Default Mode of Brain Function in Monkeys

Changes in the functional connectivity (FC) of large-scale brain networks are a prominent feature of brain aging, but defining their relationship to variability along the continuum of normal and pathological cognitive outcomes has proved challenging. Here we took advantage of a well-characterized rat model that displays substantial individual differences in hippocampal memory during aging, uncontaminated by slowly progressive, spontaneous neurodegenerative disease. By this approach, we aimed to interrogate the underlying neural network substrates that mediate aging as a uniquely permissive condition and the primary risk for neurodegeneration. Using resting state (rs) blood oxygenation level-dependent fMRI and a restrosplenial/posterior cingulate cortex seed, aged rats demonstrated a large-scale network that had a spatial distribution similar to the default mode network (DMN) in humans, consistent with earlier findings in younger animals. Between-group whole brain contrasts revealed that aged subjects with documented deficits in memory (aged impaired) displayed widespread reductions in cortical FC, prominently including many areas outside the DMN, relative to both young adults (Y) and aged rats with preserved memory (aged unimpaired, AU). Whereas functional connectivity was relatively preserved in AU rats, they exhibited a qualitatively distinct network signature, comprising the loss of an anticorrelated network observed in Y adults. Together the findings demonstrate that changes in rs-FC are specifically coupled to variability in the cognitive outcome of aging, and that successful neurocognitive aging is associated with adaptive remodeling, not simply the persistence of youthful network dynamics.resting-state fMRI | default mode network | functional connectivity | neurocognitive aging | rat model F unctional MRI (fMRI) has revealed a number of functionally interconnected brain networks. One prominent example, termed the default mode network (DMN), shows prominent temporally coherent activity under wakeful, spontaneous, and undirected conditions (i.e., "resting"), and decreased coherence in response to active cognitive engagement (1-3). Functional connectivity (FC) assessed from the blood oxygenation level-dependent (BOLD) signal provides a measure of these coincident fluctuations across brain areas (2, 4), where positive correlations are thought to reflect simultaneous neuronal activity between regions, and negative or "anticorrelations" arise from inverse, antiphase fluctuations. In this way, resting-state FC (rs-FC) maps the temporal and spatial organization of large-scale neural network dynamics.Recent studies indicate that variability in DMN FC is linked to individual differences in cognition and behavior (e.g., refs. 5 and 6), including differential trajectories of cognitive aging. For example, the strength of FC between anterior and posterior components of the DMN across the lifespan is directly related to performance on tasks measuring executive function, memory, and processing speed (7). During normal ag...

Section: Resultssupporting

confidence: 86%

mentioning

confidence: 99%

Functional connectivity with the retrosplenial cortex predicts cognitive aging in rats

Ash

Taxier

et al. 2016

“…Similar effects have been observed in both cats and monkeys (36,37). As such, dynamic opposition between activation of the CEN/SN and deactivation of the DMN has been theorized to mediate transitions between rest and task-engaged states (2,4,6,7,9,10).…”

Section: Discussionmentioning

confidence: 52%

Causal interactions between fronto-parietal central executive and default-mode networks in humans

Chen

Oathes

Chang

et al. 2013

500

358

Information processing during human cognitive and emotional operations is thought to involve the dynamic interplay of several large-scale neural networks, including the fronto-parietal central executive network (CEN), cingulo-opercular salience network (SN), and the medial prefrontal-medial parietal default mode networks (DMN). It has been theorized that there is a causal neural mechanism by which the CEN/SN negatively regulate the DMN. Support for this idea has come from correlational neuroimaging studies; however, direct evidence for this neural mechanism is lacking. Here we undertook a direct test of this mechanism by combining transcranial magnetic stimulation (TMS) with functional MRI to causally excite or inhibit TMS-accessible prefrontal nodes within the CEN or SN and determine consequent effects on the DMN. Single-pulse excitatory stimulations delivered to only the CEN node induced negative DMN connectivity with the CEN and SN, consistent with the CEN/SN's hypothesized negative regulation of the DMN. Conversely, low-frequency inhibitory repetitive TMS to the CEN node resulted in a shift of DMN signal from its normally low-frequency range to a higher frequency, suggesting disinhibition of DMN activity. Moreover, the CEN node exhibited this causal regulatory relationship primarily with the medial prefrontal portion of the DMN. These findings significantly advance our understanding of the causal mechanisms by which major brain networks normally coordinate information processing. Given that poorly regulated information processing is a hallmark of most neuropsychiatric disorders, these findings provide a foundation for ways to study network dysregulation and develop brain stimulation treatments for these disorders. task positive network | task negative network | fMRI | neuromodulation E xtensive neuroimaging work has described a set of largescale, intrinsically organized networks in the human brain, as well as those of other mammals, which are thought to underlie a broad range of functions, from basic sensory and motor capacities to cognition and higher-level functions (1-4). Three networks in particular have been the focus of work related to these higher-level functions (5): the fronto-parietal central executive network (CEN), the cingulo-opercular salience network (SN), and the medial prefrontal-medial parietal default mode network (DMN). These networks are thought to interact and together control attention, working memory, decision making, and other higher-level cognitive operations (6-8).Findings to date, however, emphasize the need for a direct test of the proposed causal relationship between these networks. On the basis of observations in resting-state functional MRI (rsfMRI) scans in humans of time-locked negative CEN/DMN and SN/DMN connectivity (9-11), as well as mathematical modeling of temporal relationships between these networks (12), it has been argued that the CEN and/or SN negatively regulate activity in the DMN. However, because a similar pattern of connectivity can be spuriously introduced du...

“…One of those networks, the proposed rodent DMN, is the primary focus of this report. The functional significance of this network and its relationship to the DMN seen in primates (1,5,6,24) remain to be explored. In light of the significant evolutionary divergence of rodents and primates, it may not be surprising that the structural homology across species, although startlingly similar, is not complete.…”

Section: Discussionmentioning

confidence: 99%

Rat brains also have a default mode network

Zou

et al. 2012

536

571

The default mode network (DMN) in humans has been suggested to support a variety of cognitive functions and has been implicated in an array of neuropsychological disorders. However, its function (s) remains poorly understood. We show that rats possess a DMN that is broadly similar to the DMNs of nonhuman primates and humans. Our data suggest that, despite the distinct evolutionary paths between rodent and primate brain, a well-organized, intrinsically coherent DMN appears to be a fundamental feature in the mammalian brain whose primary functions might be to integrate multimodal sensory and affective information to guide behavior in anticipation of changing environmental contingencies.functional MRI | resting state | intrinsic activity | connectivity | spontaneous fluctuation I n the absence of an immediate need for goal-directed attention to the surrounding environment, our minds wander from recollection of past happenings to imagination of future events. Neuroimaging studies have consistently identified a set of interconnected brain areas that becomes less active during attentiondemanding cognitive tasks (1). This so-called default mode network (DMN) is posited to play a fundamental role in brain organization and supports a variety of self-referential functions such as understanding others' mental state, recollection and imagination (2), conceptual processing (3), and even in the sustenance of conscious awareness (4). Many of these functions have been considered to be unique to humans. Intriguingly, similar coherent structures have been shown to exist in anesthetized macaque monkeys and chimpanzees (5, 6). Furthermore, the functions of the default network are disrupted in such neuropsychological disorders as schizophrenia, Alzheimer's disease, and autism (7-9), underscoring the clear and critical need for further investigating the neurobiological basis of DMN using animal models.The evolutionary clade of rodents is about 35 million years earlier than that of old world monkeys and about 60 million years earlier than humans (10). Although many of the structures and functions of subcortical nuclei are conserved across these three species, the neocortex, in particular the "association" cortex, has extensively expanded in the primate as a result of evolutionary pressure, which is considered to be crucial in the development of higher cognitive and behavioral functions (10, 11). On the other hand, such structures as cingulate cortex, prefrontal cortex, and hippocampal formation, all of which are critical elements of the DMN, are also present in rodents (11). Given the distant evolutionary paths between rodent and primate brain, an intriguing question arises: Does the rat possess a similar DMN? Such a network, once demonstrated, would not only suggest that an operational DMN is a common feature in the mammalian brain, perhaps induced via parallel evolution as a result of natural selection, it would also offer a novel platform to explore the physiological basis and behavioral significance of the DMN. Such a demonstratio...