Our patient JS suffered from generalized auditory agnosia, yet showed remarkable sparing of his ability to appreciate and emotionally respond to music. The diagnosis of generalized auditory agnosia in JS is confirmed by the near-normal pure tone audiometry with an inability to recognize words, environmental sounds, familiar music or discreet musical variables. The bitemporal injury suspected with the clinical syndrome was corroborated by neuroimaging evidence; however, the neural substrate of the preserved emotional response to music remained as elusive as the etiology of the neurodegeneration.
Recent studies suggest that attribution of affect in music arises early in development with tempo and mode as the most important determinants of happy versus sad judgments of musical excerpts (Dalla Bella, Peretz et al. 2001
; Dalla Bella, Peretz et al. 2001
). This skill is probably distinct from identification of other separable musical variables such as pitch, melodic contour, melodic interval, rhythm, or meter (Liegeois-Chauvel, Peretz et al. 1998
; Peretz, Gagnon et al. 1998
). JS was unable to identify either of the affective variables or the intended results of their manipulation, emphasizing a distinction between the identification of the affective character of music and the resultant emotional experience associated with music. For example, a tragic aria is typically perceived as conveying negative affective valence but many listeners derive pleasure from the experience (Siegwart and Scherer 1995
), which may even result in a positive musical emotion, “thrills” and “chills” (Blood and Zatorre 2001
; Panksepp and Bernatzky 2002
). Thus, it is plausible that one might not recognize the affective intent of music but still possess the capacity to experience an emotional response.
Investigations of the neural correlates of pleasurable responses to music with PET imaging demonstrate activation of reward circuitry (Cardinal, Parkinson et al. 2002
) including the ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex (Blood, Zatorre et al. 1999
; Blood and Zatorre 2001
). In particular the nucleus accumbens (NAc), ventral tegmental area (VTA), hypothalamus, and insula have demonstrated increased perfusion when subjects reported experiencing music-related pleasure in a fMRI paradigm (Menon and Levitin 2005
). This neural circuit implies involvement of the dopaminergic and opioid neurochemical systems, with dopamine release in the VTA having been associated with NAc opioid transmission (Kelley, Bakshi et al. 2002
; Zhang, Balmadrid et al. 2003
Interestingly, the potential role for opioid mediation in music-associated pleasure was suggested prior to modern functional imaging techniques as subjects reported a decrease in their positive emotional reaction to musical stimuli after administration of a known opioid antagonist, naloxone (Goldstein 1980
). Involvement of the endogenous opioid system may be further implicated by opioid receptor prominence in the inferior colliculus, a rudimentary yet important component of the auditory processing system in humans, that has been implicated in mediating affective responses related to non-musical sound perception (Panksepp and Bernatzky 2002
). Deep brain structures not pathologically involved in our patient or other reported cases of generalized auditory agnosia may therefore contribute to the emotional experience of sounds, even in the absence of the capacity to identify specific characteristics of those sounds.
While such evidence may be compelling, an attempt to explain the emotional response of JS to music by invoking only subcortical structures seems insufficient. Subcortical sound processing in the thalamus and brainstem is observed in other species (Kanwal and Rauschecker 2007
) with evidence of pre-processing extrapolated to humans (Boatman 2006
). Indeed, the acoustic startle response (arguably the most primitive human emotional response to sound) localizes to the brainstem across species (Pissiota, Frans et al. 2002
). While such explanations may begin to explain the preservation of the awareness of music onset for JS, they fail to account for the vivid, yet clearly erroneous, descriptions of the music JS experienced when confronted with auditory stimuli cognitively primed as selections from his personal music collection.
Importantly, the expectation that musical excerpts were to be extracted from his personal favorites may have been a determinant in the pattern of response that emerged when asking JS to describe his auditory experience during music testing session #2. Subjects rate musical taste as one of the most revealing preferences or activities in attributing personal qualities to themselves and others (Rentfrow and Gosling 2003
). Further experimental evidence suggests that subjects are more likely to experience musically and emotionally induced “chills” when listening to personally preferred and familiar tunes (Panksepp 1995
). Such preliminary evidence highlights experience as an important contributor to the emotional response to music, and suggests why one might strive to maintain a musical identity congruent with social expectations, even in the absence of adequately functioning auditory cortex. However, JS failed to correctly identify even the genre of music being presented, describing the classical writings of Wagner during Brubeck’s jazz stylings and later mistaking the examiner’s surprise sample of Johnny Cash for world renowned cellist, Yo-Yo Ma.
Understanding the musical experience of JS becomes even more challenging if one attempts to characterize the neurophysiological source of his experience, which is objectively a misperception of auditory stimuli. Musical hallucinosis is a well-described, albeit rare, disorder of the processing of sound, requiring a mental representation of high-level sound patterns (Berrios 1991
). Functional imaging with PET has demonstrated activity in the posterior temporal lobes, right basal ganglia, cerebellum, and inferior frontal cortices in several patients actively experiencing continuous musical hallucinations of specific tunes following acquired peripheral deafness. Based on this evidence a modular representation of sound perception was formulated that suggests the potential for generation of spontaneous neural activity in the absence of the perception of pattern in segmented sound as depicted at the top of (Griffiths 2000
). While the aforementioned model was created to describe musical hallucinosis in acquired deafness rather than auditory agnosia, it does allow for “triggering” of spontaneous activity which may be extrapolated to the experience of JS as depicted at the bottom of .
Fig. 2 (Top) Griffiths’ (2000) proposed basis for musical hallucinations due to spontaneous activity in the module for the perception and imagery of pattern in segmented sound
On the contrary, all of the subjects contributing to the development of this particular model experienced musical hallucinations as distressing. This is in concordance with a review of the literature on musical hallucinations where 41% of subjects experienced the hallucinations as frightening, compared to only 10% of cases that were described as pleasant. More consistent with the experience of JS, 78% of the patients reported in the literature described hallucination of familiar tunes (Evers and Ellger 2004
). This consistency in the familiarity of tunes has prompted other authors to suggest “neuronal irritation” resulting in stimulation of the relevant neuronal circuit with resultant re-experience of stored perceptual (in this case musical
) experiences (Keshavan, Davis et al. 1992
) Analogously, deafferentation resulting in visual hallucinations is well-known in the medical community and can result from pathology at any point along the visual system pathway (Eustache, Lambert et al. 1995
). We speculate that JS experiences personally preferred music and his associated positive emotions by a similar mechanism. Using more precise terminology, such experience would represent a type of musical illusion
rather than hallucination
, as an auditory stimulus is actually presented and subsequently misperceived.
Alternatively, Keshavan and colleagues suggest the “concept of parasitic memory”, or an unchangeable memory that can be experienced spontaneously or with some unidentified triggering mechanism. This theoretical occurrence may fit with recent functional neuroimaging data to explain the musical experience of JS and a common anecdotal experience, having a tune “stuck in one’s head.” The PET study identifies distinct neuroanatomic regions activated by semantic versus episodic musical memory tasks (Platel, Baron et al. 2003
). The experience of JS would presumably involve activation of the episodic memory network triggered at the earliest auditory perceptual level (he denied experiencing music spontaneously when directly questioned) coupled with the musical expectation generated by presentation of the personally preferred compact discs and associated discussion or recollection of previous circumstances in which the familiar music was heard. Both explanations remain equally speculative given the available data in this case.
Although the mysteries of the emotional response to music in this case may not be unraveled during the lifetime of JS or his clinicians, reflection on current models of musical processing is demanded by the unusual attributes of the experience of this patient. Proposed revision to current musical models is represented in , emphasizing the emotional response module as accessible from brainstem and subcortical regions active early in musical perceptual processing. Similarly, such early auditory processing may demonstrate previously unrecognized connectivity to an associative memory module in music.
Fig. 3 Proposed comprehensive psychoacoustic model for music perception based on musical modules described by Peretz et al. (2003). See text for details of rationale for departures from current theoretical models as highlighted with bold dashed connectors and (more ...)
Continued theoretical modeling of musical perception may move the study of the cognitive and affective neuroscience of music forward, but the therapeutic potential of music due to its intimate association with human emotion deserves future attention, as well. For example, an animal model exposed to daily music demonstrated significantly increased brain norepinephrine levels when compared to control animals (Panksepp 1986
) suggesting music as a potential for treatment of attentional deficits and mood disorders. Similarly, after presentation of stressful stimuli salivary cortisol levels were noted to decline more rapidly in human subjects exposed to pleasant music when compared to subjects exposed to silence (Khalfa, Bella et al. 2003
) suggesting the potential for music to modulate harmful effects of chronic stress on the brain (Sapolsky 1996
). While it is not known what medical benefits, if any, JS may reap as a result of his persistently rewarding emotional experience of music, his case of neurodegenerative generalized auditory agnosia provides a unique opportunity to envision the positive consequences of exposure to music, or perhaps even more primarily, the mental rehearsal of music in health and disease.