The role of medial prefrontal cortex in memory and decision making

Abstract

Some have claimed that the medial prefrontal cortex (mPFC) mediates decision making. Others suggest mPFC is selectively involved in the retrieval of remote long-term memory. Yet others suggests mPFC supports memory and consolidation on time scales ranging from seconds to days. How can all these roles be reconciled? We propose that the function of the mPFC is to learn associations between context, locations, events, and corresponding adaptive responses, particularly emotional responses. Thus, the ubiquitous involvement of mPFC in both memory and decision making may be due to the fact that almost all such tasks entail the ability to recall the best action or emotional response to specific events in a particular place and time. An interaction between multiple memory systems may explain the changing importance of mPFC to different types of memories over time. In particular, mPFC likely relies on the hippocampus to support rapid learning and memory consolidation.

Figure 1

mPFC Encodes Expectation of Positive Outcomes. (A) Brain areas correlated with subjective value in humans. Subjects were asked to accept or reject offers of different amounts of money to be delivered after a specific delay. The mPFC, together with ventral striatum and posterior cingulate cortex, showed activity during the decision process related specifically to the subjective value of the current offer. The color scale represents the t-value of the contrast testing for a significant effect of subjective value (Kable and Glimcher, 2007). (B) Rat brain areas related to expectation of reward. Bars indicate relative numbers of Fos-positive cells in different brain areas after exposure to an environment where rats had previously been given chocolate chips compared to a neutral environment. Among cortical areas, there is selective activation of prelimbic and infralimbic cortex as well as lateral orbital cortex (Schroeder et al., 2001). (C) Single neuron encoding of reward expectation in rat mPFC. Rats had to enter a specific location and stay there until a food pellet was dropped at a separate location. Top two plots show spikes from one cell over two sessions. The bottom panel shows the binned peri-event time histogram for both sessions. This cell shows ramping activity during the delay between zone entry at time 0 and pellet release at time 2 seconds (delay indicated in gray) (Burton et al., 2009).

Figure 2

mPFC Encodes Expectation of Negative Outcomes. (A) Pain-associated foci in human mPFC from a meta-analysis of 192 neuroimaging studies. Top panel: locations of individual activated foci associated with delivery of physically painful stimuli, such as heat, cold or electric shock. Bottom panel: thresholded activation likelihood estimate (Shackman et al., 2011). (B) Changes in blood flow in the rat brain during exposure to an environment previously associated with painful colorectal distention. Cerebral blood flow was imaged via radioactively labeled [¹⁴C]-iodoantipyrine. Colors indicate statistically significant differences between conditioned and control rats in positive (red) and negative (blue) directions (Wang et al., 2011). Abbreviations: fmi – forceps minor of the corpus callosum, S1, S2 – primary and secondary somatosensory cortex. (C) Development of shock-anticipatory activity in mPFC during trace eye-blink conditioning. In Box A, rats were exposed to a tone as a conditioned stimulus (CS) and, after a 500 ms delay, mild eye-shock as an unconditioned stimulus (US). In Box B, CS and US were presented randomly so that the tone was not predictive of shock (pseudo-conditioning). Within each of the two sub-plot on the left, each row shows a z-score value for averaged population activity from all neurons showing an excitatory response during CS and trace interval. The horizontal axis indicates time within a trial and spans 1800 milliseconds. Early in training (rows below “Early”), mPFC cells respond primarily during the tone. After successful acquisition (rows above “Late”), cells maintain responses throughout the delay until delivery of shock. No such shock-anticipatory activity is evident in pseudo-conditioned Box B. The two panels on the right show similar results for all neurons showing an inhibitory response during the CS and trace interval (Takehara-Nishiuchi and McNaughton, 2008).

Figure 3

Major Anatomical Connections of Ventral mPFC. Arrows indicate directionality. Connections are derived from recent surveys of efferents and afferents of the mPFC and only the anatomically most dense projections are represented (Gabbott et al., 2005; Heidbreder and Groenewegen, 2003; Hoover and Vertes, 2007; Vertes et al., 2007). Hence, some potentially important connections, such as those to the lateral habenula, are not shown. Abbreviations: ACd – dorsal anterior cingulate cortex, B9 – B9 serotonin cells, DR – dorsal raphe, FrA - frontal association cortex, HDB - horizontal limb of the diagonal band of Broca, LC – locus coeruleus, PAG – periaqueductal gray, SN – substatia nigra, STN – sub-thalamic nucleus, VTA – ventral tegmental area.

Figure 4

Schematic view of hypothesized inputs to and outputs from different regions of prefrontal cortex. The mPFC is conceived as a network mapping events within a given spatial and emotional context with the most adaptive response, which can be either action or an emotional response, depending on the area. A separate set of inputs carries information about outcomes of actions, which modulate plasticity. All frontal areas are strongly inter-connected, meaning that information about actions, emotions, and stimuli is available to all prefrontal areas. (Paxinos and Watson, 2007). Abbreviations: ACd – dorsal anterior cingulate, PL – prelimbic cortex, IL – infralimbic cortex, DP –dorsal peduncular cortex, VO – ventral orbital cortex, LO – lateral orbital cortex.

Figure 5

Proposed Timeline of mPFC's Role in Memory. Vertical axis is the strength of the memory stored in either mPFC or hippocampus while horizontal axis indicates time on a log scale. During 30 minutes of task learning, the hippocampus learns more quickly than mPFC. During early consolidation, the hippocampus supports memory replay and the development of schematic representations within mPFC. Concurrently, episodic memory traces within hippocampus decay. This process continues during late consolidation, albeit at a slower rate.