Project description:Study objectivesTo describe the time structure of leg movements (LM) in obstructive sleep apnea (OSA) syndrome, in order to advance understanding of their clinical significance.LocationSleep Research Centre, Oasi Institute (IRCCS), Troina, Italy.SettingSleep laboratory.PatientsEighty-four patients (16 females, 68 males, mean age 55.1 y, range 29-74 y).MethodsRespiratory-related leg movements (RRLM) and those unrelated to respiratory events (NRLM) were examined within diagnostic polysomnograms alone and together for their distributions within the sleep period and for their periodicity.Measurements and resultsPatients with OSA and RRLM exhibited more periodic leg movements in sleep (PLMS), particularly in NREM sleep. A gradual decrease in number of NRLM across the sleep period was observed in patients with RRLM. This pattern was less clear for RRLM. Frequency histograms of intermovement intervals of all LMs in patients with RRLM showed a prominent first peak at 4 sec, and a second peak at approximately 24 sec coincident with that of PLMS occurring in the absence of OSA. A third peak of lowest amplitude was the broadest with a maximum at approximately 42 sec. In patients lacking RRLM, NRLM were evident with a single peak at 2-4 sec. A stepwise linear regression analysis showed that, after controlling for a diagnosis of restless legs syndrome and apnea-hypopnea index, PLMS remained significantly associated with RRLM.ConclusionThe time structure of leg movements occurring in conjunction with respiratory events exhibit features of periodic leg movements in sleep occurring alone, only with a different and longer period. This brings into question the validity, both biologic and clinical, of scoring conventions with their a priori exclusion from consideration as periodic leg movements in sleep.
Project description:Awareness during general anesthesia with subsequent explicit recall is a serious and frequently preventable problem that is gaining attention from clinicians and patients alike. Cost-effective interventions that increase vigilance should be implemented to decrease the likelihood of this complication.
Project description:Recent evidence suggests that certain antidepressants are associated with an increase of periodic leg movements (PLMS) that may disturb sleep. So far, this has been shown in patients clinically treated for depression and in cross-sectional studies for various substances, but not mirtazapine. It is unclear whether antidepressants induce the new onset of PLMS or only increase preexisting PLMS, and whether this is a general property of the antidepressant or only seen in depressed patients. We report here the effect of mirtazapine on PLMS in young healthy men.Open-labeled clinical trial (NCT00878540) including a 3-week preparatory phase with standardized food, physical activity, and sleep-wake behavior, and a 10-day experimental inpatient phase with an adaptation day, 2 baseline days, and 7 days with mirtazapine.Research institute.Twelve healthy young (20-25 years) men.Seven days of nightly intake (22:00) of 30 mg mirtazapine.Sleep was recorded on 2 drug-free baseline nights, the first 2 drug nights, and the last 2 drug nights. Eight of the 12 subjects showed increased PLMS after the first dose of mirtazapine. Frequency of PLMS was highest on the first drug night and attenuated over the course of the next 6 days. Three subjects reported transient restless legs symptoms.Mirtazapine provoked PLMS in 67% of young healthy males. The effect was most pronounced in the first days. The possible role of serotonergic, noradrenergic and histaminergic mechanisms in mirtazapine-induced PLMS is discussed.
Project description:Motoneurons of neonatal rodents show synchronous activity that modulates the development of the neuromuscular system. However, the characteristics of the activity of human neonatal motoneurons are largely unknown. Using a noninvasive neural interface, we identified the discharge timings of individual spinal motoneurons in human newborns. We found highly synchronized activities of motoneurons of the tibialis anterior muscle, which were associated with fast leg movements. Although neonates' motor units exhibited discharge rates similar to those of adults, their synchronization was significantly greater than in adults. Moreover, neonatal motor units showed coherent oscillations in the delta band, which is directly translated into force generation. These results suggest that motoneuron synchronization in human neonates might be an important mechanism for controlling fast limb movements, such as those of primitive reflexes. In addition to help revealing mechanisms of development, the proposed neural interface might monitor children at risk of developing motor disorders.
Project description:We show that the general anesthetics xenon, sulfur hexafluoride, nitrous oxide, and chloroform cause rapid increases of different magnitude and time course in the electron spin content of Drosophila. With the exception of CHCl3, these changes are reversible. Anesthetic-resistant mutant strains of Drosophila exhibit a different pattern of spin responses to anesthetic. In two such mutants, the spin response to CHCl3 is absent. We propose that these spin changes are caused by perturbation of the electronic structure of proteins by general anesthetics. Using density functional theory, we show that general anesthetics perturb and extend the highest occupied molecular orbital of a nine-residue α-helix. The calculated perturbations are qualitatively in accord with the Meyer-Overton relationship and some of its exceptions. We conclude that there may be a connection between spin, electron currents in cells, and the functioning of the nervous system.
Project description:The neural substrates related to periodic leg movements during sleep (PLMS) remain uncertain, and the specific brain regions involved in PLMS have not been evaluated. We investigated the brain regions associated with PLMS and their severity using the electroencephalographic (EEG) source localization method. Polysomnographic data, including electromyographic, electrocardiographic, and 19-channel EEG signals, of 15 patients with restless legs syndrome were analyzed. We first identified the source locations of delta-band (2-4?Hz) spectral power prior to the onset of PLMS using a standardized low-resolution brain electromagnetic tomography method. Next, correlation analysis was conducted between current densities and PLMS index. Delta power initially and most prominently increased before leg movement (LM) onset in the PLMS series. Sources of delta power at -4~-3 seconds were located in the right pericentral, bilateral dorsolateral prefrontal, and cingulate regions. PLMS index was correlated with current densities at the right inferior parietal, temporoparietal junction, and middle frontal regions. In conclusion, our results suggest that the brain regions activated before periodic LM onset or associated with their severity are the large-scale motor network and provide insight into the cortical contribution of PLMS pathomechanism.
Project description:BACKGROUND:Functional connectivity across the cortex has been posited to be important for consciousness and anesthesia, but functional connectivity patterns during the course of surgery and general anesthesia are unknown. The authors tested the hypothesis that disrupted cortical connectivity patterns would correlate with surgical anesthesia. METHODS:Surgical patients (n = 53) were recruited for study participation. Whole-scalp (16-channel) wireless electroencephalographic data were prospectively collected throughout the perioperative period. Functional connectivity was assessed using weighted phase lag index. During anesthetic maintenance, the temporal dynamics of connectivity states were characterized via Markov chain analysis, and state transition probabilities were quantified. RESULTS:Compared to baseline (weighted phase lag index, 0.163, ± 0.091), alpha frontal-parietal connectivity was not significantly different across the remaining anesthetic and perioperative epochs, ranging from 0.100 (± 0.041) to 0.218 (± 0.136) (P > 0.05 for all time periods). In contrast, there were significant increases in alpha prefrontal-frontal connectivity (peak = 0.201 [0.154, 0.248]; P < 0.001), theta prefrontal-frontal connectivity (peak = 0.137 [0.091, 0.182]; P < 0.001), and theta frontal-parietal connectivity (peak = 0.128 [0.084, 0.173]; P < 0.001) during anesthetic maintenance. Additionally, shifts occurred between states of high prefrontal-frontal connectivity (alpha, beta) with suppressed frontal-parietal connectivity, and high frontal-parietal connectivity (alpha, theta) with reduced prefrontal-frontal connectivity. These shifts occurred in a nonrandom manner (P < 0.05 compared to random transitions), suggesting structured transitions of connectivity during general anesthesia. CONCLUSIONS:Functional connectivity patterns dynamically shift during surgery and general anesthesia but do so in a structured way. Thus, a single measure of functional connectivity will likely not be a reliable correlate of surgical anesthesia.
Project description:The aim of this study was to assess the frequency and potential clinical impact of periodic leg movements during sleep (PLMS), with or without arousals, as recorded incidentally from children before and after adenotonsillectomy (AT).Children scheduled for AT for any clinical indications who participated in the Washtenaw County Adenotonsillectomy Cohort II were studied at enrollment and again 6 months thereafter. Assessments included laboratory-based polysomnography, a Multiple Sleep Latency Test (MSLT), parent-completed behavioral rating scales, neuropsychological testing, and psychiatric evaluation.Participants included 144 children (81 boys) aged 3-12 years. Children generally showed mild to moderate obstructive sleep apnea (median respiratory disturbance index 4.5 (Q1 = 2.0, Q3 = 9.5)) at baseline, and 15 subjects (10%) had at least five periodic leg movements per hour of sleep (PLMI ? 5). After surgery, 21 (15%) of n = 137 subjects who had follow-up studies showed PLMI ? 5 (p = 0.0067). Improvements were noted after surgery in the respiratory disturbance index; insomnia symptoms; sleepiness symptoms; mean sleep latencies; hyperactive behavior; memory, learning, attention, and executive functioning on NEPSY assessments; and frequency of attention-deficit/hyperactivity disorder (DSM-IV criteria). However, PLMI ? 5 failed to show associations with worse morbidity in these domains at baseline or follow-up. New appearance of PLMI ? 5 after surgery failed to predict worsening of these morbidities (all p > 0.05), with only one exception (NEPSY) where the magnitude of association was nonetheless negligible. Similar findings emerged for periodic leg movements with arousals (PLMAI ? 1).PLMS, with and without arousals, become more common after AT in children. However, results in this setting did not suggest substantial clinical impact.
Project description:Electroencephalogram (EEG) approaches may provide important information about developmental changes in brain-state dynamics during general anesthesia. We used multi-electrode EEG, analyzed with multitaper spectral methods and video recording of body movement to characterize the spatio-temporal dynamics of brain activity in 36 infants 0-6 months old when awake, and during maintenance of and emergence from sevoflurane general anesthesia. During maintenance: (1) slow-delta oscillations were present in all ages; (2) theta and alpha oscillations emerged around 4 months; (3) unlike adults, all infants lacked frontal alpha predominance and coherence. Alpha power was greatest during maintenance, compared to awake and emergence in infants at 4-6 months. During emergence, theta and alpha power decreased with decreasing sevoflurane concentration in infants at 4-6 months. These EEG dynamic differences are likely due to developmental factors including regional differences in synaptogenesis, glucose metabolism, and myelination across the cortex. We demonstrate the need to apply age-adjusted analytic approaches to develop neurophysiologic-based strategies for pediatric anesthetic state monitoring.