Brain activation changes before and after PAP treatment in obstructive sleep apnea

Abstract

Study objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cognitive and functional deficits, most of which are corrected after positive airway pressure (PAP) treatment. Previous studies investigating the neural underpinnings of OSAS failed to provide consistent results both on the cerebral substrates underlying cognitive deficits and on the effect of treatment on these anomalies. The aims of the study were a) to investigate whether never-treated OSA patients demonstrated differences in brain activation compared to healthy controls during a cognitive task; and b) to investigate whether any improvements in cognitive functioning found in OSA patients after treatment reflected a change in the underlying cerebral activity.

Design: OSA patients and healthy controls underwent functional magnetic resonance imaging (fMRI) scanning. They were compared on performance and brain activation during a 2-back working-memory task. Patients were also re-evaluated after 3 months treatment with PAP. Cognitive functions were evaluated using neurocognitive tests. Sleepiness (ESS), mood (Beck Depression Inventory) and, quality-of-life (SF-36) were also assessed.

Setting: The Sleep Disorders Center and CERMAC at the Vita-Salute San Raffaele University.

Patients or participants: 17 OSA patients and 15 age- and education-matched healthy controls.

Interventions: PAP treatment for 3 months.

Measurements and results: Compared to controls, never-treated OSA patients showed increased activations in the left frontal cortex, medial precuneus, and hippocampus, and decreased activations in the caudal pons. OSA patients showed decreases in activation with treatment in the left inferior frontal gyrus and anterior cingulate cortex, and bilaterally in the hippocampus. Most neurocognitive domains, impaired at baseline, showed significant improvement after treatment.

Conclusions: OSA patients showed an overrecruitment of brain regions compared to controls, in the presence of the same level of performance on a working-memory task. Decreases of activation in prefrontal and hippocampal structures were observed after treatment in comparison to baseline. These findings may reflect a neural compensation mechanism in never-treated patients, which is reduced by effective treatment.

Figures

Figure 1

Experimental design. From top to bottom, a schematic depiction of the experimental design is shown. The study was composed of 6 functional runs, each lasting 4 m 47 s (top). The first run, in yellow, is enlarged below, to highlight its structure. Every run included 2 blocked repetitions of each task (27 s) in a pseudo-random order, separated by a rest period (fixation of a white cross; 16 s) (middle; the 3 tasks are depicted in blue, red and green colors). The colored lines link highlighted tasks with a graphical description of the sequence of stimuli in each of them (bottom). Each sequence included 9 letters, 3 of which (33%, indicated by an asterisk at the right of the corresponding panel) were “targets.” As shown in the inferior-most part of the figure, each letter within the sequence was shown for 0.5 s, and was separated by the onset of the next one by a black screen lasting 2.5 s.

Figure 2

Common parametric effects of WM load in healthy controls and pretreatment OSA patients. From top to bottom, the regions showing a significant linear increase of cerebral activation related to WM load on cerebral activity in healthy controls (a), pretreatment OSA patients (b), and in both groups (Conjunction analysis; c) are shown (P

Figure 3

Common parametric effects of WM load in pretreatment and posttreatment OSA patients. From top to bottom, the regions showing a significant linear increase of cerebral activation related to WM load in pretreatment OSA patients (a), posttreatment OSA patients (b), and in both groups (Conjunction analysis; c) are shown (P

Figure 4

Differential parametric effects of WM load in healthy controls, pretreatment OSA patients and posttreatment OSA patients. From top to bottom, the regions showing significantly stronger parametric effects of WM load on cerebral activity (i.e., increase) in pretreatment OSA patients vs. controls within (a) and outside (b) those commonly activated in the 2 groups; the areas that were more strongly activated in controls than pretreatment OSA patients, outside those highlighted by their Conjunction (c), and those that were more strongly activated in pretreatment than posttreatment OSA patients (d). Only for graphical purposes, activations are shown at an uncorrected threshold of P < 0.005. Activations were superimposed onto 3D-renderings of the MNI template and representative slices from the same brain.

Figure 5

Differential parametric effects of WM load in healthy controls and posttreatment OSA patients. From top to bottom, the regions showing significantly stronger parametric effects of WM-load on cerebral activity (i.e., increase) in posttreatment OSA patients vs. controls (a) and the regions that were more strongly activated in controls than posttreatment OSA patients (b), outside those highlighted by their Conjunction. Only for graphical purposes, activations are shown at an uncorrected threshold of P < 0.005. Activations were superimposed onto 3D-renderings of the MNI template and representative slices from the same brain.

Figure 6

Reduced right lateral prefrontal activation in both pre- and posttreatment OSA patients compared to healthy controls. Top: significantly reduced activity in the right lateral prefrontal cortex of OSA patients, before and after treatment, compared with healthy controls [P