Biology subjects

Naji, M.

Publications and source records attributed to Naji, M..

5 recordsLinked to original sources

bioRxiv2020

Differential in vitro activity of individual drugs and bedaquiline-rifabutin combinations against actively multiplying and nutrient-starved Mycobacterium abscessus

Current treatment options for lung disease caused by Mycobacterium abscessus complex infections have limited effectiveness. To maximize the use of existing antibacterials and to help inform regimen design for treatment, we assessed the in vitro bactericidal activity of single drugs against actively multiplying and net non-replicating M. abscessus populations in nutrient-rich and nutrient starvation conditions, respectively. As single drugs, bedaquiline and rifabutin exerted bactericidal activity only against nutrient-starved and actively growing M. abscessus, respectively. However, when combined, both bedaquiline and rifabutin were able to specifically contribute bactericidal activity at relatively low, clinically relevant concentrations against both replicating and non-replicating bacterial populations. The addition of a third drug, amikacin, further enhanced the bactericidal activity of the bedaquiline-rifabutin combination against nutrient-starved M. abscessus. Overall, these in vitro data suggest that bedaquiline-rifabutin may be a potent backbone combination to support novel treatment regimens for M. abscessus infections. This rich dataset of differential time-and concentration-dependent activity of drugs, alone and together, against M. abscessus also highlights several issues affecting interpretation and translation of in vitro findings.

microbiology↗

bioRxiv2020

Autonomic/Central Coupling Boosts Working Memory in Healthy Young Adults

Working memory (WM) is an executive function that can improve with training. However, the precise mechanism for this improvement is not known. Studies have shown greater WM gains after a period of sleep than a similar period of wake (Kuriyama et al. 2008a; Zinke, Noack, and Born 2018), with WM improvement correlated with slow wave activity (SWA; 0.5-1Hz) during slow wave sleep (SWS) (Sattari et al. 2019; Pugin et al. 2015; Ferrarelli et al. 2019). A different body of literature has suggested an important role for autonomic activity during wake for WM (Hansen et al. 2004; Mosley, Laborde, and Kavanagh 2018). A recent study from our group reported that the temporal coupling of autonomic and central events (ACEs) during sleep was associated with memory consolidation (Naji et al. 2019). We found that heart rate bursts (HR bursts) during non-rapid eye movement (NREM) sleep are accompanied by increases in SWA and sigma (12-15Hz) power, as well as increases in the high-frequency (HF) component of the RR interval, reflecting vagal rebound. In addition, ACEs predict long-term, episodic memory improvement. Building on these previous results, we examined whether ACEs may also contribute to gains in WM. We tested 104 young adults in an operation span task (OSPAN) in the morning and evening, with either a nap (with electroencephalography (EEG) and electrocardiography (ECG)) or wake between testing sessions. We identified HR bursts in the ECG and replicated the increases in SWA and sigma prior to peak of the HR burst, as well as vagal rebound after the peak. Furthermore, we showed sleep-dependent WM improvement, which was predicted by ACE activity. Using regression analyses, we discovered that significantly more variance in WM improvement could be explained with ACE variables than with overall sleep activity not time-locked with ECG. These results provide the first evidence that coordinated autonomic and central events play a significant role in sleep-related WM improvement and implicate the potential of autonomic interventions during sleep for cognitive enhancement.

neuroscience↗

bioRxiv2018

Timing between cortical slow oscillations and heart rate bursts during sleep predicts perceptual speed, but not offline consolidation

Central and autonomic nervous system activity are coupled during sleep. Cortical slow oscillations (SOs, <1Hz) coincide with brief bursts in heart rate (HR), but the functional consequence of this coupling in cognition remains elusive. We measured SO-HR temporal coupling (i.e., the peak-to-peak interval between downstate of SO event and HR burst) during a daytime nap, and asked whether this SO-HR timing measure was associated with perceptual speed and learning on a texture discrimination task, by testing subjects before and after a nap. The coherence of SO-HR events during sleep strongly correlated with an individuals perceptual speed in the morning and evening test sessions, but not with their change in performance after the nap (i.e., consolidation). We confirmed this result in two additional experimental visits, and also discovered that this association was visit-specific, indicating a reliable state (not trait) marker. Thus, we introduce a novel physiological index that may be a useful marker of state-dependent processing speed of an individual.\n\nSignificance StatementStudies show that autonomic and central nervous system activity is coupled. For example, increases in heart rate follow cortical slow oscillations during sleep. However, the functional significance of this coupling for cognition is not understood. In three experimental visits, we show that the timing between these sleep events (the peak-to-peak delay between the slow oscillation and the heart rate burst) is highly correlated with waking perceptual processing speed. This reliable individual difference measure may be a useful marker of generalized processing speed.

neuroscience↗

bioRxiv2017

Computational model of brainstem circuit for state dependent control of hypoglossal motoneurons

In patients with obstructive sleep apnea (OSA) the pharyngeal muscles become relaxed during sleep, which leads to a partial or complete closure of upper airway. Empirical studies suggest that withdrawal of noradrenergic and serotonergic drives importantly contribute to depression of hypoglossal motoneurons during rapid eye-movement (REM) sleep and, therefore, may contribute to OSA pathophysiology; however, specific cellular and synaptic mechanisms remain unknown. It was recently suggested that, in order to explain experimental observations, the neuronal network for monoaminergic control of excitability of hypoglossal motoneurons has to include excitatory and inhibitory perihypoglossal interneurons that would mediate noradrenergic and serotonergic drives to the motoneurons. In this study, we applied a biophysical network model to validate the rationality of the proposed circuit and to investigate the dynamics of its neuronal populations during REM sleep-induced withdrawal of noradrenergic and serotonergic drives. The state-dependent activity of the model hypoglossal motoneurons during simulated REM sleep with or without a virtual application of noradrenergic and serotonergic drugs was in qualitative agreement with in vivo data. The study predicts the dynamics of the perihypoglossal interneurons during these conditions and corroborates the hypothesis that the excitatory interneurons may integrate both noradrenergic and serotonergic drives. The latter drive has to be mediated by the inhibitory interneurons. The study suggests that perihypoglossal interneurons may serve as novel potential targets for pharmacological treatment of OSA.

neuroscience↗

bioRxiv2017

Coupling of autonomic and central events during sleep boosts declarative memory consolidation

While anatomical pathways between forebrain cognitive and brainstem autonomic nervous centers are well defined, autonomic-central interactions during sleep and their contribution to waking performance are not understood. Here, we analyzed simultaneous central activity via electroencephalography (EEG) and autonomic heart beat-to-beat intervals (RR intervals) from electrocardiography (ECG) during wake and daytime sleep. We identified bursts of ECG activity that lasted 4-5 seconds and predominated in non-rapid-eye-movement sleep (NREM). Using event-based analysis of NREM sleep, we found an increase in delta (0.5-4Hz) and sigma (12-15Hz) power and an elevated density of slow oscillations (0.5-1Hz) about 5 secs prior to peak of the heart rate burst, as well as a surge in vagal activity, assessed by high-frequency (HF) component of RR intervals. Using regression framework, we show that these Autonomic/Central Events (ACE) positively predicted post-nap improvement in a declarative memory task after controlling for the effects of spindles and slow oscillations from sleep periods without ACE. No such relation was found between memory performance and a control nap. Additionally, NREM ACE negatively correlated with REM sleep and learning in a non-declarative memory task. These results provide the first evidence that coordinated autonomic and central events play a significant role in declarative memory consolidation.

neuroscience↗