Causal role of the posterior parietal cortex for two-digit mental subtraction and addition: A repetitive TMS study

Although parietal areas of the left hemisphere are known to be involved in simple mental calculation, the possible role of the homologue areas of the right hemisphere in mental complex calculation remains debated. In the present study, we tested the causal role of the posterior parietal cortex of both hemispheres in two-digit mental addition and subtraction by means of neuronavigated repetitive TMS (rTMS), investigating possible hemispheric asymmetries in specific parietal areas. In particular, we performed two rTMS experiments, which differed only for the target sites stimulated, on independent samples of participants. rTMS was delivered over the horizontal and ventral portions of the intraparietal sulcus (HIPS and VIPS, respectively) of each hemisphere in Experiment 1, and over the angular and supramarginal gyri (ANG and SMG, respectively) of each hemisphere in Experiment 2. First, we found that each cerebral area of the posterior parietal cortex is involved to some degree in the two-digit addition and subtraction. Second, in Experiment 1, we found a stronger pattern of hemispheric asymmetry for the involvement of HIPS in addition compared to subtraction. In particular, results showed a greater involvement of the right HIPS than the left one for addition. Moreover, we found less asymmetry for the VIPS. Taken together, these results suggest that two-digit mental addition is more strongly associated with the use of a spatial mapping compared to subtraction. In support of this view, in Experiment 2, a greater role of left and right ANG was found for addition needed in verbal processing of numbers and in visuospatial attention processes, respectively. We also revealed a greater involvement of the bilateral SMG in two-digit mental subtraction, in response to greater working memory load required to solve this latter operation compared to addition

Spatial working memory and spatial attention rely on common neural processes in the intraparietal sulcus

Our ability to remember locations in space (spatial working memory) and our ability to direct attention to those locations (spatial attention) are two fundamental and closely related cognitive processes. A growing body of behavioural evidence suggests that spatial working memory and spatial attention share common resources, while neuroimaging studies show some overlap in the neural regions that mediate these two cognitive functions. The current study used fMRI to directly examine the extent to which spatial working memory and spatial attention rely on common underlying neural mechanisms. Twenty healthy participants underwent functional MRI while performing a dual task of spatial working memory incorporating a visual search task during the working memory retention interval. Working memory and visual search task loads were parametrically modulated. A wide network of prefrontal, premotor, and parietal regions showed increasing activity with increased spatial working memory load. Of these areas, part of the right supramarginal gyrus, lying along the intraparietal sulcus, showed a significant interaction such that the neural activity associated with spatial working memory load was significantly attenuated as visual search load in the dual task was increased. This interaction suggests that this part of the supramarginal gyrus, along the intraparietal sulcus, is critical for mediating both spatial working memory and shifts in spatial attention. Copyright © 2010 Elsevier Inc. All rights reserved

Differential brain mechanisms for processing distracting information in task-relevant and-irrelevant dimensions in visual search

A crucial function of our goal-directed behavior is to select task-relevant targets among distractor stimuli, some of which may share properties with the target and thus compete for attentional selection. Here, by applying functional magnetic resonance imaging (fMRI) to a visual search task in which a target was embedded in an array of distractors that were homogeneous or heterogeneous along the task-relevant (orientation or form) and/or task-irrelevant (color) dimensions, we demonstrate that for both (orientation) feature search and (form) conjunction search, the fusiform gyrus is involved in processing the task-irrelevant color information, while the bilateral frontal eye fields (FEF), the cortex along the left intraparietal sulcus (IPS), and the left junction of intraparietal and transverse occipital sulci (IPTO) are involved in processing task-relevant distracting information, especially for target-absent trials. Moreover, in conjunction (but not in feature) search, activity in these frontoparietal regions is affected by stimulus heterogeneity along the task-irrelevant dimension: heterogeneity of the task-irrelevant information increases the activity in these regions only when the task-relevant information is homogeneous, not when it is heterogeneous. These findings suggest that differential neural mechanisms are involved in processing task-relevant and task- irrelevant dimensions of the searched-for objects. In addition, they show that the top-down task set plays a dominant role in determining whether or not task-irrelevant information can affect the processing of the task-relevant dimension in the frontoparietal regions

Neural correlates of training and transfer

Cognitive training holds promise to improve cognitive ability in many people, young, old, both healthy, and those with psychiatric or neurological illness, but this field largely lacks a mechanistic understanding of the process by which training demonstrates transfer to improve underlying cognitive abilities. In Chapter 1, we examine how mapping the neural correlates of training and transfer is critical for developing a mechanistic explanation of how training drives transfer. In the current study, we trained 45 young adults with Mind Frontiers, an adaptive cognitive training game that targets executive function, attention, and reasoning. We investigate how both brain structure and resting state networks are associated with training gain and transfer. In Chapter 2, we investigate how both pre-existing and training-induced differences in brain structure are predictive of training and transfer. In Chapter 3, we assess how both pre-existing, and training-induced differences in resting state network connectivity in the default mode, cingulo-opercular, frontal-parietal, and subcortical networks predict training gain and transfer. In Chapter 4, we examine the relationship of the structural and resting state data in predicting training and transfer. We assess the extent to which these predictors overlap and dissociate with one another over predictions of training gain and transfer. To make our predictions, we utilize a simple machine learning paradigm that we developed to maximize the reliability and interpretability of our findings. We found extensive overlap in structural predictions of training gain and transfer in low level visual and auditory areas, suggesting that greater fidelity in low level sensory systems may contribute to greater signal to noise ratios during training, enabling better training quality and transfer. Furthermore, our resting state results also highlight the importance of training quality through demonstrating the importance of the cingulo-opercular network, which is critical for both the regulation of the default mode network and deployment of sustained attention during training. These results suggest that greater training fidelity through lessened distraction may play an important role in maximizing the benefits of an intervention

Covert shifts and inhibition of return in saccadic and manual responses

In jüngeren, unveröffentlichten Studien unseres Instituts, adaptierten wir das experimentelle Design von Deubel und Schneider [1996, Vision Research, 36(12), 1827-1837], um die Auswirkungen verdeckter Aufmerksamkeitsverlagerungen auf die Sakkadenlatenz zu untersuchen. Entgegen der Ergebnisse von Deubel und Schneider, fanden wir langsamere Reaktionen zu Zielreizen, die am Ort der verdeckten Aufmerksamkeitsverlagerung dargeboten wurden. Die vorliegende Studie wurde durchgeführt, um durch einen Vergleich von Sakkaden und Zeigebewegungen, diese Ergebnisse genauer zu eruieren. Wir fanden erneut IOR-Effekte, für Orte die das Ziel einer verdeckten Aufmerksamkeitsverlagerung waren, sowohl für Sakkaden, als auch für Zeigebewegungen. Wir interpretieren diese Ergebnisse im Rahmen einer Prämotor-Hypothese der Aufmerksamkeit und folgern, dass zwar eine enge Verbindung zwischen verdeckten Aufmerksamkeitsverlagerungen und dem Vorbereiten einer motorischen Reaktion existiert, die Aufmerksamkeit aber nicht an den Zielort der motorischen Reaktion gebunden ist. Ferner fanden wir für beide Modalitäten, dass Hinweisreize, die erinnert werden sollten, zu langsameren Reaktionen führten, als Störreize, die ignoriert werden sollten. Es werden die Implikationen dieser Ergebnisse für top-down und bottom-up Verarbeitung visueller Information diskutiert.In recent, unpublished studies of our institute, we adopted the experimental design of Deubel and Schneider [1996, Vision Research, 36(12), 1827-1837], to assess the effects of covert shifts on saccadic latency. Contrary to the results of the original experiment, we found slower reactions to target stimuli presented at covertly attended locations. The current study was conducted to investigate these findings further, by comparing saccades with manual pointing movements. We once again found IOR for recently attended locations, both in saccades and in manual responses. These results are interpreted in terms of a premotor theory of attention. We conclude that covert shifts are tightly coupled with movement preparation, but that attention is not necessarily locked at the location of the covert shift. Furthermore, we found slower reaction-times for to-be-remembered cues, compared to to-be-ignored distractors, for both modalities. The implications for top-down and bottom-up processes in visual search are discussed

Difficultés neurocognitives et fonctionnement cérébral chez des survivants de la leucémie lymphoblastique aiguë pédiatrique

La leucémie lymphoblastique aiguë est la forme la plus fréquente de cancer chez l’enfant. Aujourd’hui le taux de survie à ce cancer est très élevé, notamment en raison de l’efficacité des protocoles de traitement contemporains. Toutefois, malgré ce taux de survie élevé, plusieurs études soulignent la présence de troubles neurocognitifs, d’atteintes neuroanatomiques et de particularités neurofonctionnelles dans cette population, suite aux traitements. Ces atteintes peuvent affecter la qualité de vie ainsi que la réussite scolaire et professionnelle des survivants. L’objectif de cette thèse était de préciser le profil neurocognitif et d’étudier le fonctionnement neuronal de survivants de la LLA pédiatrique. La thèse est composée de trois articles, soit une revue de littérature et deux articles empiriques. Le premier article visait à recenser les difficultés neurocognitives et neuroanatomiques existantes chez les survivants de la LLA pédiatrique. Cette revue confirme que de nombreuses atteintes ont été identifiées dans cette population. Sur le plan neurocognitif, les atteintes les plus fréquemment rapportées sont des déficits des fonctions exécutives et attentionnelles. La mémoire à court terme s’avère être une fonction particulièrement touchée. Sur le plan neuroanatomique, la matière blanche cérébrale de la population survivante de LLA semble également être altérée. De plus, les atteintes paraissent persister plusieurs années après la fin des traitements. Dans certains cas, les atteintes peuvent même prendre de l’ampleur au fil des années post-diagnostic. Toutefois, peu d’études ont été menées chez des survivants à long terme d’âge adulte, soit plus d’une décennie après le diagnostic. Dans notre second article, nous décrivons le profil neurocognitif d’une cohorte d’adolescents et d’adultes survivants de la LLA. Nos résultats suggèrent la présence fréquente de difficultés au niveau de la mémoire à court terme/mémoire de travail, de la fluidité verbale phonologique, de la flexibilité cognitive et de la coordination visuo-motrice. Nous avons également validé une batterie d’évaluation neurocognitive brève auprès d’une sous-population de la cohorte initiale, composée uniquement d’adultes : la batterie DIVERGT. Nos résultats ont montré que la DIVERGT permettait de prédire avec précision le rendement intellectuel global, la performance en mathématiques et la performance en mémoire verbale. La batterie présentait une sensibilité et une spécificité acceptable, ainsi qu’une excellente valeur de prédiction négative, permettant de dépister les difficultés dans plusieurs domaines neurocognitifs. Ainsi, la batterie de dépistage pourrait facilement être utilisée dans le cadre des examens de routine chez les adultes survivants de la LLA et ainsi améliorer la qualité du suivi à long terme chez ces patients. Enfin, comme les difficultés neurocognitives en mémoire à court terme/mémoire de travail sont fréquentes, nous avons utilisé la magnétoencéphalographie (MEG) afin d’étudier le fonctionnement neuronal sous-jacent à la mémoire à court terme visuelle (MCTv) dans cette population d’adultes survivants de la LLA. En comparant les données des survivants à celles d’un groupe contrôle, nous avons cherché à mettre en lumière toute différence dans l’activation cérébrale générée lors d’une tâche de MCTv dans notre population clinique. Nos résultats ont montré que la performance en MCTv était similaire entre les survivants de la LLA et le groupe contrôle. Toutefois, une activation cérébrale atypique a été observée dans plusieurs régions cérébrales. Les survivants de la LLA présentaient une activation accrue dans la région occipitale latérale et les gyri précentraux et post-centraux, des régions habituellement associées à la MCTv. Une augmentation a aussi été observée dans certaines régions moins impliquées dans la MCTv, soit les régions temporales supérieure et médiane ainsi que le gyrus supramarginal. Une sous-activation de la région frontale inférieure a également été observée. Ces résultats pourraient suggérer l’existence de processus neuronaux compensatoires chez les survivants de la LLA. Ces processus leur permettraient d’obtenir une performance similaire à celle d’individus qui n’ont pas d’historique de traitement liés au cancer. En dernier lieu, nous avons montré que les patrons d’activation étaient modulés par l’âge d’apparition de la maladie, un facteur de risque important pour le développement de difficultés neurocognitives. Effectivement, l’activité cérébrale était réduite dans plusieurs régions chez les individus plus jeunes au moment du diagnostic. Ces résultats tendent à souligner l’importance d’étudier le fonctionnement neurocognitif et neuronal d’adultes survivants de la LLA, ainsi que les facteurs pouvant moduler leur efficacité.Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in children. Today, the survival rate of ALL is very high, mainly because of the efficiency of contemporary treatment protocols. However, several studies report neurocognitive deficits, neuroanatomical damage and neurofunctional particularities in that population. These deficits can affect quality of life as well as academic and professional achievement. The aim of the present thesis was to study the neurocognitive profile and neuronal functioning of survivors of ALL. This thesis includes three articles, one review article and two empirical articles. Our first article aimed at summarizing frequent neurocognitive difficulties and neuroanatomical damage present in ALL survivors. Our review shows that several deficits are seen in that population. Regarding cognition, executive difficulties are the most frequently reported. Amongst them, short-term memory is one of the most affected neurocognitive function. Regarding neuroanatomical damages, cerebral white matter integrity is frequently altered in that population. Moreover, these difficulties persist many years after the end of treatments. In some cases, the gravity of these deficits can even increase with passing years after diagnosis. Nevertheless, few studies have investigated long-term adult survivors, more than a decade after diagnosis. Our second article first describes the neurocognitive profile of a cohort of adolescent and adult ALL survivors. Our results suggest a high incidence of deficits in working memory, phonological verbal fluency, cognitive flexibility and visuo-motor coordination. We also aimed at validating a brief neurocognitive screening procedure in a sub-population of the same cohort, composed uniquely of adult ALL survivors: the DIVERGT screening procedure. Our results showed that the DIVERGT accurately predicted general intellectual functioning, mathematics and verbal memory. The procedure had acceptable sensitivity, specificity, and excellent negative predictive value (NPV) for the screening of difficulties in multiple neurocognitive domains. Therefore, the DIVERGT could easily be used during routine examination in adult ALL survivors and, improve the quality of cancer related long-term follow-up. Because deficits in short-term memory/ working memory are frequent in ALL survivors, we investigated neural correlates of visual short-term memory (VSTM) in that population, using magnetoencephalography (MEG) as part of our third article. Comparing ALL survivors results with healthy subjects, we aimed at uncovering VSTM related brain activation anomalies in our clinical population. Our results showed that performance in VSTM was similar between controls and survivors. However, atypical brain activation was found in multiple brain regions in ALL survivors. They displayed an over activation of regions that are usually involved in VSTM: lateral occipital, precentral and postcentral gyri, as well as regions that are not usually involved in VSTM: superior and middle temporal region and supramarginal gyrus. A sub-activation of the inferior frontal region was also found. Our results suggest the existence of compensatory neural mechanisms in ALL survivors, allowing them to perform as healthy subjects. Last, we showed that these patterns of activation were modulated by the age of onset, a well-known risk factor for the development of neurocognitive deficits. Activity was reduced in participants who were younger at the time of diagnosis. Altogether, these results highlight the importance of studying neurocognitive and neuronal functioning in ALL survivors, as well as the factors that can modulate their efficacy

Cueing Visual Spatial Working Memory: Effects of Cue Modality, Cue Type, and Age

In general, attentional control and spatial working memory (WM) decline with increasing age. It is well known that relative to non-cued targets, spatially informative visual (uni-modal) cues quicken response time in target detection attention tasks, and improve feature and spatial WM performance. Spatially informative auditory and vibrotactile (cross-modal) cues provide additional benefit in more difficult attention tasks, but their effects on spatial location WM are unknown. This dissertation presents two studies that investigated effects of uni-modal visual cues and cross-modal auditory and vibrotactile cues on visual spatial location WM in younger adults (YA) and older adults (OA), and under various conditions that modulated WM task demands. In study one, we found that both spatially informative uni-modal and cross-modal cues improved spatial location WM performance to a similar degree for YA and OA. This benefit was generally greater under higher WM load (i.e., six-item vs. four-item memory arrays) and longer maintenance delays, whereas centrally presented alerting cues generally impaired performance. Individuals with lower spatial spans also benefitted most from spatially informative cross-modal cues. Study two assessed the impact of maintenance interference on spatially informative cue effects. In contrast to study one, we found age-related cue effects, which were moderated by WM maintenance interference type. When interference was to be ignored, OA benefitted from visual, auditory, and vibrotactile cues for lower WM loads (i.e., four-item arrays), whereas YA only benefitted from vibrotactile cues at higher WM loads (i.e., six-item arrays). When interference was to be compared, OA showed increased benefit to WM performance from cross-modal auditory and vibrotactile cues, whereas YA benefitted from all cue modalities. Taken together, these findings suggest spatially informative cross-modal cues can improve spatial location WM in both YA and OA, particularly when demands on spatial attention and attentional control are high. Furthermore, OA show more consistent benefit from cross-modal cues in resource demanding conditions. These results provide insight into cognitive underpinnings of cross-modal cue effects, and age-related differences in use of environmental support. They also provide a rationale for real world applications using cross-modal cues, aimed at improving cognitive function in complex visual environments, particularly for OA