Potentiation of cholinergic and corticofugal inputs to the lateral amygdala in threat learning

Cortical determinants of loudness perception and auditory hypersensitivity

“…This idea is relatively well studied in the context of pain, where optogenetic or chemogenetic manipulation of inhibitory neurons in the somatosensory cortex, 88 can impart anti-nociceptive effects on the perception of erstwhile painful stimuli by overriding aberrant activity patterns in dense networks of descending corticofugal neurons. 89,90 In the context of hearing, auditory corticofugal neurons develop marked hyperactivity after noise-induced hearing loss, 91 underlie learned auditory threat associations 92 and play a central role in auditory hallucinations. 93 Monitoring and manipulating auditory corticofugal neurons either directly or indirectly via inhibitory circuit manipulations may provide new insights into the mechanisms and therapeutic considerations for common auditory hyperactivity disorders, such as tinnitus and hyperacusis.…”

The human pupil and face encode sound affect and provide objective signatures of tinnitus and auditory hypersensitivity disorders

“…One possibility is that the connection between elevated central gain and affective dysregulation may literally reflect abnormally strong coupling between auditory forebrain and limbic centers 33 . A recent animal study of auditory threat learning has shown that a selective plasticity in auditory corticoamygdalar projection neurons asymmetrically increased corticofugal spike-LFP coupling and sound-evoked activity in the lateral amygdala 34 , suggesting that increased neural gain in cortical projection neurons can be passed on to postsynaptic brain regions that regulate affective evaluation of valence and arousal. To this point, several neuroimaging studies in participants with tinnitus and sound sensitivity have identified abnormally strong coupling between auditory cortex and the amygdala, insula, anterior cingulate cortex, and medial prefrontal cortex 33,[35][36][37] .…”

“…Here, we hypothesized that involuntary autonomic and behavioral responses may have untapped potential as non-invasive, objective markers of tinnitus and sound sensitivity severity that are relatively easily to implement in laboratory and clinical settings. Autonomic responses (e.g., pupil dilation and skin conductance) and involuntary facial movements provide a wealth of information into affective processing of valence and arousal in humans [45][46][47][48] as well as other animals 34,49 . Although human studies have largely relied on visual stimuli, it is clear that speech, music and other sounds provide a rich medium for conveying valence and arousal cues.…”