Mnemonic introspection in macaques is dependent on superior dorsolateral prefrontal cortex but not orbitofrontal cortex

The human prefrontal cortex (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 non-human primate lesion studies. Two studies, utilizing post-decision 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 sub-regions 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 animals9 metacognitive ability (“type II sensitivity”) by two variants of meta-d9/d′ and Phi coefficient (Φ). Our results were consistent across indices: while neither lesions to superior dorsolateral PFC (sdlPFC) nor orbitofrontal cortex (OFC) impaired spatial recognition performance, only monkeys with sdlPFC lesions were impaired in meta-accuracy. Together with the observation that the same OFC 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 versus non-spatial metamemory), also need considerations in understanding the functional specialization in the neural underpinnings of introspection. SIGNIFICANCE STATEMENT This study demonstrates macaque monkeys9 meta-cognitive capability of introspecting its own memory success is causally dependent on intact superior dorsolateral prefrontal cortices (PFC) 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.