Visual gamma oscillations predict sensory sensitivity in females as they do in males.

Gamma oscillations are driven by local cortical excitatory (E)-inhibitory (I) loops and may help to characterize neural processing involving excitatory-inhibitory interactions. In the visual cortex reliable gamma oscillations can be recorded with magnetoencephalography (MEG) in the majority of individuals, which makes visual gamma an attractive candidate for biomarkers of brain disorders associated with E/I imbalance. Little is known, however, about if/how these oscillations reflect individual differences in neural excitability and associated sensory/perceptual phenomena. The power of visual gamma response (GR) changes nonlinearly with increasing stimulation intensity: it increases with transition from static to slowly drifting high-contrast grating and then attenuates with further increase in the drift rate. In a recent MEG study we found that the GR attenuation predicted sensitivity to sensory stimuli in everyday life in neurotypical adult men and in men with autism spectrum disorders. Here, we replicated these results in neurotypical female participants. The GR enhancement with transition from static to slowly drifting grating did not correlate significantly with the sensory sensitivity measures. These findings suggest that weak velocity-related attenuation of the GR is a reliable neural concomitant of visual hypersensitivity and that the degree of GR attenuation may provide useful information about E/I balance in the visual cortex.

Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation.

The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations) that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.

A 7T fMRI study investigating the influence of oscillatory phase on syllable representations.

Stimulus categorization is influenced by oscillations in the brain. For example, we have shown that ongoing oscillatory phase biases identification of an ambiguous syllable that can either be perceived as /da/ or /ga/. This suggests that phase is a cue for the brain to determine syllable identity and this cue could be an element of the representation of these syllables. If so, brain activation patterns for /da/ should be more unique when the syllable is presented at the /da/ biasing (i.e. its "preferred") phase. To test this hypothesis we presented non-ambiguous /da/ and /ga/ syllables at either their preferred or non-preferred phase (using sensory entrainment) while measuring 7T fMRI. Using multivariate pattern analysis in auditory regions we show that syllable decoding performance is higher when syllables are presented at their preferred compared to their non-preferred phase. These results suggest that phase information increases the distinctiveness of /da/ and /ga/ brain activation patterns.

High-speed video analysis of acoustically oscillated guinea pig stapes.

OBJECTIVE: We investigated the ossicular movement in the near-intact middle ear in response to acoustic stimulation using a high-speed video camera and video analysis software program. DESIGN: We have designed a good visual access to the middle ear of the guinea pig by opening the ventral wall of the otic capsule, without injuring the sound-conducting structures, from the external auditory canal to the oval window. The high-speed video camera could record analysable ossicular motion up to 4000 frames per second. RESULTS: The stapes showed reciprocal movement in the same frequency as the stimulating tone, and with an amplitude proportional to the stimulating sound intensity. Injury to the tympanic membrane attenuated the stapedial motion, which was recovered to that of the control level by patch repair of the perforation. CONCLUSION: Our experimental set-up was capable of evaluating the conductive hearing, regardless of the status of the animal's sensorineural hearing or even life. Such a video analysis may provide a powerful tool to investigate the physiology of the middle ear.

Dual/differential coherent anti-Stokes Raman scattering module for multiphoton microscopes with a femtosecond Ti:sapphire oscillator.

In the last decade, coherent anti-Stokes Raman scattering (CARS) microscopy has emerged as a powerful multiphoton imaging technique offering label-free chemical sensitivity and high three-dimensional resolution. However, its widespread application in the life sciences has been hampered by the use of costly pulsed lasers, the existence of a nonresonant background requiring involved technical solutions for its efficient suppression, and the limited acquisition speed of multiplex techniques addressing several vibrational resonances, if improved chemical specificity is needed. We have recently reported a differential CARS technique (D-CARS), which simultaneously measures two vibrational frequencies, enhancing the chemical selectivity and sensitivity without introducing costly hardware, while maintaining fast acquisition. In this study, we demonstrate a compact, fully automated, cost-effective module, which integrates on hardware and software level with a commercial multiphoton microscope based on a single 100 fs Ti:Sapphire oscillator and enables D-CARS microscopy in a user-friendly format for applications in the life sciences.

A robust reference signal generator for synchronized ventricular assist devices.

Ventricular assist devices (VADs) are blood pumps that offer an option to support the circulation of patients with severe heart failure. Since a failing heart has a remaining pump function, its interaction with the VAD influences the hemodynamics. Ideally, the heart's action is taken into account for actuating the device such that the device is synchronized to the natural cardiac cycle. To realize this in practice, a reliable real-time algorithm for the automatic synchronization of the VAD to the heart rate is required. This paper defines the tasks such an algorithm needs to fulfill: the automatic detection of irregular heart beats and the feedback control of the phase shift between the systolic phases of the heart and the assist device. We demonstrate a possible solution to these problems and analyze its performance in two steps. First, the algorithm is tested using the MIT-BIH arrhythmia database. Second, the algorithm is implemented in a controller for a pulsatile and a continuous-flow VAD. These devices are connected to a hybrid mock circulation where three test scenarios are evaluated. The proposed algorithm ensures a reliable synchronization of the VAD to the heart cycle, while being insensitive to irregularities in the heart rate.

Efficacy of metronome sound guidance via a phone speaker during dispatcher-assisted compression-only cardiopulmonary resuscitation by an untrained layperson: a randomised controlled simulation study using a manikin.

AIM: Untrained laypersons should perform compression-only cardiopulmonary resuscitation (COCPR) under a dispatcher's guidance, but the quality of the chest compressions may be suboptimal. We hypothesised that providing metronome sounds via a phone speaker may improve the quality of chest compressions during dispatcher-assisted COCPR (DA-COCPR). METHODS: Untrained laypersons were allocated to either the metronome sound-guided group (MG), who performed DA-COCPR with metronome sounds (110 ticks/min), or the control group (CG), who performed conventional DA-COCPR. The participants of each group performed DA-COCPR for 4 min using a manikin with Skill-Reporter, and the data regarding chest compression quality were collected. RESULTS: The data from 33 cases of DA-COCPR in the MG and 34 cases in the CG were compared. The MG showed a faster compression rate than the CG (111.9 vs 96.7/min; p=0.018). A significantly higher proportion of subjects in the MG performed the DA-COCPR with an accurate chest compression rate (100-120/min) compared with the subjects in the CG (32/33 (97.0%) vs 5/34 (14.7%); p<0.0001). The mean compression depth was not different between the MG and the CG (45.9 vs 46.8 mm; p=0.692). However, a higher proportion of subjects in the MG performed shallow compressions (compression depth <38 mm) compared with subjects in the CG (median % was 69.2 vs 15.7; p=0.035). CONCLUSIONS: Metronome sound guidance during DA-COCPR for the untrained bystanders improved the chest compression rates, but was associated more with shallow compressions than the conventional DA-COCPR in a manikin model.

Entrainment of the suprachiasmatic nucleus network by a light-dark cycle.

The synchronization of biological activity with the alternation of day and night (circadian rhythm) is performed in the brain by a group of neurons, constituting the suprachiasmatic nucleus (SCN). The SCN is divided into two subgroups of oscillating cells: the ventrolateral (VL) neurons, which are exposed to light (photic signal), and the dorsomedial (DM) neurons, which are coupled to the VL cells. When the coupling between these neurons is strong enough, the system synchronizes with the photic period. Upon increasing the cell coupling, the entrainment of the DM cells has been recently shown to occur via a very sharp (jumping) transition when the period of the photic input is larger than the intrinsic period of the cells. Here, we characterize this transition with a simple realistic model. We show that two bifurcations possibly lead to the disappearance of the endogenous mode. Using a mean-field model, we show that the jumping transition results from a supercritical Hopf-like bifurcation. This finding implies that both the period and strength of the stimulating photic signal, and the relative fraction of cells in the VL and DM compartments, are crucial in determining the synchronization of the system.

Dynamic changes of lipopolysaccharide levels in different phases of acute on chronic hepatitis B liver failure.

BACKGROUND: High serum levels of lipopolysaccharide (LPS) with LPS-MD-2/TLR4 complex activated NF-kb and cytokine cause hepatic necrosis in animal models. We investigated the dynamic changes of LPS levels in patients with acute on chronic hepatitis B liver failure (ACHBLF). METHODS: We enrolled ACHBLF patients for a 12-week study. Patients' LPS levels were measured along with 10 healthy controls. Patients on supportive care and recovered without intervention(s) were analyzed. Patients' LPS levels during the disease progression phase, peak phase, and remission phase were compared with healthy controls. RESULTS: Among 30 patients enrolled, 25 who received interventions or expired during the study period were excluded from the analysis, five patients on supportive care who completed the study were analyzed. Significant abnormal distributions of LPS levels were observed in patients in different phases (0.0168±0.0101 in progression phase; 0.0960±0.0680 in peak phase; 0.0249±0.0365 in remission phase; and 0.0201±0.0146 in controls; respectively, p<0.05). The highest level of LPS was in the peak phase and significantly elevated when compared to controls (0.0201±0.0146 vs. 0.0960±0.0680, p = 0.007). There were no statistically significant differences in LPS levels between healthy controls and subjects in the progression phase or remission phase. Dynamic changes of LPS were correlated with MELD-Na in the progression phase (p = 0.01, R = 0.876) and in the peak phase (p = 0.000, R = -1.00). CONCLUSIONS: Significant abnormal distributions of LPS levels were observed in ACHBLF with the highest level in the peak phase. The dynamic changes of LPS were correlated with disease severity and suggested LPS causing secondary hepatic injury.

Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.

Haploinsufficiency of RAI1 results in Smith-Magenis syndrome (SMS), a disorder characterized by intellectual disability, multiple congenital anomalies, obesity, neurobehavioral abnormalities, and a disrupted circadian sleep-wake pattern. An inverted melatonin rhythm (i.e., melatonin peaks during the day instead of at night) and associated sleep-phase disturbances in individuals with SMS, as well as a short-period circadian rhythm in mice with a chromosomal deletion of Rai1, support SMS as a circadian-rhythm-dysfunction disorder. However, the molecular cause of the circadian defect in SMS has not been described. The circadian oscillator temporally orchestrates metabolism, physiology, and behavior largely through transcriptional modulation. Data support RAI1 as a transcriptional regulator, but the genes it might regulate are largely unknown. Investigation into the role that RAI1 plays in the regulation of gene transcription and circadian maintenance revealed that RAI1 regulates the transcription of circadian locomotor output cycles kaput (CLOCK), a key component of the mammalian circadian oscillator that transcriptionally regulates many critical circadian genes. Data further show that haploinsufficiency of RAI1 and Rai1 in SMS fibroblasts and the mouse hypothalamus, respectively, results in the transcriptional dysregulation of the circadian clock and causes altered expression and regulation of multiple circadian genes, including PER2, PER3, CRY1, BMAL1, and others. These data suggest that heterozygous mutation of RAI1 and Rai1 leads to a disrupted circadian rhythm and thus results in an abnormal sleep-wake cycle, which can contribute to an abnormal feeding pattern and dependent cognitive performance. Finally, we conclude that RAI1 is a positive transcriptional regulator of CLOCK, pinpointing a novel and important role for this gene in the circadian oscillator.

Phase-locked cluster oscillations in periodically forced integrate-and-fire-or-burst neuronal populations.

The minimal integrate-and-fire-or-burst neuron model succinctly describes both tonic firing and postinhibitory rebound bursting of thalamocortical cells in the sensory relay. Networks of integrate-and-fire-or-burst (IFB) neurons with slow inhibitory synaptic interactions have been shown to support stable rhythmic states, including globally synchronous and cluster oscillations, in which network-mediated inhibition cyclically generates bursting in coherent subgroups of neurons. In this paper, we introduce a reduced IFB neuronal population model to study synchronization of inhibition-mediated oscillatory bursting states to periodic excitatory input. Using numeric methods, we demonstrate the existence and stability of 1:1 phase-locked bursting oscillations in the sinusoidally forced IFB neuronal population model. Phase locking is shown to arise when periodic excitation is sufficient to pace the onset of bursting in an IFB cluster without counteracting the inhibitory interactions necessary for burst generation. Phase-locked bursting states are thus found to destabilize when periodic excitation increases in strength or frequency. Further study of the IFB neuronal population model with pulse-like periodic excitatory input illustrates that this synchronization mechanism generalizes to a broad range of n:m phase-locked bursting states across both globally synchronous and clustered oscillatory regimes.

Neuropeptide signaling differentially affects phase maintenance and rhythm generation in SCN and extra-SCN circadian oscillators.

Circadian rhythms in physiology and behavior are coordinated by the brain's dominant circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Vasoactive intestinal polypeptide (VIP) and its receptor, VPAC(2), play important roles in the functioning of the SCN pacemaker. Mice lacking VPAC(2) receptors (Vipr2(-/-)) express disrupted behavioral and metabolic rhythms and show altered SCN neuronal activity and clock gene expression. Within the brain, the SCN is not the only site containing endogenous circadian oscillators, nor is it the only site of VPAC(2) receptor expression; both VPAC(2) receptors and rhythmic clock gene/protein expression have been noted in the arcuate (Arc) and dorsomedial (DMH) nuclei of the mediobasal hypothalamus, and in the pituitary gland. The functional role of VPAC(2) receptors in rhythm generation and maintenance in these tissues is, however, unknown. We used wild type (WT) and Vipr2(-/-) mice expressing a luciferase reporter (PER2::LUC) to investigate whether circadian rhythms in the clock gene protein PER2 in these extra-SCN tissues were compromised by the absence of the VPAC(2) receptor. Vipr2(-/-) SCN cultures expressed significantly lower amplitude PER2::LUC oscillations than WT SCN. Surprisingly, in Vipr2(-/-) Arc/ME/PT complex (Arc, median eminence and pars tuberalis), DMH and pituitary, the period, amplitude and rate of damping of rhythms were not significantly different to WT. Intriguingly, while we found WT SCN and Arc/ME/PT tissues to maintain a consistent circadian phase when cultured, the phase of corresponding Vipr2(-/-) cultures was reset by cull/culture procedure. These data demonstrate that while the main rhythm parameters of extra-SCN circadian oscillations are maintained in Vipr2(-/-) mice, the ability of these oscillators to resist phase shifts is compromised. These deficiencies may contribute towards the aberrant behavior and metabolism associated with Vipr2(-/-) animals. Further, our data indicate a link between circadian rhythm strength and the ability of tissues to resist circadian phase resetting.

Dynamic assessment of baroreflex control of heart rate during induction of propofol anesthesia using a point process method.

In this article, we present a point process method to assess dynamic baroreflex sensitivity (BRS) by estimating the baroreflex gain as focal component of a simplified closed-loop model of the cardiovascular system. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by linear and bilinear bivariate regressions on both the previous R-R intervals (RR) and blood pressure (BP) beat-to-beat measures. The instantaneous baroreflex gain is estimated as the feedback branch of the loop with a point-process filter, while the RR-->BP feedforward transfer function representing heart contractility and vasculature effects is simultaneously estimated by a recursive least-squares filter. These two closed-loop gains provide a direct assessment of baroreflex control of heart rate (HR). In addition, the dynamic coherence, cross bispectrum, and their power ratio can also be estimated. All statistical indices provide a valuable quantitative assessment of the interaction between heartbeat dynamics and hemodynamics. To illustrate the application, we have applied the proposed point process model to experimental recordings from 11 healthy subjects in order to monitor cardiovascular regulation under propofol anesthesia. We present quantitative results during transient periods, as well as statistical analyses on steady-state epochs before and after propofol administration. Our findings validate the ability of the algorithm to provide a reliable and fast-tracking assessment of BRS, and show a clear overall reduction in baroreflex gain from the baseline period to the start of propofol anesthesia, confirming that instantaneous evaluation of arterial baroreflex control of HR may yield important implications in clinical practice, particularly during anesthesia and in postoperative care.

Differential neural responses to acupuncture revealed by MEG using wavelet-based time-frequency analysis: a pilot study.

Acupoint specificity, lying at the core of the Traditional Chinese Medicine, still faces many controversies. As previous neuroimaging studies on acupuncture mainly adopted relatively low time-resolution functional magnetic resonance imaging (fMRI) technology and inappropriate block-designed experimental paradigm due to sustained effect, in the current study, we employed a single block-designed paradigm together with high temporal-resolution magnetoencephalography (MEG) technology. We applied time-frequency analysis based upon Morlet wavelet transforming approach to detect differential oscillatory brain dynamics induced by acupuncture at Stomach Meridian 36 (ST36) using a nearby nonacupoint (NAP) as control condition. We observed that frequency power changes were mainly restricted to delta band for both ST36 group and NAP group. Consistently increased delta band power in contralateral temporal regions and decreased power in the counterparts of ipsilateral hemisphere were detected following stimulation at ST36 on the right leg. Compared with ST36, no significant delta ranges were found in temporal regions in NAP group, illustrating different oscillatory brain patterns. Our results may provide additional evidence to support the specificity of acupuncture modulation effects.

The comparison between circadian oscillators in mouse liver and pituitary gland reveals different integration of feeding and light schedules.

The mammalian circadian system is composed of multiple peripheral clocks that are synchronized by a central pacemaker in the suprachiasmatic nuclei of the hypothalamus. This system keeps track of the external world rhythms through entrainment by various time cues, such as the light-dark cycle and the feeding schedule. Alterations of photoperiod and meal time modulate the phase coupling between central and peripheral oscillators. In this study, we used real-time quantitative PCR to assess circadian clock gene expression in the liver and pituitary gland from mice raised under various photoperiods, or under a temporal restricted feeding protocol. Our results revealed unexpected differences between both organs. Whereas the liver oscillator always tracked meal time, the pituitary circadian clockwork showed an intermediate response, in between entrainment by the light regimen and the feeding-fasting rhythm. The same composite response was also observed in the pituitary gland from adrenalectomized mice under daytime restricted feeding, suggesting that circulating glucocorticoids do not inhibit full entrainment of the pituitary clockwork by meal time. Altogether our results reveal further aspects in the complexity of phase entrainment in the circadian system, and suggest that the pituitary may host oscillators able to integrate multiple time cues.

Photothermal and photoacoustic Raman cytometry in vitro and in vivo.

An integrated Raman-based cytometry was developed with photothermal (PT) and photoacoustic (PA) detection of Raman-induced thermal and acoustic signals in biological samples with Raman-active vibrational modes. The two-frequency, spatially and temporally overlapping pump-Stokes excitation in counterpropagating geometry was provided by a nanosecond tunable (420-2300 nm) optical parametric oscillator and a Raman shifter (639 nm) pumped by a double-pulsed Q-switched Nd:YAG laser using microscopic and fiberoptic delivery of laser radiation. The PA and PT Raman detection and imaging technique was tested in vitro with benzene, acetone, olive oil, carbon nanotubes, chylomicron phantom, and cancer cells, and in vivo in single adipocytes in mouse mesentery model. The integration of linear and nonlinear PA and PT Raman scanning and flow cytometry has the potential to enhance its chemical specificity and sensitivity including nanobubble-based amplification (up to 10- fold) for detection of absorbing and nonabsorbing targets that are important for both basic and clinically relevant studies of lymph and blood biochemistry, cancer, and fat distribution at the single-cell level.

Electrical activities of neurones in the dorsomedial hypothalamic nucleus projecting to the supraoptic nucleus during milk-ejection reflex in the rat.

Using urethane-anesthetized lactating rats, extracellular action potentials were recorded from single cells in the dorsomedial hypothalamus (DMH), which were identified as projecting to the supraoptic nucleus (SON). Sixty-two DMH cells were identified as projecting to the SON. Of these 53, 4 and 5 cells had ipsilateral, contralateral and bilateral projections, respectively. Two cells (1 ipsilaterally and 1 contralaterally projecting cell) showed bursting activities preceding milk ejection that were similar to those of oxytocin (OT) cells in the SON or paraventricular nucleus. Two ipsilaterally and 2 bilaterally projecting cells reduced their firing rates preceding milk ejection. The results suggest that some of the projections from the DMH to the SON are contralateral or bilateral and that these projections may contribute to synchronized activation of OT cells bilaterally distributed in the hypothalamus during milk-ejection reflex.

Bioresonance hypothesis: a new mechanism on the pathogenesis of trigeminal neuralgia.

Trigeminal neuralgia (TN) is an uncommon disorder characterized by recurrent attacks of lancinating pain in the trigeminal nerve distribution. To date, the precise mechanism for TN remains unclear. Among a variety of causes of TN, the microvascular compression (MVC) hypothesis is the most popular one, but controversies still focus on the origin and pathogenesis of the disorder. A number of clinical phenomena still cannot be well explained. We propose a new hypothesis on the pathogenesis of TN - bioresonance. The bioresonance hypothesis states that when the vibration frequency of a structure surrounding the trigeminal nerve becomes close to its natural frequency, the resonance of the trigeminal nerve occurs. The bioresonance can damage trigeminal nerve fibers and lead to the abnormal transmission of the impulse, which may finally result in facial pain. Under the guidance of the bioresonance hypothesis, we hope to explore more non-invasive methods to treat or even cure TN.

Asynchronous non-invasive brain-actuated control of an intelligent wheelchair.

In this paper we present further results of our asynchronous and non-invasive BMI for the continuous control of an intelligent wheelchair. Three subjects participated in two experiments where they steered the wheelchair spontaneously, without any external cue. To do so the users learn to voluntary modulate EEG oscillatory rhythms by executing three mental tasks (i.e., mental imagery) that are associated to different steering commands. Importantly, we implement shared control techniques between the BMI and the intelligent wheelchair to assist the subject in the driving task. The results show that the three subjects could achieve a significant level of mental control, even if far from optimal, to drive an intelligent wheelchair.

Tinnitus intensity dependent gamma oscillations of the contralateral auditory cortex.

BACKGROUND: Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. METHODS AND FINDINGS: In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05). CONCLUSION: Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.