Ventromedial Prefrontal Cortex Is Necessary for Normal Associative Inference and Memory Integration

Abstract

The ability to flexibly combine existing knowledge in response to novel circumstances is highly adaptive. However, the neural correlates of flexible associative inference are not well characterized. Laboratory tests of associative inference have measured memory for overlapping pairs of studied items (e.g., AB, BC) and for nonstudied pairs with common associates (i.e., AC). Findings from functional neuroimaging and neuropsychology suggest the ventromedial prefrontal cortex (vmPFC) may be necessary for associative inference. Here, we used a neuropsychological approach to test the necessity of vmPFC for successful memory-guided associative inference in humans using an overlapping pairs associative memory task. We predicted that individuals with focal vmPFC damage ( = 5; 3F, 2M) would show impaired inferential memory but intact non-inferential memory. Performance was compared with normal comparison participants ( = 10; 6F, 4M). Participants studied pairs of visually presented objects including overlapping pairs (AB, BC) and nonoverlapping pairs (XY). Participants later completed a three-alternative forced-choice recognition task for studied pairs (AB, BC, XY) and inference pairs (AC). As predicted, the vmPFC group had intact memory for studied pairs but significantly impaired memory for inferential pairs. These results are consistent with the perspective that the vmPFC is necessary for memory-guided associative inference, indicating that the vmPFC is critical for adaptive abilities that require application of existing knowledge to novel circumstances. Additionally, vmPFC damage was associated with unexpectedly reduced memory for AB pairs post-inference, which could potentially reflect retroactive interference. Together, these results reinforce an emerging understanding of a role for the vmPFC in brain networks supporting associative memory processes. We live in a constantly changing environment, so the ability to adapt our knowledge to support understanding of new circumstances is essential. One important adaptive ability is which allows us to extract shared features from distinct experiences and relate them. For example, if we see a woman holding a baby, and later see a man holding the same baby, then we might infer that the two adults are a couple. Despite the importance of associative inference, the brain systems necessary for this ability are not known. Here, we report that damage to human ventromedial prefrontal cortex (vmPFC) disproportionately impairs associative inference. Our findings show the necessity of the vmPFC for normal associative inference and memory integration.

Event conjunction: How the hippocampus integrates episodic memories across event boundaries

“…In this division of labor, the hippocampus is thought to encode details of unfolding events and reactivate details of past events, while the mPFC is thought to find commonalities across episodes and bias hippocampal reactivation towards relevant past events (Preston & Eichenbaum, 2013). In line with these predictions, patients with lesions to either the mPFC (Spalding et al, 2018) or the hippocampus (Pajkert et al, 2017) suffer deficits in the memory integration that cannot be explained by deficits in associative memory alone. As the nature of these lesions did not change between encoding and inference, however, these studies do not clarify whether these regions specifically impair integrative encoding.…”

Brain Mechanisms of Concept Learning

“…Although many behavioral and neuroimaging studies showed that reactivation of A during BC-learning can lead to interference and forgetting of C (Anderson, 2003;Kuhl et al, 2011), another outcome is episodic inference, where a relation is inferred between A and C. Although episodic inference can be achieved on-demand, from separate memories of individual events (Kumaran and McClelland, 2012), it can also result from memory integration, whereby new events are linked with prior related memories into a combined representation (Schlichting et al, 2014;Richter et al, 2016;Zeithamova and Preston, 2017). Notably, the same hippocampal-vmPFC interactions implicated in concept learning (Kumaran et al, 2009;Bowman and Zeithamova, 2018;Frank et al, 2019) have been implicated in memory integration and inference in both neuroimaging (Zeithamova et al, 2012; and lesion work (Dusek and Eichenbaum, 1997;Ryan et al, 2016;Spalding et al, 2018). Finally, the same regions have been shown to underlie schema-related memory (Tse et al, 2007(Tse et al, , 2011van Kesteren et al, 2012;Spalding et al, 2015;Brod et al, 2017;Gilboa and Marlatte, 2017;Gilboa and Moscovitch, 2017;Baldassano et al, 2018;Romero et al, 2019).…”

Competitive interactions between motor and episodic memory systems during interleaved learning

“…The source of the competitive interaction is unclear and could be due to increased demands such as task switching 49–51 . Our finding that greater vmPFC deactivation was related to more interference suggest competition in some aspect of information integration functions supported by this region 52–55 . Most studies employing a dual-task paradigm aimed to understand interference presented in performing tasks per se by measuring reaction time and found overlapped neural representation between two tasks, supporting interference due to competition for the same brain region 36,56 .…”