Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus.

Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus. Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing neurons are active during sleep, but their effects on REM sleep remain unclear. Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes. In contrast, their acute silencing (eNpHR3.0, archaerhodopsin) reduced the frequency and amplitude of hippocampal theta rhythm without affecting REM sleep duration. In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory postsynaptic currents in wake-promoting histaminergic neurons of the tuberomammillary nucleus (TMN), and in vivo activation of MCH neuron terminals in TMN or medial septum also prolonged REM sleep episodes. Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain.

Day/Night rhythm of hemostatic factors in obstructive sleep apnea

To investigate the hypothesis that day/night patterns of prothrombotic activity differ between patients with obstructive sleep apnea (OSA) and individuals with no OSA.

Consensus statement of the European Heart Rhythm Association: updated recommendations for driving by patients with implantable cardioverter defibrillators

Patients with an implantable cardioverter defibrillator (ICD) have an ongoing risk of sudden incapacitation that might cause harm to others while driving a car. Driving restrictions vary across different countries in Europe. The most recent recommendations for driving of ICD patients in Europe were published in 1997 and focused mainly on patients implanted for secondary prevention. In recent years there has been a vast increase in the number of patients with an ICD and in the percentage of patients implanted for primary prevention. The EHRA task force on ICD and driving was formed to reassess the risk of driving for ICD patients based on the literature available. The recommendations are summarized in the following table and are further explained in the document, (Table see text). Driving restrictions are perceived as difficult for patients and their families, and have an immediate consequence for their lifestyle. To increase the adherence to the driving restrictions, adequate discharge of education and follow-up of patients and family are pivotal. The task force members hope this document may serve as an instrument for European and national regulatory authorities to formulate uniform driving regulations.

Interference with gesture production by theta burst stimulation over left inferior frontal cortex

The traditional view of a predominant inferior parietal representation of gestures has been recently challenged by neuroimaging studies demonstrating that gesture production and discrimination may critically depend on inferior frontal lobe function. The aim of the present work was therefore to investigate the effect of transient disruption of these brain sites by continuous theta burst stimulation (cTBS) on gesture production and recognition.

Theta Burst Stimulation Over the Right Broca's Homologue Induces Improvement of Naming in Aphasic Patients

Improvements of language production in aphasic patients have been reported following repeated 1-Hz transcranial magnetic stimulation over the nondamaged right hemisphere. Most studies examined aphasic patients in the chronic phase. The effect of transcranial magnetic stimulation application in acute or subacute patients has not been systematically studied. We aimed to evaluate whether continuous theta burst stimulation, an inhibitory protocol with a shorter application time than the common 1-Hz protocol, is able to improve naming performance in aphasic patients in different poststroke phases.

Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL)

Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a "local virtual lesion" which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level.

Emotions, Arousal, and Frontal Alpha Rhythm Asymmetry During Beethoven's 5th Symphony

Music is capable of inducing emotional arousal. While previous studies used brief musical excerpts to induce one specific emotion, the current study aimed to identify the physiological correlates of continuous changes in subjective emotional states while listening to a complete music piece. A total of 19 participants listened to the first movement of Ludwig van Beethoven's 5th symphony (duration: ~7.4 min), during which a continuous 76-channel EEG was recorded. In a second session, the subjects evaluated their emotional arousal during the listening. A fast fourier transform was performed and covariance maps of spectral power were computed in association with the subjective arousal ratings. Subjective arousal ratings had good inter-individual correlations. Covariance maps showed a right-frontal suppression of lower alpha-band activity during high arousal. The results indicate that music is a powerful arousal-modulating stimulus. The temporal dynamics of the piece are well suited for sequential analysis, and could be necessary in helping unfold the full emotional power of music.

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

The esophageal ECG as a novel technique for ambulant heart rhythm monitoring

Introduction: Diagnosing arrhythmias by conventional Holter-ECG can be cumbersome because of artifacts, skin irritation and poor P-waves. In contrast, esophageal electrocardiography (eECG) is promising due to the anatomic relationship of the esophagus to the atria and its favorable bioelectric properties. Methods used: In an ambulant setting, we recorded eECGs from 10 volunteers with a novel, highly-miniaturized eECG recorder that is worn discretely behind the ear (1.5×1.8×5cm, 22grams). The device continuously records two eECG leads during 3 days with 500Hz sampling frequency and 24-bit resolution. Results: Mean ± SD recording time was 21.7±19.6 hours (max. 60 hours). Test persons were not limited in daily activities (e.g. eating, speaking) and only complained mild discomfort during probe insertion, which subsided later on. During 99.8% of time, the recorder acquired signals appropriate for further analysis. In unfiltered data, QRS complexes and P-waves were identifiable during >98% of time. P waves had higher amplitudes as compared to surface ECG (0.71 ± 0.42mV vs. 0.16 ± 0.03mV, p = 0.004). No complications occurred. Conclusion: Ambulatory eECG recording is safe, well tolerated and promising due to excellent P-wave detection, overcoming some limitations of conventional Holter ECG.

Effect of continuous positive airway pressure on day/night rhythm of prothrombotic markers in obstructive sleep apnea

Obstructive sleep apnea (OSA) has been associated with an increased risk of atherothrombotic events. A prothrombotic state might partially explain this link. This study investigated OSA patients' day/night rhythm of several prothrombotic markers and their potential changes with therapeutic continuous positive airway pressure (CPAP).

Chronotropic incompetence predicts impaired response to exercise training in heart failure patients in sinus rhythm

Background: In most patients with chronic heart failure (CHF), endurance training improves exercise capacity. However, some patients do not respond favourably. The purpose of this study was to explore the reasons of non-response and to determine their predictive value.Methods: We studied a cohort of 120 consecutive CHF patients with sinus rhythm (mean age 57 ± 12 years, ejection fraction 29.3 ± 9.9%, peak VO2 17.3 ± 5.1 ml/min/kg), participating in a 3-month outpatient cardiac rehabilitation programme. Responders were defined as subjects who improved peak VO2 by more than 5%, work load by more than 10%, or VE/VCO2 slope by more than 5%. Subjects who did not fulfil at least one of the above criteria were characterized as non-responders. Multivariate regression analyses were performed to identify parameters that were predictive for a response. Receiver operating characteristic (ROC) analyses were performed for predictive parameters to identify thresholds for response or non-response.Results: Multivariate regression analyses revealed heart rate (HR) reserve, HR recovery at 1 min, and peak HR as significant predictors for a positive training response. ROC curves revealed the optimal thresholds separating responders from non-responders at less than 30 bpm for HR reserve, less than 6 bpm for HR recovery and less than 101 bpm for peak HR.Conclusions: The presence of impaired chronotropic competence is a major predictor of poor training response in CHF patients with sinus rhythm.

Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30Hz pulses repeated at intervals of 100ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8min. After theta burst rTMS, this effect lasted up to 30min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.