The primary progressive aphasias (PPA) are paradigmatic disorders of language network breakdown associated with focal degeneration of the left cerebral hemisphere. Here we addressed brain correlates of PPA in a detailed neuroanatomical analysis of the third canonical syndrome of PPA, logopenic/phonological aphasia (LPA), in relation to the more widely studied clinico-anatomical syndromes of semantic dementia (SD) and progressive nonfluent aphasia (PNFA). 32 PPA patients (9 SD, 14 PNFA, 9 LPA) and 18 cognitively normal controls had volumetric brain MRI with regional volumetry, cortical thickness, grey and white matter voxel-based morphometry analyses. Five of nine patients with LPA had cerebrospinal fluid biomarkers consistent with Alzheimer (AD) pathology (AD-PPA) and 2/9 patients had progranulin (GRN) mutations (GRN-PPA). The LPA group had tissue loss in a widespread left hemisphere network. Compared with PNFA and SD, the LPA group had more extensive involvement of grey matter in posterior temporal and parietal cortices and long association white matter tracts. Overlapping but distinct networks were involved in the AD-PPA and GRN-PPA subgroups, with more anterior temporal lobe involvement in GRN-PPA. The importance of these findings is threefold: firstly, the clinico-anatomical entity of LPA has a profile of brain damage that is complementary to the network-based disorders of SD and PNFA; secondly, the core phonological processing deficit in LPA is likely to arise from temporo-parietal junction damage but disease spread occurs through the dorsal language network (and in GRN-PPA, also the ventral language network); and finally, GRN mutations provide a specific molecular substrate for language network dysfunction.

Despite growing clinical and neurobiological interest in the brain mechanisms that process emotion in music, these mechanisms remain incompletely understood. Patients with frontotemporal lobar degeneration (FTLD) frequently exhibit clinical syndromes that illustrate the effects of breakdown in emotional and social functioning. Here we investigated the neuroanatomical substrate for recognition of musical emotion in a cohort of 26 patients with FTLD (16 with behavioural variant frontotemporal dementia, bvFTD, 10 with semantic dementia, SemD) using voxel-based morphometry. On neuropsychological evaluation, patients with FTLD showed deficient recognition of canonical emotions (happiness, sadness, anger and fear) from music as well as faces and voices compared with healthy control subjects. Impaired recognition of emotions from music was specifically associated with grey matter loss in a distributed cerebral network including insula, orbitofrontal cortex, anterior cingulate and medial prefrontal cortex, anterior temporal and more posterior temporal and parietal cortices, amygdala and the subcortical mesolimbic system. This network constitutes an essential brain substrate for recognition of musical emotion that overlaps with brain regions previously implicated in coding emotional value, behavioural context, conceptual knowledge and theory of mind. Musical emotion recognition may probe the interface of these processes, delineating a profile of brain damage that is essential for the abstraction of complex social emotions.

Salient sensory experiences often have a strong emotional tone, but the neuropsychological relations between perceptual characteristics of sensory objects and the affective information they convey remain poorly defined. Here we addressed the relationship between sound identity and emotional information using music. In two experiments, we investigated whether perception of emotions is influenced by altering the musical instrument on which the music is played, independently of other musical features. In the first experiment, 40 novel melodies each representing one of four emotions (happiness, sadness, fear, or anger) were each recorded on four different instruments (an electronic synthesizer, a piano, a violin, and a trumpet), controlling for melody, tempo, and loudness between instruments. Healthy participants (23 young adults aged 18–30 years, 24 older adults aged 58–75 years) were asked to select which emotion they thought each musical stimulus represented in a four-alternative forced-choice task. Using a generalized linear mixed model we found a significant interaction between instrument and emotion judgement with a similar pattern in young and older adults (p < .0001 for each age group). The effect was not attributable to musical expertise. In the second experiment using the same melodies and experimental design, the interaction between timbre and perceived emotion was replicated (p < .05) in another group of young adults for novel synthetic timbres designed to incorporate timbral cues to particular emotions. Our findings show that timbre (instrument identity) independently affects the perception of emotions in music after controlling for other acoustic, cognitive, and performance factors.

Despite much recent interest in the clinical neuroscience of music processing, the cognitive organization of music as a domain of non-verbal knowledge has been little studied. Here we addressed this issue systematically in two expert musicians with clinical diagnoses of semantic dementia and Alzheimer’s disease, in comparison with a control group of healthy expert musicians. In a series of neuropsychological experiments, we investigated associative knowledge of musical compositions (musical objects), musical emotions, musical instruments (musical sources) and music notation (musical symbols). These aspects of music knowledge were assessed in relation to musical perceptual abilities and extra-musical neuropsychological functions. The patient with semantic dementia showed relatively preserved recognition of musical compositions and musical symbols despite severely impaired recognition of musical emotions and musical instruments from sound. In contrast, the patient with Alzheimer’s disease showed impaired recognition of compositions, with somewhat better recognition of composer and musical era, and impaired comprehension of musical symbols, but normal recognition of musical emotions and musical instruments from sound. The findings suggest that music knowledge is fractionated, and superordinate musical knowledge is relatively more robust than knowledge of particular music. We propose that music constitutes a distinct domain of non-verbal knowledge but shares certain cognitive organizational features with other brain knowledge systems. Within the domain of music knowledge, dissociable cognitive mechanisms process knowledge derived from physical sources and the knowledge of abstract musical entities.