Tailoring Human Sleep: selective alteration through Brainstem Arousal Circuit Stimulation
Tailoring Human Sleep: selective alteration through Brainstem Arousal Circuit Stimulation
复制标题
定制人类睡眠：通过脑干唤醒回路刺激进行选择性改变
DOI：
10.1101/2023.01.18.23284688
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Deli A
中科院分区：
文献类型：
--
作者：
Deli A
脑干核团，如脚桥核，向皮层发送激活投射，调节睡眠、觉醒和唤醒水平的状态。使用脑深部电刺激（DBS）对皮层下活动进行手术调制用于疼痛和运动障碍的管理。DBS的脑干唤醒电路在一个状态依赖的方式可以提供一个有吸引力的替代严重耐药性的情况下，嗜睡症和意识障碍，在行为activationisdesired.We想要调查，如果我们可以选择性地诱导觉醒和/或改变睡眠状态，通过DBS的PPN区域（PPNR）。为此，我们在多系统萎缩的刺激初治患者中使用了植入PPNR电极的机会。PPNR活动记录在慢波睡眠（SWS）和安静的觉醒与同步皮层脑电图，以确定在不同的兴奋状态下的脑干振荡模式的差异。在相同睡眠阶段的SWS期间，以两种伽马频率方案（40 Hz和100 Hz）进行PPNR DBS，并且具有可比较的试验前慢波活动水平。我们研究了皮质振荡功率的变化，从刺激前到刺激后的功能连接（连贯性和因果关系）的变化，以及刺激期间DBS频率及其次谐波对皮质振荡的锁相。我们还评估了DBS引起的连通性变化以及SWS和清醒状态之间回路动力学的相应差异。我们通过EEG慢波的相位看到了清晰的PPNR功率调制，在慢波周期的“可兴奋”部分期间，与β功率相比，γ功率显著增加。伽马PPNR DBS诱导向觉醒和REM的过渡，而与基线相比，它缩短了睡眠时间。与100 Hz的PPNR DBS相比，40 Hz刺激方案在减少慢波活动和增加皮质β功率方面更有效。此外，与100 Hz方案相比，40 Hz PPNR DBS的内在皮质节律锁相程度显著更高，锁相存在区域差异，表明这是一种复杂的生物学现象。最后，PPNR DBS诱导的功能连接变化与SWS和觉醒之间的电路动力学差异一致。总的来说，这些结果突出了使用脑干唤醒回路的DBS来促进唤醒和觉醒的可能性，这为使用闭环方法来调节人类的警觉状态以获得治疗益处开辟了新的视角。
Brainstem nuclei, such as the pedunculopontine nucleus, send activating projections to cortex, modulating states of sleep, wakefulness and arousal levels. Surgical modulation of subcortical activity using deep brain stimulation (DBS) is utilised in the management of pain and movement disorders. DBS of brainstem arousal circuits in a state-dependent manner could offer an attractive alternative in severe pharmacoresistant cases of hypersomnia and in disorders of consciousness, where behavioural activation is desired.We wanted to investigate if we can selectively induce wakefulness and/or alter sleep state through DBS of the PPN region (PPNR). To this end, we used the opportunity of implanted PPNR electrodes in stimulation-naïve patients with multiple systems atrophy. PPNR activity was recorded during both slow wave sleep (SWS) and quiet wakefulness with simultaneous cortical EEG, in order to identify differences in brainstem oscillatory patterns during different states of excitability. PPNR DBS in two gamma frequency protocols (40Hz and 100Hz) was delivered during SWS of the same sleep stage and with comparable pre-trial levels of slow wave activity.Additionally, SHAM trials were used as a control where no stimulation was applied. We examined changes in cortical oscillatory power, changes in functional connectivity (coherence and causality) from pre- to post-stimulation and phase-locking of cortical oscillations with DBS frequencies and their sub-harmonics during stimulation. We also evaluated connectivity changes induced by DBS and corresponding differences in circuit dynamics between SWS and wakefulness.Beta and gamma PPNR oscillatory power increased when wake was compared to sleep. We saw clear PPNR power modulation by the phase of EEG slow wave, with significant increase in gamma compared to beta power during the ‘excitable’ part of the slow-wave cycle. Gamma PPNR DBS induced transitions to wakefulness and REM, while it truncated sleep time compared to baseline. The 40Hz stimulation protocol was more efficient in reducing slow wave activity and increasing cortical beta power, compared to PPNR DBS at 100Hz. Furthermore, intrinsic cortical rhythms phase-locked with 40 Hz PPNR DBS to a significantly higher degree compared to the 100Hz protocol, with regional differences in phase-locking, suggesting a complex biological phenomenon. Finally, functional connectivity changes induced by PPNR DBS were consistent with differences in circuit dynamics between SWS and wakefulness. Overall, these results highlight the possibility of using DBS of brainstem arousal circuits to promote arousal and wakefulness, which opens new perspectives for using closed-loop approaches to modulate vigilance states in humans for therapeutic benefit.
登录
查看更多内容
影响因子：
25
作者：
Hayat, Hanna;Marmelshtein, Amit;Krom, Aaron J.;Sela, Yaniv;Tankus, Ariel;Strauss, Ido;Fahoum, Firas;Fried, Itzhak;Nir, Yuval
通讯作者：
Nir, Yuval
影响因子：
4.4
作者：
Vyazovskiy, V;Borbély, AA;Tobler, I
通讯作者：
Tobler, I
睡在开关处。
影响因子：
7.7
作者：
Bouchard M;Lina JM;Gaudreault PO;Lafrenière A;Dubé J;Gosselin N;Carrier J
通讯作者：
Carrier J
DOI：
10.1212/con.0000000000000492
发表时间：
2017-08-01
期刊：
Continuum (Minneapolis, Minn.)
影响因子：
--
作者：
Dauvilliers, Yves;Barateau, Lucie
通讯作者：
Barateau, Lucie
猕猴V1中伽马同步的定量理论。
影响因子：
7.7
作者：
Lowet E;Roberts MJ;Peter A;Gips B;De Weerd P
通讯作者：
De Weerd P