The Functional Architectures of Addition and Subtraction: Network Discovery Using fMRI and DCM

The neuronal mechanisms underlying arithmetic calculations are not well understood but the differences between mental addition and subtraction could be particularly revealing. Using fMRI and dynamic causal modeling (DCM), this study aimed to identify the distinct neuronal architectures engaged by the cognitive processes of simple addition and subtraction. Our results revealed significantly greater activation during subtraction in regions along the dorsal pathway, including the left inferior frontal gyrus (IFG), middle portion of dorsolateral prefrontal cortex (mDLPFC), and supplementary motor area (SMA), compared with addition. Subsequent analysis of the underlying changes in connectivity – with DCM – revealed a common circuit processing basic (numeric) attributes and the retrieval of arithmetic facts. However, DCM showed that addition was more likely to engage (numeric) retrieval‐based circuits in the left hemisphere, while subtraction tended to draw on (magnitude) processing in bilateral parietal cortex, especially the right intraparietal sulcus (IPS). Our findings endorse previous hypotheses about the differences in strategic implementation, dominant hemisphere, and the neuronal circuits underlying addition and subtraction. Moreover, for simple arithmetic, our connectivity results suggest that subtraction calls on more complex processing than addition: auxiliary phonological, visual, and motor processes, for representing numbers, were engaged by subtraction, relative to addition. Hum Brain Mapp 38:3210–3225, 2017. © 2017 Wiley Periodicals, Inc

Neural circuits involved in mental arithmetic: Evidence from Customized Arithmetic Training

An arithmetic training study was conducted using a novel paradigm known as Customized Arithmetic Training (CAT). Using the CAT system, self-reports obtained from the participants were used to generate individually tailored problem sets. These problem sets balanced strategy use such that each participant started with an equal amount of problems solved by fact retrieval (e.g., 2 + 2 = 4) and an equal amount of problems solved by procedural calculation (e.g., 34 + 37). Following the training period, participants solved trained and untrained problems from their customized arithmetic sets while undergoing an fMRI scan, after which they again provided self-reported strategy. Through the use of the CAT paradigm, which tracks (for the first time) arithmetic strategy both pre- and post-training, the neural correlates of arithmetic learning were examined by separating calculated problems which became memorized through training from problems that were rehearsed but did not show a shift in strategy. This analysis produced results consistent with previous studies of arithmetic training, namely a shift from widespread fronto-parietal activation to focal activation of the angular gyrus. However, it also produced several novel findings relating to neural correlates of mental arithmetic, namely an association between right anterior hippocampus in fact retrieval as well as evidence of a temporal gradient which affected brain activity when comparing new vs old arithmetic facts. Furthermore, analysis of training effects on calculated problems (which did not become memorized) revealed a modulation of activity in the putamen, a structure commonly associated with the procedural memory system

Autobiographisches Gedächtnis, der Einfluss von frühkindlichem Stress und neuronalen Korrelaten

Vandekerckhove M. Autobiographical memory begins and ends with the self : autobiographical memory, consciousness, the influence of stress and neural correlates. Bielefeld (Germany): Bielefeld University; 2004.The general purpose of this thesis is to study some fundamental, yet still open questions about autobiographical memory and related consciousness, the influence of early stress on the brain and autobiographical memory and its neural correlates. The goal is to make some progress in the definitory confusion and conceptual understanding of the relationship of these concepts starting from a developmental point of view. In the attempt to throw some light on what can fall under the sum of autobiographical memory-related themes, no overview or review of the existing answers will be given but rather, after extended research of the theoretical and empirical literature and own empirical work, a new clarifying point of view of the different phenomena. Considering the close relationship between the experience of the world, consciousness and autobiographical memory, the first question that becomes addressed in the theoretical part is how a child develops autobiographical memory and what Tulving entitles as associated "autonoetic consciousness", a self-reflective mental state of awareness in time and space (Tulving, 1985; 2002). The second question is concerned with how early childhood can form the basal template in the buffering and facilitation of influences of stress on the brain and also on autobiographical memory, with psychogenic amnesia and altered autonoetic consciousness as a prototypical example. Autobiographical old memories are as a result of a high degree of anatomical interconnectivity and cognitive complexity most vulnerable to brain damage and other external and internal influences such as stress (Markowitsch, 1995; 1999; 2000; 2002; 2003; Tulving and Markowitsch, 1998). The second empirical part of the thesis is primarily focused on the fundamental research of autobiographic memory and its neural correlates. The different focuses within the chapters will bring up more questions for theoretical thinking and empirical research about the same complexity of which individuals are made of

GABA and Glutamate Levels in Occlusal Splint-Wearing Males with Possible Bruxism

Objective The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the pathophysiology of anxiety behavioural disorders such as panic disorder and post-traumatic stress disorder and is also implicated in the manifestation of tooth-grinding and clenching behaviours generally known as bruxism. In order to test whether the stress-related behaviours of tooth-grinding and clenching share similar underlying mechanisms involving GABA and other metabolites as do anxiety-related behavioural disorders, we performed a Magnetic Resonance Spectroscopy (MRS) study for accurate, in vivo metabolite quantification in anxiety-related brain regions. Design MRS was performed in the right hippocampus and right thalamus involved in the hypothalamic−pituitary−adrenal axis system, together with a motor planning region (dorsal anterior cingulate cortex/pre-supplementary motor area) and right dorsolateral prefrontal cortex (DLPFC). Eight occlusal splint-wearing men (OCS) with possible tooth-grinding and clenching behaviours and nine male controls (CON) with no such behaviour were studied. Results Repeated-measures ANOVA showed significant Group × Region interaction for GABA+ (p = 0.001) and glutamate (Glu) (p = 0.031). Between-group post hoc ANOVA showed significantly lower levels of GABA+ (p = 0.003) and higher levels of Glu (p = 0.002) in DLPFC of OCS subjects. These GABA+ and Glu group differences remained significant (GABA+, p = 0.049; Glu, p = 0.039) after the inclusion of anxiety as a covariate. Additionally, GABA and Glu levels in the DLPFC of all subjects were negatively related (Pearson's r = −0.75, p = 0.003). Conclusions These findings indicate that the oral behaviours of tooth-grinding and clenching, generally known as bruxism, may be associated with disturbances in brain GABAergic and glutamatergic systems

Hippocampal spatial mechanisms relate to the development of arithmetic symbol processing in children

Understanding the meaning of abstract mathematical symbols is a cornerstone of arithmetic learning in children. Studies have long focused on the role of spatial intuitions in the processing of numerals. However, it has been argued that such intuitions may also underlie symbols that convey fundamental arithmetic concepts, such as arithmetic operators. In the present cross-sectional study, we used fMRI to investigate how and when associations between arithmetic operators and brain regions processing spatial information emerge in children from 3rd to 10th grade. We found that the mere perception of a ‘+’ sign elicited grade-related increases of spatial activity in the right hippocampus. That is, merely perceiving ‘+’ signs – without any operands – elicited enhanced hippocampal activity after around 7th grade (12–13 years old). In these children, hippocampal activity in response to a ‘+’ sign was further correlated with the degree to which calculation performance was facilitated by the preview of that sign before an addition problem, an effect termed operator-priming. Grade-related increases of hippocampal spatial activity were operation-specific because they were not observed with ‘×’ signs, which might evoke rote retrieval rather than numerical manipulation. Our study raises the possibility that hippocampal spatial mechanisms help build associations between some arithmetic operators and space throughout age and/or education

Developmental neurocognitive pathway of psychosis proneness and the impact of cannabis use

Cette thèse fait la promotion d’une nouvelle approche ciblant le risque de psychose qui consiste à identifier les enfants et les jeunes adolescents de la communauté appartenant à différentes trajectoires développementales d’expériences psychotiques. Une identification très précoce du risque de psychose chez des jeunes de la communauté pourrait ainsi diminuer la période où les symptômes cliniques ne sont pas traités, mais aurait également le potentiel de prévenir efficacement l’émergence de symptômes avérés, et ce, si les facteurs de risque sont identifiés. Étant donné que la consommation de cannabis s’avère un important facteur de risque de la psychose et le contexte actuel où les états en sont à réviser leurs politiques de réglementation du cannabis, il s’avère primordial de mieux comprendre comment la consommation peut mener à la psychose chez les individus vulnérables. Tout d’abord, j’ai investigué la séquence temporelle entre la consommation de cannabis et les expériences psychotiques chez une population de 4000 adolescents, suivis pendant 4 ans, au moment de l’adolescence où les deux phénomènes s’initient. Ensuite, j’ai examiné, chez des adolescents suivant une trajectoire de vulnérabilité, le rôle d’un moins bon fonctionnement cognitif ainsi que celui d’une exacerbation des symptômes anxieux et dépressifs comme médiateurs du lien entre cannabis et risque de psychose. Enfin, j’ai investigué la présence de marqueurs neurocognitifs précoces (fonctionnels et structurels) qui seraient associés à l’émergence de symptômes psychotiques chez des adolescents, et exploré si la consommation de cannabis pourrait modérer l’ampleur de ces marqueurs. Les données proviennent de deux cohortes longitudinales suivant des adolescents de la population générale, l’étude Co-Venture (n=4000, âgés de 12 ans, suivis annuellement pendant 4 ans) et l’étude de neuroimagerie IMAGEN (n=2200, âgés de 14 ans, suivis pendant 2 ans), ainsi qu’un sous-échantillon de l’étude Co-Venture ayant complété des mesures de neuroimagerie (n=151, âgés de 12 ans, suivis annuellement pendant 4 ans). Les résultats ont montré que la consommation de cannabis précédait systématiquement l’augmentation des expériences psychotiques, et non l’inverse. Chez les jeunes suivant une trajectoire de vulnérabilité, la relation entre la consommation de cannabis et le risque de psychose était davantage expliquée par une augmentation des symptômes de dépression et d’anxiété. Une réduction du volume de l’hippocampe et de l’amygdale en combinaison avec une hyperactivité de ces mêmes régions en réponse à des expressions neutres étaient tous associés à l’émergence de symptômes psychotiques. Or, la consommation de cannabis n’a pas exacerbé les altérations structurelles observées chez les adolescents rapportant des expériences psychotiques. Ces résultats ont mis en évidence le rôle primordial d’un hyperfonctionnement du système limbique pouvant mener à l’attribution aberrante d’une importance émotionnelle aux stimuli de l’environnement, et ce, chez des adolescents vulnérables. Il semble que le mécanisme par lequel la consommation de cannabis mène à l’émergence de symptômes cliniques passe par son influence sur les symptômes de dépression et d’anxiété ainsi que leurs mécanismes neuronaux sous-jacents d’une hypersensibilité au stress. Enfin, de par ces résultats, cette thèse permet de contribuer au développement de nouvelles interventions visant à réduire la demande de cannabis chez des adolescents vulnérables.Following the worldwide initiative on intervening early in clinical high-risk individuals for psychosis, this thesis promotes a novel approach to identify those at risk for psychosis by studying children and adolescents from the community who report different trajectories of subclinical psychosis symptoms (i.e., psychotic-like experiences) without the confounds of iatrogenic effects such as major social and cognitive impairments. Early identification from this approach may not only reduce harm by shortening the duration of untreated symptoms, but may also have the capacity to prevent the emergence of clinically validated symptoms, particularly if early risk factors can be identified. Considering the long-standing notion that cannabis misuse is an important risk factor for psychosis and that jurisdictions around the world are currently revising their cannabis regulatory policies, there is a need to better understand how cannabis use may lead to psychosis in vulnerable youths. This thesis examined different mechanisms that may explain the complex relationship between cannabis use and psychosis risk. I first explored the temporal sequence between cannabis use and self-reported psychotic-like experiences in a population-based sample of 4000 adolescents, over a 4-year period when both phenomena have their onset. Second, in vulnerable youths, I investigated the role of impaired cognitive functioning as well as increased affective and anxious symptoms as mediators of the cannabis-to-psychosis relationship. And third, I explored the presence of early neurocognitive markers (both functional and structural) associated with the emergence of psychotic symptoms, and how cannabis use moderates these markers. Two longitudinal cohorts from the general population, the Co-Venture Study (n=4000, aged 12 years old, followed annually for 4 years) and the neuroimaging IMAGEN Study (n=2200, aged 14 years old, followed for 2 years), as well as the neuroimaging subsample from the Co-Venture Study (n=151, aged 12 years old, followed annually for 4 years) were used. It was found that an increase in cannabis use always preceded an increase in reported psychotic-like experiences throughout adolescence, but an increase in psychotic-like experiences rarely predicted an increase in cannabis use. Then, in vulnerable adolescents, the cannabis-to-psychosis risk relationship was better explained by increases in depression and anxiety symptoms relative to changes in cognitive functioning. It was demonstrated that reduced hippocampus and amygdala volumes, combined with hyperactivity of the same regions during neutral cues processing were associated with the emergence of psychotic symptoms in young adolescents reporting psychotic-like experiences. However, cannabis use did not exacerbate the structural alterations observed in youths with psychotic-like experiences. These findings have improved our understanding of the relationship between cannabis use and vulnerability to psychosis. They have also highlighted the important role of an impaired limbic network leading to an aberrant emotional salience attribution in vulnerable adolescents. Although cannabis use did not exacerbate brain structural alterations observed in vulnerable youths, it appears that cannabis will more likely interfere with depression and/or anxiety symptoms and their associated brain mechanisms underlying vulnerability to stress in the path towards psychosis risk. This thesis may inform the development of new evidence-based interventions that reduce demand for cannabis among vulnerable youths

Neural and behavioral correlates of arithmetic development and learning in children

Arithmetic learning improves mathematical competence, which is necessary for successful daily life. However, little is known about the neural underpinnings of arithmetic learning during childhood, the age when individuals learn most of the mathematical skills and the vast majority of our knowledge comes from adult studies. In this dissertation project, four studies were conducted to investigate the neural and behavioral correlates of arithmetic development and learning in children. In Study 1 arithmetic development was evaluated longitudinally to see whether it is monotonous or there are intermediate phases in which certain domain-general processes become important but disappear later. In Study 2 arithmetic complexity was evaluated to see whether it relies on both magnitude and cognitive processes, such as in adults. In Study 3 it was asked whether the findings in adults are valid for children or are there intermediate stages. Furthermore, it was evaluated whether few training sessions are reflective of more long-term learning processes. In Study 4 the brain activation changes during the course of learning were measured to see whether they reveal similar changes as in after arithmetic learning. The findings revealed that different domain-general cognitive processes are involved in different steps of arithmetic development and learning. Furthermore, arithmetic achievement occurs in two steps in children, first from slow effortful procedural processes to fast compacted procedural processes, and then to retrieval processes. These changes are distinguishable after one and several training sessions, and also during the course of learning. The findings are integrated in a theoretical model of arithmetic achievement in children, which contains two phases: (i) the efficiency increase (from slow effortful procedural processes to fast compacted procedural processes) and (ii) the strategy change (from fast compacted procedural processes to retrieval processes) phases. The model was developed based on two principles of brain function, optimum performance and energy consumption, and supported by several empirical studies. Taken together, this dissertation project provides a comprehensive framework for arithmetic development and learning in children. The findings might be helpful to develop educational and therapeutic interventions and also a new measure of intervention outcomes, particularly in individuals with mathematical learning disabilities

Childhood Trauma And Emotion Processing Neurocircuitry

Childhood trauma is one of the strongest risk factors for a range of common and debilitating neuropsychiatric disorders, including anxiety, depression, and posttraumatic stress disorder (PTSD). These emotion-related disorders have their roots in childhood and adolescence, underscoring a critical need to understand their biological bases in early life. In this dissertation, we evaluate how childhood trauma impacts emotion processing neurocircuitry in a sample of high-risk urban youth, ages 7-15. In four inter-related studies, we test neural function and functional connectivity of core emotion processing regions, including the amygdala, insula, and pregenual/subgenual anterior cingulate cortex (pgACC/sgACC). To examine the relevance of observed neurological changes, we evaluate behavioral performance on emotion processing neuropsychological tasks, as well as specific dimensions of subjective affective experience. Results indicate that, relative to matched comparison youth, trauma-exposed youth have (1) increased neural response to salient emotional cues in amygdala and insula, (2) reduced functional connectivity between amygdala and pgACC/sgACC, a pathway critical for emotion regulation, and (3) altered within- and between-network connectivity of the salience network, involved in detecting and orienting attention to salient emotional stimuli. These neurological changes are accompanied by behavioral alterations: trauma-exposed youth have a lower ability to ignore distracting emotional information, and to automatically regulate emotion. Additionally, observed neurobehavioral changes relate to a specific dimension of affective experience – reward sensitivity (RS), rather than negative affect. Moreover, trauma-exposed youth with the greatest neurobehavioral impairment report lower RS, suggesting reduced positive environmental engagement. These results suggest that RS may be a marker of stress susceptibility, a notion supported by emerging basic and clinical research. Based on our neurobehavioral findings, we discuss potential implications for intervention, and relay an emerging framework that dissociates neurological effects of different trauma types (i.e., threat/victimization vs. deprivation/neglect). In closing, we discuss future directions, including longitudinal research and evaluating the modulation of learned fear – a neurobehavioral mechanism that depends on emotion processing neurocircuitry, but has yet to be tested in trauma-exposed youth

Age-related differences in episodic memory retrieval : ERP evidence for differential developmental changes in item and source recognition memory

Two cross-sectional studies aimed at investigating the development of different episodic retrieval processes and their neural correlates from childhood over adolescence until adulthood. A particular focus was put on those processes that are mediated by cognitive control functions and which support the retrieval of source information. The results show that processes related to the conscious remembering of episodic information in item recognition memory tasks are relatively mature in middle childhood. The findings suggest, however, that strategic retrieval processing and its neural correlates follows a longer developmental trajectory until adulthood.In zwei altersvergleichenden Untersuchen wurde die Entwicklung verschiedener Abrufprozesse des episodischen Gedächtnisses und ihrer neuronalen Korrelate während Kindheit und Jugend bis zum Erwachsenenalter untersucht. Ein besonderer Schwerpunkt lag dabei auf solchen Prozessen, die kognitiven Kontrollfunktionen unterliegen und den Abruf von Quelleninformation unterstützen. Die Ergebnisse zeigen, dass Prozesse, die mit dem bewussten Erinnern episodischer Information in Itemrekognitionsaufgaben in Verbindung stehen, im mittleren Kindheitsalter ausgereift sind. Hingegen legen die Befunde nahe, dass die strategisch kontrollierte Abrufverarbeitung und ihre neuronalen Substrate einem längeren Entwicklungsgradienten unterliegt, der sich bis zum Erwachsenenalter erstreckt

Memory Performance in Children with Temporal Lobe Epilepsy: Neocortical vs. Dual Pathologies

This study investigated memory in children with temporal lobe epilepsy and the ability to discern hippocampal dysfunction with conventional memory tests that are typically used to detect more global memory impairment. All data was obtained retrospectively from the epilepsy surgery program at a local children’s hospital. The research population consisted of 54 children with intractable epilepsy of temporal onset, balanced across pathology types (with and without hippocampal disease) and other demographics. Each was given a clinical battery prior to surgical intervention, which included the WRAML/WRAML2 Verbal Learning subtest from which the dependent variables for this study were extracted. The research hypothesis had predicted that memory retention between verbal learning and recall would be worse for participants with pathology that included hippocampal sclerosis than for those with non-hippocampal temporal lobe pathology. A two-way mixed-design ANOVA was used to test the hypothesis, which allowed incorporation of variables of interest related to memory factors, pathology type, and hemispheric laterality, as well as their various interactions. There was a significant main effect for change in the number of words retained from the final learning trial to the delayed recall. Although the interaction between memory retention and pathology type was not statistically significant, the average of the memory scores as it related to pathology by side did show significance. Thus, results did not support the hypothetical relationship between retention and hippocampal function. However, additional exploratory analyses revealed that the final learning trial by itself was associated with hippocampal pathology, which applied only to those participants with left-hemisphere lesions. Logistic regression with the final learning trial correctly classified 74 percent of participants into the appropriate pathology category, with 81 percent sensitivity to hippocampal dysfunction. Mean participant memory scores were nearly one standard deviation below the normative mean for both delayed recall and total learning scaled scores, regardless of pathology type or lesion hemisphericity. Thus, while the conventionally used indices of the WRAML Verbal Learning test are useful for determining overall memory status, they are not specific to pathological substrate. The within-subject main effect showed an expected loss of information across the time of the delay, but overall the recall score showed no association with hippocampal functioning. This study revealed the possibility of measuring hippocampal function at statistically significant group levels using learning scores from a widely used measure of verbal memory, even in participants with intact contralateral mesial temporal structures. It also indicated that hippocampal structures do not play a role during recall measures given after a standard time delay. Data further demonstrated a role of the hippocampus for encoding and transferring information beyond short term/working memory into long term. During the learning process, the hippocampus appears to work in concert with short-term memory systems, but does not take over the encoding process until enough repetitions have occurred to saturate the working memory buffer. This research represents a small, yet important step forward in our understanding of the hippocampus, with potentially important implications for the future study of memory constructs and mensuration