Tinnitus: at a crossroad between phantom perception and sleep

Abstract

Sensory disconnection from the environment is a hallmark of sleep and is crucial for sleep maintenance. It remains unclear, however, whether internally generated percepts-phantom percepts-may overcome such disconnection and, in turn, how sleep and its effect on sensory processing and brain plasticity may affect the function of the specific neural networks underlying such phenomena. A major hurdle in addressing this relationship is the methodological difficulty to study sensory phantoms, due to their subjective nature and lack of control over the parameters or neural activity underlying that percept. Here, we explore the most prevalent phantom percept, subjective tinnitus-or tinnitus for short-as a model to investigate this. Tinnitus is the permanent perception of a sound with no identifiable corresponding acoustic source. This review offers a novel perspective on the functional interaction between brain activity across the sleep-wake cycle and tinnitus. We discuss characteristic features of brain activity during tinnitus in the awake and the sleeping brain and explore its effect on sleep functions and homeostasis. We ask whether local changes in cortical activity in tinnitus may overcome sensory disconnection and prevent the occurrence of global restorative sleep and, in turn, how accumulating sleep pressure may temporarily alleviate the persistence of a phantom sound. Beyond an acute interaction between sleep and neural activity, we discuss how the effects of sleep on brain plasticity may contribute to aberrant neural circuit activity and promote tinnitus consolidation. Tinnitus represents a unique window into understanding the role of sleep in sensory processing. Clarification of the underlying relationship may offer novel insights into therapeutic interventions in tinnitus management.

Keywords: neural plasticity; phantom percepts; sleep; spontaneous brain activity; tinnitus.

Graphical Abstract

Figure 1

Topographic overlap of brain areas involved in tinnitus and NREM sleep. (A) Central brain regions where functional changes have been described in tinnitus during wakefulness, as depicted by the inlet showing exemplary wake EEG (figure adapted from). (B) Hubs and trajectories of SWA (as depicted by the inlet) during NREM sleep. Under high sleep pressure, NREM SWA is most pronounced in frontal areas, with spontaneous slow waves also originating in the INS and CG. While most SWA is local, it can propagate over large distances, mostly from medial prefrontal cortex to the medial temporal lobe or hippocampus and is therefore present in most regions that show functional changes in tinnitus. (C) Graphical depiction of tinnitus as ‘local wakefulness’ in the sleeping brain. If tinnitus-related activity persists during sleep, it may locally interfere with the expression of SWA in the affected areas, resulting in local wakefulness. This, in turn, may hinder the brain from entering global, restorative sleep. ACC, anterior cingulate cortex; AMY, amygdala; A1 primary auditory cortex; CG, cingulate gyrus; dlPFC, dorsolateral prefrontal cortex; EEG, electroencephalogram; INS, insula; PHC, parahippocampus; vmPFC, ventromedial prefrontal cortex.

Figure 2

Interaction between tinnitus and sleep. (A) Proposed time course of tinnitus modulation during sleep. When homeostatic sleep pressure is high, global SWA can override local aberrant activity and may reduce the impact of tinnitus-related brain activity. As time asleep increases, sleep pressure dissipates and the magnitude and synchrony of SWA decreases, allowing aberrant brain activity to interfere with and eventually disrupt overt sleep. (B) Mechanisms for the interaction between tinnitus and sleep shown in (A). During NREM sleep under high sleep pressure (right hand side) global activity could supress local deviations in brain activity present in tinnitus via: (i) the intrinsic cellular drive to enter an ‘on-off’ firing pattern, which is further promoted by (ii) entrainment with local and global cortical SWA, which may disrupt local tinnitus-related activity and (iii) sensory decoupling during sleep, which may reduce the contribution of tinnitus-related activity in the peripheral auditory system to the perception of tinnitus. During wakefulness under low sleep pressure (left hand side), the drive for SWA is minimal and signal propagation unhindered, which may ultimately promote tinnitus saliency.

Figure 3

Sleep-mediated plasticity may contribute to tinnitus development. Following a tinnitus trigger (such as noise overexposure), neural plasticity is driving the development of tinnitus towards a brain-wide network representation as highlighted by central brain areas demonstrating altered connectivity or activity in tinnitus. This includes changes on the level of synaptic connectivity, cortical map reorganization (as depicted by a change in receptive field organization, heat maps adapted from) and systems-level plasticity affecting global connectivity—all processes directly affected or consolidated by the sleep process. The formation of persistent tinnitus may be fundamentally driven by sleep-dependent mechanisms.