The semantic representation of social groups and its neural substrate

Neuropsychological studies described brain damaged patients with a deficit at recognizing exemplars from some semantic categories while being still able to recognize exemplars from other categories, and vice versa. This evidence suggested that categories such as animals, plants, artifacts and conspecifics might be independently organized in the brain. Several theories tried to explain the category specificity, and proposed that concepts are represented in the brain according to the modality of their features, on the relevance of a domain for survival or on the degree of inter-correlation between features. Perhaps one limitation on investigation on how categories are represented in the brain has to do with the poor characterization of the concept about conspecifics often limited to famous and familiar persons as unique entities, and as such not very comparable with the other categories of stimuli. Recent findings suggested that even the knowledge about categories of conspecifics defined as social groups might well be represented independently of other categories.In the current thesis I investigated whether social group knowledge is indeed represented independently of other categories, consistently with previous findings, and the eventual neural substrates of such knowledge. In two different studies, I tested the knowledge of patients with brain tumors and neurodegenerative diseases about social groups, animate and inanimate entities. Correlating patients\u2019 behavioural performance with structural MRI data, I found that the lesion of a left-lateralized set of areas was selectively associated with the impairment in naming social group pictures. Specifically, inferior frontal gyrus, insula and anterior temporal cortex were associated with social group processing in both the studies. Since these areas were reported to be involved in emotional processing, In a third study with healthy individuals, I tested whether one of the above brain regions, within the opercular part of inferior frontal gyrus, might be involved in processing social groups per se or in processing the valence of stimuli. Results revealed that this area was involved in the processing of negative stimuli and suggested that the semantic impairment in processing social groups might be related to the intrinsic emotional value of this category of stimuli. This pattern of findings suggests that human conceptual knowledge is associated with modality-specific processing areas, and that social group representation might interacts with emotional features

The hearing hippocampus

The hippocampus has a well-established role in spatial and episodic memory but a broader function has been proposed including aspects of perception and relational processing. Neural bases of sound analysis have been described in the pathway to auditory cortex, but wider networks supporting auditory cognition are still being established. We review what is known about the role of the hippocampus in processing auditory information, and how the hippocampus itself is shaped by sound. In examining imaging, recording, and lesion studies in species from rodents to humans, we uncover a hierarchy of hippocampal responses to sound including during passive exposure, active listening, and the learning of associations between sounds and other stimuli. We describe how the hippocampus' connectivity and computational architecture allow it to track and manipulate auditory information – whether in the form of speech, music, or environmental, emotional, or phantom sounds. Functional and structural correlates of auditory experience are also identified. The extent of auditory-hippocampal interactions is consistent with the view that the hippocampus makes broad contributions to perception and cognition, beyond spatial and episodic memory. More deeply understanding these interactions may unlock applications including entraining hippocampal rhythms to support cognition, and intervening in links between hearing loss and dementia

Mechanisms of voice processing in dementia

Perception of nonverbal vocal information is essential in our daily lives. Patients with degenerative dementias commonly have difficulty with such aspects of vocal communication; however voice processing has seldom been studied in these diseases. This thesis comprises a series of linked studies of voice processing in canonical dementias: Alzheimer’s disease, behavioural variant frontotemporal dementia, semantic dementia and progressive nonfluent aphasia. A series of neuropsychological tests were developed to examine perceptual and semantic stages of voice processing and to assess two aspects of accent processing: comprehension of foreign accented speech and recognition of regional and foreign accents; patient performance was referenced to healthy control subjects. Neuroanatomical associations of voice processing performance were assessed using voxel based morphometry. Following a symptom-led approach, a syndrome of progressive associative phonagnosia was characterised in two detailed case studies. Following a disease-led approach, this work was extended systematically to cohorts of patients representing the target diseases and assessing voice processing in relation to other aspects of person recognition (faces and names). This work provided evidence for separable profiles of voice processing impairment in different diseases: associative deficits were particularly severe in semantic dementia, whilst perceptual deficits showed relative specificity for Alzheimer’s disease. Neuroanatomical associations were identified for voice recognition in the right temporal pole and anterior fusiform gyrus, and for voice discrimination in the right inferior parietal lobe. The final phase of this work addressed the neuropsychological and neuroanatomical basis of accent processing, as an important dimension of nonverbal vocal analysis that is not dependent on voice identity. This work provides evidence for impaired processing of accents in progressive nonfluent aphasia and Alzheimer’s with neuroanatomical associations in the anterior and superior temporal lobe. The thesis contributes new information about voice processing in the degenerative dementias and furthers our understanding of the mechanisms of human voice analysis

Processing of nonverbal vocalisations in dementia

Nonverbal emotional vocalisations are fundamental communicative signals used to convey a diverse repertoire of social and emotional information. They transcend the boundaries of language and cultural specificity that hamper many neuropsychological tests, making them ideal candidates for understanding impaired socio-emotional signal processing in dementia. Symptoms related to changes in social behaviour and emotional responsiveness are poorly understood yet have significant impact on patients with dementia and those who care for them. In this thesis, I investigated processing of nonverbal emotional vocalisations in patients with Alzheimer’s disease and frontotemporal dementia (FTD), a disease spectrum encompassing three canonical syndromes characterised by marked socio-emotional and communication difficulties - behavioural variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA) and nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). I demonstrated distinct profiles of impairment in identifying three salient vocalisations (laughter, crying and screaming) and the emotions they convey. All three FTD syndromes showed impairments, with the most marked deficits of emotion categorisation seen in the bvFTD group. Voxel-based morphometry was used to define critical brain substrates for processing vocalisations, identifying correlates of vocal sound processing with auditory perceptual regions (superior temporal sulcus and posterior insula) and emotion identification with limbic and medial frontal regions. The second half of this thesis focused on the more fine-grained distinction of laughter subtypes. I studied cognitive (labelling), affective (valence) and autonomic (pupillometric) processing of laughter subtypes representing dimensions of valence (mirthful versus hostile) and arousal (spontaneous versus posed). Again, FTD groups showed greatest impairment with profiles suggestive of primary perceptual deficits in nfvPPA, cognitive overgeneralisation in svPPA and disordered reward and hedonic valuation in bvFTD. Neuroanatomical correlates of explicit laughter identification included inferior frontal and cingulo-insular cortices whilst implicit processing (indexed as autonomic arousal) was particularly impaired in those conditions associated with insular compromise (nfvPPA and bvFTD). These findings demonstrate the potential of nonverbal emotional vocalisations as a probe of neural mechanisms underpinning socio-emotional dysfunction in neurodegenerative diseases

Neurocognitive networks for social cognition: Insights from diffusion weighted imaging and frontotemporal dementia

Empathy is a complex and multicomponent social cognitive function. It is underpinned by large-scale neurocognitive networks, the precise cognitive and neural structure of which remains debated. Despite this, relatively little work has considered the cognitive or neural components of empathy at the network-level. Here I present work using diffusion weighted magnetic resonance imaging (DWI) in healthy adults, and cognitive and behavioural assessment in a relatively rare form of dementia, the behavioural variant of frontotemporal dementia (bvFTD). Using these methods I explore: (a) the relationship between the microstructural properties of white matter tracts that mediate connectivity between distinct neurocognitive networks and separable cognitive components of empathic cognition (b) the cognitive and behavioural consequences of perturbation to neurocognitive networks in dementia. BvFTD is of interest here as it appears to preferentially target neural networks that support socioemotional processing. In chapters 2 and 3, evidence regarding the white matter structures that are affected by bvFTD guides investigations of the relationship between the microstructural properties of specific white matter tracts and social cognitive functioning in the healthy adult brain. In these chapters, I show that, in young healthy adults, two white matter pathways, sensitive to early changes in bvFTD, the Uncinate fasciculus (UF) and the cingulum bundle (CB), are related to individual differences in two components of empathic functioning, respectively: facial emotion decoding and mentalising. In chapter 4 I show the dissociation of performance on tasks assessing these cognitive functions in an individual with early bvFTD. I highlight the sensitivity and potential clinical utility of tasks assessing literary fiction-based mentalising. In Chapter 5 I present a detailed qualitative description of social cognitive change in frontotemporal dementia (FTD), from the perspective of family members. I consider what such detailed descriptions of everyday behaviour may tell us about the cognitive underpinnings of complex social behaviour. The findings of this thesis further our understanding of the dissociable neurocognitive networks that support empathic functioning, including their structural underpinnings and the behavioural consequences of their perturbation. In the general discussion, I consider the implications of this work for our understanding of social cognitive functioning and bvFTD

Exploring aspects of memory in healthy ageing and following stroke

Memory is critical for everyday functioning. Remembering an event with rich detail requires the ability to remember the temporal order of occurrences within the event and spatial locations associated with it. But it remains unclear whether it also requires memory for the perspective from which we encoded the event, whether these three aspects of memory are affected following stroke, and which are the key brain regions upon which they rely. These questions are explored in this thesis. In the first study presented here, I examined young and elderly healthy subjects with an autobiographical memory interview and a 2D spatial memory task assessing self-perspective, and found no correlation between performance on these tasks. In the second experimental study, by assessing stroke patients on a 3D spatio-temporal memory task, I found that damage to the right intraparietal sulcus was associated with poorer memory for temporal order. However, voxelwise analyses detected no association between parietal lobe regions and accuracy in the egocentric condition of this task, or between medial temporal lobe regions and accuracy in the allocentric condition, one possible reason being that performance was near ceiling. In the third experimental study, by assessing a considerably larger group of stroke patients on a spatial memory task, I found that, as a group, patients performed worse than healthy controls, and performance was correlated with an activities of daily living scale. A spatial memory network was identified in right (but not left) hemisphere stroke patients. These findings provide evidence that spatial memory impairment is common after stroke, highlight its potential functional relevance, and increase our understanding of which regions are critical for remembering temporal order and spatial information. Furthermore, they suggest a dissociation between the mechanisms underpinning recall of 2D scenes over relatively short intervals versus remembering of real-life events across periods of many years.Open Acces

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

Cognitive control development in adolescence

Adolescence is a transitional period in which an increasing ability to coordinate basic cognitive control abilities is also particularly challenged by contextual factors in the environment. The aim of this dissertation was to examine the development of complex cognitive control in adolescence in relation to different socio-affective contexts at the behavioural and neural level. The dissertation presents three functional magnetic resonance imaging (fMRI) experiments. The first studies explored transient and sustained aspects of cognitive control, and how the context influences behaviour and brain activation during cognitive control tasks. Study 1 used a prospective memory task where the cues were more or less salient, affecting the need to proactively monitor the stimuli vs. react to more distinctive cues. Study 2 used a working memory task and manipulated the reward context, on a trial-by-trial or run-by-run basis. Study 3 used a relational reasoning task to investigate manipulation and integration of information and its sensitivity to the nature of this information, in particular whether making judgements in the social domain elicited specific brain activations compared to the non-social domain. All three studies were run in adolescent and adult participants, to allow the study of developmental changes in complex cognitive control at the behavioural and brain level. Study 1 found behavioural evidence for development of prospective memory in adolescence and neuroimaging evidence for sustained and transient activation of the frontoparietal network associated with monitoring costs for cue detection whilst being engaged in a different task. Study 2 found that in the context of sporadic rewards, both adolescents and adults combine a proactive and a reactive strategy to maximise performance. Reward had both sustained and transient effects on frontoparietal regions as well as subcortical regions involved in reward processing. Study 3 showed parallel recruitment of the social brain and the relational reasoning network during the relational integration of social information in adolescence and adulthood. Across the three studies, there was evidence for behavioural improvement with age, but no strong differences of haemodynamic brain changes between adolescence and adulthood