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Obstructive sleep apnea (OSA) patients show impaired autonomic regulation, perhaps related to functional reorganization of the insula, which in healthy individuals shows sex-specific anterior and right dominance during sympathetic activation. We examined insular organization of responses to a Valsalva maneuver in OSA with functional magnetic resonance imaging (fMRI). We studied 43 newly diagnosed OSA (age mean ± SD: 46.8 ± 8.7 years; apnea-hypopnea index (AHI) ± SD: 32.1 ± 20.1 events/hour; 34 males) and 63 healthy (47.2 ± 8.8 years; 40 males) participants. Participants performed four 18-second Valsalva maneuvers (1-minute intervals, pressure ≥ 30 mmHg) during scanning. fMRI time trends from five insular gyri-anterior short (ASG); mid short (MSG); posterior short (PSG); anterior long (ALG); and posterior long (PLG)-were assessed for within-group responses and between-group differences with repeated measures ANOVA (p < 0.05); age and resting heart rate (HR) influences were also assessed. Right and anterior fMRI signal dominance appeared in OSA and controls, with no between-group differences. Separation by sex revealed group differences. Left ASG anterior signal dominance was lower in OSA versus control males. Left ASG and ALG anterior dominance was higher in OSA versus control females. In all right gyri, only OSA females showed greater anterior dominance than controls. Right dominance was apparent in PSG and ALG in all groups; females showed right dominance in MSG and PLG. OSA males did not show PLG right dominance. Responses were influenced substantially by HR but modestly by age. Anterior and right insular fMRI dominance appears similar in OSA versus control participants during the sympathetic phase of the Valsalva maneuver. OSA and control similarities were present in just males, but not necessarily females, which may reflect sex-specific neural injury.

Study objectivesChildren with sleep-disordered breathing (SDB) exhibit behavioral, cognitive, and autonomic deficits, suggestive of neural injury. We assessed whether the tissue alterations resulted from acute or chronic processes, and whether alterations correlated with disease severity.MethodsBrain tissue integrity was examined with mean diffusivity (MD) (3.0 T scanner) in 20 nonsnoring controls (mean age ± SEM, 12.2 ± 0.6 years; 10 males) and 18 children with SDB (12.3 ± 0.7 years; 11 males). Sleep, cognitive, and behavioral measures were compared between groups following overnight polysomnography using Student's t tests. Whole-brain MD maps were realigned and averaged, normalized, smoothed, and compared between groups using ANCOVA (covariates: age, gender, and socioeconomic status). Partial correlations were calculated between whole-brain smoothed MD maps and obstructive apnea-hypopnea indices (OAHIs).ResultsAge, gender, and sleep variables did not differ between groups. The SDB group showed higher OAHIs, body mass indices, and systolic blood pressure. Significantly reduced MD values (acute changes) appeared in the hippocampus, insula, thalamus, temporal and occipital cortices, and cerebellum, but were increased (chronic damage) in the frontal and prefrontal cortices in the SDB group over controls. Both positive and negative correlations appeared with extent of tissue changes and disease severity. Externalizing and Total Problem Behaviors were significantly higher in children with SDB. Verbal, performance, and total IQ scores trended lower, and behavioral scores trended higher.ConclusionsPediatric SDB is accompanied by predominantly acute brain changes in areas that regulate autonomic, cognitive, and mood functions, and chronic changes in frontal cortices essential for behavioral control. Interventions need to be keyed to address acute vs chronic injury.

Study objectivesObstructive sleep apnea (OSA) is accompanied by tissue injury to the insular cortices, areas that regulate autonomic pain, dyspnea, and mood, all of which are affected in the syndrome. Presumably, the dysregulation of insular-related functions are mediated by aberrant functional connections with other brain regions; however, the integrity of the functional connectivity (FC) to other sites is undescribed. Our aim was to examine resting-state FC of the insular cortices to other brain areas in OSA, relative to control subjects.MethodsWe collected resting-state functional magnetic resonance imaging (MRI) data from 67 newly diagnosed, treatment-naïve OSA and 75 control subjects using a 3.0-Tesla MRI scanner. After standard processing, data were analyzed for the left and right insular FC.ResultsOSA subjects showed complex aberrant insular FC to several brain regions, including frontal, parietal, cingulate, temporal, limbic, basal ganglia, thalamus, occipital, cerebellar, and brainstem regions. Areas of altered FC in OSA showed linear relationships with magnitudes of sleep related and neuropsychologic-related variables, whereas control subjects showed no such relationships with those measures.ConclusionsBrain functional connections from insular sites to other brain regions in OSA subjects represent abnormal autonomic, affective, sensorimotor, and cognitive control networks that may affect both impaired parasympathetic and sympathetic interactions, as well as abnormal sensorimotor integration, affected in the condition. The functional changes likely result from the previously reported structural changes in OSA subjects, as demonstrated by diverse neuroimaging studies.

Study objectivesObstructive sleep apnea (OSA) patients show brain structural injury and functional deficits in autonomic, affective, and cognitive regulatory sites, as revealed by mean diffusivity (MD) and other imaging procedures. The time course and nature of gray and white matter injury can be revealed in more detail with mean kurtosis (MK) procedures, which can differentiate acute from chronic injury, and better show extent of damage over MD procedures. Our objective was to examine global and regional MK changes in newly diagnosed OSA, relative to control subjects.MethodsTwo diffusion kurtosis image series were collected from 22 recently-diagnosed, treatment-naïve OSA and 26 control subjects using a 3.0-Tesla MRI scanner. MK maps were generated, normalized to a common space, smoothed, and compared voxel-by-voxel between groups using analysis of covariance (covariates; age, sex).ResultsNo age or sex differences appeared, but body mass index, sleep, neuropsychologic, and cognitive scores significantly differed between groups. MK values were significantly increased globally in OSA over controls, and in multiple localized sites, including the basal forebrain, extending to the hypothalamus, hippocampus, thalamus, insular cortices, basal ganglia, limbic regions, cerebellar areas, parietal cortices, ventral temporal lobe, ventrolateral medulla, and midline pons. Multiple sites, including the insular cortices, ventrolateral medulla, and midline pons showed more injury over previously identified damage with MD procedures, with damage often lateralized.ConclusionsGlobal mean kurtosis values are significantly increased in obstructive sleep apnea (OSA), suggesting acute tissue injury, and these changes are principally localized in critical sites mediating deficient functions in the condition. The mechanisms for injury likely include altered perfusion and hypoxemia-induced processes, leading to acute tissue changes in recently diagnosed OSA.

Study objectiveAdults with obstructive sleep apnea (OSA) show significant autonomic and neuropsychologic deficits, which may derive from damage to insular regions that serve those functions. The aim was to assess glial and neuronal status from anterior insular metabolites in OSA versus controls, using proton magnetic resonance spectroscopy (PMRS), and thus to provide insights for neuroprotection against tissue changes, and to reduce injury consequences.DesignCross-sectional study.SettingUniversity-based medical center.ParticipantsThirty-six patients with OSA, 53 controls.InterventionsNone.Measurements and resultsWe performed PMRS in bilateral anterior insulae using a 3.0-Tesla magnetic resonance imaging scanner, calculated N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), myo-inositol/creatine (MI/Cr), and MI/NAA metabolite ratios, and examined daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and neuropsychologic status (Beck Depression Inventory II [BDI-II] and Beck Anxiety Inventory [BAI]). Body mass index, BAI, BDI-II, PSQI, and ESS significantly differed between groups. NAA/ Cr ratios were significantly reduced bilaterally, and left-sided MI/Cr and MI/NAA ratios were increased in OSA over controls. Significant positive correlations emerged between left insular MI/Cr ratios and apnea-hypopnea index values, right insular Cho/Cr ratios and BDI-II and BAI scores, and negative correlations appeared between left insular NAA/Cr ratios and PSQI scores and between right-side MI/Cr ratios and baseline and nadir change in O2 saturation.ConclusionsAdults with obstructive sleep apnea showed bilaterally reduced N-acetylaspartate and left-side increased myo-inositol anterior insular metabolites, indicating neuronal damage and increased glial activation, respectively, which may contribute to abnormal autonomic and neuropsychologic functions in the condition. The activated glial status likely indicates increased inflammatory action that may induce more neuronal injury, and suggests separate approaches for glial and neuronal protection.

Study objectivesPatients with obstructive sleep apnea (OSA) show significant white matter injury; whether that injury represents myelin or axonal damage is unclear. The objective was to examine myelin and axonal changes in patients with newly diagnosed OSA over control subjects.DesignCross-sectional study.SettingUniversity-based medical center.ParticipantsTwenty-three newly-diagnosed, treatment-naïve OSA and 23 age- and sex-matched control subjects.InterventionsNone.Measurements and resultsRadial and axial diffusivity maps, calculated from diffusion tensor imaging data (3.0 Tesla MRI scanner), indicating diffusion perpendicular (myelin status) or parallel (axonal status) to fibers, respectively, were normalized, smoothed, and compared between groups (analysis of covariance; covariate: age). Global brain radial and axial diffusivity values, and global brain volume with myelin and axonal changes were determined, and region-of-interest analyses performed in areas of significant differences between groups based on voxel-based procedures. Global radial and axial diffusivity values were significantly reduced in OSA versus control subjects (radial, P = 0.004; axial, P = 0.019), with radial (myelin) diffusivity reduced more than axial (axonal), and more left-sided reduction for both measures. Localized declines for myelin and axonal measures appeared in the dorsal and ventral medulla, cerebellar cortex and deep nuclei, basal ganglia, hippocampus, amygdala, corpus callosum, insula, cingulate and medial frontal cortices, and other cortical areas (P < 0.005), all regions mediating functions affected in OSA.ConclusionsFiber injury appears in critical medullary respiratory regulatory sites, as well as cognitive and autonomic control areas. Myelin is more affected in newly diagnosed OSA than axons, and primarily on the left side, possibly from the increased myelin sensitivity to hypoxia and asymmetric perfusion.