Self-referential processing in our brain-A meta-analysis of imaging studies on the selfIntroductionMethods and resultsStudy selectionStatistical analysisResults of statistical analysisImaging studies and the selfSelf-referential processing in the verbal domainSelf-referential processing in the spatial domainSelf-referential processing in the memory domainSelf-referential processing in the emotional domainSelf-referential processing in the facial domainSelf-referential processing in the social domainSelf-referential processing in agency and ownership of movementsSelf-referential processing, the CMS, and the selfSensory processing and self-referential processingCortical midline structures and subcortical midline regionsCortical midline structures as functional unitFunctional specialization within the cortical midline structuresSelf-referential processing and higher-order processing in lateral prefrontal cortexNeurophilosophical perspectives on the brain and its selvesMethodological issuesConclusionAcknowledgmentsReferences1053-8119/$ - see front matter D 2005 Elsevier Inc. All rights reserved.doi:10.1016/j.neuroimage.2005.12.002Self-referential processing in our brain—A meta-analysis of imagingstudies on the selfGeorg Northoff,a,b,*Alexander Heinzel,cMoritz de Greck,bFelix Bermpohl,a,dHenrik Dobrowolny,band Jaak PankseppeaDepartment of Neurology, Harvard University, Cambridge, MA 02138, USAbDepartment of Psychiatry at Otto-von-Guericke University of Magdeburg, GermanycDepartment of Nuclear Medicine, University of Duesseldorf, GermanydDepartment of Psychiatry and Psychotherapy, University Medicine Berlin, Charite´ Campus Mitte, GermanyeScience Department of VCAPP, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6520, USAReceived 7 June 2005; revised 21 September 2005; accepted 1 December 2005Available online 7 February 2006The question of the self has intrigued philosophers and psychologistsfor a long time. More recently, distinct concepts of self have also beensuggested in neuroscience. However, the exact relationship betweenthese concepts and neural processing across different brain regionsremains unclear. This article reviews neuroimaging studies comparingneural correlates during processing of stimuli related to the self withthose of non-self-referential stimuli. All studies revealed activation inthe medial regions of our brains’ cortex during self-related stimuli. Theactivation in these so-called cortical midline structures (CMS) occurredacross all functional domains (e.g., verbal, spatial, emotional, andfacial). Cluster and factor analyses indicate functional specializationinto ventral, dorsal, and posterior CMS remaining independent ofdomains. Taken together, our results suggest that self-referentialprocessing is mediated by cortical midline structures. Since the CMSare densely and reciprocally connected to subcortical midline regions,we advocate an integrated cortical – subcortical midline system under-lying human self. We conclude that self-referential processing in CMSconstitutes the core of our self and is critical for elaboratingexperiential feelings of self, uniting several distinct concepts evidentin current neuroscience.D 2005 Elsevier Inc. All rights reserved.Keywords: Self; Imaging; Domains; Cortical midline structures; ProcessesIntroductionThe question of the self has been one of the most salientproblems throughout the history of philosophy and more recentlyalso in psychology ( Gallagher, 2000; Gallagher and Frith, 2003;Metzinger and Gall ese, 2003; Northoff, 2004). For example,William James distinguished between a physical self, a mental self,and a spiritual self. These distinctions seem to reappear in recentconcepts of self as discussed in neuroscience (Panksepp, 1998a,b,2003, 2005b; Damasio, 1999; Gallagher, 2000; Stuss et al., 2001;Churchland, 2002; Kelley et al., 2002; Lambie and Marcel, 2002;LeDoux, 2002; Turk et al., 2002; Damasio, 2003a,b; Gallagher andFrith, 2003; Keenan et al., 2003; Kircher and David, 2003; Turk etal., 2003; Vogeley and Fink, 2003; Dalgleish, 2004; Marcel andLambie, 2004; Northoff and Bermpohl, 2004). Damasio (1999) andPanksepp (1998a,b, 2003) suggest a ‘‘proto-self’’ in the sensory andmotor domains, respectively, which resembles William James’sdescription of the physical self. Similarly, what has been describedas ‘‘minimal self’’ (Gallagher, 2000; Gallagher and Frith, 2003)or‘‘core or mental self’’ (Damasio 1999) might correspond more orless to James’ concept of mental self. Finally, Damasio’s (Damasio1999) ‘‘autobiographical self’’ and Gallagher’s (Gallagher, 2000;Gallagher and Frith, 2003) ‘‘narrative self’’ strongly rely on linkingpast, present, and future events with some resemblances to James’spiritual self.The distinct concepts of self differ in the class of stimuli andtheir specific material or content reflecting what is called differentdomains. The ‘‘proto-self’’ refers to the domain of the body,whereas the ‘‘autobiographical self’’ reflects the domain ofmemory. Other concepts of self like the emotional self (Fossatiet al., 2003, 2004), the spatial self (Vogeley and Fink, 2003;Vogeley et al., 2004), the facial self (Keenan et al., 2000, 2001,2003), the verbal or interpreting self (Turk et al., 2003), and thesocial self (Frith and Frith, 1999, 2003) refer to further domains.* Corresponding author. Laboratory of Neuroimaging and Neurophiloso-phy, Department of Psychiatry, Otto-von-Guericke University of Magde-burg, Leipziger Strasse 44, 39120 Magdeburg, Germany. Fax: +49 3916715223.E-mail address: [email protected](G. Northoff).URL: www.nine3.com/gnorthoff/ (G. Northoff).Available online on ScienceDirect (www.sciencedirect.com).www.elsevier.com/locate/ynimgNeuroImage 31 (2006) 440 – 457What remains unclear, however, is what unites these distinctconcepts of self allowing us to speak of a self in all cases. In thisarticle, we assume that processing of stimuli as self-referential, self-referential processing, is common to the distinct concepts of self inthe different domains. This has also been described as Fself-related_or Fself-relevant_ processing (Craik and Hay, 1999; Kelley et al.,2002; Schore, 2003; Turk et al., 2003; Northoff and Bermpohl,2004; Phan et al., 2004a,b). Self-referential processing concernsstimuli that are experienced as strongly related to one’s own person.Typical examples are the way