Hemispheric differences in semantic cognition and their contribution to behaviour

This thesis investigated hemispheric differences in semantic cognition and their contribution to behaviour, using resting-state and task-based fMRI in conjunction with automated meta-analyses and cognitive decoding. The controlled semantic cognition framework proposes that distinct brain regions support the long-term representation of heteromodal conceptual knowledge and semantic control processes that retrieve currently-relevant aspects of knowledge. However, previous studies have not investigated whether these components have distinct patterns of lateralisation. Chapter 2 assessed intrinsic connectivity of four regions implicated in semantic cognition: anterior temporal lobe, angular gyrus, inferior frontal gyrus, and posterior middle temporal gyrus. Semantic sites in the left hemisphere showed connectivity with both control regions and default mode network, whilst their right hemisphere homotopes showed connectivity with control regions and visual and attentional systems. Semantic control regions showed the strongest lateralisation. Chapter 3 examined hemispheric specialisation of the anterior temporal lobes, strongly implicated in semantic representation. It assessed the relationship between differential intrinsic connectivity and behaviour outside the scanner on a semantic categorisation task previously shown to be sensitive to lateralisation. Graded differences in connectivity between left and right anterior temporal lobes, and from right anterior temporal cortex to the visual system related to semantic efficiency. Finally, Chapter 4 tested the specificity of the semantic control system and its relationship to domain-general control. Using a task known to engage domain-general inhibition, but introducing semantic content, this chapter yields evidence that regions implicated in semantic control are not sensitive to challenging tasks that require exercising controlled processing, and instead are specific to semantic processing. Together, these results constitute evidence for a component-process architecture in the semantic cognition system, with different patterns of lateralisation for the semantic representation and control systems. Within these systems, the results confirm the specific nature of semantic control, and fit with the graded-hub architecture of semantic representation

Changes in cortical and sub-cortical patterns of activity associated with aging during the performance of a lexical set-shifting task

Bien que le passage du temps altère le cerveau, la cognition ne suit pas nécessairement le même destin. En effet, il existe des mécanismes compensatoires qui permettent de préserver la cognition (réserve cognitive) malgré le vieillissement. Les personnes âgées peuvent utiliser de nouveaux circuits neuronaux (compensation neuronale) ou des circuits existants moins susceptibles aux effets du vieillissement (réserve neuronale) pour maintenir un haut niveau de performance cognitive. Toutefois, la façon dont ces mécanismes affectent l’activité corticale et striatale lors de tâches impliquant des changements de règles (set-shifting) et durant le traitement sémantique et phonologique n’a pas été extensivement explorée. Le but de cette thèse est d’explorer comment le vieillissement affecte les patrons d’activité cérébrale dans les processus exécutifs d’une part et dans l’utilisation de règles lexicales d’autre part. Pour cela nous avons utilisé l’imagerie par résonance magnétique fonctionnelle (IRMf) lors de la performance d’une tâche lexicale analogue à celle du Wisconsin. Cette tâche a été fortement liée à de l’activité fronto-stritale lors des changements de règles, ainsi qu’à la mobilisation de régions associées au traitement sémantique et phonologique lors de décisions sémantiques et phonologiques, respectivement. Par conséquent, nous avons comparé l’activité cérébrale de jeunes individus (18 à 35 ans) à celle d’individus âgés (55 à 75 ans) lors de l’exécution de cette tâche. Les deux groupes ont montré l’implication de boucles fronto-striatales associées à la planification et à l’exécution de changements de règle. Toutefois, alors que les jeunes semblaient activer une « boucle cognitive » (cortex préfrontal ventrolatéral, noyau caudé et thalamus) lorsqu’ils se voyaient indiquer qu’un changement de règle était requis, et une « boucle motrice » (cortex postérieur préfrontal et putamen) lorsqu’ils devaient effectuer le changement, les participants âgés montraient une activation des deux boucles lors de l’exécution des changements de règle seulement. Les jeunes adultes tendaient à présenter une augmentation de l’activité du cortex préfrontal ventrolatéral, du gyrus fusiforme, du lobe ventral temporale et du noyau caudé lors des décisions sémantiques, ainsi que de l’activité au niveau de l’aire de Broca postérieur, de la junction temporopariétale et du cortex moteur lors de décisions phonologiques. Les participants âgés ont montré de l’activité au niveau du cortex préfrontal latéral et moteur durant les deux types de décisions lexicales. De plus, lorsque les décisions sémantiques et phonologiques ont été comparées entre elles, les jeunes ont montré des différences significatives au niveau de plusieurs régions cérébrales, mais pas les âgés. En conclusion, notre première étude a montré, lors du set-shifting, un délai de l’activité cérébrale chez les personnes âgées. Cela nous a permis de conceptualiser l’Hypothèse Temporelle de Compensation (troisième manuscrit) qui consiste en l’existence d’un mécanisme compensatoire caractérisé par un délai d’activité cérébrale lié au vieillissement permettant de préserver la cognition au détriment de la vitesse d’exécution. En ce qui concerne les processus langagiers (deuxième étude), les circuits sémantiques et phonologiques semblent se fusionner dans un seul circuit chez les individus âgés, cela représente vraisemblablement des mécanismes de réserve et de compensation neuronales qui permettent de préserver les habilités langagières.As the one’s brain is structurally altered by the passage of time, cognition does not have to suffer the same faith, at least not to the same extent. Indeed, age-related compensatory mechanisms allow for some cognitive preservation. The elderly can therefore use new compensatory neuronal networks (neural compensation) or flexible pathways that are less susceptible to disruption (neural reserve) in order to maintain high levels of performance (cognitive reserve) during cognitive tasks. However, how these mechanisms affect cortical and striatal activity during set-shifting as well as during semantic and phonological processing has not been extensively explored. The purpose of this thesis was therefore to investigate how aging affects patterns of neural activity related to executive processes on the one hand and the use of lexical rules on the other. To this end we used functional Magnetic Resonance Imaging (fMRI) during the performance of a lexical analogue of the Wisconsin Card-Sorting Test. This task has been shown to strongly depend on fronto-striatal activity during set-shifting as well as on regions associated with semantic and phonological processing during semantic and phonological decisions, respectively. Two groups participated in our fMRI protocol: young individuals (18 to 35 years old) and older individuals (55 to 75 years old). Both younger and older individuals revealed significant fronto-striatal loop activity associated with planning and execution of set-shifts. However, while the younger group showed the involvement of a “cognitive loop” (including the ventrolateral prefrontal cortex, the caudate nucleus and the thalamus) when instructed that a set-shift would be required on following trial, and the involvement of a “motor loop” (including the posterior prefrontal cortex and the putamen) when the set-shift had to be performed, the older participants showed significant activation of both loops during the execution of the set-shift (matching periods) only. Young adults tended to present increased activity in the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex, the fusiform gyrus, the ventral temporal lobe and the caudate nucleus during semantic decisions and in the posterior Broca’s area, the temporoparietal junction and the motor cortical regions during phonological decisions, older individuals showed increased activity in the lateral prefrontal cortex and motor cortical regions during both semantic and phonological decisions. Furthermore, when semantic and phonological decisions were contrasted with each other, younger individuals showed significant brain activity differences in several regions while older individuals did not. In conclusion, our first study showed an age-related delayed cerebral activation phenomenon during set-shifting (previously observed only in few memory and language tasks). Based on those findings, we conceptualised the Temporal Hypothesis of Compensation (third manuscript) which is the existence of a compensatory mechanism characterised by age-related delayed cerebral activation allowing for cognitive performance to be preserved at the expense of speed processing. Regarding language processing (second study), semantic and phonological routes seem to merge into a single pathway in the elderly; these findings represent most probably neural reserve/compensation mechanisms on which the elderly rely to maintain an adequate level of performance

Prior knowledge contribution to declarative learning. A study in amnesia, aging and Alzheimer's disease

L'étude expérimentale de la mémoire humaine a connu deux moments historiques dans les soixante dernières années. 1957 marque la découverte du rôle du lobe temporal interne bilatéral dans l'apprentissage conscient, déclaratif. 1997 marque la découverte de deux systèmes de mémoire déclarative, épisodique et sémantique. Ces découvertes résultent d'études de cas en neuropsychologie. Cette thèse s'inscrit dans la tradition neuropsychologique: sa genèse doit tout à un patient souffrant d'une forme atypique d'amnésie développementale, le patient KA. Son point de départ est une étude de cas approfondie, avec deux résultats surprenants. Malgré une amnésie sévère, KA dispose de connaissances sémantiques exceptionnelles. Par ailleurs, il montre des capacités préservées d'apprentissage explicite, mais uniquement pour des stimuli concrets, pas abstraits. En conséquence, cette thèse a exploré deux pistes de recherche. Premièrement, nous avons caractérisé les processus préservés d'apprentissage déclaratif et l'anatomie cérébrale chez ce patient. Deuxièmement, nous avons étudié le rôle des connaissances préalables dans l'apprentissage: comment ce que l'on sait influence ce dont nous nous souvenons ? Une première série d'expériences montre chez ce patient une atteinte sévère et sélective de l'ensemble du système hippocampique, alors que les structures sous- hippocampiques (cortex entorhinal, périrhinal et parahippocampique) sont préservées. Malgré une amnésie épisodique sévère, nous montrons des connaissances sémantiques supranormales et des aptitudes d'apprentissage explicite rapide. Ces aptitudes sont toutefois restreintes aux stimuli associés à des connaissances préalables. Une seconde série d'expériences explore l'hypothèse selon laquelle les connaissances préalables facilitent l'apprentissage en mémoire déclarative, même dans les situations où le lobe temporal interne est fragilisé, comme dans le vieillissement, ou lésé, comme chez le patient KA ou dans la maladie d'Alzheimer. Nos résultats suggèrent l'existence de processus d'apprentissage rapide en mémoire déclarative, indépendants du système hippocampique et sensibles à la présence de représentations préexistantes. Ces processus semblent affectés par la maladie d'Alzheimer, et ce en lien avec un défaut d'activité des régions sous-hippocampiques antérieures. A l'inverse, les sujets âgés sains peuvent utiliser les connaissances préalables et pourraient ainsi compenser le déclin de la mémoire associative. Ce travail s'accorde avec les modèles postulant une dissociation fonctionnelle au sein du lobe temporal interne pour l'apprentissage déclaratif. Il soutient les propositions neurocognitives et computationnelles récentes, suggérant une voie d'apprentissage néocortical rapide mobilisable dans certaines circonstances. Il met en exergue la dynamique des apprentissages en mémoire déclarative et notamment l'intrication fondamentale entre "savoir" et "se souvenir". Ce que je sais a un impact profond sur ce dont je vais me souvenir. Cette thèse permet d'envisager de nouveaux outils cognitifs pour le diagnostic de la maladie d'Alzheimer. De plus, il semble que des lésions temporales internes auront un impact distinct sur l'apprentissage selon le statut des informations à mémoriser en mémoire à long terme, offrant un regard nouveau sur les effets stimulus-dépendants dans l'amnésie. Une considération approfondie des connaissances préalables associées au contenu de nos expériences, et leur caractérisation détaillée, est requise pour affiner les modèles de la mémoire déclarative. Ces résultats apportent de nouvelles pistes de recherche quant aux circonstances épargnant l'apprentissage, notamment associatif, lors du vieillissement. Plus généralement, ils contribuent à la compréhension des déterminants d'un apprentissage réussi, en mettant l'accent sur les recouvrements entre processus de récupération et d'acquisition. Des applications potentielles en découlent dans le domaine éducatif.The experimental study of human memory has had two historic moments in the last sixty years. 1957 marks the discovery of the role of the medial temporal lobes in conscious learning. 1997 marks the discovery of two systems of declarative memory, namely episodic and semantic memories. These major breakthroughs are owed to clinical case studies in neuropsychology. This thesis follows on from the neuropsychological tradition: its genesis owes everything to a patient suffering from an atypical form of developmental amnesia, the patient KA. The starting point of this work was a thorough neuropsychological study of this patient. Two striking findings shortly arose. First, despite lifelong amnesia, KA had acquired exceptional levels of knowledge about the world. Second, remaining explicit learning abilities were restricted to meaningful, not meaningless, memoranda. As a consequence, we have investigated two research pathways in that thesis. First, we aimed at better characterizing preserved learning abilities and brain structure of the patient KA. Second, our goal was to explore how prior knowledge affects new declarative learning or, put simply, how do we learn what we know? In a first series of behavioural and neuroimaging experiments, we have shown in this patient a severe and selective damage of the whole extended hippocampal system, but preserved subhippocampal structures (entorhinal, perirhinal and parahippocampal cortex). The patient suffers from severe episodic amnesia, but we bring striking evidence for supranormal semantic knowledge as well as normal explicit learning skills. These skills were, however, restricted to familiar stimuli, that is, stimuli carrying pre-experimental knowledge. In a second series of behavioural and neuroimaging experiments, we explored the hypothesis that prior knowledge can facilitate new learning in declarative memory, even in aging or in situations where structures of the medial temporal lobe are or injured, as in amnesia or Alzheimer's disease. Our results suggest the existence of processes allowing fast learning in declarative memory, independently of the hippocampal system, and that are sensitive to the presence of pre-existing representations in long-term memory. Such learning processes appear to be selectively affected by Alzheimer's disease at the pre-dementia stage, in relation to a lack of activation of subhippocampal regions. In contrast, healthy elderly were able to rely on these learning processes to compensate for the decline in associative memory associated with aging. This work lends support to the models postulating a functional dissociation with respect to learning in declarative memory. It indeed strengthens recent neurocognitive and computational accounts that suggest a rapid neocortical learning path under certain circumstances. It highlights the dynamics of learning in declarative memory and in particular the fundamental entanglement between "knowing" and "remembering". What I know profoundly impacts what I will remember. The present thesis points towards new cognitive tools for the diagnosis of Alzheimer's disease. It further brings evidence that medial temporal lesions differentially impact learning depending on the status of the memoranda in long-term memory, which sheds a new light on material-specific effects in amnesia. Our work speaks for a thorough consideration of whether the contents of events have prior representations within long-term memory, and to further better characterize their nature if we are to better understand learning mechanisms. It also brings additional clues for a deeper understanding of how learning and memory can be preserved in aging. More generally, it contributes to a better understanding of the factors determining successful learning, with a focus on how retrieval and acquisition processes overlap during learning. Such findings have potential applications in the educational field

Using Statistics, Computational Modelling and Artificial Intelligence Methods to Study and Strengthen the Link between Kinematic Impacts and mTBIs

Mild traumatic brain injuries (mTBIs) are frequently occurring, yet poorly understood, injuries in sports (e.g., ice hockey) and other physical recreation activities where head impacts occur. Helmets are essential pieces of equipment used to protect participants’ heads from mTBIs. Evaluating the performance of helmets to prevent mTBIs using simulations on anatomically accurate computational head finite element models is critically important for advancing the development of safer helmets. Advancing the level of detail in, and access to, such models, and their continued validation through state-of-the-art brain imaging methods and traditional head injury assessment procedures, is also essential to improve safety. The significant research contributions in this thesis involve evaluating the decrease in blunt impact-induced brain axon fiber tract strains that various helmets provide by studying outputs of existing finite element brain models and implementing open-source artificial intelligence technology to create a novel pipeline for predicting such strains

A systematic investigation into the effects ofnanodal tDCS on healthy populations across measures of language, working memory & novel language acquisition

Transcranial direct current stimulation (tDCS) is a technique thought to modify cognition via a weak electric current applied to the scalp. Several thousand papers have been published since its inception in the early 2000s, with positive effects observed across healthy and patient samples in terms of language, memory, attention and various other executive functions. However, evidence is emerging that reported effects are exaggerated, and difficult to reproduce, especially in studies using single applications of anodal tDCS on healthy individuals. This thesis documents several studies that aimed to verify whether tDCS can modify word production, working memory and novel language acquisition in healthy participants when using conventional stimulation parameters, whilst considering factors that have driven its unreliabilit

Involuntary Orienting of Attention to Irrelevant Task Goals.

Attention overcomes processing limitations by enhancing information relevant to task goals and suppressing distraction. Although researchers agree that task goals are stored in memory, it is unclear how attention and memory are linked at the moment that a goal-related stimulus is detected, thereby capturing attention. We predicted that 1) attention capture leads to an involuntary orientation of attention to the related goal in memory; and 2) only a single goal can be attended during attention capture, consistent with a memory model that posits a “focus of attention” possessing a capacity limit of one. Our findings in Chapter 2 support our first prediction: participants oriented attention to the wrong task goal when instructed by an irrelevant but salient stimulus to do so. The set-specific capture phenomenon identified in Chapter 3 is also consistent with the first prediction, and supports the second. When participants searched for visual targets matching either of two current goals (e.g., identify both green and orange letters), identification accuracy was much lower when the target and an immediately preceding distractor were different target colors (e.g., green and orange) than when they were the same color (e.g., green). In Chapter 4, we reported that this set-specific capture cost could be eliminated when participants focused attention on the goal related to the target (e.g., green) prior to the appearance of a distractor relating to a different goal (e.g., orange). In line with the second prediction, this result suggests that only one goal can be enhanced at a time. Chapter 5’s results provided direct support for our second hypothesis: only the most recently attended goal influenced current target identification, whereas previously attended goals did not. This result is only explained by the focus of attention model, and cannot be explained by an alternative graded, limited-resources model. Collectively, these studies provide a novel link between attention and memory when multiple goals guide behavior.Ph.D.PsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/78815/1/mooreks_1.pd

Brain Computations and Connectivity [2nd edition]

This is an open access title available under the terms of a CC BY-NC-ND 4.0 International licence. It is free to read on the Oxford Academic platform and offered as a free PDF download from OUP and selected open access locations. Brain Computations and Connectivity is about how the brain works. In order to understand this, it is essential to know what is computed by different brain systems; and how the computations are performed. The aim of this book is to elucidate what is computed in different brain systems; and to describe current biologically plausible computational approaches and models of how each of these brain systems computes. Understanding the brain in this way has enormous potential for understanding ourselves better in health and in disease. Potential applications of this understanding are to the treatment of the brain in disease; and to artificial intelligence which will benefit from knowledge of how the brain performs many of its extraordinarily impressive functions. This book is pioneering in taking this approach to brain function: to consider what is computed by many of our brain systems; and how it is computed, and updates by much new evidence including the connectivity of the human brain the earlier book: Rolls (2021) Brain Computations: What and How, Oxford University Press. Brain Computations and Connectivity will be of interest to all scientists interested in brain function and how the brain works, whether they are from neuroscience, or from medical sciences including neurology and psychiatry, or from the area of computational science including machine learning and artificial intelligence, or from areas such as theoretical physics

Editorial: Executive function(s): Conductor, Orchestra or Symphony? Towards a Trans-Disciplinary Unification of Theory and Practice Across Development, in Normal and Atypical Groups

There are several theories of executive function(s) that tend to share some theoretical overlap yet are also conceptually distinct, each bolstered by empirical data (Norman and Shallice, 1986; Shallice & Burgess, 1991; Stuss and Alexander, 2007; Burgess, Gilbert, & Dumentheil, 2007; Burgess & Shallice, 1996; Miyake et al., 2000). The notion that executive processes are supervisory, and most in demand in novel situations was an early conceptualization of executive function that has been adapted and refined over time (Norman & Shallice, 1986; Shallice, 2001; Burgess, Gilbert & Dumentheil, 2007). Presently there is general consensus that executive functions are multi-componential (Shallice, 2001), and are supervisory only in the sense that attention in one form or another is key to the co-ordination of other hierarchically organized ‘lower’ cognitive processes. Attention in this sense is defined as (i) independent but interrelated attentional control processes (Stuss & Alexander, 2007); (ii) automatic orientation towards stimuli in the environment or internally–driven thought (Burgess, Gilbert & Dumontheil, 2007); (iii) the automatically generated interface between tacit processes and strategic conscious thought (Barker, Andrade, Romanowski, Morton and Wasti, 2006; Morton and Barker, 2010); and (iv) distinct but interrelated executive processes that maintain, update and switch across different sources of information (Miyake et al., 2000). One problem is that executive dysfunction or dysexecutive syndrome (Baddeley & Wilson, 1988) after brain injury typically produces a constellation of deficits across social, cognate, emotional and motivational domains that rarely map neatly onto theoretical frameworks (Barker, Andrade & Romanowski, 2004). As a consequence there is debate that conceptual theories of executive function do not always correspond well to the clinical picture (Manchester, Priestley & Jackson, 2004). Several studies have reported cases of individuals with frontal lobe pathology and impaired daily functioning despite having little detectable impairment on traditional tests of executive function (Shallice & Burgess, 1991; Eslinger & Damasio, 1985; Barker, Andrade & Romanowski, 2004; Andrés & Van der Linden, 2002; Chevignard et al., 2000; Cripe, 1998; Fortin, Godbout & Braun, 2003). There is also some suggestion that weak ecological validity limits predictive and clinical utility of many traditional measures of executive function (Burgess et al, 2006; Lamberts, Evans & Spikman, 2010; Barker, Morton, Morrison, McGuire, 2011). Complete elimination of environmental confounds runs the risk of generating results that cannot be generalized beyond constrained circumstances of the test environment (Barker, Andrade & Romanowski, 2004). Several researchers have concluded that a new approach is needed that is mindful of the needs of the clinician yet also informed by the academic debate and progress within the discipline (McFarquhar & Barker, 2012; Burgess et al., 2006). Finally, translational issues also confound executive function research across different disciplines (psychiatry, cognitive science, and developmental psychology) and across typically developing and clinical populations (including Autism Spectrum Disorders, Head Injury and Schizophrenia – Blakemore & Choudhury, 2006; Taylor, Barker, Heavey & McHale, 2013). Consequently, there is a need for unification of executive function approaches across disciplines and populations and narrowing of the conceptual gap between theoretical positions, clinical symptoms and measurement

The contribution of sleep to cognitive function in children with epilepsy

Cognitive impairment is the major co-morbidity in childhood epilepsy, and in many cases will have a larger long-term impact than the seizures themselves. However, the mechanisms contributing to this are poorly understood, precluding targetted intervention. Sleep is crucial for intelllectual functioning. Yet sleep in children with epilepsy, and its impact on intellectual function has scarcely been studied. This thesis aims to examine the structure and regulation of sleep in children with epilepsy, and to provide direct evidence of the impact of sleep on cognitive function by correlating neurophysiological characteristics with performance on sleep dependent neuropsychological tasks administered over the same interval as the sleep recorded. To examine sleep architecture in children with epilepsy, I developed a modified system for visual sleep scoring, taking into account nocturnal seizures and interictal activity. This was validated in a pilot sample, then applied to the scoring of 52 recordings from children with epilepsy. Based on established memory consolidation tasks and open-source psycholinguistic data, I developed and piloted a memory consolidation task battery suitable for testing school-aged English-speaking children, comprising parallel versions of a visuospatial and a verbal task. With these tools, I performed a prospective, within-subject comparison of memory retention across similar length intervals with or without sleep, in order to determine the contribution of sleep to memory consolidation. I compared results from patient (n=22) and healthy control (n=21) samples, finding – contrary to expectations – that sleep benefits memory consolidation in children with epilepsy to the same degree as controls. However, the benefit of sleep showed an inverse relationship to the nocturnal interictal discharge load. I also employed quantitative EEG analysis of slow wave activity to examine sleep homeostasis in patients with epilepsy, studying a retrospective sample (n=16) who had undergone partial sleep deprivation. Sleep homeostasis was fundamentally intact in these patients, who had similar clinical characteristics to the prospective sample. Findings from this thesis provide the first direct evidence that sleep benefits intellectual functioning in children with epilepsy, particularly where its structure and regulation is intact. Sleep-related memory consolidation may represent a compensatory mechanism, perhaps accounting for the relative cognitive preservation in this cohort of children with epilepsy with a structural aetiology, despite the early onset of seizures