Sleep-disordered breathing: effects on brain structure and function

Abstract

Sleep-disordered breathing is accompanied by neural injury that affects a wide range of physiological systems which include processes for sensing chemoreception and airflow, driving respiratory musculature, timing circuitry for coordination of breathing patterning, and integration of blood pressure mechanisms with respiration. The damage also occurs in regions mediating emotion and mood, as well as areas regulating memory and cognitive functioning, and appears in structures that serve significant glycemic control processes. The injured structures include brain areas involved in hormone release and action of major neurotransmitters, including those playing a role in depression. The injury is reflected in a range of structural magnetic resonance procedures, and also appears as functional distortions of evoked activity in brain areas mediating vital autonomic and breathing functions. The damage is preferentially unilateral, and includes axonal projections; the asymmetry of the injury poses unique concerns for sympathetic discharge and potential consequences for arrhythmia. Sleep-disordered breathing should be viewed as a condition that includes central nervous system injury and impaired function; the processes underlying injury remain unclear.

Keywords: Autonomic; Congenital central hypoventilation; Dyspnea; Hypoxia; Magnetic resonance imaging; Neural injury; Obstructive sleep apnea.

Figure 1

Decreased mean diffusivity, an index of injury in A, the dorsal medulla, B, right ventral medulla, C, ventrolateral medulla, D, posterior insula, and E, coronal view, cerebellar cortex in 23 OSA subjects vs 23 controls (from Kumar et al., 2012).

Figure 2

Fractional anisotropy (FA) measures in 3 OSA vs 3 control subjects showing injury in the cerebellum (A-1), midbrain (A-2), and hypothalamus (A-3), midline raphe projecting to the cerebellum (B-4), and insula cortex (B-5)

Figure 3

Functional MRI signals to three Valsalva challenges (shaded areas) in the insular cortices and fastigial deep nuclei of the cerebellum; time 0 represents onset of first challenge (from Henderson et al., 2003). Asterisks indicate significant differences on curves. SI = Signal Intensity.

Figure 4

Exaggerated and asymmetric responses in left and right cerebellar Crus II areas to the Valsalva maneuver. Controls, n=62, OSA, n=43. The patterns (mean +− SEM) differ in both the challenge and recovery periods. Asterisks = significant differences, repeated-measures ANOVA.

Figure 5

Tracking of pontocerebellar fibers through comparable regions of interest in one Control (A) and one OSA (B) subject; fiber numbers are unilaterally diminished on the left side in the OSA subject.

Figure 6

Decreased fractional anisotropy values, showing loss of axonal integrity in the anterior cingulate cortex (ACC), internal capsule (IC), portions of the anterior corpus callosum (CC), and the prefrontal cortex (PFC; the anterior insula (AI) is also affected). (From Macey et al., 2008).

Figure 7

Damage to the hippocampus (A) using surface morphometry techniques; blue areas show no change, colored areas, loss of tissue; mammillary bodies (MB) in one control (B) and one OSA subject (C); scatterplot of left and right combined mammillary body volumes in 43 OSA and 66 control subjects (D). (From Kumar et al., 2008a)