Brain Structure and Function https://doi.org/10.1007/s00429-019-01945-2 REVIEW The cingulate cortex and limbic systems for emotion, action, and memory Edmund T. Rolls1,2 Received: 19 April 2019 / Accepted: 19 August 2019 © The Author(s) 2019 Abstract Evidence is provided for a new conceptualization of the connectivity and functions of the cingulate cortex in emotion, action, and memory. The anterior cingulate cortex receives information from the orbitofrontal cortex about reward and non-reward outcomes. The posterior cingulate cortex receives spatial and action-related information from parietal cortical areas. It is argued that these inputs allow the cingulate cortex to perform action–outcome learning, with outputs from the midcingulate motor area to premotor areas. In addition, because the anterior cingulate cortex connects rewards to actions, it is involved in emotion; and because the posterior cingulate cortex has outputs to the hippocampal system, it is involved in memory. These apparently multiple diferent functions of the cingulate cortex are related to the place of this proisocortical limbic region in brain connectivity. Keywords Cingulate cortex · Limbic systems · Hippocampus · Orbitofrontal cortex · Emotion · Memory · Depression Introduction: the cingulate cortex and other stream processing areas that decode ‘what’ the stimulus is limbic structures (Rolls 2014b, 2016a, 2019a, b). The hippocampus is a key structure in episodic memory with inputs from the dorsal A key area included by Broca in his limbic lobe (Broca stream cortical areas about space, action, and ‘where’ events 1878) is the cingulate cortex, which hooks around the cor- occur, as well as from the ‘what’ ventral processing stream pus callosum. The term limbic used by Broca referred to (Kesner and Rolls 2015; Rolls 2018b). Because of the dif- structures that are at the border or edge (the literal meaning ferent connectivity and functions of these limbic structures of limbic) of the hemispheres (when seen in medial view), (amygdala, orbitofrontal cortex, and hippocampus) in emo- and led to the development of the concept of a limbic system tion and in memory, it has been suggested that the concept of (Pessoa and Hof 2015). Other limbic structures include the a single ‘limbic system’ is not realistic, and that we should hippocampus, and the amygdala (which has major connec- consider separately the connectivity and functions of difer- tions with the orbitofrontal cortex). These structures appear ent limbic structures in emotion and memory (Rolls 2015). to have very diferent connections and functions. The amyg- However, that leaves the cingulate cortex in an interesting dala and orbitofrontal cortex are key structures involved in position straddling the emotional and memory domains. The emotion and reward value with connections from ventral anterior cingulate cortex receives inputs from the orbitofron- tal cortex and amygdala which receive from ventral stream areas. The posterior cingulate cortex receives from dorsal Electronic supplementary material The online version of this stream areas including the parietal cortex and has connec- article (https ://doi.org/10.1007/s0042 9-019-01945 -2) contains tions to the hippocampal memory system. Moreover, there supplementary material, which is available to authorized users. is evidence relating the cingulate cortex to what is appar- * Edmund T. Rolls ently something else, action–outcome learning, in which [email protected] actions are learned to obtain goals based on the outcomes, http://www.oxcns.org the rewards and punishers, received for diferent actions (Rushworth et al. 2012; Kolling et al. 2016; Rolls 2019a). 1 Oxford Centre for Computational Neuroscience, Oxford, UK In this paper, I provide a framework for understanding 2 Department of Computer Science, University of Warwick, the connectivity and functions of the cingulate cortex, and Coventry CV4 7AL, UK Vol.:(0123456789)1 3 Brain Structure and Function how the cingulate cortex can be involved in at least three important functions, emotion, action–outcome learning, and memory. I consider the evidence on the connectivity and 6 5 7 4 1 ips functions of the diferent parts of the cingulate cortex, and 2 LIP 9 cs 3 ls then in the synthesis I produce an integrated conceptual- ps 46 MT ization of how the cingulate cortex, with its proisocortical as V1 structure and type of connectivity, fts in to our overall con- V2 ceptual understanding of the functions performed by dif- V4 22 ferent cortical areas, and by other limbic structures (Rolls PIT AIT 2016a). Proisocortical areas can be understood in terms of brain structure and function as forming connectional bridges between neocortical areas and areas such as the hippocam- pus (which is termed allocortex) (Pandya et al. 2015) (see “Connectivity of the cingulate cortex with the hippocampal medial 7 Precuneus memory system”). This is a conceptual review of the struc- Cingulatemid 24 Cingulatepost ture and functions of the cingulate cortex, and introduces Cingulateant 32 24 (23/31) new concepts on how it relates to other limbic and cortical Retrosplenial (29/30) V1 structures, rather than an exhaustive review. The cytoarchi- OFC25 tectural details of the human cingulate cortex are provided in Fig. S1 (Vogt 2009, 2016). Entorhinal TH Many previous contributions have been valuable in (28) TF leading towards an understanding of the cingulate cortex Perirhinal (35/36) (Devinsky et al. 1995; Vogt 2009, 2016; Rushworth et al. Medial view 2011). This paper focusses on research on the cingulate and The entorhinal cortex is the gateway into and from the hippocampus orbitofrontal cortex in primates including humans, rather than on research in rodents (Izquierdo 2017; Wikenheiser Fig. 1 and Schoenbaum 2016), because of the great development of The connections of the anterior and posterior cingulate cortex with their input areas, and their outputs to the hippocampal memory these regions in primates (Passingham and Wise 2012; Rolls system. A medial view of the macaque brain is shown below, and 2014a, 2018a, 2019a). For example, rodents have no poste- a lateral view is above. The green arrows show the convergence of rior cingulate cortex (Vogt 2009) and most of the orbito- reward or outcome information from the ACC and of information frontal cortex (apart from the agranular areas posteriorly) about actions from the posterior cingulate cortex to the midcingu- late motor area, which then projects to premotor areas including the may not be present in rodents (Passingham and Wise 2012; premotor cortex area 6 and the supplementary motor area. This pro- Rolls 2019a). vides connectivity for action–outcome learning. The anterior cin- An overview of the concepts about the cingulate cortex gulate cortex receives reward outcome information from the orbito- considered here follows, to provide a framework for under- frontal cortex (OFC). The posterior cingulate cortex (23 and 31) receives information about actions from the parietal cortex. This standing the evidence included in this paper. Some of the cingulate connectivity is compared with that of the hippocampus, connections and regions of the cingulate cortex are shown which receives information from the ventral ‘what’ processing stream in Figs. 1 and 2. (blue) and the dorsal ‘where’ or ‘action’ processing stream (red), as In humans, the pregenual anterior cingulate cortex described in the text. as, arcuate sulcus; cs, central sulcus; ips, intra- parietal sulcus; ios, inferior occipital sulcus; ls, lunate sulcus; ret- receives information related to reward from the medial orbit- rosplenial cortex (29, 30) is the small region in primates including ofrontal cortex, and related to punishment and not receiving humans behind the splenium of the corpus callosum shaded grey: it reward from the lateral orbitofrontal cortex. These orbito- is present in rodents, which do not have a posterior cingulate cortex frontal cortex areas represent information about value, not (Vogt 2009); sts, superior temporal sulcus; 4, 6, motor and premotor cortex. Developed from Rolls and Wirth (2018) about actions or responses, as shown by neuronal record- ings in macaques. The value representation received by the anterior cingulate cortex includes information about the particular, to actions. The subgenual cingulate cortex (area outcome of actions, that is, whether reward or punishment 25) may link rewards and punishers to autonomic output. has been received, and is used by the cingulate cortex for The posterior cingulate cortex receives information about learning the action to perform to obtain a reward or avoid actions from the parietal cortex, including areas 7a, VIP a punisher. This is termed ‘action–outcome learning’. The and LIP laterally, and area 7m medially (as well as some anterior cingulate cortex is implicated in emotion, because inputs from ventral stream temporal lobe areas) (Vogt and it is involved in linking reward and punishment informa- Laureys 2009). The posterior cingulate cortex is therefore tion, which elicit emotional responses, to behaviour, and, in implicated in spatial including visuospatial processing. A 1 3 Brain Structure and Function Midcingulate cortex Posterior cingulate cortex Retrosplenial Supracallosal ant cingulate cortex cortex cgs Pregenual ant cingulate cortex 24 Subgenual ant cingulate cortex T 10 cf Am TH TF 28 Medial View TE 12 lo s TG cs mos 13 as ips 11 51 ps os 10 S2 14 ls fros 46 Ventral view of INS Sylvian f orbitofrontal cortex 22 TPO ios STG TE 21 sts 38 Lateral View