Tone deafness: a model complex cortical phenotype.

We all know people with tone deafness: these are the people who get thrown out of the choir at school. Although tone deafness is recognised as an output disorder, recent studies have characterised it as one of music perception in the absence of deafness or any associated cognitive disorder. The disorder can therefore be characterised as a form of auditory agnosia. This article considers how the phenotype might be deconstructed to the level of a causal deficit in the perception of pitch pattern. Based on our evolving understanding of the normal brain bases for this process a cortical deficit beyond primary cortex would be predicted. In tone deafness, structural cortical variations have been demonstrated by recent studies that detect subtle changes in the cortical mantle and underlying white matter: these changes are within a right hemisphere network for pitch pattern analysis and working memory for pitch. Studies of multiply affected families are underway to see if the disruption of this network can be caused by single genes. This disorder therefore offers the opportunity to study how a complex phenotype can be characterised as a cortical perceptual disorder potentially explained by a single gene or molecule. Although tone deafness is not pernicious, the underlying abnormality may prove to be a disorder of cortical connectivity that provides a model for disorders that are more so, such as schizophrenia.