Stability Of Rhythm Research Articles

Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord.

Dopamine is now well established as a modulator of locomotor rhythms in a variety of developing and adult vertebrates. However, in mice, while all five dopamine receptor subtypes are present in the spinal cord, it is unclear which receptor subtypes modulate the rhythm. Dopamine receptors can be grouped into two families-the D1/5 receptor group and the D2/3/4 group, which have excitatory and inhibitory effects, respectively. Our data suggest that dopamine exerts contrasting dose-dependent modulatory effects via the two receptor families. Our data show that administration of dopamine at concentrations >35 μM slowed and increased the regularity of a locomotor rhythm evoked by bath application of 5-hydroxytryptamine (5-HT) and N-methyl-d(l)-aspartic acid (NMA). This effect was independent of the baseline frequency of the rhythm that was manipulated by altering the NMA concentration. We next examined the contribution of the D1- and D2-like receptor families on the rhythm. Our data suggest that the D1-like receptor contributes to enhancement of the stability of the rhythm. Overall, the D2-like family had a pronounced slowing effect on the rhythm; however, quinpirole, the D2-like agonist, also enhanced rhythm stability. These data indicate a receptor-dependent delegation of the modulatory effects of dopamine on the spinal locomotor pattern generator.

Sleep and 24-h activity rhythms in relation to cortisol change after a very low-dose of dexamethasone

The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in sleep. Nevertheless, the association of sleep and its 24-h organization with negative feedback control of the HPA axis has received limited attention in population-based studies. We explored this association in 493 middle-aged persons of the Rotterdam Study, a large population-based study (mean age 56 years, standard deviation: 5.3 years; 57% female). The negative feedback of the HPA axis was measured as the change in morning saliva cortisol after the intake of 0.25mg dexamethasone the night before. Actigraphy allowed us to measure the stability and fragmentation of the activity rhythm and to estimate total sleep time, sleep onset latency and wake after sleep onset. A sleep diary kept during the week of actigraphy was used to assess self-reported total sleep time, sleep onset latency, number of awakenings and perceived sleep quality. In our study, enhanced negative feedback of the HPA axis was found in association with unstable activity rhythms (B=0.106, 95% confidence interval (CI): 0.002; 0.210), total sleep time (B=0.108, 95%CI: 0.001; 0.215) and poor subjective sleep quality (B=0.107, 95%CI: 0.009; 0.206) after multivariate adjustment. These results indicated that the 24-h organization, duration and experience of sleep are all associated with the negative feedback control of the HPA axis.

Electrical storm: A clinical and electrophysiological overview.

Electrical storm (ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverter-defibrillator (ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia (VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment.

Longitudinal stability of the diurnal rhythm of intraocular pressure in subjects with healthy eyes, ocular hypertension and pigment dispersion syndrome.

BackgroundThe diurnal fluctuation of intraocular pressure may be relevant in glaucoma. The aim of this study was to find out whether the timing of diurnal fluctuation is stable over the years.MethodsLong-term IOP data from the Erlangen Glaucoma Registry, consisting of several annual extended diurnal IOP profiles for each patient, was retrospectively analyzed. Normal subjects, patients with ocular hypertension and with pigment dispersion syndrome were included because these subjects had not been treated with antiglaucomatous medications at the time of data acquisition. A cosine curve was fitted to the IOP data and the stability of individual rhythms over the years was tested using the Rayleigh test. To compare the peak times among groups, means were calculated only from subjects with a significant Rayleigh test.ResultsOf the fifty-two eligible subjects, a total of 364 extended diurnal IOP profiles measured in a sitting position had been collected over a period of 114 ± 39 months. The Rayleigh test indicated intraindividual stability of phase timing only in 19 subjects (36%). In subjects with pigment dispersions syndrome, peak IOP occurred on average two hours and seven minutes later during the day compared with subjects without this condition (p = 0.05).ConclusionsFitting of cosine curves to the clinical IOP profiles was generally feasible, although careful interpretation is warranted due to lack of measurements in supine position and between midnight and 7 am. The interesting observation of a phase lag in eyes with pigment dispersion syndrome warrants confirmation and exploration in future prospective studies. The analysis of the IOP data showed no stable individual rhythm in the long term in a majority of patients.

Coordination of fictive motor activity in the larval zebrafish is generated by non-segmental mechanisms.

The cellular and network basis for most vertebrate locomotor central pattern generators (CPGs) is incompletely characterized, but organizational models based on known CPG architectures have been proposed. Segmental models propose that each spinal segment contains a circuit that controls local coordination and sends longer projections to coordinate activity between segments. Unsegmented/continuous models propose that patterned motor output is driven by gradients of neurons and synapses that do not have segmental boundaries. We tested these ideas in the larval zebrafish, an animal that swims in discrete episodes, each of which is composed of coordinated motor bursts that progress rostrocaudally and alternate from side to side. We perturbed the spinal cord using spinal transections or strychnine application and measured the effect on fictive motor output. Spinal transections eliminated episode structure, and reduced both rostrocaudal and side-to-side coordination. Preparations with fewer intact segments were more severely affected, and preparations consisting of midbody and caudal segments were more severely affected than those consisting of rostral segments. In reduced preparations with the same number of intact spinal segments, side-to-side coordination was more severely disrupted than rostrocaudal coordination. Reducing glycine receptor signaling with strychnine reversibly disrupted both rostrocaudal and side-to-side coordination in spinalized larvae without disrupting episodic structure. Both spinal transection and strychnine decreased the stability of the motor rhythm, but this effect was not causal in reducing coordination. These results are inconsistent with a segmented model of the spinal cord and are better explained by a continuous model in which motor neuron coordination is controlled by segment-spanning microcircuits.

Gender differences in masticatory movement path and rhythm in dentate adults

PurposeThe purpose of this study was to clarify whether there might be a gender difference in masticatory movement path and rhythm in dentate adults. MethodsThirty healthy males and 30 healthy females were asked to chew softened chewing gum on their habitual chewing side for 20sec, and the movement of the mandibular incisal point was recorded using mandibular kinesiograph. For 10 cycles from the fifth cycle, the spatial and temporal parameters (spatial: amounts of vertical and lateral movements; temporal: opening, closing, occluding, and cycle times) of masticatory movement path and rhythm and the parameters representing the stability of masticatory movement path and rhythm were calculated and compared between males and females. ResultsThe values of the spatial parameters were significantly greater for males than for females. The values of the temporal parameters were smaller for males than for females, and significant differences were found in all parameters except occluding time. However, there was no statistically significant difference in the parameters representing the stability of masticatory movement path and rhythm. ConclusionFrom these results it was suggested that although there were no differences in the stability of masticatory movement path and rhythm between genders, there were gender differences in the spatial and temporal parameters of masticatory movement path and rhythm.

Long-term outcome up to 10 years after concomitant ablation in cardiac surgical patients with atrial fibrillation (AF)

Objectives: Concomitant ablation therapy for AF promotes the opportunity to cure dysrhythmia. The one-year success of ablation by various energy sources are described extensively. We analyzed the rhythm stability after concomitant left atrial ablation in cardiac surgical patients (pts) during a follow-up period of up to ten years.

Body weight gain in rats by a high-fat diet produces chronodisruption in activity/inactivity circadian rhythm

In the last few decades, obesity has become one of the most important public health problems. Adipose tissue is an active endocrine tissue which follows a rhythmic pattern in its functions and may produce alterations in certain circadian rhythms. Our aim was to evaluate whether the locomotor activity circadian rhythm could be modified by a hypercaloric diet in rodents. Two groups were considered in the experiment: 16 rats were used as a control group and were fed standard chow; the other group comprised 16 rats fed a high-fat diet (35.8% fat, 35% glucides). The trial lasted 16 weeks. Body weight was measured every week, and a blood sample was extracted every two weeks to quantify triglyceride levels. The activity/inactivity circadian rhythm was logged through actimetry throughout the trial, and analysed using the DAS 24© software package. At the end of the experiment, the high-fat fed rats had obese-like body weights and high plasma triglyceride levels, and, compared with the control group, increased diurnal activity, decreased nocturnal activity, reductions in amplitude, midline estimating statistic of rhythm, acrophase and interdaily stability, and increases in intradaily variability of their activity rhythms. The results thus show how obesity can lead to symptoms of chronodisruption in the body similar to those of ageing.

Circadian activity rhythm disturbances predict mortality

Introduction Sleep and circadian rhythm changes occur during aging, and have been associated with adverse health consequences and mortality. Previous studies investigating sleep and mortality focused mainly on sleep duration and suggest that the relation between sleep duration and mortality is U-shaped. It is still unclear if other sleep characteristics and if stability and fragmentation of the circadian rhythm predict mortality. Materials and methods Actigraphy and a sleep diary were used to measure the circadian activity rhythm and sleep in 1734 middle-aged and elderly participants of the Rotterdam Study. Circadian rhythm was measured with actigraphy to calculate the interdaily stability and intradaily variability (i.e. fragmentation) of the activity rhythm. Sleep was assessed objectively with actigraphy, and subjectively with a sleep diary to estimate sleep duration, sleep onset latency and wake after sleep onset. Sleep quality was measured with the Pittsburgh Sleep Quality Index. All- cause mortality was assessed by death certificates and records of general practitioners and hospitals. The association between circadian rhythm, sleep and mortality was estimated with cox proportional hazard models. Results The mean follow-up time was 5.9 years, in total, 137 deaths (7.9%) occurred. Higher stability of the circadian activity rhythm was associated with a lower mortality risk (HR = 0.82, 95% CI = 0.71–0.96) and more fragmentation to a higher mortality risk (HR = 1.25, 95% CI = 1.07–1.45) after adjustment for confounders. Whether assessed objectively or subjectively, sleep was not related to mortality in our study. Conclusion Lower stability and higher fragmentation of the circadian activity rhythm is related to higher all-cause mortality in a middle-aged and elderly population. Loss of circadian rhythm might be a disease indicator or a parameter for aging. Future research must show if stabilizing the circadian rhythm can improve quality of life and survival. Acknowledgements L.A. Zuurbier and A.I. Luik were supported by a Netherlands Organization for Scientific Research grant (NWO-VIDI: 017.106.370) awarded to H. Tiemeier.

Ambulatory circadian monitoring (ACM), a complementary tool in sleep medicine

In developed societies it is common to suffer from sleep disorders due to primary alterations in the circadian system (CS). Moreover, sleep disorders lead to CS disturbances, thus diagnosis and treatment of circadian and sleep disorders should not be addressed separately. The aim of this work is to present the ambulatory circadian monitoring (ACM) and its utility for sleep medicine. To this, wrist temperature (T), motor activity (A), body position (P), light exposure (L) and environmental temperature (ET) were monitored in subjects suffering from different sleep pathologies. Eight healty volunteers and eight patients, attending to two sleep clinics3,4, with different pathologies (SHAOS, ASP, DSP, free-running rhythm, short sleeper, aging and menopause), participated in this study. Volunteers were subjected to ACM during a week using a multichannel device (KronowiseTM, Chronolab, Univ. of Murcia) integrating five sensors: three built into a wristwatch (T, L, ET) and two on a bracelet (A and P). Sleep-wake states were inferred using the integrated variable TAP and Circadianware software (Chronolab, Univ. Murcia). Rhythmic and sleep analysis were performed by non- parametric, Fourier and periodogram analysis. Circadian robustness was assessed by the circadian function index (CFI) calculated from rhythm stability, fragmentation and amplitude of TAP variable. Polygraphic representation of variables recorded by ACM allowed the differentiation of sleep pathologies. Accurate circadian phase estimation, and thus, ASP and DSP detection, was determined using the L5 timing (the five consecutive hours of minimum TAP). SHAOS was associated with impaired T rhythm, together with increased A during the five consecutive hours of minimum activity (L5). Sleep pathologies can be discriminated by biphasic representation of CFI and one index of sleep depth, (L5 for A or TAP). Patient with SHAOS, DSP and free-running sleep, suffered from chronodisruption (dissociation between T and A, P and sleep rhythms). The ACM allows a reliable assessment of CS status and the detection of sleep pathologies, particularly abnormal sleep phase and non-deep and fragmented sleep, such occurs in SAHOS, insomnia, and hot flushes. The proposed procedure contributes to an integrated diagnosis and treatment for sleep and circadian disorders in sleep clinics. Study supported by RETICEF (RD12/0043/0011), MINECO (BFU2010-21945-C02-01), TIN2009-14372-C03–01 to MC and INNPACTO (IPT-2011-0833-900000) to JAM.

Circadian impairment of the wrist temperature rhythm in patients with sleep disordered breathing

Introduction The effects of sleep disordered breathing (SDB) on the circadian sleep-wake rhythm are not well known. Wrist temperature (WT) rhythm is subordinated to the master circadian clock (suprachiasmatic nucleus of hypothalamus) and is related to autonomic balance, thermoregulation and sleep propensity. The aim of this study was to analyze the WT changes in a large group of SDB patients. Materials and methods WT rhythm of 98 AH patients (73 men and 25 women, 24–74years old and BMI range 20–48) were recorded during a week and PSG was performed the last night of that week while wearing an Ibuttom device (ThermoChron®, Data loggers I-button) for WT and a Deltamed (Natus) coherence system for Polysomnographic recording. Arousal Index, Apnea-Hypoapnea Index (IAH), Oxygen Desaturation Index (ODI), Mean Oxygen Saturation and Nadir of Oxygen Saturation were calculated for SDB severity; whereas Interdaily Stability (IS), Intradaily Variability (IV), Relative Amplitude (RA), Circadian Function Index (CFI), Mean Night-time Value (MN) and Night-Time phase (NTP) were determined for circadian assessment of WT rhythm. A correlation matrix was performed to select the best relationship between OSAHS severity and WT rhythm. Results Wrist temperature rhythm in SDB patients is characterized by lower temperatures during the last phase of sleep and increased temperatures during late afternoon and evening when compared with healthy subjects (34.32 ± 0.06 vs. 34.60 ± 0.06 respectively for the last phase of sleep and 33.70 ± 0.08 vs. 32.63 ± 0.09 respectively for late afternoon and evening). Most WT circadian parameters (IS, IV, RA, CFI, MN and MNP) were significantly correlated with apnea severity. The highest correlation between PSG and circadian parameters was found for ODI and CFI. Higher ODI values are related to lower IS, RA, CFI, MN, higher IV and a NTP advance. Conclusion SDB generates potent chronodisruptive effects on circadian system as measured by WT rhythm. In addition, apnea severity could be assessed by stability, fragmentation, amplitude, CFI, and Nigh-Time value of WT rhythm, indicating an increase of sympathetic activation and circadian disruption as severity of apnea progresses. Acknowledgements Study supported by RETICEF (RD12/0043/0011), MINECO (BFU2010–21945-C02–01), INNPACTO (IPT-2011–0833-900000) with FEDER cofounding to JAM, and FIS (PI07/0318) cofinanced by FEDER to JS, and a research fellowship to Antonio Martinez-Nicolas (University of Murcia).

Stability and Fragmentation of the Activity Rhythm Across the Sleep-Wake Cycle: The Importance of Age, Lifestyle, and Mental Health

The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96 h (138 ± 14 h, mean ± SD) were collected from 1734 people (age: 62 ± 9.4 yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β = 0.07, p = 0.02), but also with a more fragmented distribution of periods of activity and inactivity (β = 0.20, p < 0.001). Having more depressive symptoms was related to less stable (β = −0.07, p = 0.005) and more fragmented (β = 0.10, p < 0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β = −0.11, p < 0.001; smoking: β = −0.11, p < 0.001) and more fragmented rhythms (BMI: β = 0.09, p < 0.001; smoking: β = 0.11, p < 0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.

Chronotypes of Bipolar Patients in Remission: Validation of the French Version of the Circadian Type Inventory in the FACE-BD Sample

Circadian rhythm disturbances have been associated with bipolar disorder (BD) during both the mood episodes and the periods of remission. Circadian phase preferences for the evening have been reported for remitted patients, whereas the amplitude and stability of their rhythms have never been assessed using questionnaires. The primary aim of our study was the validation of a French version of the Circadian Type Inventory (CTI), whereas its secondary aim was the comparison between remitted patients with BD and healthy controls for rhythm stability and amplitude and for phase preference. For this purpose, we used the CTI and the Composite Scale of Morningness (CSM) that assesses phase preference (“morning” or “evening” type). First, we report here on the validation of the French version of the 11-item Circadian Type Inventory in a sample of 140 remitted patients with BD and 156 healthy controls. Principal components analysis revealed a two-factor structure (FR: flexibility/rigidity scale corresponding to rhythm stability; LV: languid/vigorous scale corresponding to rhythm amplitude) explaining 52% of the variance in the control group and 47% in the bipolar group. Cronbach’s alpha was 0.75 for FR and 0.73 for LV. The test-retest reliability was 0.74 for FR and 0.86 for LV (3 wks) and 0.62 for FR and 0.72 for LV (6 mos). LV and FR scores correlated with the Composite Scale of Morningness score (p < 0.00001 and p = 0.0002, respectively). Second, as compared with controls, patients with BD were more languid (p < 0.00001) and showed an evening preference (p = 0.0003), but they did not differ from the controls with regard to flexibility/rigidity. The French version of the CTI appeared to have satisfactory psychometrics characteristics. Bipolar patients exhibited not only abnormalities in phase preference but also in amplitude as measured by languidity. Since circadian rhythm dysfunction has been shown to predict poor functioning and mood relapses in interepisodic patients with BD, this tool would appear to be a promising, easy-to-use, measure of the amplitude and flexibility of circadian rhythms that could enrich the arsenal of assessments used in clinical settings.

Emergency Cardiac Support With Extracorporeal Membrane Oxygenation for Cardiac Arrest

A 46-year-old woman with no major medical history presented to the emergency department with chest pain and evidence of anterior, anterolateral, and inferior ST-elevation myocardial infarction. Her condition quickly deteriorated into cardiogenic shock with ventricular arrhythmia. Despite revascularization of the left anterior descending artery and intravenous inotrope and antiarrhythmic therapy, her unstable hemodynamics and arrhythmias persisted. Early emergency initiation of venoarterial extracorporeal membrane oxygenation (ECMO) led to prompt hemodynamic and rhythm stability; however, adequate endogenous cardiac output did not ensue, and she was not able to be weaned from ECMO until hospital day 8. She subsequently recovered and continues to do well in the outpatient setting. This case demonstrates the remarkable hemodynamic and rhythm stability that early initiation of ECMO can provide in the setting of unstable myocardial infarction.

Effects of Sleep Loss on the Rest–Activity Circadian Rhythm of Helpers Participating in Continuous Dogsled Races

The Finnmarksløpet dogsled race lasts up to 7 days. Helpers, who keep time, coach, and transport equipment, have to be alert though they have little and fragmented sleep. This study investigated disruptions of the rest-activity rhythm among helpers. 10 helpers were monitored by actigraph a week before, during, and after the race. Sleep logs, sleepiness rate, and self-reported quality of sleep were collected. Nonparametric circadian rhythm analysis showed significant differences between the pre- and postrace interdaily stability and amplitude of rhythm. Compared to prerace, sleepiness at bedtime was increased and number of nocturnal awakenings was reduced postrace, although the actigraphic outputs showed no improvement in sleep quality. Helpers who were engaged in the race for a longer span (5-6 days) had more difficulty recovering from the sleep loss accumulated during the race than those engaged for a shorter time (2-3 days). Poor sleep combined with prolonged and demanding mental focus for 2 days or more has a negative influence upon the rest-activity cycle, though complete restoration of the cycle occurs over 1 week or more. Being in such a condition for ≥ 5 days leads to disruptions of the circadian component of the sleep-wake cycle that hampers the sleep recovery process. Disrupted sleep and demanding mental requirements are common in long-distance sporting events as well as among shift workers. Follow-up intervention should be made in such cases to ensure the return of a healthy rest-activity rhythm and sleep quality.

Interpersonal and Social Rhythm Group Therapy for Patients with Bipolar Disorder

This article describes Interpersonal and Social Rhythm Therapy (IPSRT) adapted for use in a group setting for patients with bipolar disorder. In a preliminary efficacy study, we studied the pre-post group treatment effect on affective symptoms. One-year pre-post findings in the IPSRT group indicated that this modality was effective in reducing depressive symptoms and might reduce the number of hospital admissions. Also, group IPSRT increased stability of the social rhythm, which is thought to be important in reducing recurrence of manic and depressive episodes. These findings suggest that group IPSRT could be an additional treatment option for patients with bipolar disorder who continue to have mood episodes despite adequate pharmacotherapy and psychoeducation.

Seasonal variation of the endogenous rhythm in two sympatric amphipods: Talitrus saltator and Talorchestia deshayesii from Bizerte beach (northern Tunisia)

The locomotor activity rhythm of the supralittoral sandhoppers, Talitrus saltator and Talorchestia deshayesii, was investigated over four seasons to reveal the impact of environmental variation on these sympatric species collected from Bizerte beach (37°19′N–9°51′E). For each season, thirty adult individuals were collected by hand and transferred to individual actographs equipped with an infrared recording system, where they were subjected to two consecutive experimental light/dark regimens (natural light/dark cycle (LD) and continuous darkness (DD)) in a controlled environment cabinet at 18°C ± 0.5°C. Periodogram analysis of the resulting actograms indicates a predominantly circadian rhythm with a period close to 24 h, with a less predictable semi-diurnal component of about 12 h in both T. saltator and T. deshayesii. A seasonal comparison of the various rhythm characteristics showed that the greater mortality was observed in winter (36.6%) and in spring (70%), respectively, among the population of T. saltator and T. deshayesii; whereas, in summer, this rate was equal to zero whatever the species. Moreover, irrespective of the season and the photoperiodic regimen, circadian rhythmicity was more important than the semi-diurnal one for all seasons and both under natural Light/Dark (nLD) cycle and free-running conditions. In addition, the stability of the circadian rhythm was better defined in spring, whatever the photoperiodic regimen imposed and the species. Similarities and differences observed between T. saltator and T. deshayesii over four seasons reflect an ecological plasticity of their biological clock adapted to different changing environmental conditions.

Wenckebach Periodicity at Rest That Normalizes With Tachycardia in a Family With a NKX2.5 Mutation

A family with asymptomatic Wenckebach atrioventricular block (Wenckebach periodicity [WP]) has been followed at the investigators' institution for >4 decades. In contrast to all reported cases of WP (except in top-ranking athletes) family members have WP at rest that promptly converts to regular sinus tachycardia with exercise. They also have mild apical noncompaction that has been quite stable. Because of apparent autosomal dominant inheritance of the structural and arrhythmia disorders, deoxyribonucleic acid was obtained from 4 affected family members in 2 generations for sequence analysis of the cardiac transcription factor gene NKX2.5. A novel frame-shift mutation (c.959delC) was identified that would result in premature truncation of the protein at residue 293, with loss of the C-terminal 31 amino acids. The responsiveness of WP to exercise, the long-term stability of the WP rhythm, and the mild asymptomatic structural features expand the phenotypic presentation of diseases related to mutations in NKX2.5. In addition, the physiology of WP is reviewed in these subjects and in highly conditioned athletes. In conclusion, the investigators report familial stable WP and ventricular noncompaction caused by a mutation in NKX2.5.

Instability of syllable repetition in patients with spinocerebellar ataxia and Parkinson's disease

The aim of the current study was to test the hypothesis of a fundamental impairment of vocal pacing in patients with spinocerebellar ataxia and Parkinson's disease. Thirty-one patients with spinocerebellar ataxia, 42 patients with Parkinson's disease, and 43 healthy controls had to repeat a single syllable at a self-chosen isochronous pace. The coefficient of variance for interval length and the change in interval length with successive utterances were used to describe pace stability. Ataxic and parkinsonian patients both showed a significant instability of vocal pace performance. Ataxic speakers featured difficulties in keeping the pace immediately from the beginning of the task, whereas parkinsonian patients accelerated the pace in the course of the performance. The results support differential roles of cerebellar and basal ganglia pathways in motor speech performance. Cerebellar function may be required for the general precision of interval timing, whereas basal ganglia rather serve to maintain rhythm stability over time.

Inhibitory feedback promotes stability in an oscillatory network

Reliability and variability of neuronal activity are both thought to be important for the proper function of neuronal networks. The crustacean pyloric rhythm (∼1 Hz) is driven by a group of pacemaker neurons (AB/PD) that inhibit and burst out of phase with all follower pyloric neurons. The only known chemical synaptic feedback to the pacemakers is an inhibitory synapse from the follower lateral pyloric (LP) neuron. Although this synapse has been studied extensively, its role in the generation and coordination of the pyloric rhythm is unknown. We examine the hypothesis that this synapse acts to stabilize the oscillation by reducing the variability in cycle period on a cycle-by-cycle basis. Our experimental data show that functionally removing the LP–pyloric dilator (PD) synapse by hyperpolarizing the LP neuron increases the pyloric period variability. The increase in pyloric rhythm stability in the presence of the LP–PD synapse is demonstrated by a decrease in the amplitude of the phase response curve of the PD neuron. These experimental results are explained by a reduced mathematical model. Phase plane analysis of this model demonstrates that the effect of the periodic inhibition is to produce asymptotic stability in the oscillation phase, which leads to a reduction in variability of the oscillation cycle period.