OSA brain morphology differences: magnitude of loss approximates age-related effects.
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Age Factors↗
Biomedical subjects
P M Macey
Publications and source records attributed to P M Macey.
Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome.
Congenital central hypoventilation syndrome (CCHS) patients show deficient respiratory and cardiac responses to hypoxia and hypercapnia, despite apparently intact arousal responses to hypercapnia and adequate respiratory motor mechanisms, thus providing a model to evaluate functioning of particular brain mechanisms underlying breathing. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals, corrected for global signal changes, and evaluated them with cluster and volume-of-interest procedures, during a baseline and 2-min hypoxic (15% O(2), 85% N(2)) challenge in 14 CCHS and 14 age- and gender-matched control subjects. Hypoxia elicited significant (P < 0.05) differences in magnitude and timing of responses between groups in cerebellar cortex and deep nuclei, posterior thalamic structures, limbic areas (including the insula, amygdala, ventral anterior thalamus, and right hippocampus), dorsal and ventral midbrain, caudate, claustrum, and putamen. Deficient responses to hypoxia included no, or late, changes in CCHS patients with declining signals in control subjects, a falling signal in CCHS patients with no change in controls, or absent early transient responses in CCHS. Hypoxia resulted in signal declines but no group differences in hypothalamic and dorsal medullary areas, the latter being a target for PHOX2B, mutations of which occur in the syndrome. The findings extend previously identified posterior thalamic, midbrain, and cerebellar roles for normal mediation of hypoxia found in animal fetal and adult preparations and suggest significant participation of limbic structures in responding to hypoxic challenges, which likely include cardiovascular and air-hunger components. Failing structures in CCHS include areas additional to those associated with PHOX2B expression and chemoreceptor sites.
Adolescent↗
Hypercapnic exposure in congenital central hypoventilation syndrome reveals CNS respiratory control mechanisms.
Congenital central hypoventilation syndrome (CCHS) patients show impaired ventilatory responses and loss of breathlessness to hypercapnia, yet arouse from sleep to high CO2, suggesting intact chemoreceptor afferents. The syndrome provides a means to differentiate brain areas controlling aspects of breathing. We used functional magnetic resonance imaging to determine brain structures responding to inspired 5% CO2-95% O2 in 14 CCHS patients and 14 controls. Global signal changes induced by the challenge were removed on a voxel-by-voxel basis. A priori-defined volume-of-interest time trends (assessed with repeated measures ANOVA) and cluster analysis based on modeling each subject to a step function (individual model parameter estimates evaluated with t-test, corrected for multiple comparisons) revealed three large response clusters to hypercapnia distinguishing the two groups, extending from the 1) posterior thalamus through the medial midbrain to the dorsolateral pons, 2) right caudate nucleus, ventrolaterally through the putamen and ventral insula to the mid-hippocampus, and 3) deep cerebellar nuclei to the dorsolateral cerebellar cortex bilaterally. Smaller clusters and defined areas of group signal differences in the midline dorsal medulla, amygdala bilaterally, right dorsal-posterior temporal cortex, and left anterior insula also emerged. In most sites, early transient or sustained responses developed in controls, with little, or inverse change in CCHS subjects. Limbic and medullary structures regulating responses to hypercapnia differed from those previously shown to mediate loaded breathing ventilatory response processing. The findings show the significant roles of cerebellar and basal ganglia sites in responding to hypercapnia and the thalamic and midbrain participation in breathing control.
Adolescent↗
fMRI signal changes in response to forced expiratory loading in congenital central hypoventilation syndrome.
Congenital central hypoventilation syndrome (CCHS) patients show impaired ventilatory responses to CO2 and hypoxia and reduced drive to breathe during sleep but retain appropriate breathing patterns in response to volition or increased exercise. Breath-by-breath influences on heart rate are also deficient. Using functional magnetic resonance imaging techniques, we examined responses over the brain to voluntary forced expiratory loading, a task that CCHS patients can perform but that results in impaired rapid heart rate variation patterns normally associated with the loading challenge. Increased signals emerged in control (n = 14) over CCHS (n = 13; ventilator dependent during sleep but not waking) subjects in the cingulate and right parietal cortex, cerebellar cortex and fastigial nucleus, and basal ganglia, whereas anterior cerebellar cortical sites and deep nuclei, dorsal midbrain, and dorsal pons showed increased signals in the patient group. The dorsal and ventral medulla showed delayed responses in CCHS patients. Primary motor and sensory areas bordering the central sulcus showed comparable responses in both groups. The delayed responses in medullary sensory and output regions and the aberrant reactions in cerebellar and pontine sensorimotor coordination areas suggest that rapid cardiorespiratory integration deficits in CCHS may stem from defects in these sites. Additional autonomic and perceptual motor deficits may derive from cingulate and parietal cortex aberrations.
Adolescent↗
Functional magnetic resonance imaging responses to expiratory loading in obstructive sleep apnea.
Obstructive sleep apnea (OSA) is characterized by diminished upper airway muscle phasic and tonic activation during sleep, but enhanced activity during waking. We evaluated neural mechanisms underlying these patterns with functional magnetic resonance imaging procedures during baseline and expiratory loading conditions in nine medication-free OSA and 16 control subjects. Both groups developed similar expiratory loading pressures, but appropriate autonomic responses did not emerge in OSA cases. Reduced neural signals emerged in OSA cases within the frontal cortex, anterior cingulate, cerebellar dentate nucleus, dorsal pons, anterior insula and lentiform nuclei. Signal increases in OSA over control subjects developed in the dorsal midbrain, hippocampus, quadrangular cerebellar lobule, ventral midbrain and ventral pons. Fastigial nuclei and the amygdala showed substantially increased variability in OSA subjects. No group differences were found in the thalamus. OSA patients show aberrant responses in multiple brain areas and inappropriate cardiovascular responses to expiratory loading, perhaps as a consequence of previously-demonstrated limbic, cerebellar and motor area gray matter loss.
Adult↗
Overnight central and peripheral temperature changes in normal infants.
AIM: To explore the relationship between central and peripheral temperature in normal infants after being put down to sleep. METHODS: Overnight shin and rectal temperatures of 21 normal infants were continuously recorded at home for three nights at 2 wk, 6 wk, 3 mo and 5 mo of age. Parents documented the start and end of feed/nappy changes during the night. RESULTS: An initial fall in rectal temperature was recorded on 149 out of 161 nights. This was linearly correlated with a rise in shin temperature for 106/149 (71%) nights (median R2 = 0.95, lower quartile 0.92, upper quartile 0.97). It was not possible to rule out a change in thermal insulation over the shins as a confounding variable in this strong association. However, a similar inverse relationship was seen between shin and rectal temperature during 111 of 121 (92%) feed/nappy changes. CONCLUSION: The fall in rectal temperature after being put down to sleep may be due to redistribution of heat rather than decreased production or heat loss. If causal, the development in early infancy of an inverse relationship between shin and rectal temperature may be important for cardiovascular homeostasis. Further sleep laboratory work is required to distinguish peripheral temperature changes on falling asleep from those associated with changes in thermal insulation.
Body Temperature↗
Central and peripheral temperature change in normal infants.
The purpose was to explore the relationship between the fall in rectal temperature seen in normal infants after being put down to sleep and the concomitant rise in peripheral shin temperature. In this observational study 21 normal infants had continuous overnight peripheral shin and central rectal temperature recorded, for three nights at 2 weeks, 6 weeks, 3 months and 5 months of age. Parents documented the start and end of feed/nappy changing episodes during the night. All recordings were made in the infants' own home. A strong inverse linear correlation (median r2 = 0.95, lower quartile 0.92, upper quartile 0.97) was seen between rectal temperature and shin temperature on falling to sleep when put down on 106 (65%) of 161 nights. On many other nights a significant nonlinear association was present. It was not possible to exclude the process of being put down to sleep as a confounding variable in this strong association. However, a similar inverse relationship between shin and rectal temperature was seen overnight during 111 of 121 (92%) feed/nappy changing episodes. If causal, the development in early infancy of an inverse relationship between shin and rectal temperature may be important for cardiovascular homeostasis. Further sleep laboratory work including video recording is required to separate the peripheral and central temperature changes that take place on falling to sleep from those associated with removal of clothing during a nappy change.
Ankle↗
The relationship between inside and outside ambient temperatures in Christchurch, New Zealand.
The objective of this study was to examine and identify relationships between hourly recorded meteorological temperature and ambient temperature, measured from within the home-sleeping environment of young infants' homes in Christchurch, New Zealand. From 1991 to 1994, home polysomnography recordings were conducted for up to 6 weeks on 32 infants aged between 2 and 24 weeks. One of the recorded signals was ambient room temperature. In total, 15735 hourly recordings of this temperature were available for analysis. The New Zealand Meteorological Service supplied hourly recordings of climatic temperature, collected over this time, from an exposed site that was considered to be representative of weather conditions for Christchurch. Temperature seasonality, hourly climatic temperature recordings and the interaction of these variables were found to be significantly related to the indoor ambient temperature recordings (all had P < 0.001). Fluctuations in hourly recorded indoor temperature appeared to lag outdoor temperature fluctuations by approximately 2 h; hence, a strong autocorrelation was identified in the regression residuals. The most parsimonious autoregression model accounted for 97% of the variability in the hourly indoor temperature measurements (r2 = 0.97). In Christchurch houses, which typically have poor thermal insulation properties, yet have no central heating capabilities, a very strong association between indoor and outdoor temperatures was clearly demonstrated.
Climate↗
Weather and the risk of sudden infant death syndrome: the effect of wind.
STUDY OBJECTIVE: To examine and identify relations between sudden infant death syndrome (SIDS) and wind, particularly the föhn wind, in Christchurch, New Zealand. DESIGN: A retrospective epidemiological study combining details of regional hourly meteorological variables and reported SIDS cases. SETTING: Christchurch, New Zealand, between 1968 and 1997 inclusively. PARTICIPANTS: All 646 infants reported as dying from SIDS within the greater Christchurch region. MAIN RESULTS: Analysis of 1968-1989 data revealed nine wind variables significantly related to SIDS. When compared with corresponding variables calculated over the 1990-1997 period, only the northerly wind on the day of death and the southerly wind three days before a SIDS death had estimated associations with similar effect size and sign. However, both these variables had confidence intervals that included unity. CONCLUSIONS: No evidence was found to suspect that föhn winds influenced SIDS occurrence. The relations identified between SIDS incidence and wind, after controlling for the effects of temperature and trend, were tenuous and relatively small. More data are necessary to substantiate whether northerly winds on the day of death or southerly winds occurring three days before a death are truly associated with SIDS. It seems that wind has little, if any effect on SIDS incidence in Christchurch.
Atmosphere↗
State influences on ventral medullary surface and physiological responses to sodium cyanide challenges.
Intravenous sodium cyanide (NaCN) administration lowers ventral medullary surface (VMS) activity in anesthetized cats. Sleep states modify spontaneous and blood pressure-evoked VMS activity and may alter VMS responses to chemoreceptor input. We studied VMS activation during peripheral chemoreceptor stimulation by intravenous NaCN using optical procedures in six cats instrumented for recording sleep physiology during sham saline and control site trials. Images of scattered 660-nm light were collected at 50 frames/s with an optical device after 80-100 microg total bolus intravenous NaCN delivery during waking and sleep states. Cyanide elicited an initial ventilatory decline, followed by large inspiratory efforts and an increase in respiratory rate, except in rapid eye movement sleep, in which an initial breathing increase occurred. NaCN evoked a pronounced decrease in VMS activity in all states; control sites and sham injections showed little effect. The activity decline was faster in rapid eye movement sleep, and the activity nadir occurred later in waking. Sleep states alter the time course but not the extent of decline in VMS activity.
Animals↗
Deterministic properties of apnoeas in an abdominal breathing signal.
The paper describes a general set of properties that represent most apnoeas as found in an abdominal breathing signal. An apnoea is a pause in breathing during sleep, and only central apnoeas in infants are considered. Human experts are consulted to determine what properties of the signal they use to recognise apnoeas. A set of deterministic, or shape, properties is developed to represent expert opinion. An apnoea is modelled as a flat region with four properties: flatness, duration, thinness and smoothness. Mathematical descriptions of each property are formulated that discriminate between apnoea and non-apnoea events, and each description is tested for discrimination and independence. The average power of discrimination is 24% +/- 16% and the average correlation coefficient is 0.28 +/- 0.16. Applications include scoring apnoeas for sleep studies and developing standard definitions of apnoeas.
Algorithms↗
The febrile stress of routine vaccination does not increase central apnoea in normal infants.
We tested the hypothesis that the febrile stress of routine vaccination would increase central apnoea in normal infants. Twenty-one normal infants had continuous overnight breathing and temperature recorded at home, before and after 58 routine vaccination episodes. Central apnoea, of at least 5 sec duration, was detected by computer algorithm and confirmed by human inspection. The longest recorded apnoea was 16 sec (n = 1) during 3629 h of sleep. Overnight rectal temperature increased after vaccination (median 0.52 degrees C, 95% CI 0.40, 0.65). Apnoea density reduced on 46/53 vaccination nights (median -29%, 95% CI -20, -37) followed by an increase on subsequent nights (median +10%, 95% CI +1%,+21%). Overall, apnoea density was similar during the 3 nights preceding and 4 nights following vaccination (median +1%, 95% CI +9,-6). The febrile stress of routine vaccination did not increase central apnoea in normal infants.
Body Temperature↗
Breathing, sleep state, and rectal temperature oscillations.
Overheating may cause terminal apnoea and cot death. Rectal temperature and breathing patterns were examined in normal infants at home during the first 6 months of life. Twenty one infants had continuous overnight rectal temperature and breathing recordings for 429 nights (mean 20.4 nights, range 7-30) spaced over the first six months of life. Periods when breathing was 'regular' were directly marked on single night records. Sleep state was determined from respiratory variables. 'Regular' breathing was a reliable marker of 'quiet' sleep (specificity 93%). The duration of 'quiet' sleep increased from 6 to 22 minutes from two weeks to three months of age and then remained static, as did the proportion of sleep spent in the quiet phase (9% to 34%). Rectal temperature fell during 66% of quiet sleep and usually rose during rapid eye movement (REM) sleep. The drop in rectal temperature was maximal at the start of quiet sleep, whereas the maximum rise during REM sleep was reached after 10 to 15 minutes. Oscillations in rectal temperature are associated with changes in sleep and breathing state. The maturation of rectal temperature patterns during the first six months of life are closely related to a maturation of sleep state and breathing patterns.
Aging↗
Apnoea detection: human performance and reliability of a computer algorithm.
We examined the consistency of apnoea recognition between three human experts. The hypothesis was that computer detection of apnoea could emulate human expert apnoea recognition. The aim was to detect apnoeas with the highest possible accuracy from a single breathing signal, by both human experts and computer. Three human experts independently examined recordings of breathing wave-form from overnight sleep studies from 10 infants aged 3-17 weeks. All apnoeas of 5 s or more were identified and reviewed. However, there still remained 10% disagreement. A computer apnoea detector was implemented. An algorithm analysed statistical properties of the signal to find breathing pauses. Optimal performance was 1% missed apnoeas (compared with the agreed apnoeas identified by the three experts) and 29% false detections. This computer algorithm reliably identified most apnoeas but did not replace the human expert.
Algorithms↗
HomeLog: long-term recording of infant temperature, respiratory and cardiac signals in the home environment.
There is increasing evidence that overheating is a contributing factor for some cot deaths. The authors' hypothesis is that infant thermoregulation is closely related to respiratory control. HomeLog is a system built to investigate the developing thermal, respiratory and cardiac behaviour of infants in the home environment over several weeks. HomeLog is based on a modified laptop computer. Signals recorded include body temperature (from rectal and various skin sites), ambient temperature, thoracic impedance, abdominal movement and electrocardiogram (ECG). Continuous night-time recordings have been made for up to 6 weeks from infants between 1 and 4 months of age, in their own cots, in their own homes. Various time and frequency domain analyses of the breathing and temperature data have been developed. Analysis of breath rate variability and of body temperature fluctuations has confirmed sleep/wake changes. In addition, a periodic oscillation of body temperature every 1-2 h has been found, which closely matches oscillations of breath rate variability.
Apnea↗