BCS/NSC221, 4 March 2003
Notes and commentary on Webster, D. B. (1993) “An overview of mammalian auditory pathways with an emphasis on humans” Chapter 1 in Webster, D. B., Popper, A. N., and Fay, R. R. (Eds) The mammalian auditory pathway: Neuroanatomy. New York: Springer-Verlag, pp 1-22.
The book consists of 7 chapters, beginning with Webster’s overview, and then 6 chapters dealing with each of the major sub-divisions of the central auditory system for which Webster provides a brief introduction: the auditory nerve, by David Ryugo; the cochlear nucleus by Nell Cant; the superior olivary complex and the lateral lemniscal system by Ilsa Schwartz; the inferior and the superior colliculus by Doug Oliver and Michael Huerta; the medial geniculate and the auditory cortex by Jeffery Winer; and the olivocochlear efferent system by Bruce Warr. As the title suggests, the focus in this book is on neuroanatomy.
1: Webster begins by saying that most of what we know about the anatomy and physiology of the auditory system comes from invasive experiments on animals, using, for example, indwelling electrodes to measure neural activity; chemical markers of neurotransmitters followed by track tracing, studying the behavior of cells in isolated slices of the auditory brain, or, most recently, looking at the physiology of animals and of cells that vary in their molecular composition, and, thus, their biophysical characteristics. In humans most measures are more indirect, using evoked potential responses from the scalp, PET and MRI imaging, and anatomical studies of cadavers (though I did see a presentation at ARO on the effects of electrical stimulation and recording in auditory cortex in humans, that was possible because it was part of the investigatory workup concerning the site of epileptic foci in patients: Howard, M. A.(2003) “Functional organization of human cerebral cortex involved in hearing and speech” Association for Research in Otolaryngology, 26, #537).
Webster makes the point that there are many similarities in sensory behaviors and in physiology in humans and in other mammals, and where there are differences in sensory-behaviors there are also differences in physiology, so that it is useful and valid to make inferences from animals, largely cats, rodents, and some non-human primates, to humans. He identifies eleven significant parts of the central auditory nervous system (CANS) for discussion. (This seems like an easy bit of information to master, but it turns out that these eleven have various important subdivisions and critical interactions, and it is not so easy after all.) They are hair cells; spiral ganglion cells (auditory nerve AN); cochlear nucleus (CN); trapezoid body (and its nuclei, e.g., MNTB); superior olivary complex (SOC); lateral lemniscus (LL) and associated nuclei (such as VNLL); inferior colliculus (IC) and its divisions (e.g. CNIC; LNIC); and its brachium (BIC); the medial geniculate body in the thalamus (MGB); the thalamocortical auditory radiation; and the auditory cortex (AC).
2: Innervation of hair cells. We know most of this information already, the single row of IHC, the (usually) three rows of OHC, with AN fibers and synapses at their base and stereocilia at their apex. The basic human cochlea is typical of most mammals.
Afferent innervation has been most studied in cats, and as we said in class, one IHC will receive many AN fibers, but typically one AN fiber goes to only one IHC. Webster cites Nadol (who has done most of the cochlear anatomy over the years) as saying that humans are a bit different in that our AN fibers may contact two or three IHC. In the cat the smaller AN fibers, about 5-10%, go to the OHC, turn towards the base, and may contact as many as 15 to 20 OHC, while each OHC may receive 6-10 AN fibers. In humans the number is 4 to 8, but this does not seem to be a consequential difference. Figure 1 (page 3) shows a schematic of these connections as well as the connections of the olivocochlear efferent system (the OCB), roughly the same as we saw in Yost. As we have noted before, the OCB begins in the SOC, and consists of a medial and a lateral subdivision. Mostly the medial crosses over to innervate the opposite CN and the contralateral OHC (in big efferents at the OHC base), while the lateral innervates the ipsilateral CN and the ipsilateral IHC of the cochlea, these ending on the dendrite of the AN fiber. The lateral OCB is very similar across mammals, while humans have fewer medial OCB endings on the contralateral OHC.
3: The auditory nerve begins in the spiral ganglion in the center of the cochlea (the ‘modiolus’), and the biggest fibers (Type I) are myelinated in most animals save for where they reach out to the IHC. Webster cites Nadol et al. (1990) in saying that most of the Type I cell bodies are not myelinated in humans, but the fibers are most certainly myelinated, for otherwise information would not get rapidly to the brain; and besides, the hearing problems of some patients with MS, which is a demyelinating disease, clearly result because of their patchy patterns of myelination in the AN. As in other mammals most AN fibers are Type I (88%) and go to the IHC. The peripheral parts of the small Type II fibers cross the Tunnel of Corti and travel to the OHC, as above. Their unmyelinated central processes travel with the Type I fibers in the AN through the internal auditory meatus and enter the brain about at the junction of the cerebellum and the pons. As we have seen before, the function of the Type II fiber is unclear.
4: The cochlear nuclear complex is the terminus of the AN fibers, which branch off into three tracks to innervate the three distinct portions of the CN: the dorsal (DCN) and the ventral, which consists of two portions, the anterior (AVCN) and the posterior (PVCN). This means that one fiber that pick up one sort of information from one IHC (possibly 2 or 3 in humans) distributes that information to three distinct places, which then communicate with more rostral levels along at least three distinct pathways. As the split off they retain the tonotopic organization of the basilar membrane and the AN. The apical low frequency fibers split immediately on entering the CN into an ascending (rostral) portion in the ventrolateral AVCN and descending (caudal) branches that go to the ventrolateral PVCN and DCN. The basal high frequency portions go to the dorsomedial part of the VCN, and then go through the dorsal-medial parts of the AVCN and the PVCN and the DCN. This is very important, as the organization within the CN from high frequency in the dorsal medial sections, graded then into low frequencies in the ventral lateral sections becomes the basis for keeping a tonotopic frequency map at all of the other ascending sites of the CANS. Figure 1.2 shows a schematic of this frequency distribution plus sketches of some of the sorts of cells that inhabit these various parts of the CN. Three cells are depicted in Figure 1.2 a stellate multipolar cell in DCN, a spherical bushy cell in AVCN, and an octopus cell in PVCN: however, there are six other sorts of cells, and all have different functions.
Bushy cells live in the most anterior part of AVCN and are distinguished by huge synapses (the calyceal endbulbs of Held) from the AN onto their cell bodies, which dump large quantities of neurotransmitter (probably glutamate) onto the cell. As a result (almost) every action potential (AP) in the AN drives the bushy cell. Thus the bushy cell tends to mirror the AN input, though it turns out that because of some small inhibitory inputs and because of their membrane characteristics bushy cells show even better phase locking than do AN fibers. Their APs are transmitted along a special pathway (the ventral acoustic stria) which becomes the trapezoid body, and eventually leads to cells in the superior olivary nucleus. This pathway makes a major contribution to spatial location of sounds. Similar “globular bushy cells” live just posterior to the “spherical bushy cells” and have a similar but not identical function. Both tend to respond with a signal that is like the AN fiber - a big onset response, followed by trailing adaptation, though globular cells may have a little notch in their response just after the onset. The octopus cells of the PVCN are very peculiar, almost the opposite of the bushy cells. Bush cells necessarily fire only for one particular frequency, that of the IHC to which their AN fiber is connected; and then they come close to mirroring the post-stimulus-time-histogram (PSTH) of their AN fiber. In contrast the octopus cell has long trailing dendrites that cross the AN and so they are stimulated by many different AN fibers. In principle they can be fired by any grouping of simultaneous AN fibers, and when they fire they do so only once: they are pure onset cells, this resulting from the high proportion of potassium channels in their cell membrane that bring them back to a resting potential after an AP or an EPSP (that is a small level of depolarization, not enough by itself to cross the AP threshold). They are good for signaling the onset of complex stimuli. Their outputs pass through the intermediate acoustic stria and go to some of the nuclei in the superior olive and also to the nuclei of the lateral lemniscus, from there onto the IC. The anterior ventral cochlear nucleus also has multipolar cells (also “stellate cells”) the more posterior of which apparently go directly to the IC, also through the intermediate acoustic stria, while more anterior go through the ventral acoustic stria to the SOC. They may be specialized to respond to amplitude modulated signals, in that they tend to respond with a peculiar repetitive “on/off” rhythm to steady input, and so they are also called “chopper cells”. These cells receive direct connections from the AN, which is not surprising, but also they have inputs from higher levels of the CANS and even from other apparently non-auditory sources.
The dorsal cochlear nucleus is by far the more complex compared to the VCN, and at least in rodents and in cats is finely layered: an outer molecular layer, mostly of fibers with small cells; a deeper fusiform layer of very large fusiform cells, and a central layer made up of many types of stellate cells, some of which are “giant” cells, some of which are small “granule” cells. Many of these cells have no direct AN input, but respond to indirect AN input in many different ways, largely because of complex inhibitory and excitatory neural networks in which they are embedded. They also have many downstream connections from more rostral parts of the CANS, and parallel connections from the VCN as well as non-auditory inputs. Then there are five types of giant cells in the central stellate layers distinguished by their shape and patterns of innervation, though how they might function differently is not clear. Fusiform cells are thought to respond to patterns of acoustic input (spectral notches, those important in vertical location of sound objects, for example) together with somatosensory input from the head (and in cats etc., the pinna) and are imagined to take place in vertical localization. The DCN has major connections to the VCN, but its output from the CN is directly to the IC via the dorsal acoustic stria.
5: The superior olivary complex lies in the ventral medulla in most animals, in the posterior pons in humans. Most of their input comes from the ventral acoustic stria and from the trapezoid body (that is formed by the contralateral VAS). The three major nuclei are the lateral and the medial superior olivary nucleus (LSO and MSO) and the medial nucleus of the trapezoid body (MNTB). Then there are 6 or 8 more smaller nuclear groups (such as “the dorsal medial peri-olivary nucleus” or DMPO, etc), typically just called collectively the peri-olivary nuclei. The size of these groups varies with the size of the animal, which alters their reliance on low vs. high frequency cues to spatial location in the horizontal plane. The MSO is involved in interaural timing and so is small in small headed animals, such as the mouse; the LSO is involved in interaural level differences and so is small in large headed animals. Humans have a large MSO, and a small LSO.
The MSO consists of multipolar principle cells that receive information through the ipsilateral and the contralateral ventral acoustic stria. They are thus the very first of the binaural cells in the CANS. These cells are excited by both inputs, and have preferred delays so the activity in one set of cells can signal a particular interaural time difference and hence, a particular set of possible locations in space. Their output goes through the ipsilateral lateral lemniscus to the IC. The MNTB consists to large principle cells that have huge enveloping calyceal endings from the contralateral globular bushy cells of the AVCN, with a bias towards high frequency input. Their output goes to the ipsilateral LSO, and its most important functional characteristic is that its output is inhibitory at the LSO. The LSO has small cells that receive excitatory input from the ipsilateral VAS, ipsilateral inhibitory input from the ipsilateral MNTB (and thus from the contralateral VAS), and its output is thus some balanced representation of the interaural level difference. The output goes to both sides of the IC through the lateral lemniscal pathway. Both LSO and MSO are tonotopic and so their principle cells receive matched input from the two ears.
The periolivary nuclei consist of two major sets, the lateral and the medial, which are the origins of the lateral and the medial branches of the olivocochlear bundle (OCB). Their output is to the contralateral OHC (the medial group) and the ipsilateral IHC (the lateral group), at least mostly. They also have collaterals into the CN. The organization of the human OCB seems to resemble that of the cat. The LSO and the MSO also are part of the reflex group for the stapedius reflex, and their output is also to the facial nucleus which gives rise to the seventh cranial nerve.
6: The lateral lemniscus is a major ascending and descending pathway that also consists of several nuclear groups, such as the dorsal and the ventral nuclei of the lateral lemniscus (DNLL, VNLL, for example). The LL pathway has several sources, beginning with multipolar neurons from the contralateral VCN via the VAS and from the contralateral DCN via the DAS; ipsilateral cells of the MSO; ipsi- and contralateral cells from the LSO; and contralateral octopus cells from the PVCN. These octopus cells, which are “onset cells” in the PVCN, send collaterals to the periolivary nuclei of the SO complex but end in the VNLL. The cells of the VNLL then contribute to the lateral lemniscus on its way to the IC, but also have collaterals into the reticular formation where they can have a variety of other functions, ending in motor behavior and in arousal.
Webster makes a small point concerning the heterogeneity of the cells in the LL which is interesting. Cells in the CN tend to be “first order cells” one level above the auditory nerve; cells in the MSO and the MNTB and some cells in the LSO are second order cells, one up from the CN; some cells in the LSO are third order cells, two up from the CN. So cells in the LL can be second order cells, one step above the CN; or third order cells, two steps from the CN; or fourth order cells, three steps from the CN. Because each synapse introduces a delay in the transmission lines this means that the temporal representation of a particular stimulus will be smeared in the LL, as different sorts of information about that stimulus travel through the LL at slightly different times. This means that there must be some way in which the IC (and higher centers) can put the stimulus back together again even though it has been broken up into different chunks. Also, though most of the information coming up the LL going to the IC on that side, but some cross over the midline to go to the other side of the IC. In addition the IC has a commissure that connects the left and right IC: somehow all of this diverging and converging information has to retain the fact that it is all the product of a single sound object! Webster ends this section by saying that the human LL system is very much like the cat, to the extent that this can be determined from anatomical studies.
7: The inferior colliculus is the place in the brain stem where all of the separate neural processing starts to come together, and it is generally thought that the axons from all lower neurons stop in their connections with cells in the IC. (I heard a talk on tinnitus at ARO 2003 that suggested there was a pathway that bypassed the IC to go to the thalamus and then to the amygdala, this accounting for the emotional aspects of tinnitus. A second presentation which challenged this view was given at ARO in 2004, suggesting that some fibers go directly from the olivary nuclei to the medial geniculate, and are responsible for some few very short latency responses in a part of the geniculate responsible for timing. The two phenomena could be related, to provide fast emotional responses, for example.) The IC is composed of a very large central nucleus (called by Webster CNIC, but often just ICC in other works), which has fusiform principle cells which run across the CNIC in iso-frequency layers. Because of the way the LL splits off its components as runs into and through the CNIC the high frequency stimuli tend end up in the ventral regions, which then shift to lower frequencies more dorsally. These inputs come mostly from the lateral lemniscus and slightly from the commissure of Probst (from the contralateral LL), but cells also have an input from the contralateral CNIC via the commissure of the IC (this commissure also sends some axons to the brachium of the IC, which then directly goes up to the auditory thalamus, i.e., the medial geniculate body, MGB). All of the principle cells of the ICC go up to the MGB through the brachium, but also there are side-collaterals that go to other parts of the IC, the external nucleus (ICX) sometimes called the paracentral nucleus and especially the dorsal cortex of the IC (DCIC). Only the CNIC is tonotopic. The other areas contain cells that receive axons from the CNIC but also down-stream axons and multisensory axons. They send their axons also downstream, but they also can interact with cells in the CNIC. So there is a lot of integration of various forms of sensory input in the IC as a whole. Webster concludes by saying that the IC in the cat and the human have very similar structures.
8: The medial geniculate body (MGB) is the thalamic auditory nucleus. There are three divisions which have somewhat different functions and organization of inputs and outputs. The ventral division consists of layers of cells which are tonotopically organized, and are the targets of axons from the CNIC. In turn their targets are the primary auditory cortex. (AC), and so for a long time the ventral part of the MGB was thought of as a simple relay station along the auditory pathway. However, it turns out as well that the auditory cortex, primary and secondary areas, sends axons back to the ventral division of the MGB and so the MGB and the AC are a part of an integrated feedback system. In contrast the dorsal division of the MGB is consists of maybe 10 different regions with 8 different cell parts, with diffuse input from the CNIC, from the surrounding areas of the IC, from the brainstem reticular formation (which is typically thought of as being concerned with arousal reactions), from the ventral MGB, and from other thalamic nuclei (for somatosensory, visual, cutaneous and pain stimuli). The cells of the dorsal MGB send their axons to secondary areas of the auditory cortex.. When the cortex sends axons to the MGB these are often as collaterals of axons that ultimately end in the dorsal cortex of the IC.
The medial division of the MGB has very large cells (sometimes the medial division is also called the magnocellular division for this reason). Perhaps more than most other portions of the CANS is has many other sources of input, from the vestibular system, from spinal cord nuclei that have to do with tactile sensation, from the superior colliculus, which is a way station for visual information, and some auditory information from the superior olivary complex and from the lateral lemniscus (thus, possibly, lower brainstem auditory neurons that do not stop in the IC, as suggested above). It also has input from the cortex, not necessarily auditory cortex. Its axons project to the auditory cortex and some non-auditory cortex, plus the putamen (an area concerned with planning motor programs) and the amygdala (which is a temporal lobe nucleus concerned with emotional stimuli and responses).
The ventral division of the MGB is perhaps the only tonotopically organized part of the MGB and so is the prime source of frequency-dependent information to the AC. It is thought that the DMGB is concerned with “directing auditory attention”, while the medial division is part of a multisensory arousal system. But the levels of complexity and the variety of the connections is sufficient to suggest all sorts of hypotheses. One is that a developmental disorder in the magnocellular layers of both the MGB and the LGB (the lateral geniculate body processes visual information) is responsible for some people having problems in temporal processing, this potentially leading to dyslexia, as seen in the following abstract [which is not from Webster’s chapter, of course]:
“Witton C. Talcott JB. Hansen PC. Richardson AJ. Griffiths TD. Rees A. Stein JF. Green GG. (1998) Sensitivity to dynamic auditory and visual stimuli predicts nonword reading ability in both dyslexic and normal readers. Current Biology. 8(14):791-7.
BACKGROUND: Developmental dyslexia is a specific disorder of reading and spelling that affects 3-9% of school-age children and adults. Contrary to the view that it results solely from deficits in processes specific to linguistic analysis, current research has shown that deficits in more basic auditory or visual skills may contribute to the reading difficulties of dyslexic individuals. These might also have a crucial role in the development of normal reading skills. Evidence for visual deficits in dyslexia is usually found only with dynamic and not static stimuli, implicating the magnocellular pathway or dorsal visual stream as the cellular locus responsible. Studies of such a dissociation between the processing of dynamic and static auditory stimuli have not been reported previously. RESULTS: We show that dyslexic individuals are less sensitive both to particular rates of auditory frequency modulation (2 Hz and 40 Hz but not 240 Hz) and to dynamic visual-motion stimuli. There were high correlations, for both dyslexic and normal readers, between their sensitivity to the dynamic auditory and visual stimuli. Nonword reading, a measure of phonological awareness believed crucial to reading development, was also found to be related to these sensory measures. CONCLUSIONS: These results further implicate neuronal mechanisms that are specialized for detecting stimulus timing and change as being dysfunctional in many dyslexic individuals. The dissociation observed in the performance of dyslexic individuals on different auditory tasks suggests a sub-modality division similar to that already described in the visual system. These dynamic tests may provide a non-linguistic means of identifying children at risk of reading failure.” And now, back to Webster:
9: The auditory cortex and related areas lie in the temporal lobe for all mammals, in humans, with our very complex folded cortex, on Heschl’s gyrus (a convexity) in the depth of the lateral (Sylvian) fissure. The Sylvian fissure separates the frontal and parietal cortices from temporal cortex, and the topmost part of the temporal lobe is called the superior temporal gyrus. However Heschl’s gyrus cannot be seen on the surface of the human brain without lifting up part of the frontal and the parietal lobes. Webster describes primary auditory cortex in Heschl’s gyrus as “koniocortex” which is a name applied to a cortical region with tiny granule cells (looking like bits of grain), and is characteristic of sensory areas in general. Typically it is called A1 (as the first area of auditory cortex) but as Webster points out there are other labels. Another area surrounds A1 and is not koniocortex. It may also extend into the planum temporale. Some researchers say A1 is both of these areas, others say A1 is just koniocortex. In cats and in primates, and apparently also in humans (from recent fMRI work), A1 is tonotopically organized, alternated with binaural and monaural cells: thus one frequency sub-band finds left and right input excitatory while the next two sub-bands for that frequency have the contralateral ear excitatory and the ipsilateral ear inhibitory. The areas around A1 are also tonotopically organized, but along different axes.
10: The planum temporale and the superior temporal gyrus adjoin Heschl’s gyrus, and even extend into the parietal lobe, according to Webster. In right-handed humans (and some left handed as well) the left area is called Wernicke’s area, which is thought to be a specific speech comprehension area. Lesions of this area result in “fluent speech”, that sounds just right, save that is nonsensical. This “planum temporale”, which is larger on the left than on the right in about 2/3 of all humans. It is also larger in persons with perfect pitch. The left PT is also larger in chimpanzees (in a paper by Gannon et al. Science, 1998), suggesting either that chimpanzees have speech. or that the general features of this area and its position close to somesthetic and visual areas as well as audition may allow a combining of different sensory experiences as a form of associative “meaning”. Thus, it has been shown that Wernicke’s area is important from sign-language in deaf humans, suggesting that it is a “language” area, not just a “speech” area (see abstract, below):
MacSweeney M. Woll B. Campbell R. McGuire PK. David AS. Williams SC. Suckling J. Calvert GA. Brammer MJ. (2002) Neural systems underlying British Sign Language and audio-visual English processing in native users. Brain. 125:1583-93.
In order to understand the evolution of human language, it is necessary to explore the neural systems that support language processing in its many forms. In particular, it is informative to separate those mechanisms that may have evolved for sensory processing (hearing) from those that have evolved to represent events and actions symbolically (language). To what extent are the brain systems that support language processing shaped by auditory experience and to what extent by exposure to language, which may not necessarily be acoustically structured? In this first neuroimaging study of the perception of British Sign Language (BSL), we explored these questions by measuring brain activation using functional MRI in nine hearing and nine congenitally deaf native users of BSL while they performed a BSL sentence-acceptability task. Eight hearing, non-signing subjects performed an analogous task that involved audio-visual English sentences. The data support the argument that there are both modality-independent and modality-dependent language localization patterns in native users. In relation to modality-independent patterns, regions activated by both BSL in deaf signers and by spoken English in hearing non-signers included inferior prefrontal regions bilaterally (including Broca's area) and superior temporal regions bilaterally (including Wernicke's area). Lateralization patterns were similar for the two languages. There was no evidence of enhanced right-hemisphere recruitment for BSL processing in comparison with audio-visual English. In relation to modality-specific patterns, audio-visual speech in hearing subjects generated greater activation in the primary and secondary auditory cortices than BSL in deaf signers, whereas BSL generated enhanced activation in the posterior occipito-temporal regions (V5), reflecting the greater movement component of BSL. The influence of hearing status on the recruitment of sign language processing systems was explored by comparing deaf and hearing adults who had BSL as their first language (native signers). Deaf native signers demonstrated greater activation in the left superior temporal gyrus in response to BSL than hearing native signers. This important finding suggests that left- temporal auditory regions may be privileged for processing heard speech even in hearing native signers. However, in the absence of auditory input this region can be recruited for visual processing.
11: Other language related cortices are described by Webster, particularly the long association pathway called the “arcuate fasciculus” which runs from Wernicke’s area and the inferior parietal lobe to “area triangularis” which is better known as Broca’s area. Following lesions to this area patients may understand simple speech but be unable to speak, and besides, they do not understand grammar (“the horse kicked the cow” is understood as being the equivalent of “the cow kicked the horse”). So now we have left audition as a sensory modality to the much broader cognitive function of language: a fascinating excursion that is possible in humans without auditory function at all, but beyond the scope of this course.
12: Webster ends with a succinct summary. In these near 20 pages he takes the auditory input from the Type I spiral ganglion cells to 4 different cells in the CN: the bush cells of AVCN, the octopus cells of PVCN, the multipolar cells general to VCN, and the stellate cells of DCN. The bushy cell AN-like output is through the VAS and TB to the SOC, which receives bilateral input, and goes through the lateral lemniscus to the IC. the octopus cell sends its onset output through the intermediate acoustic stria to periolivary neurons and the contralateral VNLL, which then projects to the IC. Stellate cells receive AN information but converts it into patterns, little bursts of activity, that go through the intermediate or the VAS to the periolivary regions and to the contralateral IC through the LL. The stellate cells of DCN collect multimodality information and send it to the contralateral IC through the dorsal acoustic stria then the lateral lemniscus. Then the CNIC puts the information back together (or some of it) and sends it to the ventral nucleus of the MGB through the brachium of the IC, then through the internal capsule to the primary auditory cortex.
Webster says much more needs to be known about the functional anatomy of MGB and the properties of its various parts; and about the auditory cortex in its various parts, while the basic anatomy of the system is reasonably well understood below the level of the IC. Note however that Webster spends little time on the anatomy of the descending system (it is likely enough at this point to imagine that for every ascending path there is an important descending pathway): and, of course, the physiology of this efferent system needs considerable more research.