Structural brain changes after traditional and robot-assisted multi-domain cognitive training in community-dwelling healthy elderly

The purpose of this study was to investigate if multi-domain cognitive training, especially robot-assisted training, alters cortical thickness in the brains of elderly participants. A controlled trial was conducted with 85 volunteers without cognitive impairment who were 60 years old or older. Participants were first randomized into two groups. One group consisted of 48 participants who would receive cognitive training and 37 who would not receive training. The cognitive training group was randomly divided into two groups, 24 who received traditional cognitive training and 24 who received robot-assisted cognitive training. The training for both groups consisted of daily 90-min-session, five days a week for a total of 12 weeks. The primary outcome was the changes in cortical thickness. When compared to the control group, both groups who underwent cognitive training demonstrated attenuation of age related cortical thinning in the frontotemporal association cortices. When the robot and the traditional interventions were directly compared, the robot group showed less cortical thinning in the anterior cingulate cortices. Our results suggest that cognitive training can mitigate age-associated structural brain changes in the elderly.ope

The Aging Navigational System

The discovery of neuronal systems dedicated to computing spatial information, composed of functionally distinct cell types such as place and grid cells, combined with an extensive body of human-based behavioral and neuroimaging research has provided us with a detailed understanding of the brain's navigation circuit. In this review, we discuss emerging evidence from rodents, non-human primates, and humans that demonstrates how cognitive aging affects the navigational computations supported by these systems. Critically, we show 1) that navigational deficits cannot solely be explained by general deficits in learning and memory, 2) that there is no uniform decline across different navigational computations, and 3) that navigational deficits might be sensitive markers for impending pathological decline. Following an introduction to the mechanisms underlying spatial navigation and how they relate to general processes of learning and memory, the review discusses how aging affects the perception and integration of spatial information, the creation and storage of memory traces for spatial information, and the use of spatial information during navigational behavior. The closing section highlights the clinical potential of behavioral and neural markers of spatial navigation, with a particular emphasis on neurodegenerative disorders

Cardiorespiratory fitness and virtual navigation in healthy older adults

One of the earliest symptoms of Alzheimer’s disease (AD) and age-related cognitive decline is topographical disorientation or impairment to spatial navigation. Furthermore, aging and AD are associated with cortical gray-matter thinning, particularly in the medial temporal and posterior cingulate regions, which have been associated with spatial navigation. Aerobic exercise has been well-established as a beneficial intervention to curtail the neurodegenerative effects of aging. This study aims to explore the relationship between cardiorespiratory fitness (CRF), and two markers of AD and cognitive aging, virtual navigation ability and cortical thickness of the entorhinal, parahippocampal and retrosplenial regions. Cross-sectional data utilized in this study was collected from 23 healthy older adults (60-80 years). Measures included in our analyses consisted of estimated VO2max, T1-weighted structural MR images, and behavioral performance on a virtual navigation task, measured as numbers of objects located during recall. Cortical thickness of the regions of interest (ROIs) was determined by processing T1-weighted MR images in FreeSurfer. We hypothesized that greater CRF would correlate with improved virtual navigation performance and greater cortical thickness of ROIs. Our analyses did not reveal statistically significant relationships between CRF and navigation performance or CRF and cortical thickness. However, Pearson’s correlations found right retrosplenial cortical (RSC) thickness and navigation performance to be significantly related. Multiple regression models of right RSC thickness and navigation performance were performed controlling for age, sex, education and task version. These analyses revealed that greater right RSC thickness predicted navigation performance. Additionally, this model showed that older age predicts decline in navigation performance. Our findings did not survive multiple comparisons correction; nonetheless, the results provide promising insight to the relationship between cortical thickness and navigation performance in healthy aging. Further cross-sectional and longitudinal investigations with a larger sample size are required to assess the impact of CRF and exercise on cortical thickness and navigation abilities in healthy aging. Understanding these relationships would contribute to the expansive body of literature that has linked CRF and exercise to neuroprotective mechanisms in the aging brain

Reabilitação Neuropsicológica Grupal de Idosos Institucionalizados com declínio Cognitivo sem Demência em interação com crianças do pré-escolar

Contexto: Alterações ao nível cognitivo são naturais com o avançar da idade, mas por vezes ocorre deterioração elevada das funções cognitivas característica de envelhecimento patológico. Designa-se por declínio cognitivo sem demência (DCSD) quando tais alterações cognitivas são mais extensas do que as expectáveis para um envelhecimento normal. Independente da etiologia subjacente ao DCSD, as taxas de evolução para a demência são altas pelo que se torna essencial implementar programas de reabilitação com o intuito de prevenir a demência. Objetivo: Com este estudo pretendemos averiguar o impacto de um Programa de Reabilitação Neuropsicológica Grupal (PRNG) no funcionamento cognitivo e executivo de idosos institucionalizados com DCSD em interação com crianças. Método: Este estudo investigou o impacto de um PRNG, composto por diversos exercícios práticos que tinham como objetivo capacitar os idosos com estratégias compensatórias, propiciando a melhoria do funcionamento cognitivo e executivo. O estudo teve um desenho quase-experimental, sendo realizado com um grupo experimental e um grupo de controlo em dois momentos: avaliação pré e pós-reabilitação para todos os participantes e reabilitação com o grupo experimental. Trinta indivíduos de ambos os sexos (6 homens e 24 mulheres), com idades compreendidas entre os 65 e os 90 anos, participaram neste estudo. Todos os participantes foram submetidos a avaliação neuropsicológica pré e pós-reabilitação. A reabilitação consistiu em 10 sessões grupais com a duração de 60 minutos cada. Resultados: A comparação entre grupo experimental e de controlo nos dois momentos de avaliação (pré e pós-reabilitação) revelou diferenças significativas ao nível cognitivo (MMSE) e executivo (FAB), e ainda ao nível emocional (GDS, GAI e UCLA). Verificandose que o grupo experimental melhora significativamente nas pontuações médias cognitivas, executivas e emocionais; enquanto o grupo de controlo piora significativamente nas pontuações médias cognitivas e piora, mas não significativamente, nas pontuações médias executivas e emocionais. Conclusão: Concluímos que o PRNG em interação com crianças tem impacto relevante, pois é possível estabilizar ou mesmo recuperar as capacidades cognitivas e executivas de idosos institucionalizados com DCSD, bem como reduzir os sintomas depressivos e ansiosos e os sentimentos de solidão.||Context: Changes to the cognitive level are natural with advancing age, but sometimes occurs high deterioration of cognitive functions characteristic of pathological age. Is called Cognitive Impairment no Dementia (CIND) when such cognitive changes are more extensive than expected for normal aging. Independent of the underlying etiology to CIND, rates of progression to dementia are high, therefore is essential to implement rehabilitation programs in order to prevent dementia. Objective: In this study we intend to investigate the impact of a Neuropsychological Group Rehabilitation Program (NGRP) in cognitive and executive functioning of institutionalized elderly with CIND interacting with children. Method: This study investigated the impact of a NGRP, composed of several practical exercises that intended to empower elders with compensatory strategies, leading to improved cognitive and executive functioning. The study had an almost-experimental design, being conducted with an experimental group and a control group in two stages: pre and postrehabilitation for all participants and rehabilitation with the experimental group. Participated in this study thirty individuals of both sexes (6 men and 24 women), aged between 65 and 90 years. All participants were submitted neuropsychological evaluation pre and postrehabilitation. The rehabilitation consisted of 10 group sessions lasting 60 minutes each. Results: The comparison between experimental group and control group in the two evaluation moments (pre and post-rehabilitation) revealed significant differences both at a cognitive level (MMSE) and executive (FAB), and even the emotional level (GDS, GAI and UCLA). Verifying that the experimental group improved significantly in mean scores cognitive, executive and emotional; the control group deteriorated significantly in mean scores cognitiv

Structural asymmetry of the human cerebral cortex: Regional and between-subject variability of surface area, cortical thickness, and local gyrification

Structural asymmetry varies across individuals, brain regions, and metrics of cortical organization. The current study investigated regional differences in asymmetry of cortical surface area, thickness, and local gyrification, and the extent of between-subject variability in these metrics, in a sample of healthy young adults (N = 200). Between-subject variability in cortical structure may provide a means to assess the extent of biological flexibility or constraint of brain regions, and we explored the potential influence of this variability on the phenotypic expression of structural asymmetry. The findings demonstrate that structural asymmetries are nearly ubiquitous across the cortex, with differing regional organization for the three cortical metrics. This implies that there are multiple, only partially overlapping, maps of structural asymmetry. The results further indicate that the degree of asymmetry of a brain region can be predicted by the extent of the region’s between-subject variability. These findings provide evidence that reduced biological constraint promotes the expression of strong structural asymmetry

Cortical thickness changes following spatial navigation training in adulthood and aging

A widespread network involving cortical and subcortical brain structures forms the neural substrate of human spatial navigation. Most studies investigating plasticity of this network have focused on the hippocampus. Here, we investigate age differences in cortical thickness changes evoked by four months of spatial navigation training in 91 men aged 20-30 or 60-70 years. Cortical thickness was automatically measured before, immediately after, and four months after termination of training. Younger as well as older navigators evidenced large improvements in navigation performance that were partly maintained after termination of training. Importantly, training-related cortical thickening in left precuneus and paracentral lobule were observed in young navigators only. Thus, spatial navigation training appears to affect cortical brain structure of young adults, but there is reduced potential for experience-dependent cortical alterations in old age. (C) 2011 Elsevier Inc. All rights reserved

Modifications de la connectivité cérébrale au sein du réseau attentionnel ventral lors du vieillissement normal

Les capacités attentionnelles sont nécessaires à la plupart des tâches de la vie quotidienne. Au cours du vieillissement normal, ces habiletés se modifient. De même, les études suggèrent que l’activité neurofonctionnelle du réseau fronto-pariétal qui sous-tend les capacités attentionnelles diffère entre les individus âgés et de jeunes adultes. Par contre, les changements en contexte du vieillissement du réseau fronto-pariétal ventral, aussi appelé le réseau attentionnel ventral, ont été peu investigués. Une telle question doit être soulevée dans le contexte où les plus récents modèles décrivant les changements fonctionnels associés au vieillissement rapportent que des possibles transformations neurofonctionnelles peuvent survenir au niveau intrahémisphérique et interhémisphérique. Le but de cet ouvrage est de déterminer comment le vieillissement normal affecte le réseau attentionnel ventral et de décrire la nature des changements qui peuvent survenir sur les axes intra et interhémisphériques. Pour y parvenir, la méthode de connectivité fonctionnelle fut privilégiée puisqu’elle permet de quantifier l’interaction neurofonctionnelle entre diverses régions composant un réseau fonctionnel. La première étude de cette thèse a permis de décrire les modifications de connectivité fonctionelle intrahémisphériques du réseau attentionnel ventral en comparant des adultes jeunes et âgés lorsqu’ils réalisent une tâche d’attention sélective en imagerie par résonance magnétique. Sur le plan comportemental, les individus âgés répondaient significativement plus lentement et commettaient davantage d’erreurs que le groupe composé de jeunes adultes. Les résultats de connectivité fonctionnelle montrent que le degré d’intégration de la connectivité fonctionnelle intrahémisphérique est globalement plus élevé chez les individus âgés dans l’ensemble des régions fronto-pariétales composant ce réseau. De plus, il semble que les aires antérieures du réseau, soit les aires préfrontales et insulaires, sont moins intégrées chez les individus âgés, alors que les zones pariétales, temporales et cérébelleuses le sont davantage. Le degré d’intégration de la connectivité est également plus élevé chez les adultes âgés entre les régions postérieures et antérieures. Ainsi, les résultats de cette étude suggèrent que la dynamique des régions antérieures et postérieures du réseau attentionnel ventral est modifiée au cours du vieillissement normal et que les régions postérieures occupent au sein de ce réseau un rôle plus important avec l’âge. Cette hyperconnectivité des aires pariétales pourrait représenter une stratégie de compensation intrahémisphérique (i.e. recrutement de régions additionnelles en postérieur) qui aurait cependant atteint un certain plateau puisque bien que les âgés réussissent à réaliser la tâche, ils performent significativement plus faiblement que de jeunes adultes. La seconde étude s’est intéressée aux modifications de connectivité interhémisphériques du même réseau fonctionnel en comparant le degré de connectivité fonctionnelle entre des individus jeunes et âgés. De manière similaire à l’étude 1, sur le plan comportemental les individus âgés répondaient significativement plus lentement et commettaient plus d’erreurs que les jeunes adultes. En ce qui concerne la dimension inter-hémisphérique du réseau, les résultats des analyses de connectivité montrent que le degré d’intégration des régions hémisphériques gauches fronto-pariétales et temporales est plus faible pour les participants âgés que pour les participants jeunes. Au contraire, les régions frontales, pariétales, temporales et sous-corticales de l’hémisphère droit sont plus intégrées. Par ailleurs, les résultats montrent également que le degré d’intégration interhémisphérique est plus élevé chez les individus âgés. Ainsi, cette étude suggère que le degré de connectivité fonctionnelle entre les régions hémisphériques droites du réseau attentionnel ventral augmente au cours du vieillissement, suggérant ainsi une amplification de la latéralisation de ce réseau vers l’hémisphère droit avec l’âge. Cette étude montre également que malgré une augmentation de la latéralisation du VAN à droite, celle-ci s’accompagne d’une augmentation du degré de connectivité fonctionnelle interhémisphérique qui pourrait être envisagée comme une tentative de compensation interhémisphérique (i.e. recrutement des régions homologues) qui aurait atteint toutefois un certain plateau car même si les âgés réussissent à réaliser la tâche, leur niveau de performance reste significativement plus faible que les jeunes. En somme, ce travail a permis de contribuer à notre compréhension de l’impact du vieillissement sur le réseau attentionnel ventral sur l’axe intrahémisphérique et interhémisphérique. Cet ouvrage lance de nouvelles pistes d’investigation dans ce domaine et pourrait éventuellement mener à l’élaboration d’interventions susceptibles de promouvoir une santé cognitive optimale lors du vieillissement.Attention is necessary for most of daily life’s tasks. During aging, these cognitive abilities are changed. Studies suggest that the neurofunctional activity of the frontoparietal network, which upholds the attentional capacities, differ between young and older adults. However, age-related changes of the ventral frontoparietal network, also called the ventral attention network, have been less investigated. Such question has to be raised in context of recent models of neurofunctional changes in aging, who report possible functional transformation that could occur both at the intrahemispheric and interhemispheric levels. The goal of the present thesis is to determine how aging affects the ventral attention network and describe the nature of such changes that can occur on the intrahemispheric and interhemispheric axis. To do so, functional connectivity methods were favoured because of their capacity to measure the neurofunctional interaction between the regions of a network. The first study of the present thesis has allowed describing the age-related intrahemispheric modifications of functional connectivity in this network by comparing young and older adults while they respond on a selective attention task during a functional magnetic resonance imagery scan. On the task, aged adults performed significantly slower and made more errors than the young adults. At the functional connectivity level, the results show higher level of the functional connectivity between all frontoparietal regions of this network for the older group. Further, the integration level of functional connectivity in anterior regions of the network seems to be less integrated for the older participants, while posterior regions have more neurofunctional signal dependency. Also, the level of integration of functional connectivity is higher in older adults between anterior and posterior regions. Thus, results from this study suggest that the anterior and posterior regions of the ventral attention network interact differently during aging and that the posterior regions play a more important role with age in this network. This hyperconnectivity in the parietal regions could represent an unsuccessful intrahemispheric compensation attempt (i.e. recruitment of additional regions in posterior part of the brain) since older adults perform significantly less well than younger adults. The second study has investigated interhemispheric alterations of functional connectivity in the same functional network by comparing young and older adults. Like in the first study, younger adults were faster to respond on task and were more accurate. Regarding the neurofunctional lateralization of the network, the degree of functional connectivity is lower in older adults for the left hemisphere’s frontoparietal and temporal regions. However, older adults have a higher degree of functional connectivity in the right frontal, parietal, temporal and subcortical regions of the same network. Also, the results also show that the interhemispheric integration level is superior for the older adults. Thus, this study suggests that the level of functional connectivity with the right hemisphere’s regions of the ventral attention network increases with age, which could suggest an age-related lateralization of this network towards the right hemisphere. In this context, increased interhemispheric functional connectivity could be interpreted as a failed interhemispheric compensation attempt (i.e. recruitment of homologous regions) since the performance of older adults on task was significantly lower than younger adults. In short, this work has allowed contributing to our understanding of the impact of aging on the ventral attention network both on the intrahemispheric and interhemispheric axis. These various results bring up new hypothesis that needs to be investigated in further studies and eventually that could lead to the establishment of intervention that promote an optimal healthy cognitive aging

Fronto-striatal plasticity processes in humans: glutamatergic and genetic mechanisms

This thesis investigated fronto-striatal plasticity processes in the human brain via a multilevel (genes, brain, behavior) and multimodal neuroimaging (functional- and structural magnetic resonance imaging, magnetic resonance spectroscopy) approach. Neuroplasticity—an intrinsic property of our nervous system—can act in fronto-striatal circuits, specifically in the ‘motor-loop’. Within this circuitry, the striatum, as key structure, and glutamate, as important neurotransmitter, enable the acquisition and automatization of motor skills (e.g. playing an instrument). On a molecular level, brain-derived neurotrophic factor, a neurotrophin, is known to influence cellular plasticity processes, and a single-nucleotide polymorphism of the brain-derived neurotrophic factor gene (BDNF val66met), has been related to impairments in hippocampal learning and plasticity in humans. However, research and respective findings on the influences of this genetic variant in motor skill learning within the fronto-striatal motor-circuitry remain fragmented. 135 healthy right-handed subjects (mean age = 26.96 +/- 9.05 years, 80 females, 54 Met allele carriers) participated in this study. They received training on a sequential visual isometric pinch task in the laboratory and motor skill learning was measured via increases on a speed-accuracy trade-off function (skill measure). Subsequently, magnetic resonance imaging was performed. For functional magnetic resonance imaging, an adapted version of the pinch-force task was used, consisting of the trained, a novel and two control conditions. Furthermore, structural magnetic resonance imaging and magnetic resonance (glutamate) spectroscopy was conducted. Genomic DNA was extracted from whole blood according to standard procedures. Data were analyzed using classical toolboxes for brain imaging data (SPM8, VBM8), for spectroscopy data (LCModel) as well as Matlab-routines and statistics programs for behavioral data and further analysis. To validate the structural neuroimaging results, data of an independent replication sample of 286 healthy right-handed subjects (mean age = 33.39 +/- 9.8 years; 154 females, 101 Met allele carriers) were analyzed. The behavioral results indicated that skill measure constantly increased across the training period. Further analysis also revealed a significant difference in motor skill learning among carriers of the BDNF val66met polymorphism (i.e., impairment in motor skill learning in Met allele carriers). On a structural level, the same individuals also tended to have significantly greater gray matter volume in the striatum, a finding that was replicated in the validation sample. Neurochemically, Met allele carriers did not have altered resting state striatal glutamate concentration or deviations from Val allele carriers in any other of the measured metabolites. Functional neuroimaging data demonstrated strong task-effects within a cortico-striatal motor network and plausible training-related brain activations. However, no functional alterations in (training-related) activity within the fronto-striatal motor network for carriers of the Met variant were observed. The behavioral findings of this study complement previous findings on deficits of Met allele carriers of the BDNF val66met polymorphism in long term motor skill learning and reinforce our understanding of the molecular basis of this functional variant. The observed structural effects were interpreted as a compensatory mechanism for hippocampal deficits and are discussed in light of the limitations of the present study. The non-significant genotype results on glutamate concentration and (training-related) brain function are also consistent with the prior literature. Furthermore, this pattern of results points to the distinct qualities of the three neuroimaging methods used in this study and highlights the uniqueness of this multilevel and multimodal neuroimaging approach to study fronto-striatal learning and plasticity processes in humans. The scientific and possible clinical implications of these findings were discussed

Experience-dependent plasticity in the auditory domain: effects of expertise and training on functional brain organization

The present dissertation aims at systematically investigating manifestations of experience-dependent plasticity in the auditory domain, resulting from intensive musical training, utilizing analytical tools from network neuroscience. The dissertation is based on data acquired in the course of a longitudinal study investigating structural and functional changes in the auditory domain due to music training. A group of aspiring professional musicians, attending preparatory courses for entrance exams at universities of arts, and a group of amateur musicians, actively practicing in their everyday life, completed up to 5 behavioral and neuroimaging assessments in the course of one year. The dissertation consists of three studies addressing cross-sectional and longitudinal aspects of functional plastic differences and changes, respectively, ranging from a specific auditory process over unconstrained music listening to longitudinal changes in functional organization