Neural correlates associated with successful working memory performance in older adults as revealed by spatial ICA

To investigate which neural correlates are associated with successful working memory performance, fMRI was recorded in healthy younger and older adults during performance on an n-back task with varying task demands. To identify functional networks supporting working memory processes, we used independent component analysis (ICA) decomposition of the fMRI data. Compared to younger adults, older adults showed a larger neural (BOLD) response in the more complex (2-back) than in the baseline (0-back) task condition, in the ventral lateral prefrontal cortex (VLPFC) and in the right fronto-parietal network (FPN). Our results indicated that a higher BOLD response in the VLPFC was associated with increased performance accuracy in older adults, in the more complex task condition. This 'BOLD-performance' relationship suggests that the neural correlates linked with successful performance in the older adults are related to specific working memory processes present in the complex but not in the baseline task condition [corrected].Furthermore, the selective presence of this relationship in older but not in younger adults suggests that increased neural activity in the VLPFC serves a compensatory role in the aging brain which benefits task performance in the elderly

Correction: Neural Correlates Associated with Successful Working Memory Performance in Older Adults as Revealed by Spatial ICA

There are errors in the fourth and fifth sentences of the Abstract. The correct sentences are: Our results indicated that a higher BOLD response in the VLPFC was associated with increased performance accuracy in older adults, in the more complex task condition. This ‘BOLD-performance’ relationship suggests that the neural correlates linked with successful performance in the older adults are related to specific working memory processes present in the complex but not in the baseline task condition.There are errors in the second and third sentences of the second paragraph of the “Independent component analysis (ICA)” portion of the “fMRI image analysis” subsection of the Materials and Methods. The correct sentences are: The GLM design matrix was based on the task events (onsets), as well as the movement parameters derived from the realignment step and their first derivatives and a high pass filter of 230 seconds, implemented using a discrete cosine transform (DCT) set. The task events were convolved with three basis functions of the hemodynamic response function (HRF): the canonical HRF, its time derivative and its dispersion derivative.There are multiple errors throughout the “Performance and age” section of the Results. The correct text is: Older adults had a mean accuracy cost of.23 (SD = .12) and a mean speed cost of.47 (.19). Younger adults had a mean accuracy cost of.08 (.04) and a mean speed cost of.31 (.18). Coefficients for the main effects of age on accuracy and speed cost were based on the regression model assessing the effects of age and/or BOLD load effect in the VLPFC component. Older adults had a higher accuracy cost (β age = .147, t(74) = 7.08, p < .0005; R2 = .419, F(3,74) = 18.8, p < .0005) and speed cost (β age = .167, t(74) = 4.01, p < .0005; R2 = .215, F(3,74) = 6.5, p < .0005) than younger adults. Additional regression models, performed in each load condition, revealed that older adults had lower accuracy scores in the 2-back load than younger adults (β age = −.129, t(74) = −6.47, p < .0005; R2 = .414, F(3,74) = 16.7, p < .0005). Furthermore, older adults were slower than younger adults in both load conditions (0-back: β age = 115.32, t(74) = 9.83, p < .0005; R2 = .581, F(3,74) = 32.9, p < .0005 and 2-back: β age = 249.01, t(74) = 9.61, p < .0005; R2 = .569, F(3,74) = 31.3, p < .0005; see Table 2).There are multiple errors throughout the “Components of interest: Age and BOLD load effect” section of the Results. The correct text is: The main repeated measure ANOVA on the BOLD load effects observed in the eight ICs associated with working memory processes, showed a general interaction between age and BOLD load effect (F(7,511) = 3.1, p = .007). To identify which of these 8 ICs showed an age-related BOLD load effect, additional post-hoc two sample t-tests were performed. These tests revealed that the difference in BOLD activation between the 2-back and the 0-back load condition was larger for older than younger adults in 3 ICs. Namely, the ICs containing mainly the VLPFC (t(73) = 1.9, p = .061), the right FPN (t(73) = 2.2, p = .035) and the left FPN (t(73) = 4, p < .0005).After identifying these 3 ICs, we subsequently performed a one-sample t-test in younger and older adults, separately. The purpose of these tests was to investigate whether the BOLD activation in each of the 3 selected ICs differed significantly between the 0-back and the 2-back load condition within each age-group. The one-sample t-test was significant in all 3 ICs, for younger (VLPFC: t(37) = 6.5, p< .0005; right FPN: t(37) = 3, p = .005 and left FPN: t(37) = -4.1, p< .0005) and older adults (VLPFC (t(36) = 9.8, p< .0005), the right FPN (t(36) = 6, p< .0005 and the left FPN (t(36) = -1.7, p = .093). For all participants, the BOLD activation in the right FPN and the VLPFC increased with task load. However, the BOLD activation of the left FPN was negatively modulated by the task, as revealed by the negative beta-weights and the positive spatial map of this component (see Fig 2B and Fig 3). In young adults, the BOLD activation in the left FPN became more negative with increasing task demands. To determine whether age modulated the BOLD signal in these 3 ICs of interest in the 0-back, in the 2-back or in both load conditions, subsequent post-hoc independent two sample t-tests were performed. These tests showed that compared to younger adults, older adults had a higher BOLD activation in the VLPFC (t(73) = 3, p = .006) and the right FPN (t(73) = 2.4, p = .020), in the 2-back load condition. In the 0-back load condition, younger and older adults showed similar BOLD activation in the VLPFC and the right FPN. On the other hand, older adults had a more negative BOLD response in the left FPN than younger adults, in the 0-back load condition (t(73) = 4.5, p < .0005). Younger and older adults had comparable BOLD load effect in the other working memory related ICs

Bridging the big (data) gap: levels of control in small- and large-scale cognitive neuroscience research

Recently, cognitive neuroscience has experienced unprecedented growth in the availability of large-scale datasets. These developments hold great methodological and theoretical promise: they allow increased statistical power, the use of nonparametric and generative models, the examination of individual differences, and more. Nevertheless, unlike most ‘traditional’ cognitive neuroscience research, which uses controlled experimental designs, large-scale projects often collect neuroimaging data not directly related to a particular task (e.g., resting state). This creates a gap between small- and large-scale studies that is not solely due to differences in sample size. Measures obtained with large-scale studies might tap into different neurocognitive mechanisms and thus show little overlap with the mechanisms probed by small-scale studies. In this opinion article, we aim to address this gap and its potential implications for the interpretation of research findings in cognitive neuroscience

Acute Stress Modulates Feedback Processing in Men and Women:Differential Effects on the Feedback-Related Negativity and Theta and Beta Power

Sex-specific prevalence rates in mental and physical disorders may be partly explained by sex differences in physiological stress responses. Neural networks that might be involved are those underlying feedback processing. Aim of the present EEG study was to investigate whether acute stress alters feedback processing, and whether stress effects differ between men and women. Male and female participants performed a gambling task, in a control and a stress condition. Stress was induced by exposing participants to a noise stressor. Brain activity was analyzed using both event-related potential and time-frequency analyses, measuring the feedback-related negativity (FRN) and feedback-related changes in theta and beta oscillatory power, respectively. While the FRN and feedback-related theta power were similarly affected by stress induction in both sexes, feedback-related beta power depended on the combination of stress induction condition and sex. FRN amplitude and theta power increases were smaller in the stress relative to the control condition in both sexes, demonstrating that acute noise stress impairs performance monitoring irrespective of sex. However, in the stress but not in the control condition, early lower beta-band power increases were larger for men than women, indicating that stress effects on feedback processing are partly sex-dependent. Our findings suggest that sex-specific effects on feedback processing may comprise a factor underlying sex-specific stress responses

State and Trait Components of Functional Connectivity: Individual Differences Vary with Mental State.

Resting-state functional connectivity, as measured by functional magnetic resonance imaging (fMRI), is often treated as a trait, used, for example, to draw inferences about individual differences in cognitive function, or differences between healthy or diseased populations. However, functional connectivity can also depend on the individual's mental state. In the present study, we examined the relative contribution of state and trait components in shaping an individual's functional architecture. We used fMRI data from a large, population-based human sample (N = 587, age 18-88 years), as part of the Cambridge Centre for Aging and Neuroscience (Cam-CAN), which were collected in three mental states: resting, performing a sensorimotor task, and watching a movie. Whereas previous studies have shown commonalities across mental states in the average functional connectivity across individuals, we focused on the effects of states on the pattern of individual differences in functional connectivity. We found that state effects were as important as trait effects in shaping individual functional connectivity patterns, each explaining an approximately equal amount of variance. This was true when we looked at aging, as one specific dimension of individual differences, as well as when we looked at generic aspects of individual variation. These results show that individual differences in functional connectivity consist of state-dependent aspects, as well as more stable, trait-like characteristics. Studying individual differences in functional connectivity across a wider range of mental states will therefore provide a more complete picture of the mechanisms underlying factors such as cognitive ability, aging, and disease. SIGNIFICANCE STATEMENT: The brain's functional architecture is remarkably similar across different individuals and across different mental states, which is why many studies use functional connectivity as a trait measure. Despite these trait-like aspects, functional connectivity varies over time and with changes in cognitive state. We measured connectivity in three different states to quantify the size of the trait-like component of functional connectivity, compared with the state-dependent component. Our results show that studying individual differences within one state (such as resting) uncovers only part of the relevant individual differences in brain function, and that the study of functional connectivity under multiple mental states is essential to disentangle connectivity differences that are transient versus those that represent more stable, trait-like characteristics of an individual

Idiosyncratic responding during movie-watching predicted by age differences in attentional control.

Much is known about how age affects the brain during tightly controlled, though largely contrived, experiments, but do these effects extrapolate to everyday life? Naturalistic stimuli, such as movies, closely mimic the real world and provide a window onto the brain's ability to respond in a timely and measured fashion to complex, everyday events. Young adults respond to these stimuli in a highly synchronized fashion, but it remains to be seen how age affects neural responsiveness during naturalistic viewing. To this end, we scanned a large (N = 218), population-based sample from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) during movie-watching. Intersubject synchronization declined with age, such that older adults' response to the movie was more idiosyncratic. This decreased synchrony related to cognitive measures sensitive to attentional control. Our findings suggest that neural responsivity changes with age, which likely has important implications for real-world event comprehension and memory.This work and the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) are supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.neurobiolaging.2015.07.02

The effects of hippocampal lesions on MRI measures of structural and functional connectivity.

Focal lesions can affect connectivity between distal brain regions (connectional diaschisis) and impact the graph-theoretic properties of major brain networks (connectomic diaschisis). Given its unique anatomy and diverse range of functions, the hippocampus has been claimed to be a critical "hub" in brain networks. We investigated the effects of hippocampal lesions on structural and functional connectivity in six patients with amnesia, using a range of magnetic resonance imaging (MRI) analyses. Neuropsychological assessment revealed marked episodic memory impairment and generally intact performance across other cognitive domains. The hippocampus was the only brain structure exhibiting reduced grey-matter volume that was consistent across patients, and the fornix was the only major white-matter tract to show altered structural connectivity according to both diffusion metrics. Nonetheless, functional MRI revealed both increases and decreases in functional connectivity. Analysis at the level of regions within the default-mode network revealed reduced functional connectivity, including between nonhippocampal regions (connectional diaschisis). Analysis at the level of functional networks revealed reduced connectivity between thalamic and precuneus networks, but increased connectivity between the default-mode network and frontal executive network. The overall functional connectome showed evidence of increased functional segregation in patients (connectomic diaschisis). Together, these results point to dynamic reorganization following hippocampal lesions, with both decreased and increased functional connectivity involving limbic-diencephalic structures and larger-scale networks. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.Medical Research Council (Grant ID: MC-A060-5PR10); Biotechnology and Biological Sciences Research Council (Grant ID: BB/L02263X/1); Netherlands Organization for Scientific ResearchThis is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/hipo.2262

Robust Resilience of the Frontotemporal Syntax System to Aging.

UNLABELLED: Brain function is thought to become less specialized with age. However, this view is largely based on findings of increased activation during tasks that fail to separate task-related processes (e.g., attention, decision making) from the cognitive process under examination. Here we take a systems-level approach to separate processes specific to language comprehension from those related to general task demands and to examine age differences in functional connectivity both within and between those systems. A large population-based sample (N = 111; 22-87 years) from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) was scanned using functional MRI during two versions of an experiment: a natural listening version in which participants simply listened to spoken sentences and an explicit task version in which they rated the acceptability of the same sentences. Independent components analysis across the combined data from both versions showed that although task-free language comprehension activates only the auditory and frontotemporal (FTN) syntax networks, performing a simple task with the same sentences recruits several additional networks. Remarkably, functionality of the critical FTN is maintained across age groups, showing no difference in within-network connectivity or responsivity to syntactic processing demands despite gray matter loss and reduced connectivity to task-related networks. We found no evidence for reduced specialization or compensation with age. Overt task performance was maintained across the lifespan and performance in older, but not younger, adults related to crystallized knowledge, suggesting that decreased between-network connectivity may be compensated for by older adults' richer knowledge base. SIGNIFICANCE STATEMENT: Understanding spoken language requires the rapid integration of information at many different levels of analysis. Given the complexity and speed of this process, it is remarkably well preserved with age. Although previous work claims that this preserved functionality is due to compensatory activation of regions outside the frontotemporal language network, we use a novel systems-level approach to show that these "compensatory" activations simply reflect age differences in response to experimental task demands. Natural, task-free language comprehension solely recruits auditory and frontotemporal networks, the latter of which is similarly responsive to language-processing demands across the lifespan. These findings challenge the conventional approach to neurocognitive aging by showing that the neural underpinnings of a given cognitive function depend on how you test it.The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) research is supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the Society for Neuroscience