The auditory system processes how we hear and understand sounds within the environment. It is made up of both peripheral structures (e.g., outer, middle, and inner ear) and brain regions (cochlear nuclei, superior olivary nuclei, lateral lemniscus, inferior colliculus, medial geniculate nuclei, and auditory cortex). Auditory brain circuits encode frequency, attenuation, location in space. Some circuits also process combinations of these properties to help individuals understand and correctly interpret sounds. Processing of auditory information changes continuously by descending feedback circuits based on altered environmental, attentional, and perceived importance of environmental cues. The following chapter provides a basic description of audition and auditory processing.
Peripheral Auditory System: How sound reaches the brain.
Sounds are produced by energy waves. Energy waves travel through a medium by moving molecules. This causes increases and decreases in pressure (i.e., alternating compression and rarefaction) of air within the environment. The number of periods of compression and rarefaction within a specified amount of time is the frequency of a specific sound. We measure frequency in Hertz (Hz; cycles of compression and rarefaction per second). Humans typically hear within a frequency range of 20-20,000 Hz.
Sound waves reach the outer ear and travel down the external acoustic meatus to reach the eardrum (tympanic membrane). Contact between the eardrum and environmental pressure waves causes movement of the membrane. Movement of the tympanic membrane initiates vibration of 3 small bones within the middle ear: malleus, incus, and stapes which transfer the vibration to the inner ear at the oval (vestibular) window (Figure 1A).
The 3 middle ear bones amplify this energy and transfer it into the cochlea. Within the cochlea the mechanical energy converts to electrical energy by auditory receptor cells (hair cells). This conversion occurs within the cochlea of the inner ear. The cochlea is a fluid-filled (perilymph) structure that spirals 2 ½ turns around a central pillar (modiolus). In cross-section, each aspect of the cochlea has 3 sections: scala tympani, scala vestibule, and scala media (Figure 2). The scala tympani lies within the outer portion of the cochlea. It is continuous with the scala vestibule (lining the inner portion of the cochlea) at the helicotrema. Between these fluid-filled areas is the scala media (Figure 1B). Oscillation of the oval window induce waves through the scala tympani and then scala vestibule of the cochlea. Waves from these regions press against and transmit wave energy to the scala media through the basilar membrane (within the floor of the scala media).
The Organ of Corti resides on the basilar membrane inside the scala media. It houses mechanical receptor cells: 3 rows of outer hair cells and one row of inner hair cells. The base of these cells are embedded within the basilar membrane. At the apex of each cell, stereocilia connect to a second membrane (tectorial membrane) within the scala media (Figure 1B).
As the scala vestibule and scala tympani oscillate, the basilar membrane shifts with the tectorial membrane. This shift bends the stereocilia with respect to the cell body of the hair cells. Depending on the direction of the shift, the movement will mechanically open or closes potassium channels to facilitate activation or deactivation of the cell.
How the tectorial and basilar membranes move changes depending on the location within the cochlea. The anatomy of the region close to the oval window is more stiff and hair cell stereocilia shorter. Therefore, cells near the oval window (base of the cochlea) respond to high frequencies. As you move toward the apex of the cochlea, there is more flexibility within the cochlea and the stereocilia length is more than twice as long as hair cells at the base.  This shift in flexibility and altered anatomy influences how the basilar and tectorial membranes move and cause the hair cells to respond to lower frequencies.  In this way graded flexibility allows hair cells within the cochlea to respond to specific range of frequencies from high at the base to low at the apex of the cochlea. This arrangement of cells is called a tonotopic gradient.
Unlike other cells within the brain, hair cells within the Organ of Corti of the cochlea do not have axons. Neurons within the spinal ganglion have peripheral axons that synapse at the base of the hair cell soma. These axons make up the auditory nerve (Figure 1B). Most (90%) of auditory nerve fibers receive their input from the inner hair cells.  Thus, the inner hair cells facilitate a majority of auditory processing.
Outer hair cells synapse on only 10% of the spiral ganglion neurons. These neurons are special in that they can contract the length of their cell body which alters the stiffness of the basilar membrane. This form of stiffening can dampen excitation of hair cells and thus alter what sound transmits through the auditory system.  Because the outer hair cells receive input from cortex, cortex can start these changes to protect the health of hair cells in the presence of loud environments.  One example would be when an individual goes to a loud concert. Cortical feedback would initiate conformational changes to the outer hair cells to decrease movement within the cochlea (i.e., dampen the noise). When the individual leaves the concert, they may experience a loss of normal hearing for a few minutes and then resume normal hearing function. This delay is caused by the time needed for the descending circuits to reset anatomical morphology for optimal audition in the new quieter environment.
Central Auditory System
Information from the peripheral auditory system reaches central auditory nuclei via the auditory nerve. The auditory nerve transmits auditory information up a series of nuclei to cortex where perception occurs. These nuclei include: 1) cochlear nucleus, 2) superior olivary nuclei, 3) lateral lemniscus, 4) inferior colliculus, and 5) medial geniculate nuclei.  Auditory information ascending through the auditory pathways start at the auditory nerve. These nerves synapse within the cochlear nucleus. A majority of auditory information is then transmitted through crossing fibers into the superior olivary complex. From there, the information ascends through the contralateral side of the brainstem and brain to cortex (Figure 1C). It is of note that a significant number of neurons within the auditory system have crossing fibers at every level of the auditory system (Figure 1D). This is likely due to the need for both ipsilateral and contralateral information for many aspects of auditory processing. Therefore, all levels of the central auditory system receive and process information from both the ipsilateral and contralateral sides.
Types of Processing:
Different aspects of environmental sounds (e.g., attenuation: how loud the sound is; location in space; frequency, and combination sensitivity) are processed in each of the central auditory areas. Most of the auditory nuclei throughout the brain are tonotopically arranged. In this way, auditory signals ascending to cortex can preserve the frequency information from the environment. 
Attenuation (the intensity of a sound), is processed within the auditory system by neurons that fire action potentials at different rates based on the sound intensity. Most neurons respond by increasing their firing rate in response to increased attenuation. More specialized neurons respond maximally to environmental sounds within specific intensity ranges. 
The brain processes the location of a sound in space by comparing differences in attenuation and timing of inputs from both ears within the superior olivary complex. If a sound is directly midline (i.e., front or back of the head), it would reach both ears at the same time. If it is to the right or left of midline, a temporal delay occurs between the inputs for the two ears. Within the superior olivary complex, specialized neurons receive input from both ears and can code for this temporal delay (i.e., binaural processing). 
Combination-sensitive neurons are another subset of neurons within the auditory system that have either enhanced or inhibited responses specifically to 2 or more sounds with a specific temporal delay. Combination-sensitive neurons are located within the inferior colliculus, lateral lemniscus, medial geniculate, and auditory cortex.  Because most sounds in the environment are not pure tones, these types of combination-sensitive neurons are thought to facilitate enhancement of processing for combinations of sounds that may be important to the individual (e.g., speech, communication sounds). 
It was once thought that auditory processing was a simple relay from the environmental signals up to cortex. We now know that there is a significant descending system of circuits within the auditory system that helps to modulate auditory processing at every level. Auditory cortex has bilateral direct projections back to the inferior colliculus, superior olivary complex, and cochlear nucleus.  These circuits contact neurons in these nuclei that project to every level of the central auditory system and to the cochlea (to modulate outer hair cells) within the peripheral auditory system. Connections between descending, ascending, and crossing fibers make the auditory system highly interconnected (Figure 1D). These descending circuits help to modulate auditory attention based on the relevance, attention, learned behaviors, and emotional state of an individual. Such higher order functions originate from many regions of the brain (e.g., prefrontal cortex, hippocampus, nucleus basalis of Meynert, and limbic circuits) that have either direct and indirect connections with each other and auditory cortex. 
Development of the cochlea originate at gestational day 4 from the surface ectoderm. It begins as an otic vesicle that develops into the membranous labyrinth of the inner ear. The dorsal aspect of the labyrinth develops into the utricle and semicircular ducts while the ventral aspect transforms into the cochlea and saccule.
The brain regions associated with central auditory processing develop with the various regions of the brain (auditory cortex: telencephalon; medial geniculate: diencephalon; inferior colliculus: mesencephalon; and the cochlear and superior olivary nuclei: rhombencephalon). These areas are fully functioning by birth. These regions are highly plastic. Therefore, auditory processing is in a constant form of change and development that lasts throughout life. 
Blood supply  (Standring, 2008):
Lymphatics of the ear:
There are no muscles within the auditory system. Two muscles (levator veli palatini and tensor veli palatini) assist with opening the auditory tube.
Cauliflower ear: Repeated trauma can cause abnormalities of the outer ear. Trauma can induce a hematoma of the auricle in which blood accumulates between the perichondrium and auricular cartilage. This can distort the contours of the ear, impair blood flow to the cartilage, and lead to fibrosis and anatomical deformity (i.e., cauliflower ear). 
Otis media: Otitis media is an inflammation of the lining of the middle ear. These types of infections are common in children with more horizontally directed auditory tubes. As the skull develops, the tubes will slope in a lateral and caudal direction and allow better drainage. Therefore, otitis media is much more common in young children. The inflammation in these cases causes swelling and subsequent pressure on the tympanic membrane. In severe cases, the tympanic membrane can rupture leading to a decrease in the auditory acuity of affected individuals. 
To facilitate recovery of recurrent otitis media and prevent scarring from a ruptured tympanic membrane, surgeons can insert drainage tubes into the tympanic membrane.
Acoustic Neuroma: The auditory nerve is located at the junction between the pons, medulla, and cerebellum (Figure 1D). This is the locus of a tumor called an acoustic neuroma. Acoustic neuromas grow slowly.  As it enlarges, it can put pressure on surrounding cranial nerves (e.g., Auditory VIII, Facial VII, and Glossopharyngeal IX), the cerebellum and brainstem. Initial symptoms include decreased hearing. As the tumor gets larger, it may include additional symptoms: (e.g., VIII: tinnitus, vertigo, nystagmus; VII: facial drooping, decreased corneal reflex; IX: hoarseness and dysphagia; Cerebellum: ataxia and dysarthria). The symptoms will present ipsilateral to the side of the tumor. 
Tinnitus: Tinnitus is the perception of a sound (typically a ringing or buzzing) that is not present in the environment. The perception is induced by a hyper-excitation within a specific frequency region of auditory cortex.  Patients with tinnitus may complain of a lack of ability to differentiate sounds or conversation in noisy environments. Depending on the severity, it can also influence sleep, social, and emotional aspects of a patient’s life. 
Tinnitus typically presents after several years of repeated exposure to loud noises. It commonly has a gradual onset caused by repeated damage or stress to cochlear hair cells. However, lack of input from the cochlear cells does not necessitate a lack of input to cortex. Because neurons within the auditory system have multiple inputs, the central auditory regions receive input from other neurons about frequency, attenuation, and location in space of other sounds. They transmit these other signals to auditory cortex within the affected denervation frequency range, thus producing a phantom perception.
There is no cure for tinnitus. Biofeedback therapies have helped in some cases, however they do not eliminate the tinnitus perception. The biofeedback therapy uses one or more sounds played at or near the tinnitus perception of a patient. This form of feedback uses inhibitory limbic circuits to help depress the aberrant cortical excitation.  For individuals that have difficulty getting to sleep, playing a white noise or other sounds immediately before sleep can also assist this population. 
While most of the population can respond to a typical hearing test in which they respond to sounds presented to different ears, a proportion of the population cannot respond due to lack of speech development (infants), disease, or trauma. A more universal test is the auditory brainstem response (ABR). This test does not require patient feedback. It records the summed changes in electrical activity of auditory areas within the brainstem in response to auditory cues. Variations in activity from normal values show evidence for auditory dysfunction. Because the test shows values for multiple auditory nuclei, it also provides data for physicians to isolate regions of trauma or disease. 
|||Zhao B,Müller U, The elusive mechanotransduction machinery of hair cells. Current opinion in neurobiology. 2015 Oct [PubMed PMID: 26342686]|
|||Delacroix L,Malgrange B, Cochlear afferent innervation development. Hearing research. 2015 Dec [PubMed PMID: 26231304]|
|||Ciganović N,Warren RL,Keçeli B,Jacob S,Fridberger A,Reichenbach T, Static length changes of cochlear outer hair cells can tune low-frequency hearing. PLoS computational biology. 2018 Jan [PubMed PMID: 29351276]|
|||Brownell WE,Bader CR,Bertrand D,de Ribaupierre Y, Evoked mechanical responses of isolated cochlear outer hair cells. Science (New York, N.Y.). 1985 Jan 11 [PubMed PMID: 3966153]|
|||Mulders WH,Robertson D, Evidence for direct cortical innervation of medial olivocochlear neurones in rats. Hearing research. 2000 Jun [PubMed PMID: 10831866]|
|||Felix RA 2nd,Gourévitch B,Portfors CV, Subcortical pathways: Towards a better understanding of auditory disorders. Hearing research. 2018 May [PubMed PMID: 29395615]|
|||Wenstrup JJ, Frequency organization and responses to complex sounds in the medial geniculate body of the mustached bat. Journal of neurophysiology. 1999 Nov [PubMed PMID: 10561424]|
|||Peterson DC,Voytenko S,Gans D,Galazyuk A,Wenstrup J, Intracellular recordings from combination-sensitive neurons in the inferior colliculus. Journal of neurophysiology. 2008 Aug [PubMed PMID: 18497365]|
|||Peterson DC,Nataraj K,Wenstrup J, Glycinergic inhibition creates a form of auditory spectral integration in nuclei of the lateral lemniscus. Journal of neurophysiology. 2009 Aug [PubMed PMID: 19515958]|
|||Gans D,Sheykholeslami K,Peterson DC,Wenstrup J, Temporal features of spectral integration in the inferior colliculus: effects of stimulus duration and rise time. Journal of neurophysiology. 2009 Jul [PubMed PMID: 19403742]|
|||Yavuzoglu A,Schofield BR,Wenstrup JJ, Circuitry underlying spectrotemporal integration in the auditory midbrain. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2011 Oct 5 [PubMed PMID: 21976527]|
|||Peterson DC,Wenstrup JJ, Selectivity and persistent firing responses to social vocalizations in the basolateral amygdala. Neuroscience. 2012 Aug 16 [PubMed PMID: 22569154]|
|||Coomes DL,Schofield BR, Projections from the auditory cortex to the superior olivary complex in guinea pigs. The European journal of neuroscience. 2004 Apr [PubMed PMID: 15090045]|
|||Coomes DL,Schofield RM,Schofield BR, Unilateral and bilateral projections from cortical cells to the inferior colliculus in guinea pigs. Brain research. 2005 Apr 25 [PubMed PMID: 15823254]|
|||Schofield BR,Coomes DL, Projections from auditory cortex contact cells in the cochlear nucleus that project to the inferior colliculus. Hearing research. 2005 Aug [PubMed PMID: 16080994]|
|||Schofield BR,Coomes DL, Auditory cortical projections to the cochlear nucleus in guinea pigs. Hearing research. 2005 Jan [PubMed PMID: 15574303]|
|||Schofield BR,Coomes DL, Pathways from auditory cortex to the cochlear nucleus in guinea pigs. Hearing research. 2006 Jun-Jul [PubMed PMID: 16874906]|
|||Schofield BR,Coomes DL,Schofield RM, Cells in auditory cortex that project to the cochlear nucleus in guinea pigs. Journal of the Association for Research in Otolaryngology : JARO. 2006 Jun [PubMed PMID: 16557424]|
|||Coomes Peterson D,Schofield BR, Projections from auditory cortex contact ascending pathways that originate in the superior olive and inferior colliculus. Hearing research. 2007 Oct [PubMed PMID: 17643879]|
|||Mascagni F,McDonald AJ,Coleman JR, Corticoamygdaloid and corticocortical projections of the rat temporal cortex: a Phaseolus vulgaris leucoagglutinin study. Neuroscience. 1993 Dec [PubMed PMID: 8309532]|
|||Romanski LM,LeDoux JE, Information cascade from primary auditory cortex to the amygdala: corticocortical and corticoamygdaloid projections of temporal cortex in the rat. Cerebral cortex (New York, N.Y. : 1991). 1993 Nov-Dec [PubMed PMID: 7511012]|
|||Weinberger NM, Associative representational plasticity in the auditory cortex: a synthesis of two disciplines. Learning [PubMed PMID: 17202426]|
|||Suga N, Role of corticofugal feedback in hearing. Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology. 2008 Feb [PubMed PMID: 18228080]|
|||Witter MP,Groenewegen HJ,Lopes da Silva FH,Lohman AH, Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Progress in neurobiology. 1989 [PubMed PMID: 2682783]|
|||Carmichael ST,Price JL, Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys. The Journal of comparative neurology. 1995 Dec 25 [PubMed PMID: 8847422]|
|||Forbes CE,Grafman J, The role of the human prefrontal cortex in social cognition and moral judgment. Annual review of neuroscience. 2010 [PubMed PMID: 20350167]|
|||Litovsky R, Development of the auditory system. Handbook of clinical neurology. 2015 [PubMed PMID: 25726262]|
|||Mei X,Atturo F,Wadin K,Larsson S,Agrawal S,Ladak HM,Li H,Rask-Andersen H, Human inner ear blood supply revisited: the Uppsala collection of temporal bone-an international resource of education and collaboration. Upsala journal of medical sciences. 2018 Sep 11 [PubMed PMID: 30204028]|
|||Pan WR,le Roux CM,Levy SM,Briggs CA, Lymphatic drainage of the external ear. Head [PubMed PMID: 20848416]|
|||Lim DJ,Hussl B, Macromolecular transport by the middle ear and its lymphatic system. Acta oto-laryngologica. 1975 Jul-Aug [PubMed PMID: 1166775]|
|||Salt AN,Hirose K, Communication pathways to and from the inner ear and their contributions to drug delivery. Hearing research. 2018 May [PubMed PMID: 29277248]|
|||Greywoode JD,Pribitkin EA,Krein H, Management of auricular hematoma and the cauliflower ear. Facial plastic surgery : FPS. 2010 Dec [PubMed PMID: 21086231]|
|||Fireman P, Otitis media and eustachian tube dysfunction: connection to allergic rhinitis. The Journal of allergy and clinical immunology. 1997 Feb [PubMed PMID: 9042072]|
|||Briggs RJ,Fabinyi G,Kaye AH, Current management of acoustic neuromas: review of surgical approaches and outcomes. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2000 Nov [PubMed PMID: 11029233]|
|||Greene J,Al-Dhahir MA, Acoustic Neuroma (Vestibular Schwannoma) null. 2018 Jan [PubMed PMID: 29262098]|
|||Møller AR, The role of neural plasticity in tinnitus. Progress in brain research. 2007 [PubMed PMID: 17956769]|
|||Crocetti A,Forti S,Del Bo L, Neurofeedback for subjective tinnitus patients. Auris, nasus, larynx. 2011 Dec [PubMed PMID: 21592701]|
|||Weise C,Heinecke K,Rief W, Biofeedback-based behavioral treatment for chronic tinnitus: results of a randomized controlled trial. Journal of consulting and clinical psychology. 2008 Dec [PubMed PMID: 19045972]|
|||Handscomb L, Use of bedside sound generators by patients with tinnitus-related sleeping difficulty: which sounds are preferred and why? Acta oto-laryngologica. Supplementum. 2006 Dec [PubMed PMID: 17114145]|
|||Norrix LW,Velenovsky D, Clinicians' Guide to Obtaining a Valid Auditory Brainstem Response to Determine Hearing Status: Signal, Noise, and Cross-Checks. American journal of audiology. 2018 Mar 8 [PubMed PMID: 29392291]|