Biology subjects

Watters, H.

Publications and source records attributed to Watters, H..

3 recordsLinked to original sources

bioRxiv2024

Altered functional connectivity and spatiotemporal dynamics in individuals with sleep disorders

Idiopathic hypersomnia (IH) is a sleep disorder characterized by highly disruptive symptoms. Like narcolepsy type 1, a well-characterized sleep disorder, individuals with IH suffer from excessive daytime sleepiness, though there is little overlap in metabolic or neural biomarkers across these two disorders. This lack of common pathophysiology, combined with the clear overlap in symptoms presents an ideal paradigm for better understanding the impact of IH on an individuals functional activity and organization, and potentially, the underlying pathophysiology. This study examines the observed functional connectivity in patients with IH, and patients with narcolepsy type 1 (NT1) against healthy control individuals. Static functional connectivity is compared, as are quasi-periodic patterns, acquired from the BOLD timecourse, for all groups. In addition to baseline data comparison, the study also included a post-nap condition, where the individuals included in this analysis napped for at least 10 minutes prior to the scanning session, to explore why individuals with IH do not feel "refreshed" after a nap like individuals with NT1 do. Assessing the groups spatiotemporal patterns revealed key differences across both disorders and conditions: static connectivity revealed at baseline higher subcortical connectivity in the NT1 group. There was also observably less connectivity in the IH group both at baseline and post-nap, though none of these static analyses survived multiple comparisons correction to reach significance. The QPP results however found significant differences in the IH group in key networks, particularly the DAN/FPCN correlation is significantly different at baseline vs. post-nap, a trend not observed in either the control or NT1 groups. The DAN and FPCN are drastically altered both at baseline and post-nap when compared to the other groups, and may likely be a disorder-specific result. This study demonstrates that key networks for arousal are more heavily disrupted in IH patients, who are less affected by a nap, confirmed through both subject reporting and functional evidence through spatiotemporal patterns.

pathology↗

bioRxiv2024

Infraslow dynamic patterns in human cortical networks track a spectrum of external to internal attention

Early efforts to understand the human cerebral cortex focused on localization of function, assigning functional roles to specific brain regions. More recent evidence depicts the cortex as a dynamic system, organized into flexible networks with patterns of spatiotemporal activity corresponding to attentional demands. In functional MRI (fMRI), dynamic analysis of such spatiotemporal patterns is highly promising for providing non-invasive biomarkers of neurodegenerative diseases and neural disorders. However, there is no established neurotypical spectrum to interpret the burgeoning literature of dynamic functional connectivity from fMRI across attentional states. In the present study, we apply dynamic analysis of network-scale spatiotemporal patterns in a range of fMRI datasets across numerous tasks including a left-right moving dot task, visual working memory tasks, congruence tasks, multiple resting state datasets, mindfulness meditators, and subjects watching TV. We find that cortical networks show shifts in dynamic functional connectivity across a spectrum that tracks the level of external to internal attention demanded by these tasks. Dynamics of networks often grouped into a single task positive network show divergent responses along this axis of attention, consistent with evidence that definitions of a single task positive network are misleading. Additionally, somatosensory and visual networks exhibit strong phase shifting along this spectrum of attention. Results were robust on a group and individual level, further establishing network dynamics as a potential individual biomarker. To our knowledge, this represents the first study of its kind to generate a spectrum of dynamic network relationships across such an axis of attention. Significance StatementThis study provides significant insight into how cortical dynamics shift along a spectrum of external vs internal attention. Association and sensory networks show shifts in their relationship with the default mode network (DMN) along this spectrum. Notably, the constituent networks of the task positive network (TPN), such as the DAN, frontoparietal network (FPN), and ventral attention network (VAN) show divergent responses along this spectrum, indicating that definitions of a single "task positive" network are misleading. This is one of the first studies of large-scale spatiotemporal dynamics across such a breadth of tasks. These results provide a neurotypical reference spanning an axis of attention to interpret the growing functional dynamics literature and to help characterize functional dynamics as a potential biomarker.

neuroscience↗

bioRxiv2023

otpb functions in a Lef1-dependent transcriptional network required for expression of the stress response inhibitor crhbp in the zebrafish hypothalamus

The vertebrate hypothalamus regulates physiological and behavioral responses to environmental stimuli through the function of evolutionarily-conserved neuronal subpopulations. Our previous work found that mutation of zebrafish lef1, which encodes a transcriptional mediator of the Wnt signaling pathway, leads to the loss of hypothalamic neurons and behavioral phenotypes that are both associated with stress-related human mood disorders However, the specific Lef1 target genes that link neurogenesis to behavior remain unknown. One candidate is otpb, which encodes a transcription factor with known roles in hypothalamic development. Here we show that otpb expression in the posterior hypothalamus is Lef1-dependent, and that like lef1, its function is required for the generation of crhbp+ neurons in this region. Transgenic reporter analysis of a crhbp conserved noncoding element suggests that otpb participates in a transcriptional regulatory network with other Lef1 targets. Finally, consistent with a role for crhbp in inhibiting the stress response, zebrafish otpb mutants exhibit decreased exploration in a novel tank diving assay. Together our findings suggest a potential evolutionarily-conserved mechanism for the regulation of innate stress response behaviors through Lef1-mediated hypothalamic neurogenesis.

neuroscience↗