Youth screen use in the ABCD® study.

Adolescent screen usage is ubiquitous and influences development and behavior. Longitudinal screen usage data coupled with psychometrically valid constructs of problematic behaviors can provide insights into these relationships. We describe methods by which the screen usage questionnaire was developed in the Adolescent Brain Cognitive Development (ABCD) Study, demonstrate longitudinal changes in screen usage via child report and describe data harmonization baseline-year 2. We further include psychometric analyses of adapted social media and video game addiction scales completed by youth. Nearly 12,000 children ages 9-10 years at baseline and their parents were included in the analyses. The social media addiction questionnaire (SMAQ) showed similar factor structure and item loadings across sex and race/ethnicities, but that item intercepts varied across both sex and race/ethnicity. The videogame addiction questionnaire (VGAQ) demonstrated the same configural, metric and scalar invariance across racial and ethnic groups, however differed across sex. Video gaming and online social activity increased over ages 9/10-11/12 (p's < 0.001). Compared with boys, girls engaged in greater social media use (p < .001) and demonstrated higher ratings on the SMAQ (p < .001). Compared with girls, boys played more video games (p < .001) and demonstrated higher ratings on the VGAQ (p < .001). Time spent playing video games increased more steeply for boys than girls from age 9/10-11/12 years (p < .001). Black youth demonstrated significantly higher SMAQ and VGAQ scores compared to all other racial/ethnic groups. These data show the importance of considering different screen modalities beyond total screen use and point towards clear demographic differences in use patterns. With these comprehensive data, ABCD is poised to address critical questions about screen usage changes across adolescence.

Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Distinct Regionalization Patterns of Cortical Morphology are Associated with Cognitive Performance Across Different Domains.

Cognitive performance in children is predictive of academic and social outcomes; therefore, understanding neurobiological mechanisms underlying individual differences in cognition during development may be important for improving quality of life. The belief that a single, psychological construct underlies many cognitive processes is pervasive throughout society. However, it is unclear if there is a consistent neural substrate underlying many cognitive processes. Here, we show that a distributed configuration of cortical surface area and apparent thickness, when controlling for global imaging measures, is differentially associated with cognitive performance on different types of tasks in a large sample (N = 10 145) of 9-11-year-old children from the Adolescent Brain and Cognitive DevelopmentSM (ABCD) study. The minimal overlap in these regionalization patterns of association has implications for competing theories about developing intellectual functions. Surprisingly, not controlling for sociodemographic factors increased the similarity between these regionalization patterns. This highlights the importance of understanding the shared variance between sociodemographic factors, cognition and brain structure, particularly with a population-based sample such as ABCD.

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder.

BACKGROUND: Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder. METHODS/DESIGN: We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods. DISCUSSION: This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome. TRIAL REGISTRATION: The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results.

Polygenic risk for psychiatric disorders correlates with executive function in typical development.

Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive functions and how these factors may be related to those that predispose to psychiatric disorders. We examined the relationship between polygenic risk scores built from large genome-wide association studies of psychiatric disorders and executive functioning in typically developing children. In our discovery sample (N = 417), consistent with previous reports on general cognitive abilities, polygenic risk for autism spectrum disorder was associated with better performance on the Dimensional Change Card Sort test from the NIH Cognition Toolbox, with the largest effect in the youngest children. Polygenic risk for major depressive disorder was associated with poorer performance on the Flanker test in the same sample. This second association replicated for performance on the Penn Conditional Exclusion Test in an independent cohort (N = 3681). Our results suggest that the molecular genetic factors contributing to variability in executive function during typical development are at least partially overlapping with those associated with psychiatric disorders, although larger studies and further replication are needed.

Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci.

Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21,856) and multiple sclerosis (MS) (n=43,879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16,731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.

Apolipoprotein E epsilon4 does not modulate amyloid-ß-associated neurodegeneration in preclinical Alzheimer disease.

BACKGROUND AND PURPOSE: Among cognitively healthy older individuals, the relationship among the 2 hallmark proteins of AD (Aß and τ APOE ε4) and neurodegeneration is not well-understood. Here, we investigated the relationship between Aß, p-τ, and APOE ε4 on longitudinal brain atrophy in preclinical AD. MATERIALS AND METHODS: We examined 107 cognitively healthy older adults who underwent longitudinal MR imaging and baseline lumbar puncture. Within the same linear mixed-effects model, we concurrently investigated main and interactive effects between the APOE ε4 genotype and CSF Aß(1-42), CSF p-τ and CSF Aß(1-42), and the APOE ε4 genotype and CSF p-τ on entorhinal cortex atrophy rate. We also examined the relationship of APOE ε4, CSF p-τ, and CSF Aß(1-42) on the atrophy rate of other AD-vulnerable neuroanatomic regions. RESULTS: The full model with main and interactive effects demonstrated a significant interaction only between CSF p-τ and CSF Aß(1-42) on entorhinal cortex atrophy rate, indicating elevated atrophy with time in individuals with increased CSF p-τ and decreased CSF Aß(1-42). The APOE ε4 genotype was significantly and specifically associated with CSF Aß(1-42). However, the interaction between the APOE ε4 genotype and either CSF Aß(1-42) or CSF p-τ on entorhinal cortex atrophy rate was not significant. We found similar results in other AD-vulnerable regions. CONCLUSIONS: On the basis of our findings and building on prior experimental evidence, we propose a model of the pathogenic cascade underlying preclinical AD in which APOE ε4 primarily influences the pathology of Alzheimer disease via Aß-related mechanisms, and in turn, Aß-associated neurodegeneration occurs only in the presence of p-τ.

Predictors and moderators of time to remission of major depression with interpersonal psychotherapy and SSRI pharmacotherapy.

BACKGROUND: Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy. METHOD: A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks. RESULTS: Participants with higher scores on the need for medical reassurance factor of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission. CONCLUSIONS: This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Comparing the subjective, psychomotor and physiological effects of intravenous butorphanol and morphine in healthy volunteers.

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of butorphanol in healthy nondrug-abusing volunteers and to compare and contrast the effects of butorphanol to those of morphine. Into an antecubital vein, the subjects (seven men and five women), who had no history of opiate dependence, were injected with 0, 0.5, 1.0 or 2.0 mg/70 kg of butorphanol or 10 mg/70 kg of morphine; a randomized, double-blind, crossover design was used. The subjective effects of butorphanol included increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and Lysergic Acid Diethylamide scale of the Addiction Research Center inventory; increased visual analog scale ratings of "sedated," "coasting or spaced out" and "difficulty concentrating;" increased adjective checklist ratings of "sweating," "skin itchy" and "sleepy;" and increased "feel drug effect" and drug-liking ratings. Morphine had some subjective effects of a magnitude similar to those of an equianalgesic dose of butorphanol (2 mg) (e.g., "strength of drug effect," "sedated," "heavy or sluggish feeling" and "high"). However, other effects of morphine were lesser in magnitude (e.g., "coasting or spaced out," "drunken" and "lightheaded") than those of butorphanol. Also, morphine did not affect a number of ratings that were affected by butorphanol (e.g., "confused," "dreamy," "stimulated," "difficulty concentrating," "floating" or "sweating"). The psychomotor impairing effects of butorphanol, as measured by the Maddox Wing test, an eye-hand coordination test, and the Digit Symbol Substitution Test, were dose related; in contrast, morphine had no effect on psychomotor functioning. Both butorphanol and morphine induced miosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Succinylcholine-induced cardiac arrest in children with undiagnosed myopathy.

Two paediatric cases are reported in which unexpected, life-threatening arrhythmias occurred. Routine induction of general anaesthesia with thiopentone, 5 mg.kg-1, in one and with halothane in the other, and succinylcholine 1.25-1.5 mg.kg-1 i.v. was followed by the development of wide complex tachyarrhythmia with hypotension in the first case and asystole in the second case despite pre-treatment with atropine in both cases. The first patient was resuscitated with tracheal intubation, 100% oxygen, manual ventilation and intravenous lidocaine and bicarbonate. The second patient required intubation, manual ventilation, 12 min of CPR and i.v. calcium, epinephrine and bicarbonate, as well as DC counter shock. Neither patient received dantrolene. Early recovery in both patients was uneventful with no neurological sequelae. Subsequent investigations revealed the presence of a dystrophin-deficient muscular dystrophy, Duchenne muscular dystrophy and Becker muscular dystrophy respectively, previously unsuspected, in both patients. The aetiology of the observed arrhythmias was presumably hyperkalaemia, secondary to succinylcholine-induced rhabdomyolysis. It is suggested that when faced with sudden, life-threatening arrhythmias following succinylcholine at induction of anaesthesia for paediatric patients, clinicians should include occult myopathy in the differential diagnosis, and thus consider the aggressive management of hyperkalaemia in addition to basic resuscitative efforts.

A dose-response analysis of the subjective, psychomotor and physiological effects of intravenous morphine in healthy volunteers.

The purpose of this study was to characterize the subjective, psychomotor and physiological effects of morphine in healthy volunteers. Subjects (10 males and 2 females) without histories of opiate dependence were injected in an antecubetal vein with 0, 2.5, 5.0 or 10 mg/70 kg of morphine, by using a randomized, double-blind, cross-over design. Subjective effects, psychomotor performance and physiological measures were assessed immediately before the injection and for up to 5 hr afterward. Morphine increased the Pentobarbital-Chlorpromazine-Alcohol Group, Amphetamine, the Lysergic Acid Diethylamide and the Morphine-Benzedrine Group scores and decreased Benzedrine Group scores on the Addiction Research Center Inventory. Increased visual analog scale ratings of "stimulated," "high," "sedated," "coasting or spaced out" and "drunken" were also obtained. On an opiate adjective checklist, subjects reported increased ratings of "flushing," "dry mouth" and "tingling." Drug liking was not significantly altered by morphine, but there was substantial intersubject variability with this measure. Some aspects of psychomotor performance (reaction time, Digit Symbol Substitution Test and Maddox Wing) were impaired by morphine; however, eye-hand coordination was not. Miosis was induced by morphine. Most effects of morphine were dose-related, some effects peaked soon after morphine injection (e.g., increased stimulated and high ratings) and dissipated gradually, whereas other effects did not peak until later into the session (sedation or exophoria). Our results are fairly consistent with other studies examining morphine effects in healthy volunteers, and also indicate that the profile of morphine effects differ between healthy volunteers and those with a history of opiate dependence.

Quantitative analysis of pollination diallels of two Australian species of Pandorea (Bignoniaceae).

The genus Pandorea, family Bignoniaceae, occurs naturally in Australia. Pandorea pandorana and P. jasminoides were used in intraspecific diallel crosses in order to test for the presence of self-incompatibility and the effect of genotype. Both species were found to be highly self-incompatible. Only 2 out of 353 (0.6%) selfpollinations compared to 337 out of 485 (69.5%) of outcross-pollinations of P. pandorana set fruit. Similarly, for P. jasminoides, 4 out of 235 (1.7%) self-pollinations and 175 out of 296 (59.1%) of outcross pollinations set fruit. Both reciprocal and genotype effects were found in P. pandorana. Fruit-set differences occurred between two different genotypes of P. jasminoides, but reciprocal effects were not found. Data were analysed using generalized linear models with a logit-link function assuming a binomial error distribution. The relative merits of the various models are discussed.

The influence of dwarfing interstocks on the distribution and metabolism of xylem-applied [h]gibberellin a(4) in apple.

The influence of an interstock of the dwarfing cultivar M9 and the nondwarfing cultivar MM115 on the distribution and metabolism of labeled gibberellic acid A(4) ([(3)H]GA(4)) of high specific radioactivity (5.18 x 10(10) becquerel per millimole) applied to the xylem of the rootstock in grafted apple (Malus x domestica Borkh.) trees was compared. Free [(3)H] GA-like metabolites of [(3)H]GA(4), including putative GA(1), GA(2), GA(3), and GA(34), as well as various (3)H-putative GA glucosyl conjugates were detected in stem segments from both cultivars. M9 interstocks reduced the total uptake of [(3)H]GA(4) and decreased the proportion of (3)H metabolites transported to the shoots and leaves of scions. The M9 interstock tissue and adjacent rootstock and scion tissue retained a much greater amount and a higher proportion of the label than did comparable tissue of the nondwarfing MM115 interstock. In addition, the amount and proportion of free [(3)H]GAs was higher, and the proportion of putative [(3)H]GA glucosyl conjugates lower, in M9 interstocks compared to MM115. These effects of the dwarfing interstock on GA distribution and metabolism indicate a significant role for GAs in any satisfactory explanation of the dwarfing mechanism in apple.

High-frequency oscillation compared with standard ventilation in pulmonary injury model.

Hemorrhagic pulmonary edema was induced by intra-atrial infusion of 0.04--0.1 ml/kg of oleic acid into six anesthetized dogs. Gas exchange and cardiac outputs were then compared at identical mean airway pressures during randomized ventilation with either a volume-cycled ventilator with positive end-expiratory pressure (conventional positive-pressure ventilation, tidal volume 16--21 ml/kg, frequency 15--20 cycles/min) or a variable volume piston pump operating at 15 Hz (high-frequency oscillation). The fractional inspired oxygen concentration was maintained at 0.5 throughout. During 17 data sets matched for intratracheal mean airway pressures over a range of 7.5--27 cmH2O, measurements of systemic arterial pressure, arterial blood gas tensions, thermodilution cardiac outputs, and pulmonary arterial and capillary wedge pressures were identical (P less than 0.05) during ventilation with conventional positive-pressure ventilation and high-frequency oscillation. With both forms of ventilation, arterial oxygen tension progressively improved as mean airway pressure increased. In a shunt model of acute lung injury we were unable to show significant differences in oxygenation or cardiac output when high-frequency oscillation was compared with conventional positive-pressure ventilation with positive end-expiratory pressure at equivalent mean airway pressures.

Vagotomy reverses apnea induced by high-frequency oscillatory ventilation.

Apnea has been observed in both animals and patients during high-frequency oscillatory ventilation. The effects of vagotomy were studied during periods of oscillator-induced apnea in 11 pentobarbital-anesthetized dogs. The animals were intubated and breathing spontaneously. An arterial cannula was inserted for monitoring blood pressure and blood gases. Intratracheal airway pressure was measured, and respiratory activity was assessed using either an intrapleural catheter or esophageal balloon. The dogs then underwent high-frequency ventilation at 15 Hz. Apnea was induced by appropriate selection of volume displacement of the piston pump and the distal airway pressure in eucapnic animals. Segments of right and left vagus nerves were exposed in the neck, bathed in local anesthetic, and transected. Spontaneous ventilation resumed immediately in nine animals and could not be suppressed at the same CO2 partial pressure despite continuation of oscillation. We conclude that the apnea observed during high-frequency ventilation is mediated by active vagal inhibition of central respiratory activity and is usually reversed by vagotomy.

Treatment of RDS by high-frequency oscillatory ventilation: a preliminary report.

The feasibility of high-frequency oscillatory ventilation was investigated in eight neonates with severe RDS. Low-volume, high-frequency flow oscillations were generated by a piston pump and delivered through standard endotracheal tubes. Oscillatory frequencies ranged from 8 to 20 Hz and mean airway pressure from 9 to 20 cm H2O. Heart rate, airway pressures, and arterial blood gases and blood pressure were monitored during both continuous positive pressure ventilation and HFO. During HFO mean PaCO2 was 44.0 +/- 4.8 mm Hg. During CPPV immediately prior to oscillation an FIO2 of 0.66 +/- 0.15 resulted in a PaO2 of 59.6 +/- 17.0 mm Hg. Oxygenation improved during HFO such that a mean FIO2 of only 0.41 +/- 0.11 was needed for similar oxygenation. Improvements in oxygenation correlated directly with increases in mean airway pressure. Based on an animal model the phasic pressure swings during HFO are estimated to be 5 to 7 cm H2O in the trachea, much less than conventional ventilation. We conclude that HFO shows great promise in the support of gas exchange in infants with RDS. The use of small phasic volume and pressure swings should minimize pulmonary barotrauma. HFO should also permit the use of lower inspired oxygen fractions.

Ventilation by high-frequency oscillation.

The effect of applying a high-frequency small-volume sinusoidal oscillation at the airway was investigated in anesthetized apneic beagle dogs (mean wt 11 kg, mean VDphys 6.6 +/- 0.6 ml/kg). Oscillations generated by a piston in a cylinder were transmitter to the lungs through an uncuffed endotracheal tube (4.5 mm ID, 6.0 mm OD), which allowed a substantial leak back through the vocal cords. A bias flow of fresh gas presented inspired air to the midtracheal level. The minimum distal airway pressure (measured at the end of the endotracheal tube) was maintained between 0 and 2 cmH2O. Peak airway pressures were 4-8 cmH2O. The optimal frequency for CO2 elimination was 15 Hz. Using volumes of 1.9 ml/kg (range 1.7-2.3) at this frequency the mean PaCO2 was 33.1 +/- 0.5 Torr. In four dogs breathing 100% O2 the PaO2 was 594 +/- 9 Torr during spontaneous ventilation and 580 +/- 9 Torr after 5 h of uninterrupted oscillation. In four experiments using room air the PaO2 was 95 +/- 5 Torr during spontaneous respiration and 106 +/- 1 Torr after 5 h of oscillation. In an additional seven studies there was no difference in mean cardiac output between oscillation and conventional mechanical ventilation. This study demonstrates that high-frequency small-volume oscillations can maintain gas exchange for many hours presumably by markedly enhancing the diffusivity of gases in the lung.