Frank E. Musiek

 

There is no question that considerable research has been conducted on the cochlear nucleus in recent years. Anatomists, physiologists, psycho-acousticians, audiologists and others have made contributions to our understanding of the CNu. However, in reflection on some current research of the CNu I kept thinking about some very early research which was clinical in nature that indirectly told us about some important aspects of CNu mechanisms. These mechanisms are not highly discussed (at least in my opinion) but will be briefly reviewed here in an historical context. However, before we travel down that road let us provide some general background on the CNu for those who may not remember some of their university courses on this important auditory structure.

 

The CNu is probably best known as the first structure in the central auditory pathway. In humans it is located in the caudal most pons coursing from lateral to posterior.  It resembles a half horse shoe in its configuration. The CNu is composed of three main segments: the anterior and posterior ventral segments that run along the lateral aspect of the pons and the dorsal segment which is at the posterior- lateral segment of the caudal pons. The CNu accepts input from the auditory nerve between the two ventral nuclei groups. This area of input from the auditory nerve can be termed the “root entry zone” and is composed of termination fibers of the auditory nerve. There are many different cell types in the CNu such as pyramidal, octopus, and stellate to name a few. These specialized cells alter and preserve the input from the auditory nerve. This is a key to coding and processing of external acoustic stimuli. The CNu is tonotopically organized and is sensitive to even small intensity changes. It is likely that it generates wave III of the ABR and it is critical to function of the more rostral  structures in the central auditory nervous system (CANS) (see Musiek and Baran, 2007 for review).

 

Since the CNu is part of the CANS, many believe that damage to it may not be reflected on the pure tone audiogram. Certainly, we all know or should know that the pure tone audiogram is a very poor predictor of CANS dysfunction so this thinking is consistent with current related knowledge. However, there may be a exception to this accepted principle and in turn, a key function of the CNu may be revealed.  A classic study by Carhart (1967) with the help of research from William Dublin, a noted auditory neuropathologist, reminded me of an important function of the CNu with a clinical cue. So let me explain and also build the story behind this clinical research and basic functions of the CNu.

 

Carhart and Dublin (and I believe also Noel Matkin) had a common clinical interest back in the late 1960’s and through the 1970s. This interest was in kernicterus or the advanced stage of hyperbilirubinemia. Carhart was concerned about newborns with kernicterus or high bilirubin levels because they were showing up with hearing loss and overall difficulty in hearing. Though audiometric trends reflected by kernicterus were difficult to categorize, it did seem as though a gradually sloping high frequency high loss was perhaps the most common (Carhart, 1967, Matkin and Carhart, 1968; Dublin, 1976). However, in this writer’s view, based on the research around their audiometric findings related to kernicterus, Carhart was somewhat suspicious that their audiometric findings in kernicterus were different than the commonly seen mild to moderate high frequency sensorineural loss. Whether they suspected something different for this kernicterus population or not I cannot definitively say — but accounts of their research and related papers seem to lean in that direction. If Carhart was indeed suspicious of the nature of hearing loss in newborns with kernicterus or hyperbilirubinemia being different than most SNHLs their suspicions were indeed confirmed. Dublin’s careful neuropathological studies on the cochlea, auditory nerve and cochlear nucleus revealed new and interesting findings. Dublin showed that in individuals with kernicterus that the cochlea was in fact intact as was the auditory nerve! What Dublin did see under his microscope was damage to the cochlear nucleus (Dublin, 1976). In fact, the CNu damage was in the ventral segment and seemed to show more damage to the part of the CNu that was responsible for high frequencies — consistent with what Matkin and Carhart had seen audiometrically in their newborns and young children!

 

Learning of Dublin’s pathological findings, Matkin and Carhart synthesized all information available and made some astute observations. First that kernicterus and its effect on hearing was manifested in the CANS, specifically the CNu and not in the periphery (cochlea or auditory nerve). It should be noted that not just the CNu was damaged by kernicterus but also other nuclei along the brainstem pathway as well as the basal ganglia. The second observation by Matkin and Carhart was that the pure tone hearing loss was reflecting damage not to the cochlea, but to the CNu. Therefore, in this case, the pure tone audiogram actually was indicating that there was dysfunction of the CANS, specifically the CNu! This second observation is of course, the point of this Pathways article and for which I will make just a few more comments.

 

It is generally agreed upon that in most cases the CANS will not reflect deficits on the pure tone audiogram (Musiek, Shinn, Chermak and Bamiou; in press). However, the CANS does preserve in some manner the coding of the stimulus that occurs in the periphery. One example of this is to look at the post stimulatory time histograms (PSTH) that occur in the CNu. The various cell types in the CNu will change the incoming PSTH from a primary envelope, that is what is coded at by the auditory nerve, to a variety of other PSTHs, depending on which cells in the CNu are stimulated. However, one group of cells will retain the characteristics of the auditory nerve PSTH –hence peripheral coding is maintained (see Musiek and Baran, 2007). Now here is the point: based on what I have just mentioned, the CNu has the capacity to reflect sound detection status by the pure tone audiogram. Therefore if certain cells in the CNu are devoted to detection (threshold) functions and they are damaged then a test that reflects detection will be an indicator of this i.e. the pure tone audiogram. How far up the CANS this action can be measured is anyone’s guess. Yet, even though the preservation of detection information is maintained further up it is unlikely the pure tone audiogram can reflect it at these more rostral levels.

 

Of note are the early studies by Matkin, Carhart and Dublin which showed that in kernicterus patients, with clear evidence of damage to the CNu, that such damage can be reflected on the pure tone audiogram (at least in some cases). Therefore, interpretations must be made carefully because sometimes deficits in detection (pure tone thresholds) may reflect central not peripheral involvement. Clearly, the CANS can retain detection coding information. This information about the CANS and CNu, at least in part, may be traced back to our friends Carhart, Matkin and Dublin.

 

 

References

  1. Carhart R. (1967) Probable mechanisms underlying kernicteric hearing loss. Acta Otolaryngol. Supplement, 221.
  2. Dublin W. (1976) Fundamentals of Sensorineural Auditory Pathology. Charles C. Thomas, Springfield, Ill.
  3. Matkin ND, Carhart R. (1968) Hearing acuity and Rh incompatibility. Electrodermal thresholds. Arch Otolaryngol. 87:383–8.
  4. Musiek, F. and Baran, J. (2007) The Auditory System: Anatomy, Physiology and Clinical Correlates, Allyn and Bacon, Boston.
  5. Musiek, F., Shinn, J., Chermak, G., and Bamiou, D. (in press) Perspectives on the pure tone audiogram. Journal of the American Academy of Audiology.

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