Changes in cortical and sub-cortical patterns of activity associated with aging during the performance of a lexical set-shifting task

Bien que le passage du temps altère le cerveau, la cognition ne suit pas nécessairement le même destin. En effet, il existe des mécanismes compensatoires qui permettent de préserver la cognition (réserve cognitive) malgré le vieillissement. Les personnes âgées peuvent utiliser de nouveaux circuits neuronaux (compensation neuronale) ou des circuits existants moins susceptibles aux effets du vieillissement (réserve neuronale) pour maintenir un haut niveau de performance cognitive. Toutefois, la façon dont ces mécanismes affectent l’activité corticale et striatale lors de tâches impliquant des changements de règles (set-shifting) et durant le traitement sémantique et phonologique n’a pas été extensivement explorée. Le but de cette thèse est d’explorer comment le vieillissement affecte les patrons d’activité cérébrale dans les processus exécutifs d’une part et dans l’utilisation de règles lexicales d’autre part. Pour cela nous avons utilisé l’imagerie par résonance magnétique fonctionnelle (IRMf) lors de la performance d’une tâche lexicale analogue à celle du Wisconsin. Cette tâche a été fortement liée à de l’activité fronto-stritale lors des changements de règles, ainsi qu’à la mobilisation de régions associées au traitement sémantique et phonologique lors de décisions sémantiques et phonologiques, respectivement. Par conséquent, nous avons comparé l’activité cérébrale de jeunes individus (18 à 35 ans) à celle d’individus âgés (55 à 75 ans) lors de l’exécution de cette tâche. Les deux groupes ont montré l’implication de boucles fronto-striatales associées à la planification et à l’exécution de changements de règle. Toutefois, alors que les jeunes semblaient activer une « boucle cognitive » (cortex préfrontal ventrolatéral, noyau caudé et thalamus) lorsqu’ils se voyaient indiquer qu’un changement de règle était requis, et une « boucle motrice » (cortex postérieur préfrontal et putamen) lorsqu’ils devaient effectuer le changement, les participants âgés montraient une activation des deux boucles lors de l’exécution des changements de règle seulement. Les jeunes adultes tendaient à présenter une augmentation de l’activité du cortex préfrontal ventrolatéral, du gyrus fusiforme, du lobe ventral temporale et du noyau caudé lors des décisions sémantiques, ainsi que de l’activité au niveau de l’aire de Broca postérieur, de la junction temporopariétale et du cortex moteur lors de décisions phonologiques. Les participants âgés ont montré de l’activité au niveau du cortex préfrontal latéral et moteur durant les deux types de décisions lexicales. De plus, lorsque les décisions sémantiques et phonologiques ont été comparées entre elles, les jeunes ont montré des différences significatives au niveau de plusieurs régions cérébrales, mais pas les âgés. En conclusion, notre première étude a montré, lors du set-shifting, un délai de l’activité cérébrale chez les personnes âgées. Cela nous a permis de conceptualiser l’Hypothèse Temporelle de Compensation (troisième manuscrit) qui consiste en l’existence d’un mécanisme compensatoire caractérisé par un délai d’activité cérébrale lié au vieillissement permettant de préserver la cognition au détriment de la vitesse d’exécution. En ce qui concerne les processus langagiers (deuxième étude), les circuits sémantiques et phonologiques semblent se fusionner dans un seul circuit chez les individus âgés, cela représente vraisemblablement des mécanismes de réserve et de compensation neuronales qui permettent de préserver les habilités langagières.As the one’s brain is structurally altered by the passage of time, cognition does not have to suffer the same faith, at least not to the same extent. Indeed, age-related compensatory mechanisms allow for some cognitive preservation. The elderly can therefore use new compensatory neuronal networks (neural compensation) or flexible pathways that are less susceptible to disruption (neural reserve) in order to maintain high levels of performance (cognitive reserve) during cognitive tasks. However, how these mechanisms affect cortical and striatal activity during set-shifting as well as during semantic and phonological processing has not been extensively explored. The purpose of this thesis was therefore to investigate how aging affects patterns of neural activity related to executive processes on the one hand and the use of lexical rules on the other. To this end we used functional Magnetic Resonance Imaging (fMRI) during the performance of a lexical analogue of the Wisconsin Card-Sorting Test. This task has been shown to strongly depend on fronto-striatal activity during set-shifting as well as on regions associated with semantic and phonological processing during semantic and phonological decisions, respectively. Two groups participated in our fMRI protocol: young individuals (18 to 35 years old) and older individuals (55 to 75 years old). Both younger and older individuals revealed significant fronto-striatal loop activity associated with planning and execution of set-shifts. However, while the younger group showed the involvement of a “cognitive loop” (including the ventrolateral prefrontal cortex, the caudate nucleus and the thalamus) when instructed that a set-shift would be required on following trial, and the involvement of a “motor loop” (including the posterior prefrontal cortex and the putamen) when the set-shift had to be performed, the older participants showed significant activation of both loops during the execution of the set-shift (matching periods) only. Young adults tended to present increased activity in the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex, the fusiform gyrus, the ventral temporal lobe and the caudate nucleus during semantic decisions and in the posterior Broca’s area, the temporoparietal junction and the motor cortical regions during phonological decisions, older individuals showed increased activity in the lateral prefrontal cortex and motor cortical regions during both semantic and phonological decisions. Furthermore, when semantic and phonological decisions were contrasted with each other, younger individuals showed significant brain activity differences in several regions while older individuals did not. In conclusion, our first study showed an age-related delayed cerebral activation phenomenon during set-shifting (previously observed only in few memory and language tasks). Based on those findings, we conceptualised the Temporal Hypothesis of Compensation (third manuscript) which is the existence of a compensatory mechanism characterised by age-related delayed cerebral activation allowing for cognitive performance to be preserved at the expense of speed processing. Regarding language processing (second study), semantic and phonological routes seem to merge into a single pathway in the elderly; these findings represent most probably neural reserve/compensation mechanisms on which the elderly rely to maintain an adequate level of performance

Learned irrelevance, perseveration, and cognitive aging : a cross-sectional study of cognitively unimpaired older adults

The effect of natural aging on physiologic mechanisms that regulate attentional set-shifting represents an area of high interest in the study of cognitive function. In visual discrimination learning, reward contingency changes in categorization tasks impact individual performance, which is constrained by attention-shifting costs. Perseveration (PE) and learned irrelevance (LI) are viewed as two different mechanisms that shape responses to stimuli, which are predicated on the shift in stimulus form. To date, only studies examining patients with Parkinson’s disease have provided some insight into the relationship between individual age and performance in PE and LI tasks. We enrolled 60 healthy individuals (mean [SD] age, 63.0 [12.6]) without a history of dementia, a cerebrovascular incident, or a neurodegenerative disease. No association was observed between crystallized intelligence or verbal fluency scores and reaction time in both PE (r = 0.074, p = 0.603; r = −0.124, p = 0.346) and LI (r = −0.076, p = 0.562; r = −0.081, p = 0.536) task conditions, respectively. In contrast, a statistically significant linear relationship was observed between age and reaction time (RT) for PE (r = 0.259, p = 0.046) but not for LI (r = 0.226, p = 0.083). No significant linear relationship was observed for changing RTs in PE and LI (r = 0.209, p = 0.110). The present study is the first report that provides a descriptive overview of age-related differences in PE and LI in a sample of cognitively unimpaired middle- to older-aged adults

Normal aging and Parkinson's disease are associated with the functional decline of distinct frontal-striatal circuits.

Impaired ability to shift attention between stimuli (i.e. shifting attentional 'set') is a well-established part of the dysexecutive syndrome in Parkinson's Disease (PD), nevertheless cognitive and neural bases of this deficit remain unclear. In this study, an fMRI-optimised variant of a classic paradigm for assessing attentional control (Hampshire and Owen 2006) was used to contrast activity in dissociable executive circuits in early-stage PD patients and controls. The results demonstrated that the neural basis of the executive performance impairments in PD is accompanied by hypoactivation within the striatum, anterior cingulate cortex (vACC), and inferior frontal sulcus (IFS) regions. By contrast, in aging it is associated with hypoactivation of the anterior insula/inferior frontal operculum (AI/FO) and the pre-supplementary motor area (preSMA). Between group behavioural differences were also observed; whereas normally aging individuals exhibited routine-problem solving deficits, PD patients demonstrated more global task learning deficits. These findings concur with recent research demonstrating model-based reinforcement learning deficits in PD and provide evidence that the AI/FO and IFS circuits are differentially impacted by PD and normal aging

An exploration of executive function, its theoretical construction, and challenges encountered in its understanding and measurement: did neuropsychology get this right?

Section A argued for the importance of cognitive models in providing a theoretical foundation for complex neuropsychological constructs such as ‘executive function’ (EF). It consisted of a narrative review of 29 existing cognitive models of EF, which were reviewed, critiqued, and then integrated into a novel, unified model of EF. This unified account brought together the affective, motivational and attentional processes involved in goal-driven behaviour. Clinical implications were discussed, alongside recommendations for future research in this area. Section B applied a content analysis to systematically examine the ways that EF is described, explained and understood by currently available neuropsychological assessment measures and textbooks, and evaluate these in accordance with current evidence on EF. A total of 29 texts were included. Categories were derived from the current evidence base, including the ‘unified model’ of EF presented in Section A, as well as inductively from the texts. Results suggested that the majority of assessments and textbooks were unlikely to provide such an integrated account, however, there were exceptions. New leads for further theoretical development, and clinical implications were discusse

Learning to be inflexible: Enhanced attentional biases in Parkinson\u27s disease

Impaired attentional flexibility is considered to be one of the core cognitive deficits in Parkinson\u27s disease (PD). However, the mechanisms that underlie this impairment are contested. Progress in resolving this dispute has also been hindered by the fact that cognitive deficits in PD are heterogeneous; therefore, it is unclear whether attentional impairments are only present in a subgroup of patients. Here, we demonstrate that what differentiates PD patients from age-matched controls is an inability to shift attention away from previously relevant information (perseveration) and an inability to shift attention towards previously irrelevant information (learned irrelevance). In contrast, there was no evidence that PD patients, compared to controls, were impaired in being able to appropriately attend to, or ignore, novel information. Furthermore, when patients were stratified according to their level of executive impairment, the executively impaired group showed a selective deficit in set formation compared to the unimpaired group, a behavioural pattern reminiscent of cortical dopamine depletion. Cumulatively, these results suggest that cognitive inflexibility in PD relates to a specific form of attentional dysfunction, in which learned attentional biases cannot be overcome

Visual Acuity does not Moderate Effect Sizes of Higher-Level Cognitive Tasks.

Background/study contextDeclining visual capacities in older adults have been posited as a driving force behind adult age differences in higher-order cognitive functions (e.g., the "common cause" hypothesis of Lindenberger & Baltes, 1994, Psychology and Aging, 9, 339-355). McGowan, Patterson, and Jordan (2013, Experimental Aging Research, 39, 70-79) also found that a surprisingly large number of published cognitive aging studies failed to include adequate measures of visual acuity. However, a recent meta-analysis of three studies (La Fleur and Salthouse, 2014, Psychonomic Bulletin & Review, 21, 1202-1208) failed to find evidence that visual acuity moderated or mediated age differences in higher-level cognitive processes. In order to provide a more extensive test of whether visual acuity moderates age differences in higher-level cognitive processes, we conducted a more extensive meta-analysis of topic.MethodsUsing results from 456 studies, we calculated effect sizes for the main effect of age across four cognitive domains (attention, executive function, memory, and perception/language) separately for five levels of visual acuity criteria (no criteria, undisclosed criteria, self-reported acuity, 20/80-20/31, and 20/30 or better).ResultsAs expected, age had a significant effect on each cognitive domain. However, these age effects did not further differ as a function of visual acuity criteria.ConclusionThe current meta-analytic, cross-sectional results suggest that visual acuity is not significantly related to age group differences in higher-level cognitive performance-thereby replicating La Fleur and Salthouse (2014). Further efforts are needed to determine whether other measures of visual functioning (e.g., contrast sensitivity, luminance) affect age differences in cognitive functioning

Editorial: Executive function(s): Conductor, Orchestra or Symphony? Towards a Trans-Disciplinary Unification of Theory and Practice Across Development, in Normal and Atypical Groups

There are several theories of executive function(s) that tend to share some theoretical overlap yet are also conceptually distinct, each bolstered by empirical data (Norman and Shallice, 1986; Shallice & Burgess, 1991; Stuss and Alexander, 2007; Burgess, Gilbert, & Dumentheil, 2007; Burgess & Shallice, 1996; Miyake et al., 2000). The notion that executive processes are supervisory, and most in demand in novel situations was an early conceptualization of executive function that has been adapted and refined over time (Norman & Shallice, 1986; Shallice, 2001; Burgess, Gilbert & Dumentheil, 2007). Presently there is general consensus that executive functions are multi-componential (Shallice, 2001), and are supervisory only in the sense that attention in one form or another is key to the co-ordination of other hierarchically organized ‘lower’ cognitive processes. Attention in this sense is defined as (i) independent but interrelated attentional control processes (Stuss & Alexander, 2007); (ii) automatic orientation towards stimuli in the environment or internally–driven thought (Burgess, Gilbert & Dumontheil, 2007); (iii) the automatically generated interface between tacit processes and strategic conscious thought (Barker, Andrade, Romanowski, Morton and Wasti, 2006; Morton and Barker, 2010); and (iv) distinct but interrelated executive processes that maintain, update and switch across different sources of information (Miyake et al., 2000). One problem is that executive dysfunction or dysexecutive syndrome (Baddeley & Wilson, 1988) after brain injury typically produces a constellation of deficits across social, cognate, emotional and motivational domains that rarely map neatly onto theoretical frameworks (Barker, Andrade & Romanowski, 2004). As a consequence there is debate that conceptual theories of executive function do not always correspond well to the clinical picture (Manchester, Priestley & Jackson, 2004). Several studies have reported cases of individuals with frontal lobe pathology and impaired daily functioning despite having little detectable impairment on traditional tests of executive function (Shallice & Burgess, 1991; Eslinger & Damasio, 1985; Barker, Andrade & Romanowski, 2004; Andrés & Van der Linden, 2002; Chevignard et al., 2000; Cripe, 1998; Fortin, Godbout & Braun, 2003). There is also some suggestion that weak ecological validity limits predictive and clinical utility of many traditional measures of executive function (Burgess et al, 2006; Lamberts, Evans & Spikman, 2010; Barker, Morton, Morrison, McGuire, 2011). Complete elimination of environmental confounds runs the risk of generating results that cannot be generalized beyond constrained circumstances of the test environment (Barker, Andrade & Romanowski, 2004). Several researchers have concluded that a new approach is needed that is mindful of the needs of the clinician yet also informed by the academic debate and progress within the discipline (McFarquhar & Barker, 2012; Burgess et al., 2006). Finally, translational issues also confound executive function research across different disciplines (psychiatry, cognitive science, and developmental psychology) and across typically developing and clinical populations (including Autism Spectrum Disorders, Head Injury and Schizophrenia – Blakemore & Choudhury, 2006; Taylor, Barker, Heavey & McHale, 2013). Consequently, there is a need for unification of executive function approaches across disciplines and populations and narrowing of the conceptual gap between theoretical positions, clinical symptoms and measurement

Le caractère adaptatif du cerveau âgé sain dans le maintien des habiletés du traitement lexico-sémantique : une approche neurofonctionnelle

La majorité des modèles neurocognitifs expliquant les mécanismes de réorganisation neurofonctionnelle sous-jacents au maintien de la performance cognitive au cours du vieillissement souligne une implication accrue des régions frontales, plus généralement assimilées au contrôle exécutif, et ce dans les domaines les plus sensibles au déclin avec l’âge. La compréhension de ces mécanismes adaptatifs peut être complétée par l’exploration de l’un des domaines les mieux préservés de la cognition, celui du langage, notamment dans ses aspects lexico-sémantiques. L’objectif de cette thèse est d’explorer les mécanismes de réorganisation neurofonctionnelle sous-jacents au maintien des habiletés du traitement sémantique des mots au cours du vieillissement sain. En s’inscrivant à l’intérieur d’une approche comportementale et neurofonctionnelle, trois études ont été conduites dans le présent travail de recherche par le biais de deux tâches, une tâche de fluence verbale (étude 1) et une tâche catégorisation sémantique (études 2 et 3) lesquelles requièrent la mise en jeu des processus exécutifs de maintien et de changement. La première étude démontre, chez l’adulte âgé, une réorganisation stratégique associée à une réorganisation neurofonctionnelle adaptative au niveau des régions temporales et frontales dépendamment des processus stratégiques engagés lors de la production des mots. La seconde étude met en évidence des mécanismes de réorganisation neurofonctionnelle influencés par l’âge mais également par les caractéristiques du profil exécutif, opérant au-delà des régions frontales. Finalement, la troisième étude, axée sur l’analyse des aspects sémantiques en fonction du degré de contrôle requis lors du maintien d’un lien sémantique démontre, qu’au cours du vieillissement, des adaptations neurofonctionnelles permettent le maintien des habiletés de traitement sémantique des mots, ceci variant selon la nature de la tâche, les caractéristiques du profil cognitif, ainsi que selon le degré de contrôle requis lors du traitement sémantiques des mots. À la lumière de ce travail de recherche, le vieillissement apparait empreint d’un caractère dynamique, adaptatif et évolutif, lequel permet le maintien des habiletés de traitement sémantique des mots dans des tâches langagières, haut niveau, de production orale et de compréhension de mots.Most neurocognitive models that explain how neurofunctional reorganisation supports cognitive performance during aging emphasize the increased involvement of frontal regions, generally known to support executive control, in domains most sensitive to decline with age. An understanding of these adaptative mechanisms can be completed by exploring one of the most well-preserved domains of cognition: that of language, notably in its lexico-semantic aspects. The objective of this thesis is to explore the mechanisms of neurofunctional reorganization underlying the maintenance of semantic word processing abilities during healthy aging. A behavioral and neurofunctional approach to the current study resulted in three studies being conducted, through two principal tasks: a verbal fluency task (study 1) and a semantic categorisation task (studies 2 and 3), both of which required involvement of the executive functions of maintenance and change. The first study demonstrates a strategic reorganisation in the older adult, associated with a neurofunctional adaptive reorganisation at the level of temporal and frontal regions, depending on the strategic processes engaged during word production. The second study highlights mechanisms of neurofunctional reorganisation influenced by age but equally so by characteristics of the executive profile, operating beyond the frontal regions. Finally, the third study, which analyses semantic aspects in relation to the degree of control required in maintaining a semantic link, shows that, during aging, neurofunctional adaptation permits the maintenance of the ability to semantically process words, this adaptation varying according to the nature of the task, the cognitive profile characteristics, as well as to the degree of control required during semantic processing. In light of the present research, aging appears to be imbued with a dynamic character, adaptive and evolutionary, which permits the maintenance of semantic processing abilities for words in high-level language tasks, of oral production, and of word comprehension

The behavioral and neural correlates of cognitive control across the lifespan

This dissertation will investigate which brain mechanisms are involved in proactive and reactive cognitive control across the lifespan, how the function of those brain mechanisms is affected by age, and how those functional changes translate to differences in behavior. Chapter 1 provides a comprehensive literature review covering proactive and reactive control in an ageing context, the contributions of the left IPS and left TPJ to suppression of salient distractors, and how these two topics may be interrelated. Chapter 2 examined the neural correlates of proactive inhibition in a young and aging cohort, with focus on the contribution of left IPS and/or left TPJ. It was found that while young participants only engaged proactive mechanisms (Left IPS) to engage the task, old participants engaged both proactive (Left IPS) and reactive (Left TPJ) mechanisms simultaneously. Further, age-related reductions in resting state functional connectivity suggested that both proactive and reactive inhibition mechanisms were impaired in aging populations. Chapter 3 assessed if there are detectable behavioral deficits during a reactive inhibition task in old age. Elderly participants showed an impaired ability to reactively use a salient distractor as an anti-cue. Chapter 4 used TMS to explicitly test the role of the left TPJ during reactive control. It was found that applying TMS to the left TPJ impaired participants’ ability to reactively engage a salient distractor as an anti-cue and, surprisingly, that applying TMS to the left IPS enhanced this ability. Chapter 5 tested if the allocation of attention to a distractor prior to inhibition is impaired in aging participants. The result revealed no age-related impairment to attentional control prior to inhibition. Chapter 6 summarizes the findings, discusses their broader implications, and proposes avenues for future research