Witt, L. | Search bioRxiv

bioRxiv2025

Characterizing the frequency-specific and spatiotemporal dynamics of β-γ Phase-Amplitude Coupling in Parkinson's disease

Cross-frequency coupling (CFC) has been proposed to facilitate neural information transfer across spatial and temporal scales. Phase-amplitude coupling (PAC), a type of CFC in which the amplitude of a faster brain oscillation is coupled to the phase of a slower brain oscillation, is implicated in various higher-order cognitive functions and was shown to be pathologically altered in neurological and psychiatric disease. In Parkinsons disease (PD), the coupling between gamma amplitude (50-150 Hz) to beta phase (13-35 Hz) is exaggerated. Enhanced {beta}-{gamma} PAC was found in the subthalamic nucleus and various cortical sources and shown to be responsive to dopaminergic therapy and deep brain stimulation (DBS). Therefore, exaggerated {beta}-{gamma} PAC has been proposed to be a disease marker and a potential target for brain circuit interventions. Despite these promising findings, a significant knowledge gap remains, as the spatial and frequency-specific dynamics of {beta}-{gamma} PAC and its association with motor symptoms and therapy remain elusive. To address this knowledge gap, we employed high-density electroencephalography (EEG) with advanced source localisation techniques for PD patients at rest. We highlight three key findings: (1) a frequency-specific increase in high {beta} (23-35 Hz)-{gamma} PAC within and between sources of the cortical motor network, (2) a link between elevated high {beta}-{gamma} PAC and bradykinesia and rigidity when OFF medication, but not tremor, and (3) a medication-induced reduction in high {beta}-{gamma} PAC in the supplementary motor area correlating with clinical improvement. Altogether, this study provides novel insights into the pathophysiology of PD as an oscillopathy and identifies high {beta}-{gamma} PAC as a potential marker of Parkinsonian symptoms and treatment effects. This has important implications for invasive as well as non-invasive therapeutic strategies as high {beta}-{gamma} PAC targeting might hold greater promise than targeting {beta}-{gamma} PAC per se.

neuroscience↗

bioRxiv2023

Streptococcus agalactiae and Escherichia coli Induce Distinct Effector γδ T Cell Responses During Neonatal Sepsis and Neuroinflammation

Neonates born prematurely are highly vulnerable to life-threatening conditions such as bacterial sepsis. Streptococcus agalactiae, also known as group B Streptococcus (GBS) and Escherichia coli are frequent causative pathogens of neonatal sepsis, however, it remains unclear if distinct sepsis pathogens induce differential adaptive immune responses. In the present study, we find that {gamma}{delta} T cells in neonatal mice rapidly respond to single-organism GBS and E. coli bloodstream infections and that these pathogens induce distinct activation and cytokine production from IFN-{gamma} and IL-17 producing {gamma}{delta} T cells, respectively. We also report differential reliance on {gamma}{delta}TCR signaling to elicit effector cytokine responses during neonatal sepsis, with IL-17 production during E. coli infection being driven by {gamma}{delta}TCR signaling, and IFN-{gamma} production during GBS infection occurring independently of {gamma}{delta}TCR signaling. Furthermore, we report that the divergent effector responses of {gamma}{delta} T cells during GBS and E. coli infections impart distinctive neuroinflammatory phenotypes on the neonatal brain. The present study reveals that the neonatal adaptive immune system differentially responds to distinct bacterial stimuli, resulting in unique neuroinflammatory phenotypes.

immunology↗