predicts neural and behavioral indices of linguistic error processing during reading comprehension

The ability to detect and respond to linguistic errors is critical for successful reading comprehension, but these skills can vary considerably across readers. In the current study, healthy adults (age 18-35) read short discourse scenarios for comprehension while monitoring for the presence of semantic anomalies. Using a factor analytic approach, we examined if performance in non-linguistic conflict monitoring tasks (Stroop, AX-CPT) would predict individual differences in neural and behavioral measures of linguistic error processing. Consistent with this hypothesis, domain-general conflict monitoring predicted both readers end-of-trial acceptability judgments and the amplitude of a late neural response (the P600) evoked by linguistic anomalies. Interestingly, the influence on the P600 was non-linear, suggesting that online neural responses to linguistic errors are influenced by both the effectiveness and efficiency of domain-general conflict monitoring. These relationships were also highly specific and remained after controlling for variability in working memory capacity and verbal knowledge. Finally, we found that domain-general conflict monitoring also predicted individual variability in measures of reading comprehension, and that this relationship was partially mediated by behavioral measures of linguistic error detection. These findings inform our understanding of the role of domain-general executive functions in reading comprehension, with potential implications for the diagnosis and treatment of language impairments.

neuroscience↗

bioRxiv2017

1/f Neural Noise and Electrophysiological Indices of Contextual Prediction in Normative Aging

Prediction during language comprehension has increasingly been suggested to play a substantive role in efficient language processing. Emerging models have postulated that predictive mechanisms are enhanced when neural networks fire synchronously, but to date, this relationship has been investigated primarily through oscillatory activity in narrow frequency bands. A recently-developed measure proposed to reflect broadband neural activity - and thereby synchronous neuronal firing - is 1/f neural noise extracted from EEG spectral power. Previous research (Voytek et al., 2015) has indicated that this measure of 1/f neural noise changes across the lifespan, and these neural changes predict age-related behavioral impairments in visual working memory. Using a cross-sectional sample of young and older adults, we examined age-related changes in 1/f neural noise and whether this measure would predict ERP correlates of successful lexical prediction during discourse comprehension. 1/f neural noise across two different language tasks revealed high within-subject correlations, indicating that this measure can provide a reliable index of individualized patterns of neural activation. In addition to age, 1/f noise was a significant predictor of N400 effects of successful lexical prediction, but noise did not mediate age-related declines in other ERP effects. We discuss broader implications of these findings for theories of predictive processing, as well as potential applications of 1/f noise across research populations.

neuroscience↗