Global and Regional Brain Non-Gaussian Diffusion Changes in Newly Diagnosed Patients with Obstructive Sleep Apnea

Tummala, Sudhakar; Palomares, Jose A.; Kang, Daniel W.; Park, Bumhee; Woo, Mary A.; Harper, Ronald M.; Kumar, Rajesh

doi:10.5665/sleep.5316

Cited by 22 publications

(22 citation statements)

References 34 publications

(37 reference statements)

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“…People with OSA show altered organization of axonal tracts, reflected as higher diffusion kurtosis (Tummala et al, 2016). This measure is sensitive to various structural patterns, but in the context of the sleep disorder, the increase in kurtosis likely reflects less coherent axonal tracts, i.e., either smaller or more damaged tracts combined, or more crossing fibers in a region compared with healthy people (Jensen et al., 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The midbrain is the recipient of projections from more-rostral and more-caudal sites that are also damaged in the syndrome, and serve essential timing and modulating influences on those descending and ascending projections. Among the damaged rostral sites projecting to the midbrain, the insular and ventromedial frontal cortices (Macey et al, 2008; Yaouhi et al, 2009; Joo et al, 2013; Kumar et al, 2014; Tummala et al., 2016) exert influences on cardiovascular and breathing systems; the midbrain contains many nuclei with major cardiovascular and breathing modulation and timing roles. While the final common pathways for outflow to upper airway and diaphragmatic respiratory musculature and for sympathetic and parasympathetic outflow to the cardiovascular system lie within the medulla, many modulatory systems, including those of the midbrain, affect those outflows (Davis et al., 1996; Subramanian, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…CBF is decreased in the right midbrain of OSA subjects (Yadav et al, 2013), which may reflect lower perfusion demand, perhaps from an altered functional state (for example, lower tonic activity), or impaired cerebral perfusion. Structural changes consistent with inflammatory or glial changes, namely diffusion decreases and volume increases, appear in the hypothalamus in OSA (Lundblad et al, 2014; Tummala et al, 2016), which projects heavily to the midbrain (Sakuma and Tada, 1984; Thompson and Swanson, 1998). The combined data suggest that the midbrain is compromised in OSA, potentially interfering with regulatory roles for cardiovascular and breathing control, as well as other physiological functions in the disorder.…”

Section: Introductionmentioning

confidence: 99%

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Obstructive sleep apnea is associated with altered midbrain chemical concentrations

et al. 2017

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Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age ± SD:54.6 ± 10.6 years; AHI:35.0 ± 19.4; SAO2 min:83 ± 7%) and 26 healthy control (50.7 ± 8.5 years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24 ± 0.43, Control:1.47 ± 0.41; p = 0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23 ± 0.57, Control:0.98 ± 0.33; p = 0.03), ascorbate (Asc; OSA:0.56 ± 0.28, Control:0.42 ± 0.20; (50.7 ± 8.5 years; p = 0.03), and myo-inositol (mI; OSA:0.96 ± 0.48, Control:0.72 ± 0.35; p = 0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Obstructive sleep apnea is associated with altered midbrain chemical concentrations

et al. 2017

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“…A subset of OSA and control subjects used here were part of previously-published data examining different research questions. 15,16 All control subjects were without any medication that might change brain tissue, were compatible with the MRI scanner environment (i.e., no metallic implants or iron-based tattoos, and body weights within limits of the scanner), and were recruited through the University of California at Los Angeles (UCLA) campus and West Los Angeles Area. OSA subjects were recruited from the Sleep Disorders Laboratory at the UCLA Medical Center, newly-diagnosed via overnight polysomnography with at least moderate severity (apnea-hypopnea-index ≥ 15; i.e 15 or more apneas or hypopneas were recorded per hour of sleep) and were treatment-naïve for the breathing issue.…”

Section: Methodsmentioning

confidence: 99%

Non-Gaussian Diffusion Imaging Shows Brain Myelin and Axonal Changes in Obstructive Sleep Apnea

Tummala¹,

Roy²,

Vig³

et al. 2017

Journal of Computer Assisted Tomography

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Objective Obstructive sleep apnea (OSA) is accompanied by brain changes in areas that regulate autonomic, cognitive, and mood functions, which were initially examined by Gaussian-based diffusion tensor imaging measures, but can be better assessed with non-Gaussian measures. We aimed to evaluate axonal and myelin changes in OSA using axial (AK) and radial kurtosis (RK) measures. Materials and Methods We acquired DKI data from 22 OSA and 26 controls; AK and RK maps were calculated, normalized, smoothed, and compared between groups using ANCOVA. Results Increased AK, indicating axonal changes, emerged in the insula, hippocampus, amygdala, dorsolateral-pons, and cerebellar peduncles, and showed more axonal injury over previously-identified damage. Higher RK, showing myelin changes, appeared in the hippocampus, amygdala, temporal and frontal lobes, insula, midline-pons, and cerebellar peduncles, and showed more wide-spread myelin damage over previously-identified injury. Conclusion AK and RK measures showed wide-spread changes over Gaussian-based techniques, suggesting more-sensitive nature of kurtoses to injury.

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“…Resting state neuroimaging studies have consistently pointed to disruptions in the default mode network and frontoparietal cognitive control network in sleep apnea patients (for review, see 103). In a related approach, diffusion imaging studies reveal widespread alterations in white matter integrity in sleep apnea patients relative to controls, particularly in regions implicated in sleep/wake control and cognitive functioning (bilateral prefrontal cortex, hippocampus, amygdala, insula, cerebellum, medulla, pons, basal forebrain, basal ganglia, right posterior parietal lobe, and right occipital cortex)[104]. Greater apnea-hypopnea index [105], via acute hypoxic injury [106, 107], worsens the negative effects of sleep apnea on white matter integrity.…”

Section: Neuroimaging Studies In Patients With Sleep Disordered Breatmentioning

confidence: 99%

Do Older Adults Need Sleep? A Review of Neuroimaging, Sleep, and Aging Studies

Scullin

2017

Curr Sleep Medicine Rep

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Purpose of Review Sleep habits, sleep physiology, and sleep disorders change with increasing age. However, there is a longstanding debate regarding whether older adults need sleep to maintain health and daily functioning (reduced-sleep-need view). An alternative possibility is that all older adults need sleep, but that many older adults have lost the ability to obtain restorative sleep (reduced-sleep-ability view). Prior research using behavioral and polysomnography outcomes has not definitively disentangled the reduced-sleep-need and reduced-sleep-ability views. Therefore, this review examines the neuroimaging literature to determine whether age-related changes in sleep cause—or are caused by—age-related changes in brain structure, function, and pathology. Recent Findings In middle-aged and older adults, poorer sleep quality, greater nighttime hypoxia, and shorter sleep duration related to cortical thinning in frontal regions implicated in slow wave generation, in frontoparietal networks implicated in cognitive control, and in hippocampal regions implicated in memory consolidation. Furthermore, poor sleep quality was associated with higher amyloid burden and decreased connectivity in the default mode network, a network that is disrupted in the pathway to Alzheimer’s disease. Summary All adults need sleep, but cortical thinning and amyloidal deposition with advancing age may weaken the brain’s ability to produce restorative sleep. Therefore, sleep in older adults may not always support identical functions for physical, mental, and cognitive health as in young adults.

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Global and Regional Brain Non-Gaussian Diffusion Changes in Newly Diagnosed Patients with Obstructive Sleep Apnea

Cited by 22 publications

References 34 publications

Obstructive sleep apnea is associated with altered midbrain chemical concentrations

Obstructive sleep apnea is associated with altered midbrain chemical concentrations

Non-Gaussian Diffusion Imaging Shows Brain Myelin and Axonal Changes in Obstructive Sleep Apnea

Do Older Adults Need Sleep? A Review of Neuroimaging, Sleep, and Aging Studies

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