RT Journal Article SR Electronic T1 Mnemonic Introspection in Macaques Is Dependent on Superior Dorsolateral Prefrontal Cortex But Not Orbitofrontal Cortex JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5922 OP 5934 DO 10.1523/JNEUROSCI.0330-19.2019 VO 39 IS 30 A1 Kwok, Chai, Sze (Kwok郭 Chai思齊) A1 Cai, Yudian (蔡禹甸) A1 Buckley, Mark J. YR 2019 UL http://www.jneurosci.org/content/39/30/5922.abstract AB The human PFC has been associated more with meta-perceptual as opposed to meta-memory decisions from correlational neuroimaging investigations. Recently, metacognitive abilities have also been shown to be causally dependent upon anterior and dorsal PFC in nonhuman primate lesion studies. Two studies, using postdecision wagering paradigms and reversible inactivation, challenged this meta-perceptual versus meta-memory notion and showed that dorsal and anterior prefrontal areas are associated with metamemory for experienced objects and awareness of ignorance, respectively. Causal investigations are important but scarce; nothing is known, for example, about the causal contributions of prefrontal subregions to spatial metamemory. Here, we investigated the effects of dorsal versus ventral PFC lesions on two-alternative forced-choice spatial discrimination tasks in male macaque monkeys. Importantly, we were rigorous in approach and applied three independent but complementary indices used to quantify individual animals' metacognitive ability (“Type II sensitivity”) by two variants of meta-d′/d′ and phi coefficient (φ). Our results were consistent across indices: while neither lesions to superior dorsolateral PFC nor orbitofrontal cortex impaired spatial recognition performance, only monkeys with superior dorsolateral PFC lesions were impaired in meta-accuracy. Together with the observation that the same orbitofrontal cortex lesioned monkeys were impaired in updating rule value in a Wisconsin Card Sorting Test analog, we therefore document a functional double-dissociation between these two PFC regions. Our study presents important causal evidence that other dimensions, namely, domain-specific processing (e.g., spatial vs nonspatial metamemory), also need considerations in understanding the functional specialization in the neural underpinnings of introspection.SIGNIFICANCE STATEMENT This study demonstrates macaque monkeys' metacognitive capability of introspecting its own memory success is causally dependent on intact superior dorsolateral prefrontal cortices but not the orbitofrontal cortices. Combining neurosurgical techniques on monkeys and state-of-the-art measures of metacognition, we affirm a critical role of the PFC in supporting spatial meta-recognition memory and delineate functional specificity within PFC for distinct elements of metacognition.