Neuroanatomy, Auditory Pathway (2023)

Introduction

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 informationchanges 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.

Structure and Function

Peripheral Auditory System: How sound reaches the brain.

Sounds areproduced 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: the 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, 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: the 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 is 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 stiffer 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.[1]This shift in flexibility and altered anatomy influences how the basilar and tectorial membranes moveand cause the hair cells to respond to lower frequencies.[2]In this way graded flexibility allows hair cells within the cochlea to respond to a 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. [2]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 the excitation of hair cells and thus alter what sound transmitsthrough the auditory system.[3]Because the outer hair cells receive input from cortex, the cortex canstartthese changes to protect the health of hair cells in the presence of loud environments.[4][5]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 the 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 the 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. [6]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 the 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 the cortex can preserve the frequency information from the environment. [6]

Attenuation (the intensity of a sound),isprocessed 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. [6]

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).[6]

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.[7][8][9][10][11]Because most sounds in the environment are not pure tones,these types of combination-sensitive neurons are thought to facilitate the enhancement of processing for combinations of sounds that may be important to the individual (e.g., speech, communication sounds). [12]

Descending Circuits

It was once thought thatauditory processing was a simple relay from the environmental signals up to the cortex. We now know thatthere is a significant descending system of circuits within the auditory system that helps to modulate auditory processing at every level. The auditory cortex has bilateral direct projections back to the inferior colliculus, superior olivary complex, and cochlear nucleus.[13][14][15][16][17][18][19]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). Thesedescending 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.[20][21][22][23][24][25][26]

Embryology

The development of the cochlea originates 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.[27]

Blood Supply and Lymphatics

Blood supply [28](Standring, 2008):

External ear:

• Posterior auricular branch of the external carotid artery

Middle ear:

• Mastoid branches from the posterior auricular arteries

• Occipital arteries

• Deep auricular arteries

Inner ear:

• Anterior tympanic branch of the maxillary artery

• Stylomastoid branch of the posterior auricular artery

• Petrosal branch of the middle meningeal artery

• Labyrinthine artery (branch of the basilar or anterior inferior cerebellar artery)

Lymphatics of the ear:

External ear:

• Pre-auricular lymph nodes[29]

Middle ear:

• Retroauricular and junctional lymph nodes [30]

Inner ear:

• It is unclear whether the inner ear drains via a normal lymphatic system. Salt and Hirose [31]proposed thatthe inner ear drainsdiffusely through the perilymph and bone.

Muscles

There are no muscles within the auditory system. Two muscles (levator veli palatini and tensor veli palatini) assist with opening the auditory tube.

Physiologic Variants

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).[32]

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. [33]

Surgical Considerations

To facilitate recovery of recurrent otitis media and prevent scarring from a ruptured tympanic membrane, surgeons can insertdrainage tubesinto the tympanic membrane.

Clinical Significance

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.[34]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. [35]

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 the auditory cortex.[36][37]Patients with tinnitus may complain of a lack of ability to differentiate sounds or conversations in noisy environments. Depending on the severity, it can also influence sleep, social, and emotional aspects of a patient’s life. [37][38]

Tinnitus typically presents after several years of repeated exposure to loud noises. It commonly has a gradual onsetcaused by repeated damage or stress to cochlear hair cells. However, a lack of input from the cochlear cells does not necessitate a lack of input to the 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 the 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. [37]For individuals that have difficulty getting to sleep, playing white noise or other sounds immediately before sleep can also assist this population.[39]

Other Issues

While most of the population canrespond to a typical hearing test in which they respond to sounds presented to different ears, aproportionof the population cannot respond dueto 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 summedchanges in the electrical activity of auditory areas within the brainstem in response to auditory cues. Variations in activity from normal valuesshowevidence 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. [40]

References

1.

Zhao B, Müller U. The elusive mechanotransduction machinery of hair cells. Curr Opin Neurobiol. 2015 Oct;34:172-9. [PMC free article: PMC4632855] [PubMed: 26342686]

2.

Delacroix L, Malgrange B. Cochlear afferent innervation development. Hear Res. 2015 Dec;330(Pt B):157-69. [PubMed: 26231304]

3.

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 Comput Biol. 2018 Jan;14(1):e1005936. [PMC free article: PMC5792030] [PubMed: 29351276]

4.

Brownell WE, Bader CR, Bertrand D, de Ribaupierre Y. Evoked mechanical responses of isolated cochlear outer hair cells. Science. 1985 Jan 11;227(4683):194-6. [PubMed: 3966153]

5.

Mulders WH, Robertson D. Evidence for direct cortical innervation of medial olivocochlear neurones in rats. Hear Res. 2000 Jun;144(1-2):65-72. [PubMed: 10831866]

6.

Felix RA, Gourévitch B, Portfors CV. Subcortical pathways: Towards a better understanding of auditory disorders. Hear Res. 2018 May;362:48-60. [PMC free article: PMC5911198] [PubMed: 29395615]

7.

Wenstrup JJ. Frequency organization and responses to complex sounds in the medial geniculate body of the mustached bat. J Neurophysiol. 1999 Nov;82(5):2528-44. [PubMed: 10561424]

8.

Peterson DC, Voytenko S, Gans D, Galazyuk A, Wenstrup J. Intracellular recordings from combination-sensitive neurons in the inferior colliculus. J Neurophysiol. 2008 Aug;100(2):629-45. [PMC free article: PMC2525731] [PubMed: 18497365]

9.

Peterson DC, Nataraj K, Wenstrup J. Glycinergic inhibition creates a form of auditory spectral integration in nuclei of the lateral lemniscus. J Neurophysiol. 2009 Aug;102(2):1004-16. [PMC free article: PMC2724328] [PubMed: 19515958]

10.

Gans D, Sheykholeslami K, Peterson DC, Wenstrup J. Temporal features of spectral integration in the inferior colliculus: effects of stimulus duration and rise time. J Neurophysiol. 2009 Jul;102(1):167-80. [PMC free article: PMC2712279] [PubMed: 19403742]

11.

Yavuzoglu A, Schofield BR, Wenstrup JJ. Circuitry underlying spectrotemporal integration in the auditory midbrain. J Neurosci. 2011 Oct 05;31(40):14424-35. [PMC free article: PMC3226782] [PubMed: 21976527]

12.

Peterson DC, Wenstrup JJ. Selectivity and persistent firing responses to social vocalizations in the basolateral amygdala. Neuroscience. 2012 Aug 16;217:154-71. [PMC free article: PMC3586201] [PubMed: 22569154]

13.

Coomes DL, Schofield BR. Projections from the auditory cortex to the superior olivary complex in guinea pigs. Eur J Neurosci. 2004 Apr;19(8):2188-200. [PubMed: 15090045]

14.

Coomes DL, Schofield RM, Schofield BR. Unilateral and bilateral projections from cortical cells to the inferior colliculus in guinea pigs. Brain Res. 2005 Apr 25;1042(1):62-72. [PubMed: 15823254]

15.

Schofield BR, Coomes DL. Projections from auditory cortex contact cells in the cochlear nucleus that project to the inferior colliculus. Hear Res. 2005 Aug;206(1-2):3-11. [PubMed: 16080994]

16.

Schofield BR, Coomes DL. Auditory cortical projections to the cochlear nucleus in guinea pigs. Hear Res. 2005 Jan;199(1-2):89-102. [PubMed: 15574303]

17.

Schofield BR, Coomes DL. Pathways from auditory cortex to the cochlear nucleus in guinea pigs. Hear Res. 2006 Jun-Jul;216-217:81-9. [PubMed: 16874906]

18.

Schofield BR, Coomes DL, Schofield RM. Cells in auditory cortex that project to the cochlear nucleus in guinea pigs. J Assoc Res Otolaryngol. 2006 Jun;7(2):95-109. [PMC free article: PMC2504579] [PubMed: 16557424]

19.

Coomes Peterson D, Schofield BR. Projections from auditory cortex contact ascending pathways that originate in the superior olive and inferior colliculus. Hear Res. 2007 Oct;232(1-2):67-77. [PMC free article: PMC2682707] [PubMed: 17643879]

20.

Mascagni F, McDonald AJ, Coleman JR. Corticoamygdaloid and corticocortical projections of the rat temporal cortex: a Phaseolus vulgaris leucoagglutinin study. Neuroscience. 1993 Dec;57(3):697-715. [PubMed: 8309532]

21.

Romanski LM, LeDoux JE. Information cascade from primary auditory cortex to the amygdala: corticocortical and corticoamygdaloid projections of temporal cortex in the rat. Cereb Cortex. 1993 Nov-Dec;3(6):515-32. [PubMed: 7511012]

22.

Weinberger NM. Associative representational plasticity in the auditory cortex: a synthesis of two disciplines. Learn Mem. 2007 Jan-Feb;14(1-2):1-16. [PMC free article: PMC3601844] [PubMed: 17202426]

23.

Suga N. Role of corticofugal feedback in hearing. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2008 Feb;194(2):169-83. [PubMed: 18228080]

24.

Witter MP, Groenewegen HJ, Lopes da Silva FH, Lohman AH. Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Prog Neurobiol. 1989;33(3):161-253. [PubMed: 2682783]

25.

Carmichael ST, Price JL. Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys. J Comp Neurol. 1995 Dec 25;363(4):642-664. [PubMed: 8847422]

26.

Forbes CE, Grafman J. The role of the human prefrontal cortex in social cognition and moral judgment. Annu Rev Neurosci. 2010;33:299-324. [PubMed: 20350167]

27.

Litovsky R. Development of the auditory system. Handb Clin Neurol. 2015;129:55-72. [PMC free article: PMC4612629] [PubMed: 25726262]

28.

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. Ups J Med Sci. 2018 Sep;123(3):131-142. [PMC free article: PMC6198224] [PubMed: 30204028]

29.

Pan WR, le Roux CM, Levy SM, Briggs CA. Lymphatic drainage of the external ear. Head Neck. 2011 Jan;33(1):60-4. [PubMed: 20848416]

30.

Lim DJ, Hussl B. Macromolecular transport by the middle ear and its lymphatic system. Acta Otolaryngol. 1975 Jul-Aug;80(1-2):19-31. [PubMed: 1166775]

31.

Salt AN, Hirose K. Communication pathways to and from the inner ear and their contributions to drug delivery. Hear Res. 2018 May;362:25-37. [PMC free article: PMC5911243] [PubMed: 29277248]

32.

Greywoode JD, Pribitkin EA, Krein H. Management of auricular hematoma and the cauliflower ear. Facial Plast Surg. 2010 Dec;26(6):451-5. [PubMed: 21086231]

33.

Fireman P. Otitis media and eustachian tube dysfunction: connection to allergic rhinitis. J Allergy Clin Immunol. 1997 Feb;99(2):S787-97. [PubMed: 9042072]

34.

Briggs RJ, Fabinyi G, Kaye AH. Current management of acoustic neuromas: review of surgical approaches and outcomes. J Clin Neurosci. 2000 Nov;7(6):521-6. [PubMed: 11029233]

35.

Greene J, Al-Dhahir MA. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jun 4, 2022. Acoustic Neuroma. [PubMed: 29262098]

36.

Møller AR. The role of neural plasticity in tinnitus. Prog Brain Res. 2007;166:37-45. [PubMed: 17956769]

37.

Crocetti A, Forti S, Del Bo L. Neurofeedback for subjective tinnitus patients. Auris Nasus Larynx. 2011 Dec;38(6):735-8. [PubMed: 21592701]

38.

Weise C, Heinecke K, Rief W. Biofeedback-based behavioral treatment for chronic tinnitus: results of a randomized controlled trial. J Consult Clin Psychol. 2008 Dec;76(6):1046-57. [PubMed: 19045972]

39.

Handscomb L. Use of bedside sound generators by patients with tinnitus-related sleeping difficulty: which sounds are preferred and why? Acta Otolaryngol Suppl. 2006 Dec;(556):59-63. [PubMed: 17114145]

40.

Norrix LW, Velenovsky D. Clinicians' Guide to Obtaining a Valid Auditory Brainstem Response to Determine Hearing Status: Signal, Noise, and Cross-Checks. Am J Audiol. 2018 Mar 08;27(1):25-36. [PubMed: 29392291]