Järvelä Matti, Kananen Janne, Helakari Heta, Korhonen Vesa, Huotari Niko, Väyrynen Tommi, Hautamäki Katariina, Raitamaa Lauri, Tuunanen Johanna, Kallio Mika, Piispala Johanna, Ansakorpi Hanna, Kiviniemi Vesa
Oulu Functional Neuroimaging, Research unit of Health Sciences and Technology, Faculty of Medicine, Medical Research Center, University of Oulu, Oulu 90014, Finland.
Clinical Neurophysiology, Research unit of Health Sciences and Technology, Faculty of Medicine, Medical Research Center, University of Oulu, Oulu 90014, Finland.
Proc Natl Acad Sci U S A. 2025 Aug 5;122(31):e2501578122. doi: 10.1073/pnas.2501578122. Epub 2025 Aug 1.
Sleep promotes cerebrospinal fluid (CSF) to interstitial fluid (ISF) exchange in the brain facilitated by brain pulsations. Especially brain vasomotion and arterial pulsations modulated by noradrenaline drive the intracranial fluid dynamics. Narcolepsy type 1 (NT1) entails lessened orexinergic output to wake-promoting systems including the noradrenergic locus coeruleus. As arousal state and noradrenergic signaling affect CSF-ISF clearance, we chose patients with NT1 as a human orexin-targeted model of sleep-related pathology bridging the gap between healthy awake and sleep with respect to CSF flow pulsations. We also investigated the sensitivity of magnetic resonance encephalography to detect flow with a phantom model and sought to replicate earlier pulsation findings in sleep. In this case-control study, we used fast functional MRI to map brain pulsations in groups of healthy sleeping controls (n = 13), healthy awake controls (n = 79), and awake NT1 (n = 21) patients. We measured the very low frequency (0.008 to 0.1) and cardiorespiratory frequencies and calculated in each frequency band the coefficient of variation, spectral power, and full band spectral entropy to obtain brain pulsation maps. We uncovered a brain pulsation profile from healthy waking to sleep to a sleep-related pathology NT1 prominently affected in the vascular-related vasomotor and brain arterial pulsations. Our results established how drivers of brain hydrodynamics are affected by a specific loss of key neurotransmitter governing arousal compared to healthy sleep. We also showed with a phantom model that MREG is sensitive to flow-related signal changes and solidified evidence of brain pulsations in the healthy states of sleep and wakefulness.
睡眠促进脑内脑脊液（CSF）与细胞间液（ISF）的交换，这一过程由脑搏动推动。特别是去甲肾上腺素调节的脑血管运动和动脉搏动驱动着颅内液体动力学。1型发作性睡病（NT1）会减少对包括去甲肾上腺素能蓝斑在内的促醒系统的食欲素能输出。由于觉醒状态和去甲肾上腺素能信号传导会影响CSF-ISF清除，我们选择NT1患者作为一种针对食欲素的人类睡眠相关病理模型，该模型在CSF流动搏动方面弥合了健康清醒与睡眠之间的差距。我们还使用体模模型研究了磁共振脑成像检测血流的敏感性，并试图复制早期睡眠中搏动的研究结果。在这项病例对照研究中，我们使用快速功能磁共振成像来绘制健康睡眠对照组（n = 13）、健康清醒对照组（n = 79）和清醒NT1患者组（n = 21）的脑搏动图。我们测量了极低频（0.008至0.1）和心肺频率，并在每个频段计算变异系数、频谱功率和全频段频谱熵，以获得脑搏动图。我们发现了从健康清醒到睡眠再到与睡眠相关的病理状态NT1的脑搏动特征，在与血管相关的血管运动和脑动脉搏动中受到显著影响。我们的结果确定了与健康睡眠相比，脑流体动力学的驱动因素如何受到控制觉醒的关键神经递质的特定缺失的影响。我们还通过体模模型表明，磁共振脑成像对与血流相关的信号变化敏感，并巩固了在健康睡眠和清醒状态下脑搏动的证据。
