Acute effects and after-effects of acoustic coordinated reset neuromodulation in patients with chronic subjective tinnitus.
Acute effects and after-effects of acoustic coordinated reset neuromodulation in patients with chronic subjective tinnitus.
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DOI：
10.1016/j.nicl.2017.05.017
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Tass PA
中科院分区：
文献类型：
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作者：
Adamchic I;Toth T;Hauptmann C;Walger M;Langguth B;Klingmann I;Tass PA
慢性主观性耳鸣是一种以中枢听觉系统神经元同步性异常为特征的听觉幻象现象。如计算所示，声学协调重置（CR）神经调节通过下调异常突触连接导致病理同步的长期去同步化。在先前的概念验证研究中，将采用针对主导耳鸣频率定制的刺激音调模式的声学CR神经调节与嘈杂的CR样刺激进行比较，CR版本通过保留耳鸣相关的音调范围并包括频率轴上音调间隔的大量随机变化而显著失谐。两种刺激方案都引起了急性缓解，如在刺激开启条件下用耳鸣响度（VAS-L）和烦恼（VAS-A）的视觉模拟量表评分所测量的（即刺激开始后15分钟），但只有听觉CR神经调节在治疗12周后具有持续的持久治疗效果，如VAS-L所评估的，VAS-A评分和耳鸣问卷（TQ）在刺激关闭条件下（即患者关闭刺激至少2.5小时）。为了了解持久的治疗效果的来源，我们在这里研究是否有不同的电生理效应的听觉CR神经调制振荡的大脑活动相比，嘈杂的CR样刺激下的刺激条件下，立即停止刺激。为此，我们在18例慢性音调性主观性耳鸣患者中使用了单盲、单次应用、交叉设计，并实施了三种不同的16分钟刺激方案：声学CR神经调节、嘈杂的CR样刺激和低频范围（LFR）刺激，作为对照刺激，CR型刺激具有故意失谐的音调和刺激音调的重复率。我们测量了VAS-L和VAS-A评分以及刺激前、刺激中和刺激后的自发EEG活动。在刺激ON条件下，听觉CR神经调节和噪声CR样刺激具有相似的效果：VAS-L和VAS-A评分降低，听觉δ功率降低，听觉α和γ功率增加，无显著差异。相比之下，LFR刺激具有显著较弱的EEG效应，并且在刺激开启条件下没有显著的临床效应。听觉CR神经调制与噪声类CR刺激的区别在于电生理后效。听觉CR神经调节引起听觉皮层区域中δ和γ的最长显著降低和α功率的增加。噪声类CR刺激有较弱的和LFR刺激几乎没有任何电生理后效应。这种质的差异进一步支持了听觉CR神经调节对耳鸣的长期影响是由同步神经活动的特定中断介导的断言。此外，我们的研究结果表明，急性电生理后效可能作为一个标记，以进一步提高deserminizing声音刺激。用脑电图研究专门耳鸣声音治疗的急性效应和急性后效。声音治疗造成持久的，持续的影响会导致明显的急性后遗症。急性脑电后遗效应可作为开发降颤声疗法的标志。
Chronic subjective tinnitus is an auditory phantom phenomenon characterized by abnormal neuronal synchrony in the central auditory system. As shown computationally, acoustic coordinated reset (CR) neuromodulation causes a long-lasting desynchronization of pathological synchrony by downregulating abnormal synaptic connectivity. In a previous proof of concept study acoustic CR neuromodulation, employing stimulation tone patterns tailored to the dominant tinnitus frequency, was compared to noisy CR-like stimulation, a CR version significantly detuned by sparing the tinnitus-related pitch range and including substantial random variability of the tone spacing on the frequency axis. Both stimulation protocols caused an acute relief as measured with visual analogue scale scores for tinnitus loudness (VAS-L) and annoyance (VAS-A) in the stimulation-ON condition (i.e. 15 min after stimulation onset), but only acoustic CR neuromodulation had sustained long-lasting therapeutic effects after 12 weeks of treatment as assessed with VAS-L, VAS-A scores and a tinnitus questionnaire (TQ) in the stimulation-OFF condition (i.e. with patients being off stimulation for at least 2.5 h). To understand the source of the long-lasting therapeutic effects, we here study whether acoustic CR neuromodulation has different electrophysiological effects on oscillatory brain activity as compared to noisy CR-like stimulation under stimulation-ON conditions and immediately after cessation of stimulation. To this end, we used a single-blind, single application, cross over design in 18 patients with chronic tonal subjective tinnitus and administered three different 16-minute stimulation protocols: acoustic CR neuromodulation, noisy CR-like stimulation and low frequency range (LFR) stimulation, a CR type stimulation with deliberately detuned pitch and repetition rate of stimulation tones, as control stimulation. We measured VAS-L and VAS-A scores together with spontaneous EEG activity pre-, during- and post-stimulation. Under stimulation-ON conditions acoustic CR neuromodulation and noisy CR-like stimulation had similar effects: a reduction of VAS-L and VAS-A scores together with a decrease of auditory delta power and an increase of auditory alpha and gamma power, without significant differences. In contrast, LFR stimulation had significantly weaker EEG effects and no significant clinical effects under stimulation-ON conditions. The distinguishing feature between acoustic CR neuromodulation and noisy CR-like stimulation were the electrophysiological after-effects. Acoustic CR neuromodulation caused the longest significant reduction of delta and gamma and increase of alpha power in the auditory cortex region. Noisy CR-like stimulation had weaker and LFR stimulation hardly any electrophysiological after-effects. This qualitative difference further supports the assertion that long-term effects of acoustic CR neuromodulation on tinnitus are mediated by a specific disruption of synchronous neural activity. Furthermore, our results indicate that acute electrophysiological after-effects might serve as a marker to further improve desynchronizing sound stimulation. Acute effects and acute after-effects of dedicated tinnitus sound therapy are studied with EEG. Sound therapy causing long-lasting, sustained effects causes pronounced acute after-effects. Acute EEG after-effects might serve as marker to develop desynchronizing sound therapy.