Prefrontal Engagement and Reduced Default Network Suppression Co-occur and Are Dynamically Coupled in Older Adults: The Default-Executive Coupling Hypothesis of Aging

Abstract ■ Reduced executive control is a hallmark of neurocognitive aging. Poor modulation of lateral pFC activity in the context of increasing task challenge in old adults and a "failure to deactivate" the default network during cognitive control tasks have been observed. Whether these two patterns represent discrete mechanisms of neurocognitive aging or interact into older adulthood remains unknown. We examined whether altered pFC and default network dynamics co-occur during goal-directed planning over increasing levels of difficulty during performance on the Tower of London task. We used fMRI to investigate taskand age-related changes in brain activation and functional connectivity across four levels of task challenge. Frontoparietal executive control regions were activated and default network regions were suppressed during planning relative to counting performance in both groups. Older adults, unlike young, failed to modulate brain activity in executive control and default regions as planning demands increased. Critically, functional connectivity analyses revealed bilateral dorsolateral pFC coupling in young adults and dorsolateral pFC to default coupling in older adults with increased planning complexity. We propose a default-executive coupling hypothesis of aging. First, this hypothesis suggests that failure to modulate control and default network activity in response to increasing task challenge are linked in older adulthood. Second, functional brain changes involve greater coupling of lateral pFC and the default network as cognitive control demands increase in older adults. We speculate that these changes reflect an adaptive shift in cognitive approach as older adults come to rely more upon stored representations to support goal-directed task performance.

Spatiotemporal mixed modeling of multi-subject task fMRI via method of moments

Estimating spatiotemporal models for multi-subject fMRI is computationally challenging. We propose a mixed model for localization studies with spatial random effects and time-series errors. We develop method-of-moment estimators that leverage population and spatial information and are scalable to massive datasets. In simulations, subject-specific estimates of activation are considerably more accurate than the standard voxel-wise general linear model. Our mixed model also allows for valid population inference. We apply our model to cortical data from motor and theory of mind tasks from the Human Connectome Project (HCP). The proposed method results in subject-specific predictions that appear smoother and less noisy than those from the popular single-subject univariate approach. In particular, the regions of motor cortex associated with a left-hand finger-tapping task appear to be more clearly delineated. Subject-specific maps of activation from task fMRI are increasingly used in pre-surgical planning for tumor removal and in locating targets for transcranial magnetic stimulation. Our findings suggest that using spatial and population information is a promising avenue for improving clinical neuroimaging

Longitudinal basal forebrain degeneration interacts with TREM2/C3 biomarkers of inflammation in presymptomatic Alzheimer’s disease

Copyright © 2020 the authors Cholinergic inputs originating from the peripheral nervous system regulate the inflammatory immune responses of macrophages during clearance of blood-based pathogens. Because microglia are involved in clearing amyloid and tau pathology from the central nervous system, we hypothesized that cholinergic input originating from the basal forebrain might similarly regulate inflammatory immune responses to these pathologies in the aging brain. To explore this hypothesis, we leveraged the Alzheimer’s Disease Neuroimaging Initiative dataset. Cognitively normal older male and female human adults were differentiated according to the relative concentration of phosphorylated tau and amyloid in their cerebrospinal fluid, yielding neurotypical and preclinical, cognitively healthy, subgroups. We then tracked these two groups longitudinally with structural MRI and biomarkers of inflammation, including soluble sTREM2 levels in the CSF and complement C3 expression in the blood transcriptome. Longitudinal loss of basal forebrain volume was larger in the preclinical compared with the neurotypical subgroup. Across preclinical adults, loss of basal forebrain volume was associated with greater longitudinal accumulation of sTREM2 and higher peripheral blood C3 expression. None of these relationships were attributable to degeneration in the whole-brain gray matter volume. Preclinical APOE e4 carriers exhibited the largest loss of basal forebrain volume and highest C3 expression. Consistent with the known anti-inflammatory influence of the peripheral cholinergic pathways on macrophages, our findings indicate that a loss of central cholinergic input originating from the basal forebrain might remove a key check on microglial inflammation induced by amyloid and tau accumulation

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.Psycholog

The wandering brain: Meta-analysis of functional neuroimaging studies of mind-wandering and related spontaneous thought processes

AbstractThe neural basis and cognitive functions of various spontaneous thought processes, particularly mind-wandering, are increasingly being investigated. Although strong links have been drawn between the occurrence of spontaneous thought processes and activation in brain regions comprising the default mode network (DMN), spontaneous thought also appears to recruit other, non-DMN regions just as consistently. Here we present the first quantitative meta-analysis of neuroimaging studies of spontaneous thought and mind-wandering in order to address the question of their neural correlates. Examining 24 functional neuroimaging studies of spontaneous thought processes, we conducted a meta-analysis using activation likelihood estimation (ALE). A number of key DMN areas showed consistent recruitment across studies, including medial prefrontal cortex, posterior cingulate cortex, medial temporal lobe, and bilateral inferior parietal lobule. Numerous non-DMN regions, however, were also consistently recruited, including rostrolateral prefrontal cortex, dorsal anterior cingulate cortex, insula, temporopolar cortex, secondary somatosensory cortex, and lingual gyrus. These meta-analytic results indicate that DMN activation alone is insufficient to adequately capture the neural basis of spontaneous thought; frontoparietal control network areas, and other non-DMN regions, appear to be equally central. We conclude that further progress in the cognitive and clinical neuroscience of spontaneous thought will therefore require a re-balancing of our view of the contributions of various regions and networks throughout the brain, and beyond the DMN

Longitudinal Alzheimer\u27s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections

© 2018 The Author(s) The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain\u27s cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer\u27s disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To further assess whether structural degeneration of these regions in AD reflects cholinergic denervation, we used the [ 18 F] FEOBV radiotracer, which binds to cortico-amygdalar cholinergic terminals. We found that the two BF subregions explain spatially distinct patterns of cortico-amygdalar degeneration, which closely reflect their cholinergic projections, and overlap with [ 18 F] FEOBV indices of cholinergic denervation

Differentiating Phrase Structure Parsing and Memory Retrieval in the Brain

On some level, human sentence comprehension must involve both memory retrieval and structural composition. This study differentiates these two processes using neuroimaging data collected during naturalistic listening. Retrieval is formalized in terms of multiword expressions while structure-building is formalized in terms of bottom-up parsing. The results most strongly implicate Anterior Temporal regions for structure-building and Precuneus Cortex for memory retrieval

The Future of Memory: Remembering, Imagining, and the Brain

During the past few years, there has been a dramatic increase in research examining the role of memory in imagination and future thinking. This work has revealed striking similarities between remembering the past and imagining or simulating the future, including the finding that a common brain network underlies both memory and imagination. Here we discuss a number of key points that have emerged during recent years, focusing in particular on the importance of distinguishing between temporal and non-temporal factors in analyses of memory and imagination, the nature of differences between remembering the past and imagining the future, the identification of component processes that comprise the default network supporting memory- based simulations, and the finding that this network can couple flexibly with other networks to support complex goal-directed simulations. This growing area of research has broadened our conception of memory by highlighting the many ways in which memory supports adaptive functioning.Psycholog