RESUMO
OBJECTIVES: To investigate the efficacy of closed-loop acoustic stimulation (CLAS) during slow-wave sleep (SWS) to enhance slow-wave activity (SWA) and SWS in patients with Alzheimer's disease (AD) across multiple nights and to explore associations between stimulation, participant characteristics, and individuals' SWS response. DESIGN: A 2-week, open-label at-home intervention study utilizing the DREEM2 headband to record sleep data and administer CLAS during SWS. SETTING AND PARTICIPANTS: Fifteen older patients with AD (6 women, mean age: 76.27 [SD = 6.06], mean MOCA-score: 16.07 [SD = 6.94]), living at home with their partner, completed the trial. INTERVENTION: Patients first wore the device for two baseline nights, followed by 14 nights during which the device was programmed to randomly either deliver acoustic stimulations of 50 ms pink noise (± 40 dB) targeted to the slow-wave up-phase during SWS or only mark the wave (sham). RESULTS: On a group level, stimulation significantly enhanced SWA and SWS with consistent SWS enhancement throughout the intervention. However, substantial variability existed in individual responses to stimulation. Individuals received more stimulations on nights with increased SWS compared to baseline than on nights with no change or a decrease. In individuals, having lower baseline SWS correlated with receiving fewer stimulations on average during the intervention. CONCLUSION: CLAS during SWS is a promising nonpharmacological method to enhance SWA and SWS in AD. However, patients with lower baseline SWS received fewer stimulations during the intervention, possibly resulting in less SWS enhancement. Individual variability in response to stimulation underscores the need to address personalized stimulation parameters in future research and therapy development.
RESUMO
The piriform cortex (PCx) is essential for the adaptive processing of olfactory information. Neuromodulatory systems, including those utilizing serotonin, acetylcholine, noradrenaline, and dopamine, innervate and regulate neuronal activity in the PCx. Previous research has demonstrated the importance of acetylcholine, noradrenaline and serotonin in odor learning and memory. In contrast, the role of dopamine in the PCx remains under-explored. Here we examined how dopamine modulates the intrinsic electrical properties of identified classes of neurons in the PCx. We found that dopamine had no consistent effect on the intrinsic electrical properties of two types of glutamatergic neurons (semilunar and superficial pyramidal cells) or three types of GABAergic interneurons (horizontal, neurogliaform and somatastatin-expressing regular-spiking cells). However, dopamine had a striking effect on the intrinsic excitability of the parvalbumin-expressing fast-spiking (FS) class of GABAergic interneuron. Dopamine depolarized the resting potential, increased the input resistance and increased the firing frequency of FS cells. Co-application of dopamine with the D1-class dopamine receptor antagonist SCH 23390 blocked the effects of dopamine modulation on FS cells. Conversely, co-application of dopamine with the D2-class antagonist RS-(±)-sulpiride had no effect on dopamine modulation of these cells. Our results indicate that dopamine binds to D1-class dopamine receptors to increase the intrinsic excitability of FS cells. These findings suggest that dopamine has a highly targeted effect in the PCx and reveal how dopamine may modulate the balance between excitation and inhibition, with consequences for odor processing. In addition, our findings provide clues for understanding why neurodegenerative disorders that modify the dopamine system, such as Parkinson's disease, have a deleterious effect on the sense of smell, and may suggest novel diagnostics for the early detection of such disorders.
