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The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain–body communication, and is often studied for its role in “fight-or-flight” and “freezing” responses to threat. We used ultra-high-field 7 T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task (N = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (BOLD) response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. Subject-specific masks were group aligned to examine PAG response. In PAG, both mild and moderate demands elicited a well-defined response in ventrolateral PAG, a region thought to be functionally related to anticipated painful threat in humans and nonhuman animals—yet, the present task posed only the most minimal (if any) “threat,” with the cognitive tasks used being approximately as challenging as remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat. 

The theory of constructed emotion is a systems neuroscience approach to understanding the nature of emotion. It is also a general theoretical framework to guide hypothesis generation for how actions and experiences are constructed as the brain continually anticipates metabolic needs and attempts to meet those needs before they arise (termed allostasis). In this review, we introduce this framework and hypothesize that allostatic dysregulation is a trans-disorder vulnerability for mental and physical illness. We then review published findings consistent with the hypothesis that several symptoms in major depressive disorder (MDD), such as fatigue, distress, context insensitivity, reward insensitivity, and motor retardation, are associated with persistent problems in energy regulation. Our approach transforms the current understanding of MDD as resulting from enhanced emotional reactivity combined with reduced cognitive control and, in doing so, offers novel hypotheses regarding the development, progression, treatment, and prevention of MDD. 

Abstract Gradient mapping is an important technique to summarize high dimensional biological features as low dimensional manifold representations in exploring brain structure-function relationships at various levels of the cerebral cortex. While recent studies have characterized the major gradients of functional connectivity in several brain structures using this technique, very few have systematically examined the correspondence of such gradients across structures under a common systems-level framework. Using resting-state functional magnetic resonance imaging, here we show that the organizing principles of the isocortex, and those of the cerebellum and hippocampus in relation to the isocortex, can be described using two common functional gradients. We suggest that the similarity in functional connectivity gradients across these structures can be meaningfully interpreted within a common computational framework based on the principles of predictive processing. The present results, and the specific hypotheses that they suggest, represent an important step toward an integrative account of brain function. 

Abstract This paper integrates emerging evidence from two broad streams of scientific literature into one common framework: (a) hierarchical gradients of functional connectivity that reflect the brain’s large-scale structural architecture (e.g., a lamination gradient in the cerebral cortex); and (b) approaches to predictive processing and one of its specific instantiations called allostasis (i.e., the predictive regulation of energetic resources in the service of coordinating the body’s internal systems). This synthesis begins to sketch a coherent, neurobiologically inspired framework suggesting that predictive energy regulation is at the core of human brain function, and by extension, psychological and behavioral phenomena, providing a shared vocabulary for theory building and knowledge accumulation.