Brain activity changes associated with pain perception variability.

Pain perception can be modulated by several factors. Phenomena like temporal summation leads to increased perceived pain, whereas behavioral conditioning can result in analgesic responses. Furthermore, during repeated, identical noxious stimuli, pain intensity can vary greatly in some individuals. Understanding these variations is important, given the increase in investigations that assume stable baseline pain for accurate response profiles, such as studies of analgesic mechanisms. We utilized functional magnetic resonance imaging to examine the differences in neural circuitry between individuals displaying consistent pain ratings and those who experienced variable pain during a series of identical noxious stimuli. We investigated 63 healthy participants: 31 were assigned to a "consistent" group, and 32 were assigned to a "variable" group dependent on pain rating variability. Variable pain ratings were associated with reduced signal intensity in the dorsolateral prefrontal cortex (dlPFC). Furthermore, the dlPFC connectivity with the primary somatosensory cortex and temperoparietal junction was significantly reduced in variable participants. Our results suggest that investigators should consider variability of baseline pain when investigating pain modulatory paradigms. Additionally, individuals with consistent and variable pain ratings differ in their dlPFC activity and connectivity with pain-sensitive regions during noxious stimulation, possibly reflecting the differences in attentional processing and catastrophizing during pain.

Anatomical changes within the medullary dorsal horn in chronic temporomandibular disorder pain.

Accumulated evidence from experimental animal models suggests that neuroplastic changes at the dorsal horn are critical for the maintenance of various chronic musculoskeletal pain conditions. However, to date, no study has specifically investigated whether neuroplastic changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in subjects with the chronic musculoskeletal pain. In twenty-two subjects with painful temporomandibular disorders (TMDs) and forty pain-free controls voxel based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional grey matter volume and microstructural changes within the brainstem and, in addition, the integrity of ascending pain pathways. Voxel based morphometry revealed significant regional grey matter volume decreases in the medullary dorsal horn, in conjunction with alterations in diffusivity properties, namely an increase in mean diffusivity, in TMD subjects. Volumetric and mean diffusivity changes also occurred in TMD subjects in regions of the descending pain modulation system, including the midbrain periaqueductal grey matter and nucleus raphe magnus. Finally, tractography revealed altered diffusivity properties, namely decreased fractional anisotropy, in the root entry zone of the trigeminal nerve, the spinal trigeminal tract and the ventral trigeminothalamic tracts of TMD subjects. These data reveal that chronic musculoskeletal pain in humans is associated with discrete alterations in the anatomy of the medullary dorsal horn, as well as its afferent and efferent projections. These neural changes may be critical for the maintenance of pathological pain.

Anatomical changes in human motor cortex and motor pathways following complete thoracic spinal cord injury.

A debilitating consequence of complete spinal cord injury (SCI) is the loss of motor control. Although the goal of most SCI treatments is to re-establish neural connections, a potential complication in restoring motor function is that SCI may result in anatomical and functional changes in brain areas controlling motor output. Some animal investigations show cell death in the primary motor cortex following SCI, but similar anatomical changes in humans are not yet established. The aim of this investigation was to use voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) to determine if SCI in humans results in anatomical changes within motor cortices and descending motor pathways. Using VBM, we found significantly lower gray matter volume in complete SCI subjects compared with controls in the primary motor cortex, the medial prefrontal, and adjacent anterior cingulate cortices. DTI analysis revealed structural abnormalities in the same areas with reduced gray matter volume and in the superior cerebellar cortex. In addition, tractography revealed structural abnormalities in the corticospinal and corticopontine tracts of the SCI subjects. In conclusion, human subjects with complete SCI show structural changes in cortical motor regions and descending motor tracts, and these brain anatomical changes may limit motor recovery following SCI.

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.

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.

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.

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.

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.

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.

Accelerated echo-planar J-resolved spectroscopic imaging in the human brain using compressed sensing: a pilot validation in obstructive sleep apnea.

BACKGROUND AND PURPOSE: Echo-planar J-resolved spectroscopic imaging is a fast spectroscopic technique to record the biochemical information in multiple regions of the brain, but for clinical applications, time is still a constraint. Investigations of neural injury in obstructive sleep apnea have revealed structural changes in the brain, but determining the neurochemical changes requires more detailed measurements across multiple brain regions, demonstrating a need for faster echo-planar J-resolved spectroscopic imaging. Hence, we have extended the compressed sensing reconstruction of prospectively undersampled 4D echo-planar J-resolved spectroscopic imaging to investigate metabolic changes in multiple brain locations of patients with obstructive sleep apnea and healthy controls. MATERIALS AND METHODS: Nonuniform undersampling was imposed along 1 spatial and 1 spectral dimension of 4D echo-planar J-resolved spectroscopic imaging, and test-retest reliability of the compressed sensing reconstruction of the nonuniform undersampling data was tested by using a brain phantom. In addition, 9 patients with obstructive sleep apnea and 11 healthy controls were investigated by using a 3T MR imaging/MR spectroscopy scanner. RESULTS: Significantly reduced metabolite differences were observed between patients with obstructive sleep apnea and healthy controls in multiple brain regions: NAA/Cr in the left hippocampus; total Cho/Cr and Glx/Cr in the right hippocampus; total NAA/Cr, taurine/Cr, scyllo-Inositol/Cr, phosphocholine/Cr, and total Cho/Cr in the occipital gray matter; total NAA/Cr and NAA/Cr in the medial frontal white matter; and taurine/Cr and total Cho/Cr in the left frontal white matter regions. CONCLUSIONS: The 4D echo-planar J-resolved spectroscopic imaging technique using the nonuniform undersampling-based acquisition and compressed sensing reconstruction in patients with obstructive sleep apnea and healthy brain is feasible in a clinically suitable time. In addition to brain metabolite changes previously reported by 1D MR spectroscopy, our results show changes of additional metabolites in patients with obstructive sleep apnea compared with healthy controls.

Selectively diminished corpus callosum fibers in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS), a condition associated with mutations in the PHOX2B gene, is characterized by loss of breathing drive during sleep, insensitivity to CO2 and O2, and multiple somatomotor, autonomic, neuropsychological, and ophthalmologic deficits, including impaired intrinsic and extrinsic eye muscle control. Brain structural studies show injury in peri-callosal regions and the corpus callosum (CC), which has the potential to affect functions disturbed in the syndrome; however, the extent of CC injury in CCHS is unclear. Diffusion tensor imaging (DTI)-based fiber tractography procedures display fiber directional information and allow quantification of fiber integrity. We performed DTI in 13 CCHS children (age, 18.2±4.7 years; eight male) and 31 control (17.4±4.9 years; 18 male) subjects using a 3.0-Tesla magnetic resonance imaging scanner; CC fibers were assessed globally and regionally with tractography procedures, and fiber counts and densities compared between groups using analysis-of-covariance (covariates; age and sex). Global CC evaluation showed reduced fiber counts and densities in CCHS over control subjects (CCHS vs. controls; fiber-counts, 4490±854 vs. 5232±777, P<0.001; fiber-density, 10.0±1.5 vs. 10.8±0.9 fibers/mm2, P<0.020), and regional examination revealed that these changes are localized to callosal axons projecting to prefrontal (217±47 vs. 248±32, P<0.005), premotor (201±51 vs. 241±47, P<0.012), parietal (179±64 vs. 238±54, P<0.002), and occipital regions (363±46 vs. 431±82, P<0.004). Corpus callosum fibers in CCHS are compromised in motor, cognitive, speech, and ophthalmologic regulatory areas. The mechanisms of fiber injury are unclear, but may result from hypoxia or perfusion deficits accompanying the syndrome, or from consequences of PHOX2B action.

Central autonomic regulation in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show significant autonomic dysfunction in addition to the well-described loss of breathing drive during sleep. Some characteristics, for example, syncope, may stem from delayed sympathetic outflow to the vasculature; other symptoms, including profuse sweating, may derive from overall enhanced sympathetic output. The dysregulation suggests significant alterations to autonomic regulatory brain areas. Murine models of the genetic mutations present in the human CCHS condition indicate brainstem autonomic nuclei are targeted; however, the broad range of symptoms suggests more widespread alterations. We used functional magnetic resonance imaging (fMRI) to assess neural response patterns to the Valsalva maneuver, an autonomic challenge eliciting a sequence of sympathetic and parasympathetic actions, in nine CCHS and 25 control subjects. CCHS patients showed diminished and time-lagged heart rate responses to the Valsalva maneuver, and muted fMRI signal responses across multiple brain areas. During the positive pressure phase of the Valsalva maneuver, CCHS responses were muted, but were less so in recovery phases. In rostral structures, including the amygdala and hippocampus, the normal declining patterns were replaced by increasing trends or more modest declines. Earlier onset responses appeared in the hypothalamus, midbrain, raphé pallidus, and left rostral ventrolateral medulla. Phase-lagged responses appeared in cerebellar pyramis and anterior cingulate cortex. The time-distorted and muted central responses to autonomic challenges likely underlie the exaggerated sympathetic action and autonomic dyscontrol in CCHS, impairing cerebral autoregulation, possibly exacerbating neural injury, and enhancing the potential for cardiac arrhythmia.

Reduced caudate nuclei volumes in patients with congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) children show cognitive and affective deficits, in addition to state-specific loss of respiratory drive. The caudate nuclei serve motor, cognitive, and affective roles, and show structural deficits in CCHS patients, based on gross voxel-based analytic procedures. However, the magnitude and regional sites of caudate injury in CCHS are unclear. We assessed global caudate nuclei volumes with manual volumetric procedures, and regional volume differences with three-dimensional surface morphometry in 14 CCHS (mean age+/-SD: 15.1+/-2.3 years; 8 male) and 31 control children (15.1+/-2.4 years; 17 male) using brain magnetic resonance imaging (MRI). Two high-resolution T1-weighted image series were collected using a 3.0 Tesla MRI scanner; images were averaged and reoriented (rigid-body transformation) to common space. Both left and right caudate nuclei were outlined in the reoriented images, and global volumes calculated; surface models were derived from manually-outlined caudate structures. Global caudate nuclei volume differences between groups were evaluated using a multivariate analysis of covariance (covariates: age, gender, and total intracranial volume). Both left and right caudate nuclei volumes were significantly reduced in CCHS over control subjects (left, 4293.45+/-549.05 vs. 4626.87+/-593.41 mm(3), P<0.006; right, 4376.29+/-565.42 vs. 4747.81+/-578.13 mm(3), P<0.004). Regional deficits in CCHS caudate volume appeared bilaterally, in the rostral head, ventrolateral mid, and caudal body. Damaged caudate nuclei may contribute to CCHS neuropsychological and motor deficits; hypoxic processes, or maldevelopment in the condition may underlie the injury.

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.

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.

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.

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.

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.

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.

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.