A neural mechanism of cognitive reserve: The case of bilingualism.

Cognitive Reserve (CR) refers to the preservation of cognitive function in the face of age- or disease-related neuroanatomical decline. While bilingualism has been shown to contribute to CR, the extent to which, and what particular aspect of, second language experience contributes to CR are debated, and the underlying neural mechanism(s) unknown. Intrinsic functional connectivity reflects experience-dependent neuroplasticity that occurs across timescales ranging from minutes to decades, and may be a neural mechanism underlying CR. To test this hypothesis, we used voxel-based morphometry and resting-state functional connectivity analyses of MRI data to compare structural and functional brain integrity between monolingual and bilingual older adults, matched on cognitive performance, and across levels of second language proficiency measured as a continuous variable. Bilingualism, and degree of second language proficiency specifically, were associated with lower gray matter integrity in a hub of the default mode network - a region that is particularly vulnerable to decline in aging and dementia - but preserved intrinsic functional network organization. Bilingualism moderated the association between neuroanatomical differences and cognitive decline, such that lower gray matter integrity was associated with lower executive function in monolinguals, but not bilinguals. Intrinsic functional network integrity predicted executive function when controlling for group differences in gray matter integrity and language status. Our findings confirm that lifelong bilingualism is a CR factor, as bilingual older adults performed just as well as their monolingual peers on tasks of executive function, despite showing signs of more advanced neuroanatomical aging, and that this is a consequence of preserved intrinsic functional network organization.

Occipital and parietal cortex participate in a cortical network for transsaccadic discrimination of object shape and orientation.

Saccades change eye position and interrupt vision several times per second, necessitating neural mechanisms for continuous perception of object identity, orientation, and location. Neuroimaging studies suggest that occipital and parietal cortex play complementary roles for transsaccadic perception of intrinsic versus extrinsic spatial properties, e.g., dorsomedial occipital cortex (cuneus) is sensitive to changes in spatial frequency, whereas the supramarginal gyrus (SMG) is modulated by changes in object orientation. Based on this, we hypothesized that both structures would be recruited to simultaneously monitor object identity and orientation across saccades. To test this, we merged two previous neuroimaging protocols: 21 participants viewed a 2D object and then, after sustained fixation or a saccade, judged whether the shape or orientation of the re-presented object changed. We, then, performed a bilateral region-of-interest analysis on identified cuneus and SMG sites. As hypothesized, cuneus showed both saccade and feature (i.e., object orientation vs. shape change) modulations, and right SMG showed saccade-feature interactions. Further, the cuneus activity time course correlated with several other cortical saccade/visual areas, suggesting a 'functional network' for feature discrimination. These results confirm the involvement of occipital/parietal cortex in transsaccadic vision and support complementary roles in spatial versus identity updating.

Altered Brain Functional Connectivity in Female Athletes Over the Course of a Season of Collision or Contact Sports.

University athletes are exposed to numerous impacts to the body and head, though the potential cumulative effects of such hits remain elusive. This study examined resting-state functional connectivity (rsFC) of brain networks in female varsity athletes over the course of a season. Nineteen female university athletes involved in collision (N = 12) and contact (N = 7) sports underwent functional magnetic resonance imaging scans at both pre- and post-season. A group-level independent component analysis (ICA) was used to investigate differences in rsFC over the course of a season and differences between contact and collision sport athletes. Decreased rsFC was observed over the course of the season between the default mode network (DMN) and regions in the frontal, parietal, and occipital lobe (p false discovery rate, ≤0.05) driven by differences in the contact group. There was also a main effect of group in the dorsal attention network (DAN) driven by differences between contact and collision groups at pre-season. Differences identified over the course of a season of play indicate largely decreased rsFC within the DMN, and level of contact was associated with differences in rsFC of the DAN. The association between exposure to repetitive head impacts (RHIs) and observed changes in network rsFC supplements the growing literature suggesting that even non-concussed athletes may be at risk for changes in brain functioning. However, the complexity of examining the direct effects of RHIs highlights the need to consider multiple factors, including mental health and sport-specific training and expertise, that may potentially be associated with neural changes.

Age differences in the functional architecture of the human brain.

The intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience-dependent changes, or both, is uncertain. We employed a multimethod strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n = 181) and older (n = 120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multiscale, multimethod approaches to characterize the architecture of functional brain aging.

Investigation of baseline attention, executive control, and performance variability in female varsity athletes.

To examine attention, executive control, and performance variability in healthy varsity athletes and identify unique resting-state functional connectivity (rsFC) patterns associated with measures of speed, stability, and attention. A sample of 29 female university varsity athletes completed cognitive testing using the Attention Network Test- Interactions (ANT-I) and underwent resting-state functional MRI (rsfMRI) scans. Performance was characterized by examining mean reaction time (RT), variability in performance (ISD), and attention network scores on the ANT-I. RsfMRI data were analyzed using an independent component analysis (ICA) in the frontoparietal (FPN), dorsal attention (DAN), default mode, (DMN), salience (SN), and sensorimotor (SMN) networks. Group-level analyses using the performance variables of interest were conducted. Athletes' performance on the ANT-I revealed a main effect of orienting and executive control (ps<0.001; partial η2 = 0.68 and 0.89, respectively), with performance facilitated (i.e., faster RT) when athletes were presented with valid cues and congruent flankers. Alerting, orienting, and executive control performance were associated with differences in rsFC within the SN, DMN, and FPN, respectively. Slower RTs were associated with greater rsFC between DAN and bilateral postcentral gyri (p<.001), whereas more stable performance was associated with greater FC between the SMN and the left precuneus (p<.05). Consistent with prior studies, we observed that efficiency in alerting, orienting, and executive control aspects of attention was associated with differences in rsFC in regions associated with the SN, DMS, and FPN. In addition, we observed differential patterns of rsFC for overall speed and variability of performance.

Substance use is associated with worse mental health and altered resting state functional connectivity in female university athletes at baseline: A pilot study.

University athletes are at high risk for both substance use and mental health problems. This study examined associations between substance use, mental health symptoms, and the resting state functional connectivity (rsFC) of key neural regions involved in self-monitoring and emotional regulation in a sample of female varsity athletes. 31 female university athletes completed measures of substance use, mental health symptoms, and underwent functional MRI scans during the pre-season. Athletes who were substance users had higher symptoms of depression than non-users (p = 0.04; Hedge's g = 0.81). RsFC differences were observed between users and non-users in orbital frontal cortex (OFC) and bilateral hippocampal seeds, and negative associations between depression symptoms and rsFC in the left hippocampus and posterior cingulate cortex were observed in cannabis users. In female athletes, substance use is associated with greater self-reported depression symptoms and altered rsFC in self-monitoring and emotional regulation regions of the brain.

Occipital cortex is modulated by transsaccadic changes in spatial frequency: an fMRI study.

Previous neuroimaging studies have shown that inferior parietal and ventral occipital cortex are involved in the transsaccadic processing of visual object orientation. Here, we investigated whether the same areas are also involved in transsaccadic processing of a different feature, namely, spatial frequency. We employed a functional magnetic resonance imaging paradigm where participants briefly viewed a grating stimulus with a specific spatial frequency that later reappeared with the same or different frequency, after a saccade or continuous fixation. First, using a whole-brain Saccade > Fixation contrast, we localized two frontal (left precentral sulcus and right medial superior frontal gyrus), four parietal (bilateral superior parietal lobule and precuneus), and four occipital (bilateral cuneus and lingual gyri) regions. Whereas the frontoparietal sites showed task specificity, the occipital sites were also modulated in a saccade control task. Only occipital cortex showed transsaccadic feature modulations, with significant repetition enhancement in right cuneus. These observations (parietal task specificity, occipital enhancement, right lateralization) are consistent with previous transsaccadic studies. However, the specific regions differed (ventrolateral for orientation, dorsomedial for spatial frequency). Overall, this study supports a general role for occipital and parietal cortex in transsaccadic vision, with a specific role for cuneus in spatial frequency processing.

Inhibit, switch, and update: A within-subject fMRI investigation of executive control.

An influential model of executive control suggests that it comprises three dissociable processes: working memory, inhibition, and task switching. Multiple studies have investigated how these processes are individually implemented in the human brain. However, few have directly investigated this question using a common task architecture and a within-subject design. Here, healthy adult humans (N = 22) performed a novel executive control task during fMRI scanning. The paradigm independently manipulated working memory updating, inhibition, and task switching demands, while keeping all other task features constant. Direct contrasts of each executive task with a closely matched control condition revealed a differentiated pattern of recruitment across control tasks: working memory was associated with activity in dorsolateral prefrontal, lateral parietal and insular cortices bilaterally; Inhibition engaged right lateral and superior medial prefrontal cortex, inferior parietal lobules bilaterally, right middle and inferior temporal cortex, and ventral visual processing regions; Task switching was associated with bilateral activity in medial prefrontal cortex, posterior cingulate cortex and precuneus, as well as left inferior parietal lobule, lateral temporal cortex and right thalamus. A conjunction of all executive versus control task activations revealed common areas of activation overlapping regions of canonical frontoparietal control and dorsal attention networks. Further, multivariate analyses suggest that working memory may be a putative common factor supporting executive functioning. Taken together, these results are consistent with a hybrid model of executive control in the human brain.

Meta-analyses of the n-back working memory task: fMRI evidence of age-related changes in prefrontal cortex involvement across the adult lifespan.

Working memory, a fundamental cognitive function that is highly dependent on the integrity of the prefrontal cortex, is known to show age-related decline across the typical healthy adult lifespan. Moreover, we know from work in neurophysiology that the prefrontal cortex is disproportionately susceptibly to the pathological effects of aging. The n-back task is arguably the most ubiquitous cognitive task for investigating working memory performance. Many functional magnetic resonance imaging (fMRI) studies examine brain regions engaged during performance of the n-back task in adults. The current meta-analyses are the first to examine concordance and age-related changes across the healthy adult lifespan in brain areas engaged when performing the n-back task. We compile data from eligible fMRI articles that report stereotaxic coordinates of brain activity from healthy adults in three age-groups: young (23.57 ±â€¯5.63 years), middle-aged (38.13 ±â€¯5.63 years) and older (66.86 ±â€¯5.70 years) adults. Findings show that the three groups share concordance in the engagement of parietal and cingulate cortices, which have been consistently identified as core areas involved in working memory; as well as the insula, claustrum, and cerebellum, which have not been highlighted as areas involved in working memory. Critically, prefrontal cortex engagement is concordant for young, to a lesser degree for middle-aged adults, and absent in older adults, suggesting a gradual linear decline in concordance of prefrontal cortex engagement. Our results provide important new knowledge for improving methodology and theories of cognition across the lifespan.

Privileged Functional Connectivity between the Visual Word Form Area and the Language System.

The visual word form area (VWFA) is a region in the left occipitotemporal sulcus of literate individuals that is purportedly specialized for visual word recognition. However, there is considerable controversy about its functional specificity and connectivity, with some arguing that it serves as a domain-general, rather than word-specific, visual processor. The VWFA is a critical region for testing hypotheses about the nature of cortical organization, because it is known to develop only through experience (i.e., reading acquisition), and widespread literacy is too recent to have influenced genetic determinants of brain organization. Using a combination of advanced fMRI analysis techniques, including individual functional localization, multivoxel pattern analysis, and high-resolution resting-state functional connectivity (RSFC) analyses, with data from 33 healthy adult human participants, we demonstrate that (1) the VWFA can discriminate words from nonword letter strings (pseudowords); (2) the VWFA has preferential RSFC with Wernicke's area and other core regions of the language system; and (3) the strength of the RSFC between the VWFA and Wernicke's area predicts performance on a semantic classification task with words but not other categories of visual stimuli. Our results are consistent with the hypothesis that the VWFA is specialized for lexical processing of real words because of its functional connectivity with Wernicke's area.SIGNIFICANCE STATEMENT The visual word form area (VWFA) is critical for determining the nature of category-related organization of the ventral visual system. However, its functional specificity and connectivity are fiercely debated. Recent work concluded that the VWFA is a domain-general, rather than word-specific, visual processor with no preferential functional connectivity with the language system. Using more advanced techniques, our results stand in stark contrast to these earlier findings. We demonstrate that the VWFA is highly specialized for lexical processing of real words, and that a fundamental factor driving this specialization is its preferential intrinsic functional connectivity with core regions of the language system. Our results support the hypothesis that intrinsic functional connectivity contributes to category-related specialization within the human ventral visual system.

Attenuated anticorrelation between the default and dorsal attention networks with aging: evidence from task and rest.

Anticorrelation between the default and dorsal attention networks is a central feature of human functional brain organization. Hallmarks of aging include impaired default network modulation and declining medial temporal lobe (MTL) function. However, it remains unclear if this anticorrelation is preserved into older adulthood during task performance, or how this is related to the intrinsic architecture of the brain. We hypothesized that older adults would show reduced within- and increased between-network functional connectivity (FC) across the default and dorsal attention networks. To test this hypothesis, we examined the effects of aging on task-related and intrinsic FC using functional magnetic resonance imaging during an autobiographical planning task known to engage the default network and during rest, respectively, with young (n = 72) and older (n = 79) participants. The task-related FC analysis revealed reduced anticorrelation with aging. At rest, there was a robust double dissociation, with older adults showing a pattern of reduced within-network FC, but increased between-network FC, across both networks, relative to young adults. Moreover, older adults showed reduced intrinsic resting-state FC of the MTL with both networks suggesting a fractionation of the MTL memory system in healthy aging. These findings demonstrate age-related dedifferentiation among these competitive large-scale networks during both task and rest, consistent with the idea that age-related changes are associated with a breakdown in the intrinsic functional architecture within and among large-scale brain networks.

Functional connectivity constrains the category-related organization of human ventral occipitotemporal cortex.

One of the most robust and oft-replicated findings in cognitive neuroscience is that several spatially distinct, functionally dissociable ventral occipitotemporal cortex (VOTC) regions respond preferentially to different categories of concrete entities. However, the determinants of this category-related organization remain to be fully determined. One recent proposal is that privileged connectivity of these VOTC regions with other regions that store and/or process category-relevant properties may be a major contributing factor. To test this hypothesis, we used a multicategory functional magnetic resonance imaging (MRI) localizer to individually define category-related brain regions of interest (ROIs) in a large group of subjects (n = 33). We then used these ROIs in resting-state functional connectivity MRI analyses to explore spontaneous functional connectivity among these regions. We demonstrate that during rest, distinct category-preferential VOTC regions show differentially stronger functional connectivity with other regions that have congruent category-preference, as defined by the functional localizer. Importantly, a "tool"-preferential region in the left medial fusiform gyrus showed differentially stronger functional connectivity with other left lateralized cortical regions associated with perceiving and knowing about common tools-posterior middle temporal gyrus (involved in perception of nonbiological motion), lateral parietal cortex (critical for reaching, grasping, manipulating), and ventral premotor cortex (involved in storing/executing motor programs)-relative to other category-related regions in VOTC of both the right and left hemisphere. Our findings support the claim that privileged connectivity with other cortical regions that store and/or process category-relevant properties constrains the category-related organization of VOTC.

Resting-state functional connectivity MRI reveals active processes central to cognition.

Analysis of spontaneously correlated low-frequency activity fluctuations across the brain using functional magnetic resonance imaging (MRI)-commonly referred to as resting-state functional connectivity (RSFC) MRI-was initially seen as a useful tool for mapping functional-anatomic networks in the living human brain, characterizing brain changes and differences in clinical populations, and studying comparative anatomy across species. However, little was known about the potential relevance of RSFC to cognitive processes. Indeed, there has been considerable controversy and debate as to the utility of studying the resting-state in cognitive neuroscience. However, recent work has shown that RSFC, rather than merely reflecting passive or epiphenomenal activity within underlying functional-anatomic networks, reveals important dynamic processes that play an active role in cognition. RSFC has been associated with individual differences in a number of behavioral and cognitive domains, including perception, language, learning and memory, and the organization of conceptual knowledge. In this article, we review and integrate the latest research demonstrating that RSFC is functionally relevant to human behavior and higher-level cognition, and propose a hypothesis regarding its mechanism of action on functional network dynamics and cognition. We conclude that RSFC MRI will be an invaluable tool for future discovery of the fundamental neurocognitive interactions that underlie cognition. WIREs Cogn Sci 2014, 5:233-245. doi: 10.1002/wcs.1275 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.

Intrinsic architecture underlying the relations among the default, dorsal attention, and frontoparietal control networks of the human brain.

Human cognition is increasingly characterized as an emergent property of interactions among distributed, functionally specialized brain networks. We recently demonstrated that the antagonistic "default" and "dorsal attention" networks--subserving internally and externally directed cognition, respectively--are modulated by a third "frontoparietal control" network that flexibly couples with either network depending on task domain. However, little is known about the intrinsic functional architecture underlying this relationship. We used graph theory to analyze network properties of intrinsic functional connectivity within and between these three large-scale networks. Task-based activation from three independent studies were used to identify reliable brain regions ("nodes") of each network. We then examined pairwise connections ("edges") between nodes, as defined by resting-state functional connectivity MRI. Importantly, we used a novel bootstrap resampling procedure to determine the reliability of graph edges. Furthermore, we examined both full and partial correlations. As predicted, there was a higher degree of integration within each network than between networks. Critically, whereas the default and dorsal attention networks shared little positive connectivity with one another, the frontoparietal control network showed a high degree of between-network interconnectivity with each of these networks. Furthermore, we identified nodes within the frontoparietal control network of three different types--default-aligned, dorsal attention-aligned, and dual-aligned--that we propose play dissociable roles in mediating internetwork communication. The results provide evidence consistent with the idea that the frontoparietal control network plays a pivotal gate-keeping role in goal-directed cognition, mediating the dynamic balance between default and dorsal attention networks.

Hemispheric asymmetry of visual scene processing in the human brain: evidence from repetition priming and intrinsic activity.

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.

Default network activity, coupled with the frontoparietal control network, supports goal-directed cognition.

Tasks that demand externalized attention reliably suppress default network activity while activating the dorsal attention network. These networks have an intrinsic competitive relationship; activation of one suppresses activity of the other. Consequently, many assume that default network activity is suppressed during goal-directed cognition. We challenge this assumption in an fMRI study of planning. Recent studies link default network activity with internally focused cognition, such as imagining personal future events, suggesting a role in autobiographical planning. However, it is unclear how goal-directed cognition with an internal focus is mediated by these opposing networks. A third anatomically interposed 'frontoparietal control network' might mediate planning across domains, flexibly coupling with either the default or dorsal attention network in support of internally versus externally focused goal-directed cognition, respectively. We tested this hypothesis by analyzing brain activity during autobiographical versus visuospatial planning. Autobiographical planning engaged the default network, whereas visuospatial planning engaged the dorsal attention network, consistent with the anti-correlated domains of internalized and externalized cognition. Critically, both planning tasks engaged the frontoparietal control network. Task-related activation of these three networks was anatomically consistent with independently defined resting-state functional connectivity MRI maps. Task-related functional connectivity analyses demonstrate that the default network can be involved in goal-directed cognition when its activity is coupled with the frontoparietal control network. Additionally, the frontoparietal control network may flexibly couple with the default and dorsal attention networks according to task domain, serving as a cortical mediator linking the two networks in support of goal-directed cognitive processes.

Correlated low-frequency BOLD fluctuations in the resting human brain are modulated by recent experience in category-preferential visual regions.

The resting brain is associated with significant intrinsic activity fluctuations, such as the correlated low-frequency (LF) blood oxygen level-dependent (BOLD) fluctuations measured by functional magnetic resonance imaging. Despite a recent expansion of studies investigating resting-state LF-BOLD correlations, their nature and function are poorly understood. A major constraint on LF-BOLD correlations appears to be stable properties of anatomic connectivity. There is also evidence that coupling can be modulated by recent or ongoing task performance, suggesting that certain components of correlated dynamics are malleable on short timescales. Here, we compared activity during extended periods of rest following performance of 2 distinct cognitive tasks using different categories of visual stimuli-faces and complex scenes. Prolonged exposure to these distinct categories of visual information caused frontal networks to couple differentially with posterior category-preferential visual regions during subsequent periods of rest. In addition, we report preliminary evidence suggesting that conditions exist in which the degree of modulation of LF-BOLD correlations predicts subsequent memory. The finding that resting-state LF-BOLD correlations are modulated by recent experience in functionally specific brain regions engaged during prior task performance clarifies their role as a dynamic phenomenon which may be involved in mnemonic processes.

A neural mechanism underlying memory failure in older adults.

Older adults have reduced memory, primarily for recall, but also for recognition (Craik and McDowd, 1987), particularly for unfamiliar faces (Bartlett et al., 1989). Behavioral studies have shown that age-related memory declines are due in part to distraction from impaired inhibition of task-irrelevant input during encoding (Healey et al., 2008). Functional magnetic resonance imaging (fMRI) has been used to uncover the sources of memory deficits associated with aging. To date, this work has focused on successful encoding, while the neural correlates of unsuccessful encoding are unknown. Here, we provide novel evidence of a neural mechanism underlying memory failures exclusively affecting older adults. Whereas both younger and older adults showed reduced activation of brain regions important for encoding (e.g., hippocampus) during unsuccessful encoding, only older adults showed increased activity in brain regions mediating distraction (e.g., auditory cortex) and in left prefrontal cortex. Further, these regions were functionally connected with medial parietal areas, previously identified as default mode regions (Raichle and Snyder, 2007), which may reflect environmental monitoring. Our results suggest that increased distraction from task-irrelevant input (auditory in this case), associated with the unfamiliar and noisy fMRI environment, may increase environmental monitoring. This in turn could hinder suppression of default mode processing, resulting in memory failures in older adults. These findings provide novel evidence of a brain mechanism underlying the behavioral evidence that impaired inhibition of extraneous input during encoding leads to memory failure in older adults and may have implications for the ubiquitous use of fMRI for investigating neurocognitive aging.