Neural Markers of Individual Differences in Decision-making

In the last few years, neuroscientists have begun to identify associations between individual differences in decision-making and features of neuroanatomy and neurophysiology. Different tendencies in decision making, such as tolerance for risk, delay or effort, have been linked to various neurobiological measures, such as morphometry, structural connectivity, functional connectivity or the function of neurotransmitter systems. Though far from immutable, these neural features may nonetheless be suitable as relatively stable biomarkers for different decision traits. The establishment of such markers would achieve one of the stated goals of neuroeconomics, which is to improve the prediction of economic behavior across different contexts

Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals.

Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia

Biological Mechanisms Linking Stress and Anhedonia

Evidence from research across species suggests that stress exposure is linked with anhedonia (loss of pleasure and/or decreased motivation). However, the mechanisms through which stress might impact anhedonia remain unclear. Chapters 1 and 2 of this dissertation review putative etiological pathways from stress to anhedonia and discuss stressor characteristics that could inform experimental models of stress-induced anhedonia. Chapter 3 describes an attempt to identify which types of stress are most associated with anhedonia using stress interview data from multiple datasets. Unexpectedly, we found no credible effects on anhedonic symptoms for stressor chronicity, severity, dependence on behavior, or interpersonal focus. Instead, number of stressors endorsed was the best predictor of anhedonic symptoms. Next, Chapters 4 and 5 report on two studies that tested possible biological mediators of the stress-anhedonia link. Chapter 4 describes an analysis of the UK Biobank dataset aimed at evaluating frontostriatal functional connectivity as a mechanism of stress-induced anhedonia. Although stress exposure predicted anhedonia, analyses uncovered no stable relation between frontostriatal connectivity and anhedonia, and no support for the proposed mediation model. Chapter 5 details a study that implemented a laboratory-based stressor to assess its potential impact on motivated behavior (thought to be a key component of anhedonia), and whether any such effects might be mediated by inflammatory responding. Low concentrations of salivary cytokines suggested questionable validity of inflammatory assessment, and no effect of stress on inflammatory responding was observed. Additionally, stress produced no measurable changes in motivated behavior. Thus, analyses revealed no evidence consistent with inflammation as a mechanism of stress-induced anhedonia. Finally, Chapter 6 discusses conclusions and implications of the current findings, and provides ideas for future directions

The role of physical activity and bilingualism in the development of neurodegenerative disorders: Cross-sectional and neuroimaging evidence

Delaying Alzheimer’s disease (AD), the most common form of dementia, by five years could decrease the global prevalence of AD by 57% and halve the annual economic impact which is currently estimated to surpass US$2 trillion by 2030. Since no treatment or cure for dementia exist, identifying modifiable factors to reduce the incidence of dementia has become a public health priority. Increased physical activity (PA) has been associated with a lower risk of developing dementia in observational studies. Observational studies have also linked bilingualism (the ability to speak two languages) with a delayed onset of dementia but no risk-reduction in dementia in bilinguals relative to monolinguals. Differences in study outcomes in the fields of PA- and bilingualism- related research to methodological limitations including poor measurement of the exposure (PA and language profiles), small sample sizes, and recruitment of participants with different dementia etiologies. The purpose of this thesis was twofold: i) to explore the roles of PA and bilingualism in dementia risk and ii) to inform the development of a randomized controlled trial (RCT) to test whether studying a foreign language combined with increasing PA can improve cognitive performance in seniors who are at a higher risk of developing AD. The aim of Chapter two was to review the available evidence linking PA with the risk of developing dementia as well as to explore the effects of increasing PA on cognition in individuals with dementia. Results showed that aerobic, and high-intensity, habitual PA was associated with improved cognition-related biomarkers and lower dementia risk in epidemiological studies. Experimental evidence showed increasing PA improved cognition-related biomarkers and cognition in preclinical phases of dementia, but not in clinical phases. The findings showed that PA is linked with a lower risk of dementia in epidemiological studies, but experimental studies showed little to no improvements in cognition in participants with dementia following a structured PA program. There was evidence indicating that increasing PA levels in the preclinical phase of AD may result in greater translation impact than in participants at the more advanced clinical stage of AD. Most studies assessed PA with self-report measures questioning the accuracy and precision of exposure and recruited participants with dementia irrespective of aetiology, which makes it problematic to discern whether PA is differentially related to varying dementia aetiologies. The aim of Chapter three was to systematically review the association between bilingualism and the delay in the diagnosis of dementia and AD. Here, we retrieved a total of 20 studies, 15 of which were meta-analysed. Results showed that bilinguals were on average 3.2 (95% CI: 1.5, 4.9) years older than monolinguals at the time of dementia. Moreover, at the time of dementia diagnosis, bilinguals and monolinguals demonstrated a similar level of global cognitive impairment (Hedges’ g = 0.05 95% CI: -0.10, 0.21). Prediction intervals however showed a large dispersion of effect sizes in the meta-analysis comparing monolinguals to bilinguals on the age of dementia diagnosis. To explore possible reasons for the observed dispersion in effect sizes, we conducted subgroup analyses. In one subgroup meta-analysis comparing studies that had recruited participants with dementia to studies that had recruited participants with AD, bilinguals were 4.2 (95% CI: 2.0, 6.2) and 1.7 (95% CI: -1.4, 4.7) years older than monolinguals at dementia and AD diagnosis, respectively. Meta-analytic results combining prospective longitudinal studies showed no risk reduction in dementia among bilinguals compared to monolinguals (Odds Ratio: 0.85; 95% CI: 0.69-1.05). Risk of bias assessment revealed that most studies carried several methodological limitations including poor measurement of participants’ language profiles and small sample sizes. The aim of Chapter four was to explore the underlying mechanisms in the brain that may be responsible for the observed findings in the first systematic review (Chapter three). In this study, we observed that bilinguals compared to monolinguals had greater brain volume in the frontostriatal and frontoparietal circuits. Also, functional neuroimaging studies showed that bilinguals made use of relevant brain areas more efficiently than monolinguals when completing interference cognitive tasks. Results from the cross-sectional studies showed that higher levels of language acculturation were associated with significantly greater verbal and psychomotor speed performance than lower levels of language acculturation. The aim of the Chapter five was to explore the link between language acculturation and cognition in older individuals from ethnic minorities (Hispanic and Asian) living in the United States of America using an epidemiological dataset. In this cross-sectional epidemiological study, we analyzed data from the National Health and Nutrition Examination Survey using a larger sample size than previous studies. We found that higher levels of language acculturation (i.e. speaking the native language and that of the recipient’s country at home) was associated with greater psychomotor speed processing than lower levels of language acculturation (mostly speaking the native language at home) and some, but not all, measures of verbal fluency. Overall, the findings suggest that higher levels of language acculturation are associated with greater cognitive performance in older individuals from ethnic minorities. Overall, the evidence gathered in the previous chapters indicate that i) increasing PA in individuals who are at a higher risk of developing AD might be more useful in improving cognitive performance than in individuals who already have developed AD and ii) bilingualism might render the brain areas typically affected by AD such as the frontostriatal and frontoparietal brain circuits more resilient against neurodegeneration and in turn, delay the onset of AD symptoms and diagnosis. Therefore, because no randomized-controlled trial (RCT) testing the combined effects of increased PA with studying a foreign language currently exist, Chapter five presents a detailed study protocol for an RCT addressing this gap in the literature while addressing the limitations of previous studies in the fields of PA- and bilingualism-based research. The purpose of this thesis was to explore the roles of PA and bilingualism in dementia onset and risk and to inform the development of a randomized controlled trial (RCT) testing the effects of studying a foreign language with increased PA in individuals at a higher risk of dementia. Increasing PA levels are associated with greater cognition in individuals at the preclinical phase of AD rather than in participants with a diagnosis of dementia or AD. Bilingualism was also associated with later age of AD diagnosis on average by 4.7 years. This finding is clinically relevant because a five-year delay in the onset of AD could lower the number of individuals with AD worldwide by 57% and as a consequence, halving the associated economic costs. Moreover, we also showed that bilingualism may be responsible for rendering brain areas typically affected by AD more resilient against neuropathology. Moreover, this thesis revealed that studies in the field of exercise science and bilingualism research in dementia carry important methodological limitations that question the internal validity of these two lines of research. Consequently, the evidence gathered within this thesis led us to propose a novel RCT exploring the effects of increasing PA levels and studying a foreign language in monolingual individuals at a higher risk of AD while addressing the most important limitations of previous research

The role of high-field magnetic resonance imaging in parkinsonian disorders:Pushing the boundaries forward

Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron- and neuromelanin-sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time-dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high-field (3T) and ultra high field-imaging (7T) in PD and atypical parkinsonism. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Brain training in progress: a review of trainability in healthy seniors

The cognitive deterioration associated with aging is accompanied by structural alterations and loss of functionality of the frontostriatal dopamine system. The question arises how such deleterious cognitive effects could be countered. Brain training, currently highly popular among young and old alike, promises that users will improve on certain neurocognitive skills, and this has indeed been confirmed in a number of studies. Based on these results, it seems reasonable to expect beneficial effects of brain training in the elderly as well. A selective review of the existing literature suggests, however, that the results are neither robust nor consistent, and that transfer and sustained effects thus far appear limited. Based on this review, we argue for a series of elements that hold potential for progress in successful types of brain training: (1) including flexibility and novelty as features of the training, (2) focusing on a number of promising, yet largely unexplored domains, such as decision-making and memory strategy training, and (3) tailoring the training adaptively to the level and progress of the individual. We also emphasize the need for covariance-based MRI methods in linking structural and functional changes in the aging brain to individual differences in neurocognitive efficiency and trainability in order to further uncover the underlying mechanisms

Viewing the personality traits through a cerebellar lens. A focus on the constructs of novelty seeking, harm avoidance, and alexithymia

The variance in the range of personality trait expression appears to be linked to structural variance in specific brain regions. In evidencing associations between personality factors and neurobiological measures, it seems evident that the cerebellum has not been up to now thought as having a key role in personality. This paper will review the most recent structural and functional neuroimaging literature that engages the cerebellum in personality traits, as novelty seeking and harm avoidance, and it will discuss the findings in the context of contemporary theories of affective and cognitive cerebellar function. By using region of interest (ROI)- and voxel-based approaches, we recently evidenced that the cerebellar volumes correlate positively with novelty seeking scores and negatively with harm avoidance scores. Subjects who search for new situations as a novelty seeker does (and a harm avoiding does not do) show a different engagement of their cerebellar circuitries in order to rapidly adapt to changing environments. The emerging model of cerebellar functionality may explain how the cerebellar abilities in planning, controlling, and putting into action the behavior are associated to normal or abnormal personality constructs. In this framework, it is worth reporting that increased cerebellar volumes are even associated with high scores in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. On such a basis, it seems necessary to go over the traditional cortico-centric view of personality constructs and to address the function of the cerebellar system in sustaining aspects of motivational network that characterizes the different temperamental trait

On the neurobiology of apathy and depression in cerebral small vessel disease

Cerebral small vessel disease (SVD) is a cerebrovascular pathology that affects the small vessels of the brain, resulting in heterogeneous brain tissue changes. These can lead to neuropsychiatric symptoms such as apathy, a loss of motivation, and depression, which is characterised by low mood and a loss of pleasure. Apathy and depression are both prevalent symptoms in SVD, but an understanding of the relationship between underlying disease processes and the expression of these neuropsychiatric symptoms remains poor. This thesis uses magnetic resonance imaging techniques to examine the neurobiological basis of apathy and depression in SVD. We show that apathy is related to focal grey matter damage and distributed white matter microstructural change. These microstructural changes underlie large-scale white matter network disruption, which is related to apathy, but not depression. We then show that depression, as a construct, can be dissociated into distinct symptoms which are associated with overlapping and distinct areas of cortical atrophy over time. This suggests that depression as a general syndrome may be characterised by atrophy in core structures, while different symptoms are associated with atrophy in more specialised areas. Consistent with these patterns of overarching tissue damage, we find that apathy, but not depression, predicts conversion to dementia in patients with SVD. Our findings suggest that different types of SVD-related pathology lead to apathy and depression. Diffuse white matter damage may lead to widespread network disruption, resulting in apathy and cognitive impairment. In contrast, depressive symptoms are associated with focal patterns of grey matter atrophy over time. This highlights the importance of differentiating neuropsychiatric symptoms, and paves the way for targeted treatment approaches.Cambridge International Scholarship (Cambridge Trust)

Perception and cognition in Parkinson's disease: a neural network perspective

Parkinson’s disease (PD) is a neurodegenerative disorder commonly presenting with perceptual and cognitive dysfunction. Whereas previous work in PD suggests that abnormal basal ganglia activity has profound effects on integrated functioning of widespread cortical networks, the relation of specific network functions to the perceptual and cognitive impairments is still poorly understood. Here, I present a series of fMRI investigations of network-level functioning in non-demented individuals with PD with the aim of elucidating these associations. Study 1 examined the neural correlates of optic flow processing in 23 individuals with PD and 17 age-matched control participants (MC). An optic flow network comprising visual motion areas V6, V3A, MT+ and visuo-vestibular areas PIVC and CSv is known to be important for parsing egomotion depth cues in humans. The hypothesis was that individuals with PD would show less activation in these regions than MC when processing optic flow. While MC participants showed robust activation in this network, PD participants showed diminished activity within MT+ and CSv. Diminished CSv activity also correlated with greater disease severity. Study 2 investigated intrinsic network organization in PD with a focus on the functional coupling among three neurocognitive networks: the default-mode network (DMN), the salience network (SN), and the central executive network (CEN). Twenty-four individuals with PD and 20 MC participants were scanned at rest. The hypothesis was that PD participants would demonstrate dysfunctional SN coupling with the DMN and CEN. Relative to MC, in PD the CEN was less positively coupled with the SN and less anti-correlated with the DMN. Study 3 investigated the association between functional coupling and cognition in the same group that participated in Study 2. As hypothesized, anti-correlated functional coupling between the SN and DMN was related to successful performance on tests of executive function, psychomotor speed, and memory retrieval in MC but not in PD, suggesting that dysfunction within these networks could underlie early cognitive deficits in PD. Together, the results from the three studies suggest that dysfunctional activity in cortical networks important for visual motion processing and neurocognitive efficiency may underlie aspects of perceptual and cognitive impairment in PD.2017-12-06T00:00:00