Rohani Omar

The structural neuroanatomy of music emotion recognition: Evidence from frontotemporal lobar degeneration

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.

Flavour processing in semantic dementia

The cognitive mechanisms for the analysis of flavour information remain poorly understood. Patients with semantic dementia (SD) could potentially provide a window on these mechanisms; however, while abnormal eating behaviour and altered food preferences are common in SD, flavour processing has been little studied in this disorder. Here we undertook a detailed investigation of flavour processing in three patients at different stages of SD. One patient with a clinical syndrome of logopenic aphasia (LPA) was studied as a disease control, and six healthy control subjects also participated. Olfaction was assessed using the University of Pennsylvania Smell Identification Test and processing of flavours was assessed using a novel battery to assess flavour perception, flavour identification, and congruence and affective valence of flavour combinations. Patients with SD performed equivalently to healthy controls on the perceptual subtest, while their ability to identify flavours or to determine congruence of flavour combinations was impaired. Classification of flavours according to affective valence was comparable to healthy controls. In contrast, the patient with LPA exhibited a perceptual deficit with relatively preserved identification of flavours, but impaired ability to determine flavour congruence, which did not benefit from affective valence. Olfactory and flavour identification performance was correlated in both patients and controls. We propose that SD produces a true deficit of flavour knowledge (an associative agnosia), while other peri-Sylvian pathologies may lead to deficient flavour perception. Our findings are consistent with emerging evidence from healthy subjects for a cortical hierarchy for processing flavour information, instantiated in a brain network that includes the insula, anterior temporal lobes and orbitofrontal cortex. The findings suggest a potential mechanism for the development of food fads and other abnormal eating behaviours.

Tracking progression in frontotemporal lobar degeneration Serial MRI in semantic dementia

Background: Semantic dementia is a sporadic neurodegenerative disorder characterized by the progressive erosion of semantic processing and is one of the canonical subtypes of frontotemporal lobar degeneration. This study aimed to characterize the pattern of global and regional longitudinal brain atrophy in semantic dementia and to identify imaging biomarkers that could underpin therapeutic trials. Methods: Twenty-one patients with semantic dementia (including eight pathologically confirmed cases) underwent whole-brain and region-of-interest analyses on volumetric brain MRI scans at two time points. Sample size estimates for trials were subsequently calculated using these data. Results: Mean (SD) whole-brain atrophy rate was 39.6 (31.9) mL/y [3.2 (12.0) mL/y in controls], with ventricular enlargement of 8.9 (4.4) mL/y [1.0 (1.0) mL/y in controls]. All patients had a smaller left temporal lobe at baseline [left mean 31.9 (6.9) mL, right mean 49.2 (9.5) mL; p < 0.0001]; however, the mean rate of atrophy was significantly greater in the right temporal lobe [right 3.9 (1.7) mL/y, left 2.8 (1.2) mL/y; p = 0.02]. Similarly, whereas the left hippocampus was smaller at baseline, the mean atrophy rate was significantly greater in the right hippocampus. Using the atrophy rates generated, sample size requirements for clinical trials were found to be smallest for temporal lobe measurement. Conclusions: These findings show that the rate of tissue loss in the right temporal lobe overtakes the left temporal lobe as semantic dementia evolves, consistent with the later development of symptoms attributable to right temporal lobe dysfunction. Furthermore, our findings demonstrate that MRI measures of temporal lobe volume loss could provide a feasible and sensitive index of disease progression in semantic dementia.

The cognitive organization of music knowledge: a clinical analysis

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.

It's not what you play, it's how you play it: Timbre affects perception of emotion in music

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.

Measuring disease progression in frontotemporal lobar degeneration: A clinical and MRI study

Objectives: There is currently much interest in biomarkers of disease activity in frontotemporal lobar degeneration (FTLD). We assessed MRI and behavioral measures of progression in a longitudinal FTLD cohort. Methods: Thirty-two patients with FTLD (11 behavioral variant frontotemporal dementia [bvFTD], 11 semantic dementia [SemD], 10 progressive nonfluent aphasia [PNFA]) and 24 age-matched healthy controls were assessed using volumetric brain MRI and standard behavioral measures (Mini-Mental State Examination, Frontal Assessment Battery, Clinical Dementia Rating Scale, Neuropsychiatric Inventory with Caregiver Distress scale) at baseline and 1 year later. A semi-automated image registration protocol was used to calculate annualized rates of brain atrophy (brain boundary shift integral [BBSI]) and ventricular expansion (ventricular boundary shift integral [VBSI]). Associations between these rates and changes in behavioral indices were investigated. Results: Rates of whole brain atrophy were greater in the entire FTLD cohort and in each subgroup compared with controls (all p ≤ 0.004). Rates of ventricular expansion were greater in the entire cohort (p < 0.001) and the SemD (p = 0.002) and PNFA (p = 0.05) subgroups compared with controls. Changes in Mini-Mental State Examination, Frontal Assessment Battery, and Clinical Dementia Rating Scale scores were associated with MRI measures of progression, though not uniformly across FTLD subgroups. Both BBSI and VBSI yielded feasible sample size estimates for detecting meaningful treatment effects in SemD and PNFA language subgroups. Sample sizes were substantially larger using MRI biomarkers for the bvFTD subgroup, and using behavioral biomarkers in general. Conclusions: Semi-automated MRI atrophy measures are potentially useful objective biomarkers of progression in frontotemporal lobar degeneration (FTLD); however, careful stratification of FTLD subtypes will be important in future clinical trials of disease-modifying therapies.

Structural neuroanatomy of face processing in frontotemporal lobar degeneration

Impairments of face processing occur frequently in frontotemporal lobar degeneration (FTLD) but the neuroanatomical basis for these deficits has seldom been studied systematically. Here a prospective voxel based morphometry study is described addressing the neuroanatomy of two key dimensions of face processing—face identification and facial emotion recognition—in a single cohort of 32 patients with FTLD (19 with frontal variant and 13 with temporal variant FTLD). For the FTLD group as a whole, face identification was positively associated with grey matter in the right anterior fusiform gyrus while recognition of angry expressions was positively associated with grey matter in the bilateral insula cortex. FTLD provides a perspective on the neuroanatomy of face processing that is complementary to focal lesion and normal functional imaging work.

Flavour identification in frontotemporal lobar degeneration

Background Deficits of flavour processing may be clinically important in frontotemporal lobar degeneration (FTLD). Objective To examine flavour processing in FTLD. Methods We studied flavour identification prospectively in 25 patients with FTLD (12 with behavioural variant frontotemporal dementia (bvFTD), eight with semantic variant primary progressive aphasia (svPPA), five with non-fluent variant primary progressive aphasia (nfvPPA)) and 17 healthy control subjects, using a new test based on cross-modal matching of flavours to words and pictures. All subjects completed a general neuropsychological assessment, and odour identification was also assessed using a modified University of Pennsylvania Smell Identification Test. Brain MRI volumes from the patient cohort were analysed using voxel-based morphometry to identify regional grey matter associations of flavour identification. Results Relative to the healthy control group, the bvFTD and svPPA subgroups showed significant (p<0.05) deficits of flavour identification and all three FTLD subgroups showed deficits of odour identification. Flavour identification performance did not differ significantly between the FTLD syndromic subgroups. Flavour identification performance in the combined FTLD cohort was significantly (p<0.05 after multiple comparisons correction) associated with grey matter volume in the left entorhinal cortex, hippocampus, parahippocampal gyrus and temporal pole. Conclusions Certain FTLD syndromes are associated with impaired flavour identification and this is underpinned by grey matter atrophy in an anteromedial temporal lobe network. These findings may have implications for our understanding of abnormal eating behaviour in these diseases.

Delusions in frontotemporal lobar degeneration

We assessed the significance and nature of delusions in frontotemporal lobar degeneration (FTLD), an important cause of young-onset dementia with prominent neuropsychiatric features that remain incompletely characterised. The case notes of all patients meeting diagnostic criteria for FTLD attending a tertiary level cognitive disorders clinic over a three year period were retrospectively reviewed and eight patients with a history of delusions were identified. All patients underwent detailed clinical and neuropsychological evaluation and brain MRI. The diagnosis was confirmed pathologically in two cases. The estimated prevalence of delusions was 14 %. Delusions were an early, prominent and persistent feature. They were phenomenologically diverse; however paranoid and somatic delusions were prominent. Behavioural variant FTLD was the most frequently associated clinical subtype and cerebral atrophy was bilateral or predominantly right-sided in most cases. We conclude that delusions may be a clinical issue in FTLD, and this should be explored further in future work.

Parietal Lobe Deficits in Frontotemporal Lobar Degeneration Caused by a Mutation in the Progranulin Gene

OBJECTIVE To describe the clinical, neuropsychologic, and radiologic features of a family with a C31LfsX35 mutation in the progranulin gene CCDS11483.1). DESIGN Case series. PATIENTS A large British kindred (DRC255) with a PGRN mutation was assessed. Affected individuals presented with a mean age of 57.8 years (range, 54-67 years) and a mean disease duration of 6.1 years (range, 2-11 years). RESULTS All patients exhibited a clinical and radiologic phenotype compatible with frontotemporal lobar degeneration based on current consensus criteria. However, unlike sporadic frontotemporal lobar degeneration, parietal deficits, consisting of dyscalculia, visuoperceptual /visuospatial dysfunction, and/or limb apraxia, were a common feature, and brain imaging showed posterior extension of frontotemporal atrophy to involve the parietal lobes. Other common clinical features included language output impairment with either dynamic aphasia or nonfluent aphasia and a behavioral syndrome dominated by apathy. CONCLUSION We suggest that parietal deficits may be a prominent feature of PGRN mutations and that these deficits may be caused by disruption of frontoparietal functional pathways.