Autonomic and central nervous system correlates of cognitive control training for attentional disorders

Deficits in cognitive control and attentional processing are commonly observed in people with Attention-Deficit/Hyperactivity Disorder (ADHD) and Specific Learning Difficulties (SpLDs) such as Dyslexia. Poorer performance in the pro/antisaccade task have been observed in these individuals, which suggests impaired visual attention and inhibitory control mechanisms. Atypical cognitive processing is also related to a state of autonomic hypoarousal in conditions such as ADHD. In this thesis, I examined whether the computer-based gaze-control RECOGNeyes training program using the pro/antisaccade task could improve cognitive control of visual attention by targeting the visual attention network and whether such improvements correlate with increased arousal. A group of 35 volunteers with SpLDs and/or ADHD completed the pro/antisaccade task before and after two weeks of training their visual attention using RECOGNeyes. Magnetoencephalography (MEG), pupillometry and electrocardiography were recorded, while they performed the pro/antisaccade task. Our task performance measures, reaction time (RT) and accuracy, and reading indices improved after RECOGNeyes training. Our findings demonstrate for the first time that autonomic measures of sympathetic pupil dilation and parasympathetic cardiac deceleration both correlate with faster saccadic RTs together (which was stronger for antisaccade trials than prosaccade trials) and account for separate variance in RT. Additionally, distinct MEG oscillatory profiles were uncovered in different frequency bands within regions of the visual attention network during the pro/antisaccade task. Slow-wave oscillations of delta and theta bands show anteriorising effects, suggested to mediate timing responses and bottom-up communication from the posterior to anterior network regions. Alpha-oscillations are proposed to have top-down preparatory inhibitory effects, particularly from the bilateral frontal eye field, and alpha-suppression in the right parietal eye field. Beta amplitude presents an additional “anticipatory” event-related desynchronisation (ERD) prior to target onset that is stronger on day 2 and antisaccade trials, which could relate to generalised inhibitory control mechanisms. This thesis supports the existence of complex central and autonomic processes underlying attention and arousal that are not yet fully understood and warrant further investigation. By increasing our understanding of the integrated attentional processes and inhibitory control, this could help the development of targeted treatment solutions, such as RECOGNeyes, for ADHD and SpLDs, to improve outcomes in these individuals

Exposing Internal Attentional Brain States using Single-Trial EEG Analysis with Combined Imaging Modalities

The goal of this dissertation is to explore the neural correlates of endogenous task-related attentional modulations. Natural fluctuations in task engagement are challenging to study, primarily because they are by nature not event related and thus cannot be controlled experimentally. Here we exploit well-accepted links between attention and various measures of neural activity while subjects perform simple target detection tasks that leave their minds free to wander. We use multimodal neuroimaging, specifically simultaneous electroencephalograpy and functional magnetic resonance imaging (EEG-fMRI) and EEG-pupillometry, with data-driven machine learning methods and study activity across the whole brain. We investigate BOLD fMRI correlates of EEG variability spanning each trial, enabling us to unravel a cascade of attention-related activations and determine their temporal ordering. We study activity during auditory and visual paradigms independently, and we also combine data to investigate supra modal attention systems. Without aiming to study known attention-related functional brain networks, we found correlates of attentional modulations in areas representative of the default mode network (DMN), ventral attention network (VAN), locus coeruleus norepinephrine (LC-NE) system, and regions implicated in generation of the extensively-studied P300 EEG response to target stimuli. Our results reveal complex interactions between known attentional systems, and do so non-invasively to study normal fluctuations of task engagement in the human brain

Parkinson\u27s Disease, the Amygdala, and Non-motor Symptoms

This study sought to explore the relationship between Parkinson’s Disease (PD), the amygdala, and the plethora of non-motor symptoms that plague individuals with PD. Previous research gave insights about the amygdala’s function as the emotional center of the brain, its role in depression, and its participation in the non-motor symptoms of PD. The research proved to still be inconclusive on its own because of a variety of limitations. The methods of this study consist of the analysis of Functional Magnetic Resonance Imaging (fMRI) scans from 93 individuals with PD and 18 individuals without PD while in a resting state. The analysis showed that the amygdalae experienced decreased functional connectivity (FC) to the right posterior areas of the superior frontal gyrus (SFG). Because this depletion of FC is similar to the neurological effects of Major Depression Disorder (MDD), it is suggested that depression in PD is caused by the amygdala’s inability to communicate effectively with the right posterior SFG

Neural mechanisms of treatment for mental disorders

“Cognitive control” refers to the ability to regulate thoughts and actions in the service of goals or plans (Braver, 2012). Coordination between the central and peripheral autonomic nervous systems (ANS) maintains arousal and attention levels, which are essential for effective cognitive control. Diamond (2013) proposed a cognitive control model that builds on three core cognitive functions: cognitive flexibility, inhibitory control, and working memory. Abnormality in active inhibitory cognitive control is implicated in a broad range of psychiatric and personality disorders, including schizophrenia, attention deficit hyperactivity disorder (ADHD), impulsivity, and substance abuse, among many others. Transcranial direct current stimulation (tDCS) and cognitive training are two neuromodulation techniques which have the potential to modulate cortical functions to introduce long-lasting neuronal plasticity. The antisaccade task is a visual inhibitory control task frequently used to assess cognitive control. It requires the participant to suppress an automatic stimulus-driven saccadic eye movement and instead make a goal-driven saccade in the opposite direction. In this thesis, by conducting two separate studies, we used the antisaccade task to examine the effect of tDCS and computerised cognitive training on inducing neuroplastic changes for the oculomotor control network (OCN). ‎Chapter 1¢introduces relevant concepts to the subject of this thesis with a technical account of the methods used. The details of the first study are discussed in ‎Chapter 2 - ‎Chapter 4, where we used eye-tracking during antisaccade performance with the continuous assessment of cortical activity using Magnetoencephalography (MEG). Chapter 2 will discuss the short-term neuroplastic changes introduced by the tDCS on the functional connectivity within the resting state networks assessed using MEG. We found evidence of increased connectivity following the engagement in the antisaccade task for both active tDCS and sham conditions, but with different spatial patterns. Following tDCS delivered over the frontal cortex, there was increased connectivity with the frontal cortex. In contrast, in the sham condition there was increased connectivity with the posterior cortex. The effects of tDCS stimulation on the ANS activity during the task performance were further assessed via pupillometry as a measure of Locus Coeruleus (LC) activity in ‎Chapter 3. Our results showed that faster pupil dilation, reflecting increased arousal and sympathetic activity, was associated with faster saccade reaction times. In ‎Chapter 4, we investigated the immediate effects of tDCS stimulation on the cerebral cortex during active cognitive inhibition followed by a correct saccadic response. The tDCS introduced neuromodulatory changes in the putative Alpha and low-Beta band during the anticipatory and post-stimulus periods, reflecting enhanced cortical engagement in a task-beneficial pattern. ‎Chapter 5 reports on the second study in which we used functional magnetic resonance imaging (fMRI) to evaluate the neuromodulatory effects of prolonged computerised cognitive training games (RECOGNeyes) on the resting state functional connectivity of the OCN and pupil dilation. Following gaze-control training, the connectivity within the left hemisphere was strengthened, while the intra-right hemisphere and the interhemispheric connectivity were diminished. ‎Chapter 6 provides a summary of the findings and concluding remarks. Our result furthers our knowledge of the processes involved in the performance of the antisaccade task, the mechanisms of action and the neuroplastic effects of two neuromodulation techniques. However, the exact mechanisms underlying these methods' beneficial effects demand further exploration

Neural mechanisms of treatment for mental disorders

“Cognitive control” refers to the ability to regulate thoughts and actions in the service of goals or plans (Braver, 2012). Coordination between the central and peripheral autonomic nervous systems (ANS) maintains arousal and attention levels, which are essential for effective cognitive control. Diamond (2013) proposed a cognitive control model that builds on three core cognitive functions: cognitive flexibility, inhibitory control, and working memory. Abnormality in active inhibitory cognitive control is implicated in a broad range of psychiatric and personality disorders, including schizophrenia, attention deficit hyperactivity disorder (ADHD), impulsivity, and substance abuse, among many others. Transcranial direct current stimulation (tDCS) and cognitive training are two neuromodulation techniques which have the potential to modulate cortical functions to introduce long-lasting neuronal plasticity. The antisaccade task is a visual inhibitory control task frequently used to assess cognitive control. It requires the participant to suppress an automatic stimulus-driven saccadic eye movement and instead make a goal-driven saccade in the opposite direction. In this thesis, by conducting two separate studies, we used the antisaccade task to examine the effect of tDCS and computerised cognitive training on inducing neuroplastic changes for the oculomotor control network (OCN). ‎Chapter 1¢introduces relevant concepts to the subject of this thesis with a technical account of the methods used. The details of the first study are discussed in ‎Chapter 2 - ‎Chapter 4, where we used eye-tracking during antisaccade performance with the continuous assessment of cortical activity using Magnetoencephalography (MEG). Chapter 2 will discuss the short-term neuroplastic changes introduced by the tDCS on the functional connectivity within the resting state networks assessed using MEG. We found evidence of increased connectivity following the engagement in the antisaccade task for both active tDCS and sham conditions, but with different spatial patterns. Following tDCS delivered over the frontal cortex, there was increased connectivity with the frontal cortex. In contrast, in the sham condition there was increased connectivity with the posterior cortex. The effects of tDCS stimulation on the ANS activity during the task performance were further assessed via pupillometry as a measure of Locus Coeruleus (LC) activity in ‎Chapter 3. Our results showed that faster pupil dilation, reflecting increased arousal and sympathetic activity, was associated with faster saccade reaction times. In ‎Chapter 4, we investigated the immediate effects of tDCS stimulation on the cerebral cortex during active cognitive inhibition followed by a correct saccadic response. The tDCS introduced neuromodulatory changes in the putative Alpha and low-Beta band during the anticipatory and post-stimulus periods, reflecting enhanced cortical engagement in a task-beneficial pattern. ‎Chapter 5 reports on the second study in which we used functional magnetic resonance imaging (fMRI) to evaluate the neuromodulatory effects of prolonged computerised cognitive training games (RECOGNeyes) on the resting state functional connectivity of the OCN and pupil dilation. Following gaze-control training, the connectivity within the left hemisphere was strengthened, while the intra-right hemisphere and the interhemispheric connectivity were diminished. ‎Chapter 6 provides a summary of the findings and concluding remarks. Our result furthers our knowledge of the processes involved in the performance of the antisaccade task, the mechanisms of action and the neuroplastic effects of two neuromodulation techniques. However, the exact mechanisms underlying these methods' beneficial effects demand further exploration

Coupling of pupil- and neuronal population dynamics reveals diverse influences of arousal on cortical processing

Fluctuations in arousal, controlled by subcortical neuromodulatory systems, continuously shape cortical state, with profound consequences for information processing. Yet, how arousal signals influence cortical population activity in detail has so far only been characterized for a few selected brain regions. Traditional accounts conceptualize arousal as a homogeneous modulator of neural population activity across the cerebral cortex. Recent insights, however, point to a higher specificity of arousal effects on different components of neural activity and across cortical regions. Here, we provide a comprehensive account of the relationships between fluctuations in arousal and neuronal population activity across the human brain. Exploiting the established link between pupil size and central arousal systems, we performed concurrent magnetoencephalographic (MEG) and pupillographic recordings in a large number of participants, pooled across three laboratories. We found a cascade of effects relative to the peak timing of spontaneous pupil dilations: Decreases in low-frequency (2-8 Hz) activity in temporal and lateral frontal cortex, followed by increased high-frequency (>64 Hz) activity in mid-frontal regions, followed by monotonic and inverted U relationships with intermediate frequency-range activity (8-32 Hz) in occipito-parietal regions. Pupil-linked arousal also coincided with widespread changes in the structure of the aperiodic component of cortical population activity, indicative of changes in the excitation-inhibition balance in underlying microcircuits. Our results provide a novel basis for studying the arousal modulation of cognitive computations in cortical circuits

L’étude de la contribution des mécanismes dépendants de la répétition aux processus de consolidation des mémoires motrices dans le cortex moteur primaire et de la manifestation électrophysiologique du traitement des récompenses monétaires au-dessus des aires cérébrales motrices

Abstract : The present thesis seeks to provide insights into the contribution of the two major learning mechanisms driving motor memory consolidation in the primary motor cortex (M1): repetition-dependent and reward-based learning mechanisms. However, because evidence remains scarce on this last learning mechanism, the study of the neural manifestation of reward processing in motor areas was investigated. More specifically, the first scientific contribution presented in this thesis sought to address the contribution of repetition-dependent mechanisms to motor memory consolidation in M1. As such, the first project used single-pulse transcranial magnetic stimulation (TMS) to interfere with M1 activity as participants executed newly learned motor behaviors during a performance asymptote. Results revealed that motor memory formation in M1 was initiated when behaviors were repeating, suggesting that repetition-dependent mechanisms contributed to retention in M1. The second scientific contribution sought to use scalp electroencephalography (EEG) recordings to investigate the electrophysiological manifestations of reward processing over cortical motor areas. Overall, results revealed that increases in beta-band power (20-30 Hz) over contralateral motor electrodes are modulated by reward processing. Although these results did not allow specifically addressing the contribution of reward-based learning mechanisms to consolidation in M1, they nonetheless provide the plausible neural substrates involved in this learning mechanism. The discussion first sought to integrate these two projects and second to provide an overview of the future perspectives that the two projects have led to. Overall, the proposed research projects mainly revolve around the demonstration of the associations– even maybe causality – between motor memory consolidation in M1, reward processing, beta-band power and dopaminergic activity. Throughout the discussion, working hypotheses as well as the methodological means to test them – ranging from non-invasive brain stimulation to electroencephalography recordings and even to the study of interindividual variations in the expression of dopamine-related genes – are outlined.Le présent mémoire cherche à fournir un aperçu des mécanismes neurophysiologiques qui sous-tendent les deux mécanismes principaux d’apprentissage impliqués dans la consolidation des mémoires motrices dans le cortex moteur primaire (M1). Bien que le modèle cellulaire le plus accepté pour la formation des mémoires motrices soit la potentialisation à long-terme (long-term potentiation, en anglais), la littérature suggère que les mécanismes d’apprentissage qui initient le stockage synaptique des mémoires motrices dépendent de la plasticité Hebienne (i.e., répétitions dans les mouvements) et des récompenses vécues pendant l’acquisition d’une nouvelle habileté motrice. La première contribution scientifique du présent mémoire aborde la contribution des mécanismes Hebbiens d’apprentissage à la consolidation des mémoires motrices dans le M1. Dans ce premier projet, la stimulation magnétique transcrânienne (SMT) a été utilisée pour interférer avec l’activité neuronale du M1 lorsque les participants acquéraient et exécutaient de nouveaux comportements moteurs pendant l’atteinte d’un plateau de performance (i.e., répétitions dans les mouvements). Les résultats démontrent que la formation des mémoires motrices dans le M1 est initiée lorsque les comportements moteurs sont de plus en plus répétés, ce qui suggère que le stockage synaptique des mémoires motrices dans M1 est dépendant de la répétition des comportements pendant l’acquisition. Le deuxième projet scientifique a cherché à mettre en lumière la contribution des régions motrices au traitement des récompenses dans un contexte moteur en utilisant l’enregistrement d’activités électroencéphalographiques. Entre autres, suite à l’octroi d’une récompense, les résultats démontrent une augmentation de la puissance spectrale dans la bande de fréquences bêta (20-30 Hz) des électrodes motrices contralatérales à la main utilisée pendant la tâche motrice. Dans l’ensemble, bien que ce deuxième projet ne puisse statuer sur la contribution spécifique du M1 dans la consolidation des mémoires motrices sur la base des récompenses vécues pendant l’acquisition, les résultats qui en émergent pourraient être un reflet des substrats neuronaux impliqués dans ce mécanisme d’apprentissage. Dans un premier temps, la discussion intègre ces deux contributions et, dans un deuxième temps, donne un aperçu des perspectives futures de recherche qui émanent de ces deux contributions scientifiques. Globalement, les hypothèses de recherche suggérées se concentrent principalement autour de la démonstration d’une association ou d’un lien causal entre la formation des mémoires motrices dans le M1, le traitement de récompenses, les réponses spectrales en bêta ainsi que l’activité dopaminergique. Au travers de la discussion, les hypothèses spécifiques ainsi que les moyens méthodologiques pour les tester – qui vont des techniques de stimulation cérébrale non invasives à l’enregistrement d’activité électroencéphalographique et même jusqu’à l’étude des variations génétiques interindividuelles dans l’expression des gènes régulant l’activité dopaminergique – sont décrits

What computations support response inhibition? The roles of context-monitoring, selective stopping, and strategic control

Response inhibition is thought to be central to the function of the frontal lobes and intimately related to all higher cognitive functions. The effortful and controlled component to response inhibition is often assumed to be the act of motoric stopping per se, such that motoric stopping can be strategically directed either at all actions (thus taking a global form) or only a subset (thus taking a more selective form). Here we challenge these core assumptions, first by offering a more viable alternative to dominant accounts of global stopping, and second by raising both empirical and computational dilemmas for dominant accounts of selective stopping. Using behavioral, neuroimaging, electroencephalographic and computational approaches, we demonstrate that the global stopping of responses does not require control mechanisms beyond those involved in detecting contexts in which old behaviors are inappropriate - in other words, the ability to monitor context in the service of goals. A computational model is used to demonstrate that these context-monitoring processes may underlie the behavioral, neuroimaging, and pharmacological phenomena of global stopping in the absence of any controlled stopping mechanisms. This work also challenges claims that more strategically selective forms of stopping are enabled by the controlled use of a slower but more response-specific stopping mechanism. We find a developmental double dissociation between the speed of stopping and its specificity, indicating that they cannot unambiguously be taken to reflect the use of a single neural mechanism. A computational model raises further challenges for extant theories of selective stopping, raising the possibility that the control mechanisms supporting this ability are not actually directed at specific responses. Together these results challenge dominant accounts of both global and selective inhibitory control, and clarify emerging debates on the frontal substrates of response inhibition, while raising novel questions about the substrates and processes that support selective stopping. More broadly, this work provides a coherent account of prefrontal cortex function across inhibitory domains, which may in turn enable both a more precise characterization of frontal disinhibitory syndromes as well as enable more targeted diagnosis and treatment of pathologies associated with response inhibition deficits