scholarly journals An Infant Sleep Electroencephalographic Marker of Thalamocortical Connectivity Predicts Behavioral Outcome in Late Infancy

2021 ◽  
Author(s):  
Valeria Jaramillo ◽  
Sarah Fiona Schoch ◽  
Andjela Markovic ◽  
Malcolm Kohler ◽  
Reto Huber ◽  
...  

Infancy represents a critical period during which thalamocortical brain connections develop and mature. Deviations in the maturation of thalamocortical connectivity are linked to neurodevelopmental disorders. There is a lack of early biomarkers to detect and localize neuromaturational deviations, which can be overcome with mapping through high-density electroencephalography (hdEEG) assessed in sleep. Specifically, slow waves and spindles in non-rapid eye movement (NREM) sleep are generated by the thalamocortical system, and their characteristics, slow wave slope and spindle density, are closely related to neuroplasticity and learning. Recent studies further suggest that information processing during sleep underlying sleep-dependent learning is promoted by the temporal coupling of slow waves and spindles, yet slow wave-spindle coupling remains unexplored in infancy. Thus, we evaluated three potential biomarkers: 1) slow wave slope, 2) spindle density, and 3) the temporal coupling of slow waves with spindles. We use hdEEG to first examine the occurrence and spatial distribution of these three EEG features in healthy infants and second to evaluate a predictive relationship with later behavioral outcomes. We report four key findings: First, infants' EEG features appear locally: slow wave slope is maximal in occipital and frontal areas, whereas spindle density is most pronounced frontocentrally. Second, slow waves and spindles are temporally coupled in infancy, with maximal coupling strength in the occipital areas of the brain. Third, slow wave slope, spindle density, and slow wave-spindle coupling are not associated with concurrent behavioral status (6 months). Fourth, spindle density in central and frontocentral regions at age 6 months predicts later behavioral outcomes at 12 and 24 months. Neither slow wave slope nor slow wave-spindle coupling predict behavioral development. Our results propose spindle density as an early EEG biomarker for identifying thalamocortical maturation, which can potentially be used for early diagnosis of neurodevelopmental disorders in infants. These findings are complemented by our companion paper that demonstrates the linkage of spindle density to infant nighttime movement, framing the possible role of spindles in sensorimotor microcircuitry development. Together, our studies suggest that early sleep habits, thalamocortical maturation, and behavioral outcome are closely interwoven. A crucial next step will be to evaluate whether early therapeutic interventions may be effective to reverse deviations in identified individuals at risk.

2005 ◽  
Vol 289 (5) ◽  
pp. G898-G903 ◽  
Author(s):  
Wim J. E. P. Lammers

In contrast to the mechanisms of segmental and peristaltic contractions in the small intestine, not much is known about the mechanism of pendular contractions. High-resolution electrical and mechanical recordings were performed from isolated segments of the rabbit ileum during pendular contractions. The electrical activities were recorded with 32 extracellular electrodes while motility was assessed simultaneously by video tracking the displacements of 20–40 serosal markers. The electrical activities consisted of slow waves, followed by spikes, that propagated in either the aboral or oral direction. The mechanical activity always followed the initial electrical activity, describing a contraction phase in one direction followed by a relaxation phase in the opposite direction. Pendular displacements were always in rhythm with the slow wave, whereas the direction of the displacements was dictated by the origin of the slow wave. If the slow wave propagated aborally, then the pendular displacement occurred in the oral direction, whereas if the slow wave propagated in the oral direction, then the displacement occurred in the aboral direction. In the case of more complex propagation patterns, such as in the area of pacemaking or collision, direction of displacements remained always opposite to the direction of the slow wave. In summary, the direction and pattern of propagation of the slow wave determine the rhythm and the direction of the pendular motility. The well-known variability in pendular movements is caused by the variability in the propagation of the underlying slow wave.


SLEEP ◽  
2020 ◽  
Vol 43 (9) ◽  
Author(s):  
Valeria Jaramillo ◽  
Carina Volk ◽  
Angelina Maric ◽  
Melanie Furrer ◽  
Sara Fattinger ◽  
...  

Abstract Study Objectives The restorative function of sleep has been linked to a net reduction in synaptic strength. The slope of slow-waves, a major characteristic of non-rapid eye movement (NREM) sleep, has been shown to directly reflect synaptic strength, when accounting for amplitude changes across the night. In this study, we aimed to investigate overnight slope changes in the course of development in an age-, amplitude-, and region-dependent manner. Methods All-night high-density electroencephalography data were analyzed in a cross-sectional population of 60 healthy participants in the age range of 8–29 years. To control for amplitude changes across the night, we matched slow-waves from the first and the last hour of NREM sleep according to their amplitude. Results We found a reduction of slow-wave slopes from the first to the last hour of NREM sleep across all investigated ages, amplitudes, and most brain regions. The overnight slope change was largest in children and decreased toward early adulthood. A topographical analysis revealed regional differences in slope change. Specifically, for small amplitude waves the decrease was smallest in an occipital area, whereas for large amplitude waves, the decrease was smallest in a central area. Conclusions The larger slope decrease in children might be indicative of a boosted renormalization of synapses during sleep in childhood, which, in turn, might be related to increased plasticity during brain maturation. Regional differences in the extent of slow-wave slope reduction may reflect a “smart” down-selection process or, alternatively, indicate amplitude-dependent differences in the generation of slow-waves.


SLEEP ◽  
2021 ◽  
Author(s):  
Brice V McConnell ◽  
Eugene Kronberg ◽  
Peter D Teale ◽  
Stefan H Sillau ◽  
Grace M Fishback ◽  
...  

Abstract Study Objectives Slow wave and spindle coupling supports memory consolidation, and loss of coupling is linked with cognitive decline and neurodegeneration. Coupling is proposed to be a possible biomarker of neurological disease, yet little is known about the different subtypes of coupling that normally occur throughout human development and aging. Here we identify distinct subtypes of spindles within slow wave upstates and describe their relationships with sleep stage across the human lifespan. Methods Coupling within a cross-sectional cohort of 582 subjects was quantified from stages N2 and N3 sleep across ages 6-88 years old. Results were analyzed across the study population via mixed model regression. Within a subset of subjects, we further utilized coupling to identify discrete subtypes of slow waves by their coupled spindles. Results Two different subtypes of spindles were identified during the upstates of (distinct) slow waves: an “early-fast” spindle, more common in stage N2 sleep, and a “late-fast” spindle, more common in stage N3. We further found stages N2 and N3 sleep contain a mixture of discrete subtypes of slow waves, each identified by their unique coupled-spindle timing and frequency. The relative contribution of coupling subtypes shifts across the human lifespan, and a deeper sleep phenotype prevails with increasing age. Conclusions Distinct subtypes of slow waves and coupled spindles form the composite of slow wave sleep. Our findings support a model of sleep-dependent synaptic regulation via discrete slow wave/spindle coupling subtypes and advance a conceptual framework for the development of coupling-based biomarkers in age-associated neurological disease.


2001 ◽  
Vol 280 (6) ◽  
pp. G1370-G1375 ◽  
Author(s):  
Xuemei Lin ◽  
Jiande Z. Chen

The aim of this study was to utilize multichannel electrogastrography to investigate whether patients with functional dyspepsia had impaired propagation or coordination of gastric slow waves in the fasting state compared with healthy controls. The study was performed in 10 patients with functional dyspepsia and 11 healthy subjects. Gastric myoelectrical activity was measured by using surface electrogastrography with a specially designed four-channel device. The study was performed for 30 min or more in the fasting state. Special computer programs were developed for the computation of the propagation and coupling of the gastric slow wave. It was found that, compared with the healthy controls, the patients showed a significantly lower percentage of slow wave propagation (58.0 ± 8.9 vs. 89.9 ± 2.6%, P < 0.002) and a significantly lower percentage of slow wave coupling (46.9 ± 4.4 vs. 61.5 ± 6.9%, P < 0.04). In addition, the patients showed inconsistencies in the frequency and regularity of the gastric slow wave among the four-channel electrogastrograms (EGGs). It was concluded that patients with functional dyspepsia have impaired slow wave propagation and coupling. Multichannel EGG has more information than single-channel EGG for the detection of gastric myoelectrical abnormalities.


1990 ◽  
Vol 259 (2) ◽  
pp. G264-G273 ◽  
Author(s):  
S. M. Ward ◽  
K. M. Sanders

Morphological and electrophysiological experiments were performed to characterize the pacemaker areas of the circular muscle in the canine proximal colon. Morphological studies showed interstitial cells of Cajal lining the submucosal surface of the circular layer and the septal structures that separate the circular layer into bundles. Electrical measurements suggested that slow waves may propagate into the thickness of the circular muscle in a regenerative manner along the surface of these septa. Removal of the submucosal pacemaker region blocked generation of slow waves in nonseptal regions of the circular muscle, but slow-wave activity continued in the circular muscle near septa. These data suggest that slow-wave pacemaker activity is not limited to a two-dimensional surface at the submucosal surface but extends into the interior of the circular layer along septal invaginations. Experiments were also performed to determine the dominance of pacemaker activity (i.e., septal vs. submucosal), and examples were found in which both areas appeared to initiate slow waves in intact muscles. Other studies showed that slow waves could propagate across septa, suggesting some form of electrical coupling between circular muscle bundles. This study provides a more complete view of the structure and function of pacemaker areas in the canine proximal colon.


1991 ◽  
Vol 260 (2) ◽  
pp. C375-C382 ◽  
Author(s):  
J. M. Post ◽  
R. J. Stevens ◽  
K. M. Sanders ◽  
J. R. Hume

The effects of cromakalim (BRL 34915) and its optical isomer lemakalim (BRL 38227) were investigated in intact tissue and freshly dispersed circular muscle cells from canine proximal colon. Cromakalim and lemakalim hyperpolarized resting membrane potential, shortened the duration of slow waves by abolishing the plateau phase, and decreased the frequency of slow waves. Glyburide, a K channel blocker, prevented the effect of cromakalim on slow-wave activity. The mechanisms of these alterations in slow-wave activity were studied in isolated myocytes under voltage-clamp conditions. Cromakalim and lemakalim increased the magnitude of a time-independent outward K current, but cromakalim also reduced the peak outward K current. Glyburide inhibited lemakalim stimulation of the time-independent background current. Nisoldipine also reduced the peak outward current, and in the presence of nisoldipine, cromakalim did not affect the peak outward component of current. This suggested that cromakalim may block a Ca-dependent component of the outward current. Lemakalim did not affect the peak outward current. We tested whether the effects of cromakalim on outward current might be indirect due to an effect on inward Ca current. Cromakalim, but not lemakalim, was found to inhibit L-type Ca channels; however, glyburide did not alter cromakalim inhibition of inward Ca current. We conclude that the effects of cromakalim and lemakalim on membrane potential and slow waves in colonic smooth muscle appear to result primarily from stimulation of a time-independent background K conductance. The effects of these compounds on channel activity may explain the inhibitory effect of these compounds on contractile activity.


2020 ◽  
Vol 31 (1) ◽  
pp. 324-340
Author(s):  
Pavel Sanda ◽  
Paola Malerba ◽  
Xi Jiang ◽  
Giri P Krishnan ◽  
Jorge Gonzalez-Martinez ◽  
...  

Abstract The dialogue between cortex and hippocampus is known to be crucial for sleep-dependent memory consolidation. During slow wave sleep, memory replay depends on slow oscillation (SO) and spindles in the (neo)cortex and sharp wave-ripples (SWRs) in the hippocampus. The mechanisms underlying interaction of these rhythms are poorly understood. We examined the interaction between cortical SO and hippocampal SWRs in a model of the hippocampo–cortico–thalamic network and compared the results with human intracranial recordings during sleep. We observed that ripple occurrence peaked following the onset of an Up-state of SO and that cortical input to hippocampus was crucial to maintain this relationship. A small fraction of ripples occurred during the Down-state and controlled initiation of the next Up-state. We observed that the effect of ripple depends on its precise timing, which supports the idea that ripples occurring at different phases of SO might serve different functions, particularly in the context of encoding the new and reactivation of the old memories during memory consolidation. The study revealed complex bidirectional interaction of SWRs and SO in which early hippocampal ripples influence transitions to Up-state, while cortical Up-states control occurrence of the later ripples, which in turn influence transition to Down-state.


1975 ◽  
Vol 229 (2) ◽  
pp. 484-488 ◽  
Author(s):  
AK Mukhopadhyay ◽  
LR Johnson ◽  
EM Copeland ◽  
NW Weisbrodt

The effect of intravenously administered secretin (0.5, 2.0, 6.0 U/kg-h) and intraduodenal acidification (13.2 meq/h HCl) on the electrical activity of the small bowel of three conscious dogs with gastric and duodenal cannulas was observed. Electrical activity was recorded in fasted as well as fed conditions through silver wire electrodes implanted along the entire length of the small bowel. Intravenous infusion of secretin in all dosages and in all dogs delayed the onset of the interdigestive myoelectric complex and reduced the total percentage of slow waves with superimposed spike potentials. Intraduodenal acidification also inhibited the interdigestive myoelectric complex, which developed incompletely with fewer action potentials on slow waves. Secretin did not produce any alteration in the fed pattern of activity, slow-wave frequency, or the caudal migration of the interdigestive myoelectric complex. The present study indicates that the nuerohumoral mechanisms responsible for initiation of the interdigestive myoelectric complex may be different from those responsible for its caudal migration.


1999 ◽  
Vol 277 (2) ◽  
pp. G306-G313 ◽  
Author(s):  
Harold G. Preiksaitis ◽  
Nicholas E. Diamant

A myogenic control system (MCS) is a fundamental determinant of peristalsis in the stomach, small bowel, and colon. In the esophagus, attention has focused on neuronal control, the potential for a MCS receiving less attention. The myogenic properties of the cat esophagus were studied in vitro with and without nerves blocked by 1 μM TTX. Muscle contraction was recorded, while electrical activity was monitored by suction electrodes. Spontaneous, nonperistaltic, electrical, and mechanical activity was seen in the longitudinal muscle and persisted after TTX. Spontaneous circular muscle activity was minimal, and peristalsis was not observed without pharmacological activation. Direct electrical stimulation (ES) in the presence of bethanechol or tetraethylammonium chloride (TEA) produced slow-wave oscillations and spike potentials accompanying smooth muscle contraction that progressed along the esophagus. Increased concentrations of either drug in the presence of TTX produced slow waves and spike discharges, accompanied by peristalsis in 5 of 8 TEA- and 2 of 11 bethanechol-stimulated preparations without ES. Depolarization of the muscle by increasing K+ concentration also produced slow waves but no peristalsis. We conclude that the MCS in the esophagus requires specific activation and is manifest by slow-wave oscillations of the membrane potential, which appear to be necessary, but are not sufficient for myogenic peristalsis. In vivo, additional control mechanisms are likely supplied by nerves.


1990 ◽  
Vol 259 (2) ◽  
pp. G258-G263 ◽  
Author(s):  
K. M. Sanders ◽  
R. Stevens ◽  
E. Burke ◽  
S. W. Ward

Colonic slow waves originate from pacemaker cells along the submucosal surface of the circular layer in the dog proximal colon. These events propagate in a nonregenerative manner into the bulk of the circular layer. Conduction velocities consistent with an active mechanism for slow-wave propagation in the longitudinal and circumferential axes of the colon have been reported. Experiments were performed using intracellular recording techniques on canine colonic muscles to determine the regenerative pathway for slow-wave propagation. In a thin band of muscle adjacent to the submucosal border of the circular layer, slow-wave amplitude was independent of distance from a pacing source, and events propagated at a rate of approximately 17 mm/s in the long axis of the circular fibers and 6 mm/s in the transverse axis of the circular fibers. These findings suggest that slow waves propagate in a regenerative manner in this region. Slow waves decayed as they conducted through regions from which the pacemaker cells had been removed with space constants of a few millimeters. Thus the integrity of the thin pacemaker region along submucosal surface is critical for propagation of slow waves and the organization of motility into segmental contractions.


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