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Article

Neural Mechanisms of Tinnitus  

Adam Hockley and Susan E. Shore

Tinnitus is the perception of sound that is independent from an external stimulus. Despite the word tinnitus being derived from the Latin verb for ring, tinnire, it can present as buzzing, hissing, or clicking. Tinnitus is generated centrally in the auditory pathway; however, the neural mechanisms underlying this generation have been disputed for decades. Although it is well accepted that tinnitus is produced by damage to the auditory system by exposure to loud sounds, the level of damage required and how this damage results in tinnitus are unclear. Neural recordings in the auditory brainstem, midbrain, and forebrain of animals with models of tinnitus have revealed increased spontaneous firing rates, capable of being perceived as a sound. There are many proposed mechanisms of how this increase is produced, including spike-timing-dependent plasticity, homeostatic plasticity, central gain, reduced inhibition, thalamocortical dysrhythmia, and increased inflammation. Animal studies are highly useful for testing these potential mechanisms because the noise damage can be carefully titrated and recordings can be made directly from neural populations of interest. These studies have advanced the field greatly; however, the limitations are that the variety of models for tinnitus induction and quantification are not well standardized, which may explain some of the variability seen across studies. Human studies use patients with tinnitus (but an unknown level of cochlear damage) to probe neural mechanisms of tinnitus. They use noninvasive methods, often recoding gross evoked potentials, oscillations, or imaging brain activity to determine if tinnitus sufferers show altered processing of sounds or silence. These studies have also revealed putative neural mechanisms of tinnitus, such as increased delta- or gamma-band cortical activity, altered Bayesian prediction of incoming sound, and changes to limbic system activity. Translation between animal and human studies has allowed some neural correlates of tinnitus to become more widely accepted, which has in turn allowed deeper research into the underlying mechanism of the correlates. As the understanding of neural mechanisms of tinnitus grows, the potential for treatments is also improved, with the ultimate goal being a true treatment for tinnitus perception.

Article

Pain and Its Modulation  

Asaf Keller

Sensory perceptions are inherently subjective, being influenced by factors such as expectation, attention, affect, and past experiences. Nowhere is this more commonly experienced than with the perception of pain, whose perceived intensity and emotional impact can fluctuate rapidly. The perception of pain in response to the same nociceptive signal can also vary substantially between individuals. Pain is not only a sensory experience. It also involves profound affective and cognitive dimensions, reflecting the activation of and interactions among multiple brain regions. The modulation of pain perception by such interactions has been most extensively characterized in the context of the “descending pain modulatory system.” This system includes a variety of pathways that directly or indirectly modulate the activity of neurons in the spinal dorsal horn, the second-order neurons that receive inputs directly from nociceptors. Less understood are the interactions among brain regions that modulate the affective and cognitive aspects of pain perception. Emerging data suggest that certain pain conditions result from dysfunction in pain modulation, suggesting that targeting these dysfunctions might have therapeutic value. Some therapies that are thought to target pain modulation pathways—such as cognitive behavior therapy, mindfulness-based stress reduction, and placebo analgesia—are safer and less expensive than pharmacologic or surgical approaches, further emphasizing the importance of understanding these modulatory mechanisms. Understanding the mechanisms through which pain modulation functions may also illuminate fundamental mechanisms of perception and consciousness.