Coherent spontaneous blood oxygen level-dependent (BOLD) fluctuations have been intensely investigated as a measure of functional connectivity (FC) in the primate neocortex. BOLD-FC is commonly assumed to be constrained by the underlying anatomical connectivity (AC); however, cortical area pairs with no direct AC can also have strong BOLD-FC. On the mechanism generating FC in the absence of direct AC, there are 2 possibilities: 1) FC is determined by signal flows via short connection patterns, such as serial relays and common afferents mediated by a third area; 2) FC is shaped by collective effects governed by network properties of the cortex. In this study, we conducted functional magnetic resonance imaging in anesthetized macaque monkeys and found that BOLD-FC between unconnected areas depends less on serial relays through a third area than on common afferents and, unexpectedly, common efferents, which does not match the first possibility. By utilizing a computational model for interareal BOLD-FC network, we show that the empirically detected AC-FC relationships reflect the configuration of network building blocks (motifs) in the cortical anatomical network, which supports the second possibility. Our findings indicate that FC is not determined solely by interareal short connection patterns but instead is substantially influenced by the network-level cortical architecture.

We know how confidently we know: Metacognitive self-monitoring of memory states, so-called "metamemory," enables strategic and efficient information collection based on past experiences. However, it is unknown how metamemory is implemented in the brain. We explored causal neural mechanism of metamemory in macaque monkeys performing metacognitive confidence judgments on memory. By whole-brain searches via functional magnetic resonance imaging, we discovered a neural correlate of metamemory for temporally remote events in prefrontal area 9 (or 9/46d), along with that for recent events within area 6. Reversible inactivation of each of these identified loci induced doubly dissociated selective impairments in metacognitive judgment performance on remote or recent memory, without impairing recognition performance itself. The findings reveal that parallel metamemory streams supervise recognition networks for remote and recent memory, without contributing to recognition itself.

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Activation of cardiac STAT3 by IL-6 cytokine family contributes to cardioprotection. Previously, we demonstrated that IL-11, an IL-6 cytokine family, has the therapeutic potential to prevent adverse cardiac remodeling after myocardial infarction; however, it remains to be elucidated whether IL-11 exhibits postconditioning effects. To address the possibility that IL-11 treatment improves clinical outcome of recanalization therapy against acute myocardial infarction, we examined its postconditioning effects on ischemia/reperfusion (I/R) injury. C57BL/6 mice were exposed to ischemia (30 min) and reperfusion (24 h), and IL-11 was intravenously administered at the start of reperfusion. I/R injury mediated the activation of STAT3, which was enhanced by IL-11 administration. IL-11 treatment reduced I/R injury, analyzed by triphenyl tetrazolium chloride staining [PBS, 46.7 ± 14.4%; IL-11 (20 μg/kg), 28.6 ± 7.5% in the ratio of infarct to risk area]. Moreover, echocardiographic and hemodynamic analyses clarified that IL-11 treatment preserved cardiac function after I/R. Terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining revealed that IL-11 reduced the frequency of apoptotic cardiomyocytes after I/R. Interestingly, IL-11 reduced superoxide production assessed by in situ dihydroethidium fluorescence analysis, accompanied by the increased expression of metallothionein 1 and 2, reactive oxygen species (ROS) scavengers. Importantly, with the use of cardiac-specific STAT3 conditional knockout (STAT3 CKO) mice, it was revealed that cardiac-specific ablation of STAT3 abrogated IL-11-mediated attenuation of I/R injury. Finally, IL-11 failed to suppress the ROS production after I/R in STAT3 CKO mice. IL-11 administration exhibits the postconditioning effects through cardiac STAT3 activation, suggesting that IL-11 has the clinical therapeutic potential to prevent I/R injury in heart.

Self-evaluation of one's own ignorance requires us to peer into our own mind retrospectively. Here, we found that only the bilateral frontopolar cortices (area 10) are recruited for metacognitive evaluation of non-experienced events in macaque monkeys performing metacognitive confidence judgment on memory under fMRI scanning and that targeted reversible inactivation of the localized spots in area 10 selectively impaired the confidence judgment of non-experienced events. In contrast, fMRI experiments revealed that area 10 was not recruited for metacognition of experienced events like the way that the dorsal prefrontal cortex (area 9) was and, correspondingly, the inactivation of area 10 did not impair confidence judgment of experienced events. Notably, this inactivation did not impair the ability to identify novel events by distinguishing from repetitive events. Our findings elucidate that the frontopolar cortex plays a causal role to confer not awareness of past experience in general but awareness of one's own ignorance.