UNASSIGNED: The unexpected observation of calretinin immunoreactivity in smooth muscle cells in the muscularis propria of the cecum led to a more detailed examination of calretinin expression and its possible relationship to propulsive contractile activity around the vermiform appendix.
UNASSIGNED: Immunohistochemistry and RNA in situ hybridization were performed to analyze calretinin expression in intestinal samples from 33 patients at ages ranging from mid-gestation fetuses to adults, as well as in some potentially relevant animal models. Dual immunolabeling was done to compare calretinin localization with markers of smooth muscle and interstitial cells of Cajal.
UNASSIGNED: Calretinin expression was observed consistently in the innermost smooth muscle layers of the muscularis interna in the human cecum, appendiceal base, and proximal ascending colon, but not elsewhere in the intestinal tract. Calretinin-positive smooth muscle cells did not co-express markers located in adjacent interstitial cells of Cajal. Muscular calretinin immunoreactivity was not detected in the ceca of mice or macaques, species which lack appendices, nor in the rabbit cecum or appendix.
UNASSIGNED: Localized expression of calretinin in cecal smooth muscle cells may reduce the likelihood of retrograde, calcium-mediated propulsive contractions from the proximal colon and suppress pro-inflammatory fecal stasis in the appendix.

OBJECTIVE: In aging, reduced delta power (0.5-4 Hz) during N2 and N3 sleep has been associated with gray matter (GM) atrophy and hypometabolism within frontal regions. Some studies have also reported associations between N2 and N3 sleep delta power in specific sub-bands and amyloid pathology. Our objective was to better understand the relationships between spectral power in delta sub-bands during N2-N3 sleep and brain integrity using multimodal neuroimaging.
METHODS: In-home polysomnography was performed in 127 cognitively unimpaired older adults (mean age ± SD: 69.0 ± 3.8 years). N2-N3 sleep EEG power was calculated in delta (0.5-4 Hz), slow delta (0.5-1 Hz), and fast delta (1-4 Hz) frequency bands. Participants also underwent magnetic resonance imaging and Florbetapir-PET (early and late acquisitions) scans to assess GM volume, brain perfusion, and amyloid burden. Amyloid accumulation over ~21 months was also quantified.
RESULTS: Higher delta power was associated with higher GM volume mainly in fronto-cingular regions. Specifically, slow delta power was positively correlated with GM volume and perfusion in these regions, while the inverse association was observed with fast delta power. Delta power was neither associated with amyloid burden at baseline nor its accumulation over time, whatever the frequency band considered.
CONCLUSIONS: Our results show that slow delta is particularly associated with preserved brain structure, and highlight the importance of analyzing delta power sub-bands to better understand the associations between delta power and brain integrity. Further longitudinal investigations with long follow-ups are needed to disentangle the associations among sleep, amyloid pathology, and dementia risk in older populations.
BACKGROUND: Name: Study in Cognitively Intact Seniors Aiming to Assess the Effects of Meditation Training (Age-Well). URL: https://clinicaltrials.gov/ct2/show/NCT02977819?term=Age-Well&draw=2&rank=1. See STROBE_statement_AGEWELL in supplemental materials.
BACKGROUND: EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.

Intestinal motility is governed in part by bioelectrical slow-waves and spike-bursts. Mesenteric ischemia is a substantial clinical challenge, but its electrophysiological and contractile mechanisms are not well understood. Simultaneous high-resolution bioelectrical and video mapping techniques were used to capture the changes in slow-waves, spike-bursts, and contractile activity during baseline, ischemia, and reperfusion periods. Experiments were performed on anesthetized pigs where intestinal contractions were quantified using surface strain and diameter measurements, while slow-wave and spike-bursts were quantified using frequency and amplitude. Slow-waves entrainment within the ischemic region diminished during ischemia, resulting in irregular slow-wave activity and a reduction in the frequency from 12.4 ± 3.0 cycles-per-minute (cpm) to 2.5 ± 2.7 cpm (p = 0.0006). At the end of the reperfusion period, normal slow-wave entrainment was observed at a frequency of 11.5 ± 2.9 cpm. There was an increase in spike-burst activity between the baseline and ischemia periods (1.1 ± 1.4 cpm to 8.7 ± 3.3 cpm, p = 0.0003) along with a spasm of circumferential contractions. At the end of the reperfusion period, the frequency of spike-bursts decreased to 2.7 ± 1.4 cpm, and contractions subsided. The intestine underwent tonal contraction during ischemia, with the diameter decreasing from 29.3 ± 2.6 mm to 21.2 ± 6.2 mm (p = 0.0020). At the end of the reperfusion period, the intestinal diameter increased to 27.3 ± 3.9 mm. The decrease in slow-wave activity, increase in spike-bursts, and tonal contractions can objectively identify ischemic segments in the intestine. It is anticipated that the use of electrophysiological slow-wave and spike-burst biomarkers, along with contractile measures, could identify mesenteric ischemia in surgical settings and allow an objective biomarker for successful revascularization.

Objective. Slow-wave modulation occurs during states of unconsciousness and is a large-scale indicator of underlying brain states. Conventional methods typically characterize these large-scale dynamics by assuming that slow-wave activity is sinusoidal with a stationary frequency. However, slow-wave activity typically has an irregular waveform shape with a non-stationary frequency, causing these methods to be highly unpredictable and inaccurate. To address these limitations, we developed a novel method using tau-modulation, which is more robust than conventional methods in estimating the modulation of slow-wave activity and does not require assumptions on the shape or stationarity of the underlying waveform.Approach. We propose a novel method to estimate modulatory effects on slow-wave activity. Tau-modulation curves are constructed from cross-correlation between slow-wave and high-frequency activity. The resultant curves capture several aspects of modulation, including attenuation or enhancement of slow-wave activity, the temporal synchrony between slow-wave and high-frequency activity, and the rate at which the overall brain activity oscillates between states.Main results. The method\'s performance was tested on an open electrocorticographic dataset from two monkeys that were recorded during propofol-induced anesthesia, with electrodes implanted over the left hemispheres. We found a robust propagation of slow-wave modulation along the anterior-posterior axis of the lateral aspect of the cortex. This propagation preferentially originated from the anterior superior temporal cortex and anterior cingulate gyrus. We also found the modulation frequency and polarity to track the stages of anesthesia. The algorithm performed well, even with non-sinusoidal activity and in the presence of real-world noise.Significance. The novel method provides new insight into several aspects of slow-wave modulation that have been previously difficult to evaluate across several brain states. This ability to better characterize slow-wave modulation, without spurious correlations induced by non-sinusoidal signals, may lead to robust and physiologically-plausible diagnostic tools for monitoring brain functions during states of unconsciousness.

BACKGROUND: Cyclic motor patterns (CMP) are the predominant motor pattern in the distal colon, and are important in both health and disease. Their origin, mechanism and relation to bioelectrical slow-waves remain incompletely understood. During abdominal surgery, an increase in the CMP occurs in the distal colon. This study aimed to evaluate the feasibility of detecting propagating slow waves and spike waves in the distal human colon through intraoperative, high-resolution (HR), serosal electrical mapping.
METHODS: HR electrical recordings were obtained from the distal colon using validated flexible PCB arrays (6 × 16 electrodes; 4 mm inter-electrode spacing; 2.4 cm2, 0.3 mm diameter) for up to 15 min. Passive unipolar signals were obtained and analysed.
RESULTS: Eleven patients (33-71 years; 6 females) undergoing colorectal surgery under general anaesthesia (4 with epidurals) were recruited. After artefact removal and comprehensive manual and automated analytics, events consistent with regular propagating activity between 2 and 6 cpm were not identified in any patient. Intermittent clusters of spike-like activities lasting 10-180 s with frequencies of each cluster ranging between 24 and 42 cpm, and an average amplitude of 0.54 ± 0.37 mV were recorded.
CONCLUSIONS: Intraoperative colonic serosal mapping in humans is feasible, but unlike in the stomach and small bowel, revealed no regular propagating electrical activity. Although sporadic, synchronous spike-wave events were identifiable. Alternative techniques are required to characterise the mechanisms underlying the hyperactive CMP observed in the intra- and post-operative period.
RESULTS: The aim of this study was to assess the feasibility of detecting propagating electrical activity that may correlate to the cyclic motor pattern in the distal human colon through intraoperative, high-resolution, serosal electrical mapping. High-resolution electrical mapping of the human colon revealed no regular propagating activity, but does reveal sporadic spike-wave events. These findings indicate that further research into appropriate techniques is required to identify the mechanism of hyperactive cyclic motor pattern observed in the intra- and post-operative period in humans.

Gastric peristalsis is critically dependent on an underlying electrical conduction system. Recent years have witnessed substantial progress in clarifying the operations of this system, including its pacemaking units, its cellular architecture, and slow-wave propagation patterns. Advanced techniques have been developed for assessing its functions at high spatiotemporal resolutions. This review synthesizes and evaluates this progress, with a focus on human and translational physiology. A current conception of the initiation and conduction of slow-wave activity in the human stomach is provided first, followed by a detailed discussion of its organization at the cellular and tissue level. Particular emphasis is then given to how gastric electrical disorders may contribute to disease states. Gastric dysfunction continues to grow in their prevalence and impact, and while gastric dysrhythmia is established as a clear and pervasive feature in several major gastric disorders, its role in explaining pathophysiology and informing therapy is still emerging. New insights from high-resolution gastric mapping are evaluated, together with historical data from electrogastrography, and the physiological relevance of emerging biomarkers from body surface mapping such as retrograde propagating slow waves. Knowledge gaps requiring further physiological research are highlighted.

UNASSIGNED: We used functional connectivity measures from brain resting state functional magnetic resonance imaging to identify human neural correlates of sedation with dexmedetomidine or propofol and their similarities with natural sleep.
UNASSIGNED: Connectivity within the resting state networks that are proposed to sustain consciousness generation was compared between deep non-rapid-eye-movement (N3) sleep, dexmedetomidine sedation, and propofol sedation in volunteers who became unresponsive to verbal command. A newly acquired dexmedetomidine dataset was compared with our previously published propofol and N3 sleep datasets.
UNASSIGNED: In all three unresponsive states (dexmedetomidine sedation, propofol sedation, and N3 sleep), within-network functional connectivity, including thalamic functional connectivity in the higher-order (default mode, executive control, and salience) networks, was significantly reduced as compared with the wake state. Thalamic functional connectivity was not reduced for unresponsive states within lower-order (auditory, sensorimotor, and visual) networks. Voxel-wise statistical comparisons between the different unresponsive states revealed that thalamic functional connectivity with the medial prefrontal/anterior cingulate cortex and with the mesopontine area was reduced least during dexmedetomidine-induced unresponsiveness and most during propofol-induced unresponsiveness. The reduction seen during N3 sleep was intermediate between those of dexmedetomidine and propofol.
UNASSIGNED: Thalamic connectivity with key nodes of arousal and saliency detection networks was relatively preserved during N3 sleep and dexmedetomidine-induced unresponsiveness as compared to propofol. These network effects may explain the rapid recovery of oriented responsiveness to external stimulation seen under dexmedetomidine sedation.
UNASSIGNED: Committee number: \'Comité d\'Ethique Hospitalo-Facultaire Universitaire de Liège\' (707); EudraCT number: 2012-003562-40; internal reference: 20121/135; accepted on August 31, 2012; Chair: Prof G. Rorive. As it was considered a phase I clinical trial, this protocol does not appear on the EudraCT public website.

BACKGROUND: Mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members, Veterans, and civilians. However, few treatments are available for mTBI, partially because the mechanism of persistent mTBI deficits is not fully understood.
METHODS: We used magnetoencephalography (MEG) to investigate neuronal changes in individuals with mTBI following a passive neurofeedback-based treatment programme called IASIS. This programme involved applying low-intensity pulses using transcranial electrical stimulation (LIP-tES) with electroencephalography monitoring. Study participants included six individuals with mTBI and persistent post-concussive symptoms (PCS). MEG exams were performed at baseline and follow-up to evaluate the effect of IASIS on brain functioning.
RESULTS: At the baseline MEG exam, all participants had abnormal slow-waves. In the follow-up MEG exam, the participants showed significantly reduced abnormal slow-waves with an average reduction of 53.6 ± 24.6% in slow-wave total score. The participants also showed significant reduction of PCS scores after IASIS treatment, with an average reduction of 52.76 ± 26.4% in PCS total score.
CONCLUSIONS: The present study demonstrates, for the first time, the neuroimaging-based documentation of the effect of LIP-tES treatment on brain functioning in mTBI. The mechanisms of LIP-tES treatment are discussed, with an emphasis on LIP-tES\'s potentiation of the mTBI healing process.

Gastrointestinal (GI) motility disorders represent a group of problems that more constantly encountered in preterm infants. However, whether hypoxia exposure contributes to the GI dysfunctions is still unclear.
Newborn mice were exposed to hypoxia (10%) from P1 to P7. Intestinal motilities were examined by a strain gauge transducer. The proliferation of ICCs was detected by using immunostaining for BrdU, Ki67, Kit, Ano1, and insulin-like growth factor 1 receptor (IGF-1R+). Smooth muscle cells and enteric neurons were revealed by immunostaining for α-SMA and NF200, respectively. Apoptosis was assessed by TUNEL assay. Kit signal pathway was examined by western blot and qPCR.
Intestinal motilities were found weakened significantly in the hypoxic small intestines as compared to controls on P8. Kit+ or Ano1+ interstitial cells of Cajal (ICCs) were found obviously decreased in the myenteric ICCs (ICC-MY) of neonatal mice after exposed to hypoxia. A large number of ICC progenitors (IGF-1R+) were found highly mitotic (BrdU+ Ki67+) to populate ICC during early postnatal development in the normoxic mice. We found the ICC proliferation was significantly inhibited upon hypoxia exposure, without increasing apoptosis (TUNEL+). We next identified that Kit phosphorylation was inhibited 3 days after hypoxia exposure. The inhibition of Kit signaling was largely due to decreased the expression of the ligand of Kit receptor, stem cell factor (SCF), in the intestinal walls. Exposure to imatinib, a Kit receptor inhibitor, for 3 days from P4 phenocopied the effect of hypoxia on the neonatal pups that resulted in inhibited intestinal motilities and decreased Kit+ ICC numbers.
All together, our findings indicate the SCF/Kit signaling insufficiency may contribute to the underdevelopment of ICCs and intestinal motility dysfunction upon hypoxia exposure. The decease in ICC density is likely due to the cell cycle arrest of ICC progenitor cells.

OBJECTIVE: Gastrointestinal motility disorders are presumed to be associated with abnormalities of the generation of slow-wave electric impulses. A requirement for the development of non-invasive clinical methods for the diagnosis of motility disorders is the identification of these signals. We set out to separate and characterize the signals from the various sections of the gastrointestinal tract and to detect changes in the smooth muscle electromyography (SEMG) signals.
METHODS: Partially resected (stomach-small intestine, stomach-large intestine or small and large intestine) or non-resected male SPRD rats were measured under deep anaesthesia. Bipolar thread and disk electrodes and strain gauge sensors were used for SEMG and the detection of mechanical contractions, respectively. The electric activity was characterized by cycle per minute (cpm) and power spectrum density maximum (PsDmax) W by fast Fourier transformation analysis. Contractions were evaluated by area under the curve analysis.
RESULTS: The myoelectric signals of the stomach, ileum and caecum were at 3-5, 20-25 and 1-3cpm, respectively. Neostigmine increased (40-60%), while atropine decreased (30-50%) the PsDmax values. However, the cpm values remained unchanged. Linear regression revealed a good correlation between the PsDmax values and the smooth muscle contractions.
CONCLUSIONS: Electric signals of the same character were recorded from the organ and from the abdominal surface. The change in PsDmax perfectly reflects the change in the contractions of the smooth muscle. These results may serve as the basis for non-invasive gastrointestinal measurements in experimental animals, which can be translated into clinical practice for motility studies.