Neural reorganization and compensation in aging

According to prominent theories of aging, the brain may reorganize in order to compensate for neural deterioration, and prevent or offset cognitive decline. A frequent and striking finding in functional imaging studies is that older adults recruit additional regions relative to young adults performing the same task. This is often interpreted as evidence for functional reorganization, suggesting that as people age, different regions or networks may support the same cognitive functions. Associations between additional recruitment and better performance in older adults have led to the suggestion that the additional recruitment may contribute to preserved cognitive function in old age, and may explain some of the variation among individuals in preservation of function. However, many alternative explanations are possible, and recent findings and methodological developments have highlighted the need for more systematic approaches to determine whether reorganization occurs with age and whether it benefits performance. We re-evaluate current evidence for compensatory functional reorganization in the light of recent moves to address these challenges

Neural Dedifferentiation in Relation to Risk for Alzheimer\u27s Disease

Functional magnetic resonance imaging (fMRI) research indicates that as an individual\u27s age increases, the task-related spatial extent of neural activation increases. This decrease in neural specificity, or dedifferentiation, is often demonstrated by older adults during challenging cognitive tasks. Cognitively intact individuals at-risk for Alzheimer\u27s disease (AD), as deemed by having an apolipoprotein-E ε4 allele or a family history of AD, demonstrate increased fMRI activation as compared to individuals at lower risk. Using a low effort, high accuracy event-related semantic memory task involving the presentation of famous and non-famous names, we examined spatial neural specificity through a measure of dedifferentiation using fMRI. In particular, the goal was to look at degree of dedifferentiation between older healthy subjects with or without risk factors for AD. Our results indicated that while there was not a significant difference between the two groups on the total amount of neural dedifferentiation, there was a significant interaction between stimulus type and risk group. Individuals at-risk for AD displayed greater dedifferentiation for non-famous names yet greater differentiation (i.e., less dedifferentiation) for famous names as compared to the low-risk group. These findings may reflect disturbances in memory formation for individuals at-risk for AD

Neurofunctional reorganization to support semantic processing during aging : an fMRI study

Le langage est dans son ensemble bien préservé pendant le vieillissement (Meyer & Federmeier, 2010) tandis que la mémoire sémantique peut même s'améliorer (Kavé, Samuel-Enoch, & Adiv, 2009; Prinz, Bucher, & Marder, 2004; Salthouse, 2009; Verhaegen & Poncelet, 2013 ; Wingfield & Grossman, 2006), malgré de nombreux changements neurophysiologiques se produisant dans le cerveau (Grady, Springer, Hongwanishkul, McIntosh, & Winocur, 2006 ; Kemper & Anagnopoulos, 1989 ; Wingfield & Grossman, 2006). Cette thèse se concentre sur la préservation de la mémoire sémantique dans le vieillissement, « l'acte cognitif d'accéder aux connaissances stockées sur le monde » (Binder, Desai, Graves et Conant, 2009) à travers une tâche de jugement sémantique manipulant le contrôle sémantique avec deux niveaux de demande (faible et élevé) et deux types de relations sémantiques (taxonomique et thématique). Nous avons développé une nouvelle tâche variant les niveaux de demande (faible et élevé) chez 39 adultes jeunes et 39 adultes âgés. Plus précisément, les objectifs de notre étude étaient 1) d'identifier si le vieillissement affecte l'activité cérébrale liée à la mémoire sémantique conformément aux prédictions du modèle CRUNCH, à travers une tâche de jugement sémantique à deux niveaux d'exigences. 2) de combler le vide de la littérature sur l'existence et l'évolution des hubs sémantiques dans le vieillissement, à la lumière des théories single hub et dual-hub, en évaluant l'effet du vieillissement sur le rôle des lobes temporaux antérieurs (ATL) et du jonction temporo-pariétale (TPJ) en tant que représentations neuronales des centres sémantiques responsables respectivement du traitement taxonomique et thématique. Une soumission par rapport pré-enregistré (registered report) a été utilisée pour ce projet de recherche. Nos participants, adultes plus jeunes et plus âgés, étaient globalement appariés en termes de réserve cognitive, plus précisément en ce qui concerne le niveau d'éducation et comme le montrent les questionnaires évaluant l'engagement dans des activités cognitivement stimulantes, les tests MoCA et WAIS-III. Les résultats comportementaux ont confirmé que la tâche varie correctement la difficulté de la tâche puisque les taux d'erreur et les temps de réponse (RT) augmentent de manière linéaire avec l'augmentation des exigences de la tâche, à savoir dans la condition de forte demande. Nous avons constaté que la participation à des activités stimulantes sur le plan cognitif avait un impact positif à la fois sur les RT de référence et sur la précision. Nous n’avons pas observé de différence statistiquement significative dans la précision entre les participants jeunes et plus âgés, quelle que soit la condition. Nous avons constaté que des scores plus élevés aux tests WAIS-III et PPTT étaient positivement corrélés avec la précision chez les personnes âgées. En termes de RT, nous avons observé une différence statistiquement significative entre les participants jeunes et plus âgés pour la tâche et les conditions de référence, les adultes plus âgés étant plus lents à répondre en général. Les RT augmentent linéairement avec l'âge du participant. En tant que telle, la tâche de mémoire sémantique a réussi à a) manipuler la difficulté de la tâche sur deux niveaux d'exigences et b) démontrer une performance comportementale invariante selon l'âge pour le groupe plus âgé, comme l'exige le test du modèle CRUNCH (Fabiani, 2012 ; Schneider-Garces et al., 2010). Pour l'objectif n°1, les tests cruciaux du modèle CRUNCH, l'interaction IRMf groupe par difficulté, n'étaient pas cohérents avec les prédictions du modèle. Malgré nos résultats comportementaux, lorsque nous avons comparé directement la condition de faible demande avec la condition de forte demande, il n'y avait pas de différence statistiquement significative dans l'activation entre les conditions de faible et de forte demande. Nous n'avons pas non plus obtenu d'interaction entre tranche d'âge et difficulté. Nous avons obtenu des interactions significatives en comparant les conditions de demande faible et élevée avec la ligne de référence. Au niveau neuronal, indépendamment de l'âge, la tâche de jugement de similarité sémantique a activé un large réseau bilatéral fronto-temporo-pariétal. Pour l'objectif n°2 concernant l'effet de relation sémantique, le contraste de la condition taxonomique avec la condition thématique directement n'a pas trouvé d'activation robuste à un seuil corrigé. La condition taxonomique a donné des résultats intéressants par rapport à la condition de base. Sept groupes distincts dans le cortex fronto-temporo-pariétal ont été activés dans les deux hémisphères, y compris les lobes temporaux antérieurs (ATL) et la jonction temporo-pariétale gauche (TPJ). De plus, l'activation était significative dans le gyrus supérieur frontal gauche, le gyrus angulaire gauche (AG) et le gyrus frontal inférieur (partie orbitale) sur l'hémisphère droit. Cette découverte pourrait être en partie conforme à la théorie du double-hub, qui propose que les ATL bilatéralement et le TPJ agissent comme des hubs sémantiques. Bien que nous n'ayons pas trouvé d'activation significative dans les ATL pendant la condition taxonomique et dans le TPJ pendant la condition thématique, nous avons cependant constaté que dans la condition taxonomique parmi les sept clusters significativement activés, l'activation dans le gyrus frontal supérieur gauche était significativement corrélée avec la performance dans la condition taxonomique pour les deux groupes d'âge. L'activation dans le gyrus temporal moyen droit était également corrélée à l'amélioration des performances, mais cela n'était pas significatif dans le groupe plus âgé. En ce qui concerne la condition thématique, par contraste avec condition de référence, dix groupes distincts ont été activés, y compris la jonction temporo-pariétale (TPJ), alors que les ATL n'ont pas été activés de manière robuste pendant la condition thématique. Plus précisément, les régions activées comprenaient bilatéralement le gyrus angulaire, le gyrus temporal moyen, le gyrus frontal inférieur (partie triangulaire) et le gyrus frontal moyen. Nous visons à poursuivre des analyses supplémentaires pour explorer la relation entre les exigences de la tâche, le type de relation sémantique et la réorganisation neurofonctionnelle liée à l'âge. Cependant, ces résultats relatifs à la préservation avec l'âge des capacités à traiter les différentes relations sémantiques de mots sont associés à un certain nombre de réorganisations neurofonctionnelles. Celles-ci peuvent être spécifiques au traitement de différentes relations sémantiques et de différentes demandes de tâches. Il reste à déterminer si cette réorganisation est induite par les changements structurels du cerveau avec l'âge, ou par l'utilisation accrue de telles relations sémantiques tout au long de la trajectoire de la vie.Language overall is well preserved in aging (Meyer & Federmeier, 2010) whereas semantic memory may even improve (Kavé, Samuel-Enoch, & Adiv, 2009; Prinz, Bucher, & Marder, 2004; Salthouse, 2009; Verhaegen & Poncelet, 2013; Wingfield & Grossman, 2006), despite numerous neurophysiological changes taking place in the brain (Grady, Springer, Hongwanishkul, McIntosh, & Winocur, 2006; Kemper & Anagnopoulos, 1989; Wingfield & Grossman, 2006). The present study focuses on the preservation of semantic memory in aging, the ‘cognitive act of accessing stored knowledge about the world’ (Binder, Desai, Graves, & Conant, 2009) by means of a semantic judgment task manipulating semantic control with two demand levels (low and high) and two types of semantic relations (taxonomic-thematic). We used a novel task that varied task demands (low versus high) in 39 younger and 39 older adults. More specifically, the aims of this study was 1) to identify whether aging affects the brain activity subserving semantic memory in accordance with the CRUNCH predictions, through a semantic judgment task with two levels of demands (low and high). 2) To bridge the gap in the literature on the existence and evolution of semantic hubs in aging, in light of the dual and single-hub theories, by evaluating the effect of aging on the role of the Anterior Temporal Lobes (ATLs) and the Temporo-parietal junction (TPJ) as neural representations of the semantic hubs responsible for taxonomic and thematic processing, respectively. A submission by registered report was opted for this research project. Our participants, younger and older adults, were overall matched in regards to level of education and as shown in questionnaires assessing engagement in cognitively stimulating activities, MoCA and WAIS-III tests. The behavioral results confirmed that the task was successful in manipulating task difficulty, with error rates and RTs increasing with increasing task demands, namely in the high-demand condition. We found that engaging in cognitively stimulating activities impacted positively on both baseline RTs and accuracy and that higher scores on the WAIS-III and the PPTT tests were positively correlated with accuracy in older adults. There was no statistical difference in accuracy between younger and older participants regardless of the condition, so there was no age effect in accuracy. In terms of RTs, there was a statistically significant difference between younger and older participants for both the task and the baseline conditions, with older adults being slower to respond in general. RTs increased the more the participant’s age increased, which is in line with findings in the literature. As such, the semantic memory task was successful in a) manipulating task difficulty across two levels of demands and b) demonstrating age-invariant behavioural performance for the older group, as requires to test the CRUNCH model (Fabiani, 2012; Schneider-Garces et al., 2010). For objective no 1, the crucial test of CRUNCH model, the fMRI age group by task demand interaction was not found. We did not find statistically significant interaction neither between task demands and age group for RTs or accuracy, nor in regards to brain activation. At the neural level, independently of age, the semantic similarity judgment task activated a large network including bilateral inferior frontal, parietal, supplementary motor, temporal and occipital brain regions, which correspond overall with the semantic network, as suggested in the literature. Region of interest analyses demonstrated task demand effect in these regions, most notably in the left and right inferior frontal gyrus, the left posterior middle temporal gyrus, the posterior inferior temporal gyrus and the pre-frontal gyrus, regions which are typically associated with semantic control requirements. We did not find any significant interactions between task demands and activation in the regions of interest either. Several possible reasons may justify the lack of findings as predicted by the CRUNCH hypothesis. For objective no 2 in regards to the semantic relation effect, the contrast of the taxonomic with the thematic condition directly did not produce any robust activation at a corrected threshold. The taxonomic condition yielded interesting results when contrasted with the baseline one. Seven distinct clusters in the fronto-temporo-parietal cortex were activated across the two hemispheres, including the anterior temporal lobes (ATLs) and the left temporo-parietal junction (TPJ). Additionally, activation was significant in the left frontal syperior gyrus, the left angular gyrus (AG) and the inferior frontal gyrus (orbital part) on the right hemisphere. This finding could be partly in line with the dual-hub theory, that proposes that the ATLs bilaterally and the TPJ act as semantic hubs. Though we did not find the expected double dissociation e.g., significant activation in the ATLs during the taxonomic condition only and in the TPJ during the thematic condition only, we found however that in the taxonomic condition among the seven significantly activated clusters, activation in the left superior frontal gyrus was significantly correlated with performance in both age groups. Activation in the right middle temporal gyrus was also correlated with improved performance, but this was not significant in the older group. During the thematic condition, when contrasted with baseline, ten distinct clusters were activated, including the temporo-parietal junction (TPJ), whereas the ATLs were not robustly activated during the thematic condition. We aim to pursue additional analyses to explore the relation between task demands, type of semantic relation and age-related neurofunctional reorganization. However, these results in relation to the preservation with age of the abiliites to process the different semantic word relations is associated with a number of neurofunctional reorganizations. These can be specific to the processing of different semantic relations and different task demands. Whether this reorganization is induced by the structural changes in the brain with age, or by the enhanced use of such semantic relations along the trajectory of life is still under exploration

Medial temporal lobe contributions to intra-item associative recognition memory in the aging brain

Aging is associated with a decline in episodic memory function. This is accompanied by degradation of and functional changes in the medial temporal lobe (MTL) which subserves mnemonic processing. To date no study has investigated age-related functional change in MTL substructures during specific episodic memory processes such as intra-item associative memory. The aim of this study was to characterize age-related change in the neural correlates of intra-item associative memory processing. Sixteen young and 10 older subjects participated in a compound word intra-item associative memory task comprising a measure of associative recognition memory and a measure of recognition memory. There was no difference in performance between groups on the associative memory measure but each group recruited different MTL regions while performing the task.The young group recruited the left anterior hippocampus and posterior parahippocampal gyrus whereas the older participants recruited the hippocampus bilaterally. In contrast, recognition memory was significantlyworse in the older subjects.The left anterior hippocampuswas recruited in the young group during successful recognition memory whereas the older group recruited a more posterior region of the left hippocampus and showed a more bilateral activation of frontal brain regions than was observed in the young group. Our results suggest a reorganization of the neural correlates of intra-item associative memory in the aging brain

Language in the aging brain: the network dynamics of cognitive decline and preservation.

Language is a crucial and complex lifelong faculty, underpinned by dynamic interactions within and between specialized brain networks. Whereas normal aging impairs specific aspects of language production, most core language processes are robust to brain aging. We review recent behavioral and neuroimaging evidence showing that language systems remain largely stable across the life span and that both younger and older adults depend on dynamic neural responses to linguistic demands. Although some aspects of network dynamics change with age, there is no consistent evidence that core language processes are underpinned by different neural networks in younger and older adults.Preparation of this review was supported by grants to LKT from the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1) and the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ ERC Grant agreement no. 249640.This is the accepted manuscript. The final version is available from Science at http://www.sciencemag.org/content/346/6209/583

Effect of Sensory Attenuation on Cortical Movement-Related Oscillations

This study examined the impact of induced sensory deficits on cortical, movement-related oscillations measured using electroencephalography (EEG). We hypothesized that EEG patterns in healthy subjects with induced sensory reduction would be comparable to EEG found after chronic loss of sensory feedback. EEG signals from 64 scalp locations were measured from 10 healthy subjects. Participants dorsiflexed their ankle after prolonged vibration of the tibialis anterior (TA). Beta band time frequency decompositions were calculated using wavelets and compared across conditions. Changes in patterns of movement-related brain activity were observed following attenuation of sensory feedback. A significant decrease in beta power of event-related synchronization was associated with simple ankle dorsiflexion after prolonged vibration of the TA. Attenuation of sensory feedback in young, healthy subjects led to a corresponding decrease in beta band synchronization. This temporary change in beta oscillations suggests that these modulations are a mechanism for sensorimotor integration. The loss of sensory feedback found in spinal cord injury patients contributes to changes in EEG signals underlying motor commands. Similar alterations in cortical signals in healthy subjects with reduced sensory feedback implies these changes reflect normal sensorimotor integration after reduced sensory input rather than brain plasticity

Neural correlates of cognitive intervention in persons at risk of developing Alzheimer's disease.

Cognitive training is an emergent approach that has begun to receive increased attention in recent years as a non-pharmacological, cost-effective intervention for Alzheimer's disease (AD). There has been increasing behavioral evidence regarding training-related improvement in cognitive performance in early stages of AD. Although these studies provide important insight about the efficacy of cognitive training, neuroimaging studies are crucial to pinpoint changes in brain structure and function associated with training and to examine their overlap with pathology in AD. In this study, we reviewed the existing neuroimaging studies on cognitive training in persons at risk of developing AD to provide an overview of the overlap between neural networks rehabilitated by the current training methods and those affected in AD. The data suggest a consistent training-related increase in brain activity in medial temporal, prefrontal, and posterior default mode networks, as well as increase in gray matter structure in frontoparietal and entorhinal regions. This pattern differs from the observed pattern in healthy older adults that shows a combination of increased and decreased activity in response to training. Detailed investigation of the data suggests that training in persons at risk of developing AD mainly improves compensatory mechanisms and partly restores the affected functions. While current neuroimaging studies are quite helpful in identifying the mechanisms underlying cognitive training, the data calls for future multi-modal neuroimaging studies with focus on multi-domain cognitive training, network level connectivity, and individual differences in response to training

Computational neurorehabilitation: modeling plasticity and learning to predict recovery

Despite progress in using computational approaches to inform medicine and neuroscience in the last 30 years, there have been few attempts to model the mechanisms underlying sensorimotor rehabilitation. We argue that a fundamental understanding of neurologic recovery, and as a result accurate predictions at the individual level, will be facilitated by developing computational models of the salient neural processes, including plasticity and learning systems of the brain, and integrating them into a context specific to rehabilitation. Here, we therefore discuss Computational Neurorehabilitation, a newly emerging field aimed at modeling plasticity and motor learning to understand and improve movement recovery of individuals with neurologic impairment. We first explain how the emergence of robotics and wearable sensors for rehabilitation is providing data that make development and testing of such models increasingly feasible. We then review key aspects of plasticity and motor learning that such models will incorporate. We proceed by discussing how computational neurorehabilitation models relate to the current benchmark in rehabilitation modeling – regression-based, prognostic modeling. We then critically discuss the first computational neurorehabilitation models, which have primarily focused on modeling rehabilitation of the upper extremity after stroke, and show how even simple models have produced novel ideas for future investigation. Finally, we conclude with key directions for future research, anticipating that soon we will see the emergence of mechanistic models of motor recovery that are informed by clinical imaging results and driven by the actual movement content of rehabilitation therapy as well as wearable sensor-based records of daily activity