Biology subjects

Kennedy, B. L.

Publications and source records attributed to Kennedy, B. L..

3 recordsLinked to original sources

bioRxiv2021

Behavioral and fMRI evidence that arousal enhances bottom-up attention and memory selectivity in young but not older adults

During a challenge or emotional experience, increases in arousal help us focus on the most salient or relevant details and ignore distracting stimuli. The noradrenergic system integrates signals about arousal states throughout the brain and helps coordinate this adaptive attentional selectivity. However, age-related changes in the noradrenergic system and attention networks in the brain may reduce the efficiency of arousal to modulate selective processing in older adults. In the current neuroimaging study, we examined age differences in how arousal affects bottom-up attention to category-selective stimuli differing in perceptual salience. We found a dissociation in how arousal modulates selective processing in the young and older brain. In young adults, emotionally arousing sounds enhanced selective incidental memory and brain activity in the extrastriate body area for salient versus non-salient images of bodies. Older adults showed no such advantage in selective processing under arousal. These age differences could not be attributed to changes in the arousal response or less neural distinctiveness in old age. Rather, our results suggest that, relative to young adults, older adults become less effective at focusing on salient over non-salient details during increases in emotional arousal.

neuroscience↗

bioRxiv2019

Inhibition of ATR Reverses a Mitochondrial Respiratory Insufficiency

Diseases that affect the mitochondrial electron transport chain (ETC) often manifest as threshold effect disorders, meaning patients only become symptomatic once a certain level of ETC dysfunction is reached. Multiple processes work to control proximity to the critical ETC threshold and as a consequence there can be significant variability in disease presentation among patients. Identification of such control processes remains an ongoing goal. Checkpoint signaling comprises a collection of alert mechanisms activated in cells in response to nuclear DNA damage. Well-defined hierarchies of proteins are involved in both sensing and signaling DNA damage, with ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) acting as pivotal signaling kinases. In the nematode C. elegans, severe reduction of mitochondrial ETC activity shortens life, as in humans, but mild reduction extends life as a consequence of survival strategies that are invoked under these circumstances. Here we show that removal of ATL-1, the worm ortholog of ATR, unexpectedly lessens the severity of ETC dysfunction, but removal of ATM does not. Multiple genetic and biochemical tests show no evidence for increased mutation or DNA breakage in animals exposed to ETC disruption. Instead, we find that reduced ETC function alters nucleotide ratios within both the ribo- and deoxyribo-nucleotide pools, and causes stalling of RNA polymerase, which is also known to activate ATR. Unexpectedly, atl-1 mutants confronted with mitochondrial ETC disruption maintain normal levels of oxygen consumption and have an increased abundance of translating ribosomes. This suggests checkpoint signaling by ATL-1 normally dampens cytoplasmic translation. Taken together, our data suggests a model whereby ETC insufficiency in C. elegans results in nucleotide imbalances leading to stalling of RNA polymerase, activation of ATL-1, dampening of global translation and magnification of ETC dysfunction. Loss of ATL-1 effectively reverses the severity of ETC disruption so that animals become phenotypically closer to wild type.

pathology↗

bioRxiv2017

Neural signatures of dynamic emotion constructs in the human brain

How is emotion represented in the brain: is it categorical or along dimensions? In the present study, we applied multivariate pattern analysis (MVPA) to magnetoencephalography (MEG) to study the brains temporally unfolding representations of different emotion constructs. First, participants rated 525 images on the dimensions of valence and arousal and by intensity of discrete emotion categories (happiness, sadness, fear, disgust, and sadness). Thirteen new participants then viewed subsets of these images within an MEG scanner. We used Representational Similarity Analysis (RSA) to compare behavioral ratings to the unfolding neural representation of the stimuli in the brain. Ratings of valence and arousal explained significant proportions of the MEG data, even after corrections for low-level image properties. Additionally, behavioral ratings of the discrete emotions fear, disgust, and happiness significantly predicted early neural representations, whereas rating models of anger and sadness did not. Different emotion constructs also showed unique temporal signatures. Fear and disgust - both highly arousing and negative - were rapidly discriminated by the brain, but disgust was represented for an extended period of time relative to fear. Overall, our findings suggest that 1) dimensions of valence and arousal are quickly represented by the brain, as are some discrete emotions, and 2) different emotion constructs exhibit unique temporal dynamics. We discuss implications of these findings for theoretical understanding of emotion and for the interplay of discrete and dimensional aspects of emotional experience.

neuroscience↗