Predictive cognition in dementia: the case of music

The clinical complexity and pathological diversity of neurodegenerative diseases impose immense challenges for diagnosis and the design of rational interventions. To address these challenges, there is a need to identify new paradigms and biomarkers that capture shared pathophysiological processes and can be applied across a range of diseases. One core paradigm of brain function is predictive coding: the processes by which the brain establishes predictions and uses them to minimise prediction errors represented as the difference between predictions and actual sensory inputs. The processes involved in processing unexpected events and responding appropriately are vulnerable in common dementias but difficult to characterise. In my PhD work, I have exploited key properties of music – its universality, ecological relevance and structural regularity – to model and assess predictive cognition in patients representing major syndromes of frontotemporal dementia – non-fluent variant PPA (nfvPPA), semantic-variant PPA (svPPA) and behavioural-variant FTD (bvFTD) - and Alzheimer’s disease relative to healthy older individuals. In my first experiment, I presented patients with well-known melodies containing no deviants or one of three types of deviant - acoustic (white-noise burst), syntactic (key-violating pitch change) or semantic (key-preserving pitch change). I assessed accuracy detecting melodic deviants and simultaneously-recorded pupillary responses to these deviants. I used voxel-based morphometry to define neuroanatomical substrates for the behavioural and autonomic processing of these different types of deviants, and identified a posterior temporo-parietal network for detection of basic acoustic deviants and a more anterior fronto-temporo-striatal network for detection of syntactic pitch deviants. In my second chapter, I investigated the ability of patients to track the statistical structure of the same musical stimuli, using a computational model of the information dynamics of music to calculate the information-content of deviants (unexpectedness) and entropy of melodies (uncertainty). I related these information-theoretic metrics to performance for detection of deviants and to ‘evoked’ and ‘integrative’ pupil reactivity to deviants and melodies respectively and found neuroanatomical correlates in bilateral dorsal and ventral striatum, hippocampus, superior temporal gyri, right temporal pole and left inferior frontal gyrus. Together, chapters 3 and 4 revealed new hypotheses about the way FTD and AD pathologies disrupt the integration of predictive errors with predictions: a retained ability of AD patients to detect deviants at all levels of the hierarchy with a preserved autonomic sensitivity to information-theoretic properties of musical stimuli; a generalized impairment of surprise detection and statistical tracking of musical information at both a cognitive and autonomic levels for svPPA patients underlying a diminished precision of predictions; the exact mirror profile of svPPA patients in nfvPPA patients with an abnormally high rate of false-alarms with up-regulated pupillary reactivity to deviants, interpreted as over-precise or inflexible predictions accompanied with normal cognitive and autonomic probabilistic tracking of information; an impaired behavioural and autonomic reactivity to unexpected events with a retained reactivity to environmental uncertainty in bvFTD patients. Chapters 5 and 6 assessed the status of reward prediction error processing and updating via actions in bvFTD. I created pleasant and aversive musical stimuli by manipulating chord progressions and used a classic reinforcement-learning paradigm which asked participants to choose the visual cue with the highest probability of obtaining a musical ‘reward’. bvFTD patients showed reduced sensitivity to the consequence of an action and lower learning rate in response to aversive stimuli compared to reward. These results correlated with neuroanatomical substrates in ventral and dorsal attention networks, dorsal striatum, parahippocampal gyrus and temporo-parietal junction. Deficits were governed by the level of environmental uncertainty with normal learning dynamics in a structured and binarized environment but exacerbated deficits in noisier environments. Impaired choice accuracy in noisy environments correlated with measures of ritualistic and compulsive behavioural changes and abnormally reduced learning dynamics correlated with behavioural changes related to empathy and theory-of-mind. Together, these experiments represent the most comprehensive attempt to date to define the way neurodegenerative pathologies disrupts the perceptual, behavioural and physiological encoding of unexpected events in predictive coding terms

Music models aberrant rule decoding and reward valuation in dementia.

Aberrant rule- and reward-based processes underpin abnormalities of socio-emotional behaviour in major dementias. However, these processes remain poorly characterized. Here we used music to probe rule decoding and reward valuation in patients with frontotemporal dementia (FTD) syndromes and Alzheimer's disease (AD) relative to healthy age-matched individuals. We created short melodies that were either harmonically resolved ('finished') or unresolved ('unfinished'); the task was to classify each melody as finished or unfinished (rule processing) and rate its subjective pleasantness (reward valuation). Results were adjusted for elementary pitch and executive processing; neuroanatomical correlates were assessed using voxel-based morphometry. Relative to healthy older controls, patients with behavioural variant FTD showed impairments of both musical rule decoding and reward valuation, while patients with semantic dementia showed impaired reward valuation but intact rule decoding, patients with AD showed impaired rule decoding but intact reward valuation and patients with progressive non-fluent aphasia performed comparably to healthy controls. Grey matter associations with task performance were identified in anterior temporal, medial and lateral orbitofrontal cortices, previously implicated in computing diverse biological and non-biological rules and rewards. The processing of musical rules and reward distils cognitive and neuroanatomical mechanisms relevant to complex socio-emotional dysfunction in major dementias

Music models aberrant rule decoding and reward valuation in dementia.

Aberrant rule- and reward-based processes underpin abnormalities of socio-emotional behaviour in major dementias. However, these processes remain poorly characterized. Here we used music to probe rule decoding and reward valuation in patients with frontotemporal dementia (FTD) syndromes and Alzheimer's disease (AD) relative to healthy age-matched individuals. We created short melodies that were either harmonically resolved ('finished') or unresolved ('unfinished'); the task was to classify each melody as finished or unfinished (rule processing) and rate its subjective pleasantness (reward valuation). Results were adjusted for elementary pitch and executive processing; neuroanatomical correlates were assessed using voxel-based morphometry. Relative to healthy older controls, patients with behavioural variant FTD showed impairments of both musical rule decoding and reward valuation, while patients with semantic dementia showed impaired reward valuation but intact rule decoding, patients with AD showed impaired rule decoding but intact reward valuation and patients with progressive non-fluent aphasia performed comparably to healthy controls. Grey matter associations with task performance were identified in anterior temporal, medial and lateral orbitofrontal cortices, previously implicated in computing diverse biological and non-biological rules and rewards. The processing of musical rules and reward distils cognitive and neuroanatomical mechanisms relevant to complex socio-emotional dysfunction in major dementias

BitBox!:A case study interface for teaching real-time adaptive music composition for video games

Real-time adaptive music is now well-established as a popular medium, largely through its use in video game soundtracks. Commercial packages, such as fmod, make freely available the underlying technical methods for use in educational contexts, making adaptive music technologies accessible to students. Writing adaptive music, however, presents a significant learning challenge, not least because it requires a different mode of thought, and tutor and learner may have few mutual points of connection in discovering and understanding the musical drivers, relationships and structures in these works. This article discusses the creation of ‘BitBox!’, a gestural music interface designed to deconstruct and explain the component elements of adaptive composition through interactive play. The interface was displayed at the Dare Protoplay games exposition in Dundee in August 2014. The initial proof-of- concept study proved successful, suggesting possible refinements in design and a broader range of applications

Musical development during adolescence: Perceptual skills, cognitive resources, and musical training

Longitudinal studies on musical development can provide very valuable insights and potentially evidence for causal mechanisms driving the development of musical skills and cognitive resources, such as working memory and intelligence. Nonetheless, quantitative longitudinal studies on musical and cognitive development are very rare in the published literature. Hence, the aim of this paper is to document available longitudinal evidence on musical development from three different sources. In part I, data from a systematic literature review are presented in a graphical format, making developmental trends from five previous longitudinal studies comparable. Part II presents a model of musical development derived from music-related variables that are part of the British Millennium Cohort Study. In part III, data from the ongoing LongGold project are analyzed answering five questions on the change of musical skills and cognitive resources across adolescence and on the role that musical training and activities might play in these developmental processes. Results provide evidence for substantial near transfer effects (from musical training to musical skills) and weaker evidence for far-transfer to cognitive variables. But results also show evidence of cognitive profiles of high intelligence and working memory capacity that are conducive to strong subsequent growth rates of musical development

Finding Structure in Silence: The Role of Pauses in Aligning Speaker Expectations

The intelligibility of speech relies on the ability of interlocutors to dynamically align their expectations about the rates at which informative changes in signals occur. Exactly how this is achieved remains an open question. We propose that speaker alignment is supported by the statistical structure of spoken signals and show how pauses offer a time-invariant template for structuring speech sequences. Consistent with this, we show that pause distributions in conversational English and Korean provide a memoryless information source. We describe how this can facilitate both the initial structuring and maintenance of predictability in spoken signals over time, and show how the properties of this signal change predictably with speaker experience. These results indicate that pauses provide a structuring signal that interacts with the morphological and rhythmical structure of languages, allowing speakers at all stages of lifespan development to distinguish signal from noise and maintain mutual predictability in time.Comment: 25 pages, 5 figure

Persistent effects of musical training on mathematical skills of children with developmental dyscalculia

Musical training (MT) is perceived as a multi-sensory program that simultaneously integrates visual, aural, oral, and kinesthetic senses. Furthermore, MT stimulates cognitive functions in a ludic way instead of tapping straight into the traditional context of school learning, including mathematics. Nevertheless, the efficacy of MT over mathematics remains understudied, especially concerning longstanding effects. For this reason, this longitudinal study explored the impact of MT on numerical cognition and abstract visual reasoning using a double-blind and quasi-experimental design. We assessed two groups of children from primary schools, namely one with developmental dyscalculia [DD; n = 22] and another comprising typically developing children [TD; n = 22], who concomitantly underwent MT. Numerical cognition measurement was carried out at four different time points: Baseline (pre-MT assessment), mid-test (after 7 weeks of MT), post-test (after 14 weeks of MT), and follow-up (10 weeks after the end of MT). Significant interactions were found between time and group for numerical cognition performance, in which the DD group showed higher scores in number comprehension, number production at mid-test, and calculation at post-test compared to baseline. A key finding was that number production, number comprehension, and calculation effects were time-resistant for the DD group since changes remained on follow-up. Moreover, no significant differences over time were found for abstract visual reasoning for both groups. In conclusion, the findings of this study showed that MT appears to be a useful tool for compensatory remediation of DD.info:eu-repo/semantics/publishedVersio

Social Signal Decoding in Frontotemporal Lobar Degeneration

Frontotemporal lobar degeneration (FTLD) is associated with progressive social cognitive impairment. Currently a comprehensive pathophysiological model allowing disease effects to be understood and anticipated at the level of the whole brain is lacking. In this thesis I explored candidate cognitive operations underpinning complex behaviours in patients with the canonical syndromes of FTLD; behavioural variant frontotemporal dementia (bvFTD) and semantic dementia (SD). I correlated behavioural deficits with brain network disintegration using the structural magnetic resonance imaging (MRI) technique, voxel based morphometry (VBM). I created synthetic scenes to manipulate congruity across semantic and emotional domains (Chapter 3) and showed deficits across both patient groups. The deficits have grey matter correlates in prefronto-parieto-temporo-insular network and a temporo-insulo-striatal network. I used music as a non-verbal syntactic probe to investigate reward anticipation and valuation (Chapter 4) and demonstrated dissociable deficits across dementias. Performance was associated with grey matter in a distributed network including anterior temporal cortex and orbitofrontal cortex (OFC), previously implicated in computing diverse rewards. I created a novel neuropsychological test of humorous intent (Chapter 5) to model incongruity processing. bvFTD demonstrates a particular difficulty decoding novel humorous situations while SD produces a more general deficit of humour detection. Humour detection accuracy was associated with temporoparietal junction (TPJ) and anterior superior temporal cortical volume which are hubs for processing incongruity and semantic associations. To assess the relevance of these findings (Chapter 5) to daily life behaviour I explored humour preferences across dementias (Chapter 6). Altered sense of humour is particularly salient in bvFTD and SD, but also frequent in AD and may predate more typical symptoms. In conclusion, impairment in incongruity processing and reward allocation was shown across paradigms. The neuroanatomical networks underpinning these processes overlapped with areas known to be targeted by FTLD. These processes have implications for our understanding of the social dysfunction that defines bvFTD