(PDF) Introspective Minds: Using ALE meta-analyses to study commonalities in the neural correlates of emotional processing, soci

Introspective Minds: Using ALE Meta-Analyses to Study Commonalities in the Neural Correlates of Emotional Processing, Social & Unconstrained Cognition Leonhard Schilbach1,2*, Danilo Bzdok3,4, Bert Timmermans2, Peter T. Fox5, Angela R. Laird5, Kai Vogeley2,6, Simon B. Eickhoff3,4,7 1 Max-Planck-Institute for Neurological Research, Cologne, Germany, 2 Department of Psychiatry, University of Cologne, Cologne, Germany, 3 Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany, 4 Department of Psychiatry, University of Aachen, Aachen, Germany, 5 Research Imaging Center, UT Health Science Center, San Antonio, Texas, United States of America, 6 Institute of Neuroscience and Medicine (INM-3), Research Center Juelich, Juelich, Germany, 7 Cognitive Neuroscience Group, Institute of Clinical Neuroscience and Medical Psychology, University of Duesseldorf, Duesseldorf, Germany Abstract Previous research suggests overlap between brain regions that show task-induced deactivations and those activated during the performance of social-cognitive tasks. Here, we present results of quantitative meta-analyses of neuroimaging studies, which confirm a statistical convergence in the neural correlates of social and resting state cognition. Based on the idea that both social and unconstrained cognition might be characterized by introspective processes, which are also thought to be highly relevant for emotional experiences, a third meta-analysis was performed investigating studies on emotional processing. By using conjunction analyses across all three sets of studies, we can demonstrate significant overlap of task- related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have, indeed, recently been linked to introspective abilities. Our findings, therefore, provide evidence for the existence of a core neural network, which shows task-related signal change during socio-emotional tasks and during resting states. Citation: Schilbach L, Bzdok D, Timmermans B, Fox PT, Laird AR, et al. (2012) Introspective Minds: Using ALE Meta-Analyses to Study Commonalities in the Neural Correlates of Emotional Processing, Social & Unconstrained Cognition. PLoS ONE 7(2): e30920. doi:10.1371/journal.pone.0030920 Editor: Carles Soriano-Mas, Bellvitge Biomedical Research Institute-IDIBELL, Spain Received October 13, 2011; Accepted December 24, 2011; Published February 3, 2012 Copyright: ß 2012 Schilbach et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by the German Research Council (DFG, IRTG 1328: SBE & DB), the Human Brain Project/01-MH074457-01A1: SBE), the Koeln Fortune Program/Medical Faculty, University of Cologne (LS), the VolkswagenFoundation (LS, BT & KV), the German Ministery of Research and Education (Project: ‘‘Other minds’’, KV) and the Helmholtz Initiative on Systems Biology ‘‘The Human Brain Model’’ (SBE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail:

Introduction capacity to attend to one’s own feelings and/or thoughts, which is to an important degree forged in the process of social interaction. Previous research suggests overlap between those brain regions In the context of neuroimaging studies into socio-emotional and that show task-induced deactivations across a wide range of resting state cognition, we see introspection, thus defined, as a different fMRI studies (the so-called ‘default mode network’ or possible ‘common denominator’ of both socio-emotional and ‘resting state’ of brain function; e.g. [1]) and brain regions, which resting state cognition. are activated during the performance of social-cognitive tasks In order to address whether social-cognitive (hereafter: SOC), (often referred to as the ‘mentalizing network’, e.g. [2,3]). The set resting state (hereafter: DMN) and emotional processing (hereafter: of brain areas thus implicated includes medial prefrontal cortex, EMO) rely on a common core network of brain regions we took posterior cingulate cortex/precuneus and the temporo-parietal the following approach: we used the activation likelihood junction. The observed similarities have led to the suggestion that estimation (ALE) approach, which allows to statistically investigate a relationship may exist between the physiological baseline of the the convergence of published neuroimaging findings on activations human brain and a psychological baseline or predisposition for or deactivations to delineate brain regions, that are consistently social cognition, which may be characterized by a reliance on activated by social-cognitive and emotional tasks, as well as those internally-directed attention or introspective processes (cf. [4–6]). that consistently deactivate following the engagement in a wide A close relationship is also thought to exist between activity change range of other experimental tasks [12–14]. in the ‘default mode network’ and emotional processing (e.g. [7– In a first step, the neural correlates of these different processes 9]), which could be related to a close link between emotional (SOC, EMO and DMN) were analyzed separately. In a second experiences and introspection (e.g. [10]). In this respect, it has step, conjunction analyses were performed to reveal brain areas, been suggested that introspective competence may initially emerge which show consistent task-related signal change across two sets of from an infant’s social interactions with others and the emotional studies. Given the phenomenal and conceptual similarities of experiences made in this context (e.g. [11]). Consequently, our social-cognitive and emotional processes and their allegedly notion of introspection is one, which sees introspective abilities as a comparable importance for the understanding of other minds PLoS ONE | www.plosone.org 1 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds (e.g. [15]), we used the conjunction of SOC > EMO to validate in an externally structured task (DMN: n = 533), while excluding our approach and map out commonalities in task-related brain those studies, which were part of the other individual meta- activity between the two independent sets of studies. In order to analyses. That is, the individual meta-analyses were based on investigate neurofunctional overlap between social and uncon- independent pools of experiments. Furthermore, we profited from strained cognition, we performed the conjunction of SOC > the BrainMap taxonomy, to identify the sub-pools of the DMN. Lastly, and most important for the objective of our study, databased neuroimaging experiments that have been labelled as a triple conjunction analysis was carried out to investigate being closely related to emotional and social processing, convergence across all three types of studies (SOC > EMO > respectively. Here, the considered studies on emotional process- DMN) based on the assumption that introspective processes could ing are defined as pertaining to ‘‘the mental faculty of be equally relevant across all studies. In order to investigate experiencing an affective state of consciousness such as joy, whether the core neural network common to all three sets of sorrow, fear, hate’’. In particular, facial emotion is thought to be studies shows overlap with findings from a recent study by an evolutionarily shaped adaption that allows for the efficient Fleming et al., which investigated the relationship of gray matter transmission of affective states [18]. Experimental psychology has volume differences and introspective abilities [16], we performed later detailed that experiencing one’s own and witnessing others’ a minimum conjunction analysis as the intersection of the emotions is closely related to autonomic arousal [19,20]. statistical maps. In the study by Fleming and colleagues Importantly, a number of facial emotions are known to be participants were asked to perform a (two interval, forced choice) interculturally stable [21], which underlines the psychological visual judgment task presented near (individually determined) importance of automatically sharing arousing affective states, that sensory thresholds and to provide ratings of confidence in their is, emotions. The considered studies on social processing, on the decisions after each trial. Introspective ability was determined at other hand, are defined as pertaining to ‘‘the mental faculty an individual level through the construction of type II receiver associated with how people process social information, especially operating characteristic (ROC) curves, which provide a measure its encoding, storage, retrieval, and application to social of the ability to link confidence to perceptual performance, i.e. of situations’’. Notably, even stimuli with simple geometrical shapes being able to (subjectively) report how well one is (objectively) are perceived as human-like agents if they enact social situations doing the task. (e.g. [22]). Also from a developmental perspective, it is known that neurotypically developing infants have a preference to attend Methods to social cues (e.g. [23]). Likewise, it is known that memory encoding and retrieval is biased towards social content, such as Data used for the meta-analysis interactions and relationships (e.g. [24,25]), which underscores Functional imaging experiments for the meta-analyses were the psychological distinctness of social-cognitive processes. In obtained from the BrainMap database [12], which contained, at particular when considering the focus of the current investigation, the time of analysis, the location of reported activation foci and i.e., to assess the convergence between social cognition and associated meta-data of approximately 10,000 neuroimaging unconstrained processing in the ‘‘default mode’’, it is important to experiments. Of these, only databased functional magnetic note, that the employed definition of social-cognitive processes resonance (fMRI) and positron emission tomography (PET) did not include primarily self-referential processing such as self- studies that reported functional mapping experiments were evaluations/-descriptions. That is, our meta-analysis on social- considered. The inclusion criteria comprised considering only data cognitive processing only included studies dealing with the from neurotypicals (i.e. healthy subjects), exclusive consideration impression and evaluation of other persons, not the self. This of studies that report coordinates provided in a standard restriction should be important, as it is well-known that anatomical reference space (Talairach/Tournoux or MNI) and processing of the self (or close others) shows is supported brain reliance on full-brain coverage (versus analyses based on regions regions that are discernable from those sustaining social-cognitive of interest (ROIs) or functional localizers). The exclusion criteria processing focusing on other, unfamiliar people (cf. [26,27]). consisted in non-consideration of neuroimaging experiments that Taken together, based on the BrainMap meta-data, we identified investigate age, gender, patient groups or drug effects. For all experiments corresponding to contrasts isolating emotional retrieval of the relevant experiments, the BrainMap database was processing (EMO: n = 1474) as well as those experiments that filtered based on the metadata of the archived experiments that probed social-cognitive processes (SOC: n = 75). For those two describe the experimental paradigm used in the respective analyses (EMO, SOC) only task-associated activations were experiment as well as the specific mental process isolated by a considered. given statistical contrast. Behavioural domains (BD) include the main categories of cognition, action, perception, emotion, Meta-analysis algorithm interoception, as well as their related subcategories. The Meta-analyses were carried out using the revised version [28] of respective paradigm classes (PC) classify the specific task the activation likelihood estimation (ALE) approach for coordi- employed (a complete list of BDs and PCs can be found at nate-based meta-analysis of neuroimaging results [29,30]. The http://brainmap.org/scribe/). The BDs and PCs together algorithm aims at identifying areas showing a statistical conver- constitute a complete cognitive taxonomy for the conceptual gence of reported activations across different experiments. distinction of mental processes conceived by leaders of the Inference is then based on the assessment if this clustering is neuroscientific community [17]. Furthermore, labels denoting the higher than expected under the null distribution of a random characterization of the reported coordinates as task-dependent spatial association. The key idea behind ALE is to treat the activation or deactivation are provided by the BrainMap reported foci not as single points, but rather as centers for 3D metadata for each experiment. Gaussian probability distributions capturing the spatial uncertainty In the current analysis of the DMN, we included all associated with each focus. The width of these uncertainty experiments that reported deactivations relative to a low-level functions was determined based on empirical data on the (resting) baseline, i.e. all experiments providing coordinates for between-subject and between-template variance, which represent regions that decreased their activity when subjects were engaged the main components of this uncertainty. Importantly, the applied PLoS ONE | www.plosone.org 2 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds algorithm weights the between-subject variance by the number of examined subjects per study, accommodating the notion that larger sample sizes should provide more reliable approximations of the ‘true’ activation effect and should therefore be modelled by ‘tighted’ Gaussian distributions [28]. The probabilities of all activation foci in a given experiment were combined for each voxel, resulting in a modelled activation map (MA map). Taking the union across these MA maps yields voxel-wise ALE scores describing the convergence of results at each particular location. Since neurophysiologically, neuronal effects should predominantly be localized within the grey matter, all analyses were restricted to those voxels where a probability of at least 10% for grey matter could be assumed based on the International Consortium of Brain Mapping (ICBM) tissue probability maps. To distinguish ‘true’ convergence between studies from random convergence, i.e., noise, ALE scores were compared to an empirical null-distribution reflecting a random spatial association between experiments. Hereby, a random-effects inference is invoked, focusing on inference on the above-chance convergence between studies, not clustering of foci within a particular study. Computationally, deriving this null-hypothesis involved sampling a voxel at random from each of the MA maps and taking the union of these values in the same manner as done for the (spatially contingent) voxels in the true analysis. The p- value of a ‘true’ ALE was then given by the proportion of equal or higher values obtained under the null-distribution. The resulting non-parametric p-values for each meta-analysis were thresholded at a cluster-level family wise error (FWE) corrected threshold of p,0.05 and transformed into Z-scores for display. Conjunction analyses between the separate meta-analyses were carried out by calculating a voxel-wise minimum statistic [31]. Computationally, this is equivalent to determining the intersection between the thresholded meta-analyses results (cf. [32]). Results Figure 1. Significant results of the ALE meta-analysis for social cognition tasks (SOC). All results are displayed on the left and right were thus significant in individual analyses at a corrected p,0.05. lateral surface view, the anterior/posterior and dorsal/ventral view of The resulting areas were anatomically labelled by reference to the Montreal Neurological Institute (MNI) single subject template. ATC: probabilistic cytoarchitectonic maps of the human brain [33,34]. anterior temporal cortex, DMPFC: dorso-medial prefrontal cortex, MTG: In order to formally test whether the core ‘introspection middle temporal gyrus, PCC: posterior cingulate cortex, PREC: network’ - represented by the results of our triple conjunction precuneus, TPJ: temporo-parietal junction. analysis (SOC > EMO > DMN) – shows anatomical overlap with doi:10.1371/journal.pone.0030920.g001 the findings from the study by Fleming and colleagues [16], which investigated the relationship of grey matter differences and supramarginal gyrus, bilateral TPJ, left superior and right introspective abilities, a minimum conjunction analysis was middle temporal gyrus, left middle occipital gyrus and left computed as the intersection of the thresholded statistical middle frontal gyrus (Figure 3, Table 3). parametric maps. Conjunction analyses Results Brain regions, which showed consistent activation across both Individual meta-analyses the emotional and social-cognitive tasks (SOC > EMO), comprise ‘Social-cognitive network’ (SOC). Consistent activation DMPFC, precuneus, middle and anterior superior temporal gyrus across the social-cognitive tasks was found in left dorso-medial and VS (Figure 4, Table 4). prefrontal cortex (DMPFC), the left precuneus, bilateral middle Brain regions, which showed consistent involvement both in the temporal gyrus, anterior temporal cortex (ATC) and the temporo- social- cognitive tasks and those studies that investigated the DMN parietal junction (TPJ) area as well as the left superior frontal gyrus (SOC > DMN), comprise DMPFC, precuneus and the TPJ (Figure 1, Table 1). bilaterally (Figure 5, Table 5). ‘Emotional processing network’ (EMO). Consistent Using a triple conjunction analysis, we formally tested for brain activation across the emotional processing tasks was found in the regions, which show consistent involvement across all different amygdala (AMY) bilaterally, the ventral (VS) and dorsal striatum types of studies, i.e. social-cognitive, emotional processing and (DS) bilaterally, middle and superior temporal gyrus and insular resting state experiments (SOC > EMO > DMN). Results of this cortex, anterior cingulate cortex (ACC), posterior cingulate cortex analysis demonstrate the involvement of DMPFC and the (PCC) and the precuneus, area V5 and fusiform gyrus (FG) precuneus across these three domains (Figure 6, Table 6). (Figure 2, Table 2). To assess whether these are the same regions as the ones ‘Default mode network’ (DMN). Consistent task-induced reported to underlie introspective abilities (Fleming et al. 2010), we deactivation was found in PCC extending into the precuneus, calculated a minimum conjunction analysis across the thresholded ACC, ventro- and dorso-medial prefrontal cortex, bilateral maps from the triple conjunction analysis and results from the PLoS ONE | www.plosone.org 3 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds Table 1. Activation peaks of ALE meta-analysis of the neural correlates of social cognition tasks (SOC). Macroanatomical location MNI coordinates Cluster size Maximum z-score x y z Left Superior Medial Gyrus 4 46 32 1083 7.40 Left Precuneus 26 252 28 642 6.67 Left Middle Temporal Gyrus 248 259 18 456 5.22 Left Middle Temporal Gyrus 253 238 0 385 5.56 Right Middle Temporal Gyrus 48 265 10 259 5.42 Right Middle Temporal Gyrus 52 213 210 236 3.98 Left Middle Temporal Gyrus 250 25 219 179 4.60 Left Superior Frontal Gyrus 217 25 55 116 4.31 All peaks were assigned to the most probable brain area by using the SPM Anatomy Toolbox. doi:10.1371/journal.pone.0030920.t001 morphometric study by Fleming and colleagues (2010). This overlap between their results and the triple-conjunction of meta- additional analysis, indeed, demonstrates involvement of DMPFC analyses. (MNI coordinates: 23, 54, 21; T = 3.18) and precuneus (MNI coordinates: 2, 251, 19; T = 3.28), thereby confirming anatomical Discussion Using ALE-based meta-analyses of neuroimaging studies from the BrainMap database, we were able to demonstrate consistent patterns of activations and deactivations across different types of experimental paradigms. Providing such a quantitative assessment of convergence across studies crucially goes beyond what qualitative reviews of studies investigating social cognition and emotional processing can provide. Furthermore, our approach allows to formally investigate commonalities in the neural networks subserving different types of tasks by applying conjunc- tion analyses, which test for convergence across different pairs and across all three individual meta-analyses. By using the latter type of analysis, we can demonstrate overlap of task-related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have recently been linked to introspective abilities. ‘Social-cognitive network’ (SOC) The meta-analysis targeting consistent activations across studies exploring the neural correlates of social cognition revealed activations in the DMPFC, the precuneus, the TPJ and anterior temporal cortex (Figure 1), which is in very good agreement with previous descriptions of the neural network subserving social cognition (e.g. [3,27,35]). More specifically, DMPFC has commonly been related to mental state attribution or ‘mentalizing’ as e.g. classical false-belief tasks and stories, which require (cognitively) taking someone else’s perspective, have been shown to result in a differential increase of neural activity in this area [36]. Activity of ATC has been related to the understanding of social concepts [37,38] while activation of more posterior temporal areas and the temporo-parietal junction (TPJ), in particular, have been connected to the perception of biological motion cues, but also the understanding of intentions and perspective-taking behavior [27,39,40]. Weighting these putative functional contributions, activations of the TPJ have Figure 2. Significant results of the ALE meta-analysis of been understood as contributing to the inference of temporary emotional processing tasks (EMO). All results are displayed on goals and intentions at a perceptual level, while DMPFC has been the left and right lateral surface view, the anterior/posterior and dorsal/ discussed in terms of an integration of social information across ventral view of the MNI single subject template. ACC: anterior cingulate cortex, AMY: amygdala, DS: dorsal striatum, FG: fusiform gyrus, INS: time and at a more abstract level [26]. Recruitment of the insula cortex, PREC: precuneus, PCC: posterior cingulate cortex, VS: precuneus (and PCC) have been related to the generation of ventral striatum. ‘‘internally directed thoughts’’ [41,42], which is likely to be doi:10.1371/journal.pone.0030920.g002 important for our understanding of the – at least in part – PLoS ONE | www.plosone.org 4 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds Table 2. Activation peaks of ALE meta-analysis of the neural correlates of emotional processing tasks (EMO). Macroanatomical location MNI coordinates Cluster size Maximum z-score x y z Left Amygdala 222 26 214 11445 8.70 Left Superior Medial Gyrus 22 50 20 3636 8.37 Right Middle Temporal Gyrus 48 266 0 1775 8.01 Left Inferior Temporal Gyrus 242 262 210 1357 7.10 Left Precuneus 26 254 20 495 6.12 Left Middle Temporal Gyrus 256 234 24 299 4.88 Right Middle Temporal Gyrus 52 240 4 444 5.52 All peaks were assigned to the most probable brain area by using the SPM Anatomy Toolbox. doi:10.1371/journal.pone.0030920.t002 unobservable aspects of another person’s mental life. Similarly, the which the integration of both personally and interpersonally role of medial parietal lobe in autobiographical memory has been available information may be crucial [2]. emphasized by Spreng and Mar, who see overlapping activations in mentalizing and memory tasks as an indication for the ‘Emotional network’ (EMO) importance of the role of memory for social cognition, during Our analysis of consistent brain activations for emotional processing revealed a highly significant, bilateral pattern of activation, which comprises the AMY, the VS and DS, the ACC/DMPFC and PCC/precuneus, area V5 and insular cortex (Figure 2). Co-activations of ACC and anterior insular cortex bilaterally have commonly been described as a ‘‘salience network’’ believed to be involved in the attribution of salience to both internal events and extrapersonal stimuli, thereby guiding behavior [43–45]. Also, this network has been implicated in the experience of and empathy for pain [46,47]. More specifically, anterior insula cortex may be involved in re-mapping of interoceptive afferences, thus contrib- uting to integrative representations of feelings from the body [48,49]. ACC has classically been described as a brain region involved in the processing of cognitive control and conflict monitoring [50,51], but more recent data suggests a role as a ‘‘hub where information about reinforcers can be linked to motor centers responsible for expressing affect and executing goal- directed behavior’’ [52]. Additionally, our analysis revealed involvement of the bilateral amygdala, a brain region whose primary function appears to reside in signaling what is important and to then modulate appropriate (response) processes to deal with the challenges and opportunities present in a given situation [53,54]. Neuroanatom- ically, this appears to be reflected by a multitude of interconnec- tions of the amygdala and other brain areas [55–57]. Consistent with the suggestion of the amygdala as an emotional significance detector, studies have indicated that intact functioning of the amygdala is important for the generation of adaptive responses [58] and for the attending of emotionally relevant information [59,60]. In line with these views, the anatomical volume of the amygdala has been shown to correlate with the size and complexity of social networks in adult humans [61]. Finally, our meta-analysis also provides evidence for the recruitment of the ventral and dorsal striatum during emotional Figure 3. Significant results of the ALE meta-analysis of tasks: while the ventral striatum has been described as a core node unconstrained cognition (DMN). All results are displayed on the of the neural network of reward, especially involved in the left and right lateral surface view, the anterior/posterior and dorsal/ anticipation and experience of the hedonic aspects of rewards ventral view of the MNI single subject template. ACC: anterior cingulate cortex, MFG: middle frontal gyrus, PCC: posterior cingulate cortex, PREC: [62,63]. The dorsal striatum, on the other hand, has been linked to precuneus, SMG: supramarginal gyrus, TPJ: temporo-parietal junction, reward-related aspects of action selection and action release VMPFC: ventro-medial prefrontal cortex. mechanisms, thereby contributing to reward-based decision- doi:10.1371/journal.pone.0030920.g003 making (e.g. [64]). PLoS ONE | www.plosone.org 5 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds Table 3. Activation peaks of ALE meta-analysis of unconstrained cognition (DMN). Macroanatomical location MNI coordinates Cluster size Maximum z-score x y z Left Posterior Cingulate Cortex 22 254 24 2383 7.26 Right Mid Orbital Gyrus 4 34 214 1023 8.26 Right Supramarginal Gyrus 56 228 24 711 6.01 Left Superior Medial Gyrus 24 52 10 723 5.64 Right Middle Temporal Gyrus 48 270 18 442 6.29 Left Middle Occipital Gyrus 242 272 22 280 5.61 Left Middle Frontal Gyrus 226 18 44 240 6.40 Left SupraMarginal Gyrus 258 234 28 190 4.94 Left Amygdala 222 24 226 122 4.32 All peaks were assigned to the most probable brain area by using the SPM Anatomy Toolbox. doi:10.1371/journal.pone.0030920.t003 ‘Default mode network’ (DMN) (Figure 3). These results are in line with findings from our own The meta-analysis that explored consistent, task-induced previous investigation of task-induced deactivations, but also other deactivations across a large number of neuroimaging studies from analyses, which have repeatedly demonstrated that these brain different task domains demonstrated involvement of ACC/ regions exhibit task-related decreases in neural activity during DMPFC and PCC/precuneus, VMPFC and TPJ bilaterally tasks which require engagement with external stimuli [5,12,65,66]. Convergence across the different pairs of meta-analyses The conjunction analysis of social-cognitive and emotional processing (SOC > EMO) demonstrates involvement of DMPFC, the precuneus, middle and anterior superior temporal gyrus and the ventral striatum (Figure 4). Consistent with intuition of commonalities of the phenomenal content and construct similar- ities between social-cognitive and emotional processes, our results, thus, suggest a common neural network across these two types of experiments. As many regions in this network (DMPFC, PCC/ precuneus, TPJ) have been implicated as a core network for social cognition, we would interpret the observed convergence with emotional processing as strong evidence for the fundamental contribution of affective information to social cognition [3,26]. Furthermore, our analysis reveals consistent overlap in the ventral striatum (Figure 4 A1), which has been described as a core element of the functional neuroanatomy of reward and is thought to be involved in the anticipation and experience of the hedonic aspects of rewards (e.g. [62]). The current data is thus in line with recent evidence suggesting that being able to successfully initiate and lead social interactions recruits this subcortical brain region and leads to positive subjective experiences [63]. Also, higher activity in this brain region in response to social stimuli (such as faces) has been shown to correlate with increases in reaction time needed by participants to disengage from a social stimulus [51]. Results of the conjunction analysis between social cognition and the task-related deactivations (SOC > DMN), demonstrate involvement of DMPFC, precuneus and the TPJ bilaterally (Figure 5). Based on this striking convergence between the resting state and the social cognition network, one could be tempted to speculate about similarities in the associated cognitive processes. Indeed, different strands of evidence exist to suggest that human beings may have a predisposition for thinking about themselves and others, to which they return when they have nothing else to Figure 4. Significant results of the conjunction analysis of SOC think about (see [5]). Recent findings reported by Andrews-Hanna > EMO. All results are displayed on the left and right lateral surface view, the anterior/posterior and dorsal/ventral view of the MNI single and colleagues, indeed, lend empirical support to this idea: In their subject template. DMPFC: dorso-medial prefrontal cortex, PREC: study, the authors manipulated factors that promote internally precuneus, STG: superior temporal gyrus, VS: ventral striatum. directed, spontaneous cognition separately from those that doi:10.1371/journal.pone.0030920.g004 influence attention to external task demands. Results demonstrate PLoS ONE | www.plosone.org 6 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds Table 4. Activation peaks of conjunction analysis of SOC > EMO. Macroanatomical location MNI coordinates Cluster size Maximum z-score x y z Left Superior Medial Gyrus 22 48 28 857 7.21 Left Precuneus 26 254 22 271 5.85 Left Middle Temporal Gyrus 256 234 3 211 4.88 Left Middle Temporal Gyrus 250 256 16 92 4.03 Right Middle Temporal Gyrus 52 262 6 69 3.73 All peaks were assigned to the most probable brain area by using the SPM Anatomy Toolbox. doi:10.1371/journal.pone.0030920.t004 that areas of the DMN increased their activity when spontaneous neurocomputational formats of social and unconstrained cognition cognition was maximized [67]. Future research could extend the (cf. [70]). use of thought probes and experience sampling during resting state fMRI measurements in combination with multivariate pattern Convergence across all three meta-analyses analysis techniques to investigate such matters in further detail As the key finding of our study, the conjunction analysis [68,69]. The latter approach may also be useful to assess the performed by including the results of all individual ALE meta- commonalities of the cognitive correlates and region-specific analyses (SOC > EMO > DMN) provides compelling empirical activity changes as well as possible similarities concerning the evidence for a shared neural network, which comprises the precuneus and DMPFC (Figure 6). This analysis was performed based on the idea that in cognitive terms a commonality may exist between all three types of states, namely that they may all be characterized by introspective processing, which could be -at times- equally relevant for coming to terms with one’s own or other people’s states. Consistently, the results of the triple conjunction analysis (Figure 6) converge with findings of a recent study, which has related structural brain differences in DMPFC and the precuneus to introspective abilities ([16]; see Figure 3a). Here, the dorsal part of the MPFC seems to be specifically related to prospective metacognition [71] – indeed, thinking of oneself in the context of one’s future behavior would be crucial to our capacity at social interaction. Consistent with the suggestion of these two brain regions being relevant for introspection, activity changes in precuneus have been observed when individuals direct their attention internally [72]. Similarly, the DMPFC has been related to the ability of generating stimulus-independent thoughts to explain aspects of another person’s mental states that might not be directly observable in their behavior [73]. Both regions have, therefore, been implicated in the generation of stimulus-indepen- dent thoughts [74,75]. Furthermore, recent work indicates that this midline network could be related to automatically tagging the ‘self-relevance’ of stimuli (e.g. [67,76,77]). If this was the case, the network might play an interestingly dual role in being part of and shaping bottom-up processes, while at other times also contribut- ing to the top-down regulation of social behavior by means of introspective processes. In other words, it may serve as an interface between neural networks, which subserve internally as compared to externally directed cognition [42,78]. Thereby, the idea of introspective processes being related to activity in anterior medial prefrontal cortex may help to reconcile previous controversy [74,79], as introspection can be applied to both external and internal stimuli. Findings, which suggest that introspection can be enhanced via social interaction [80], also prompt the intriguing question of the Figure 5. Significant results of the conjunction analysis of SOC interrelation of socio-emotional and introspective abilities and > DMN. All results are displayed on the left and right lateral surface their respective neural correlates. Evidence from developmental view, the anterior/posterior and dorsal/ventral view of the MNI single subject template. DMPFC: dorso-medial prefrontal cortex, PREC: psychology has been taken to suggest that introspective precuneus, TPJ: temporo-parietal junction. competence emerges through the infant’s social interactions with doi:10.1371/journal.pone.0030920.g005 others by relating one’s own states with those of others [11]. PLoS ONE | www.plosone.org 7 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds Table 5. Activation peaks of conjunction analysis of SOC > DMN. Macroanatomical location MNI coordinates Cluster size Maximum z-score x y z Left Precuneus 26 254 24 401 5.91 Left Superior Medial Gyrus 22 52 14 195 4.84 Right Middle Temporal Gyrus 52 262 16 101 3.98 Left Middle Temporal Gyrus 246 266 18 69 4.15 All peaks were assigned to the most probable brain area by using the SPM Anatomy Toolbox. doi:10.1371/journal.pone.0030920.t005 However, a more radical approach holds that it may be only via (gaze-based) social interactions including joint attention in the social interaction and in virtue of the fact that we are constantly absence of an explicit mentalizing task [63]. Consequently, one trying to model other minds in interaction that we learn to be could speculate that it might be exactly via such (gaze-based) conscious and develop both an understanding of ourselves [81] social interactions, which include deictic elements, that children’s (Carruthers 2009) and a conscious percept of the world at all introspective competence emerges. On the neural level, we [82,83]. In line with the suggestion that activity changes in the suggest that activity changes in medial prefrontal cortex-posterior cortical midline structures may primarily be forged during social cingulate connectivity - initially not found in infants [84] - are a interactions before they may be brought under top-down control likely candidate in terms of the neural correlate of such changes. and used for ‘offline’ social cognition, a recent fMRI study was The study by Bahrami and colleagues [80] further indicates that able to demonstrate the recruitment of DMPFC and PCC during interaction-based changes of introspective abilities continue to be effective during adulthood. Taken together, or results suggest that on the neural level, introspective, social and affective processes converge and rely upon recruitment of a network that comprises dorso-medial prefrontal and medial parietal cortex. Conclusions & Outlook In this study, we took a meta-analytic approach to delineating brain regions, which consistently show activations during social cognition and emotional processing and deactivations across a wide range of experimental tasks. By applying conjunction analyses, we demonstrated a close convergence of the brain regions involved. These results provide robust empirical evidence for a shared neural network that underlies emotional processing, social and unconstrained cognition, which localizes to the precuneus and anterior medial prefrontal cortex. These two regions are known to be critical hubs in the neurofunctional architecture of the human brain [1,41,85–89]. Moreover, these regions have been shown as closely related to introspective abilities [16]. Crucially, comparing the results of our triple conjunction analysis to the findings by Fleming and colleagues demonstrates significant anatomical overlap. Consequently, we argue that these findings are consistent with the idea that a ‘common denominator’ may exist in cognitive terms, which could consist in introspective processes. By making use of these, we may become aware of our own or others’ states, equally relevant for social cognition, emotional processing and uncon- strained thought [5,24]. Future research into the functional and effective connectivity of the different nodes of this shared neural network and its susceptibility to intervention and plasticity during social interac- tions are likely to be informative concerning the exact functional roles of the different brain regions. One important question our findings raise is whether social cognition, emotional processing, Figure 6. Significant results of the conjunction analysis of SOC and resting state cognition simply recruit brain structures that > EMO > DMN. All results are displayed on the left and right lateral surface view, the anterior/posterior and dorsal/ventral view of the MNI subtend conscious introspection or meta-cognitive abilities, or single subject template. DMPFC: dorso-medial prefrontal cortex, PREC: whether they are in fact instrumental in the shaping of such precuneus. introspective abilities. One possibility is that in social or emotional doi:10.1371/journal.pone.0030920.g006 contexts, not only adequate behavior is important, but that the PLoS ONE | www.plosone.org 8 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds Table 6. Activation peaks of conjunction analysis of SOC > EMO > DMN. Macroanatomical location MNI coordinates Cluster size Maximum z-score x y z Left Precuneus 26 254 22 251 5.85 Left Superior Medial Gyrus 22 52 14 179 4.84 All peaks were assigned to the most probable brain area by using the SPM Anatomy Toolbox. doi:10.1371/journal.pone.0030920.t006 successful prediction and monitoring of the outcomes of this Author Contributions behavior is equally essential. Such re-description of one’s behavior Analyzed the data: LS DB SBE. Contributed reagents/materials/analysis could turn out to be exactly the mechanism that underlies tools: DB ARL PTF SBE. Wrote the paper: LS DB BT ARL PTF KV introspection [90–92]. SBE. References 1. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, et al. (2001) 25. Mesoudi A, Whiten A, Dunbar R (2006) A bias for social information in human A default mode of brain function. Proc Natl Acad Sci U S A 98(2): 676–682. cultural transmission. Br J Psychol 97: 405–423. 2. Spreng RN, Mar RA, Kim AS (2009) The common neural basis of 26. Van Overwalle F (2009) Social cognition and the brain: a meta-analysis. Hum autobiographical memory, prospection, navigation, theory of mind, and the Brain Mapp 30(3): 829–858. default mode: a quantitative meta-analysis. J Cogn Neurosci 21(3): 489–510. 27. Van Overwalle F, Baetens K (2009) Understanding others’ actions and goals by 3. Frith U, Frith C (2010) The social brain: allowing humans to boldly go where no mirror and mentalizing systems: a meta-analysis. Neuroimage 48(3): 564–584. other species has been. Philos Trans R Soc Lond B Biol Sci 365(1537): 165–176. 28. Eickhoff SB, Laird AR, Grefkes C, Wang LE, Zilles K, Fox PT (2009) 4. Buckner RL, Carroll DC (2007) Self-projection and the brain. Trends Cogn Sci Coordinate-based activation likelihood estimation meta-analysis of neuroimag- 11(2): 49–57. ing data: a random-effects approach based on empirical estimates of spatial 5. Schilbach L, Eickhoff SB, Rotarska-Jagiela A, Fink GR, Vogeley K (2008) uncertainty. Hum Brain Mapp 30(9): 2907–2926. Minds at rest? Social cognition as the default mode of cognizing and its putative 29. Turkeltaub PE, Eden GF, Jones KM, Zeffiro TA (2002) Meta-analysis of the relationship to the ‘‘default system’’ of the brain. Conscious Cogn 17(2): functional neuroanatomy of single-word reading: method and validation. 457–467. Neuroimage 16(3 Pt 1): 765–780. 6. Mitchell JP (2009) Social psychology as a natural kind. Trends Cogn Sci 13(6): 30. Turkeltaub PE, Eickhoff SB, Laird AR, Fox M, Wiener M, et al. (2011) 246–251. Minimizing within-experiment and within-group effects in activation likelihood 7. Wiebking C, de Greck M, Duncan NW, Heinzel A, Tempelmann C, et al. estimation meta-analyses. Hum Brain Mapp. (2011) Are emotions associated with activity during rest or interoception? An 31. Nichols T, Brett M, Andersson J, Wager T, Poline JB (2005) Valid conjunction exploratory fMRI study in healthy subjects. Neurosci Lett 491(1): 87–92. inference with the minimum statistic. Neuroimage 25(3): 653–660. 8. Salgado-Pineda P, Fakra E, Delaveau P, McKenna PJ, Pomarol-Clotet E, et al. 32. Caspers S, Zilles K, Laird AR, Eickhoff SB (2010) ALE meta-analysis of action (2011) Correlated structural and functional brain abnormalities in the default observation and imitation in the human brain. Neuroimage 50(3): 1148–1167. mode network in schizophrenia patients. Schizophr Res 125(2–3): 101–109. 33. Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, et al. (2005) A new 9. Kunisato Y, Okamoto Y, Okada G, Aoyama S, Demoto Y, et al. (2011) SPM toolbox for combining probabilistic cytoarchitectonic maps and functional Modulation of default-mode network activity by acute tryptophan depletion is imaging data. Neuroimage 25(4): 1325–1335. associated with mood change: a resting state functional magnetic resonance 34. Eickhoff SB, Paus T, Caspers S, Grosbras MH, Evans AC, et al. (2007) imaging study. Neurosci Res 69(2): 129–134. Assignment of functional activations to probabilistic cytoarchitectonic areas 10. Immordino-Yang MH (2011) Me, my ‘‘self’’ and you: Neuropsychological revisited. Neuroimage 36(3): 511–521. relations between social emotion, self awareness, and morality. Emotion Review 35. Mar RA (2011) The neural bases of social cognition and story comprehension. 3(3): 313–315. doi:10.1177/1754073911402391. Annu Rev Psychol 62: 103–134. 11. Rochat P, Striano T (2002) Who’s in the mirror? Self–other discrimination in 36. Amodio DM, Frith CD (2006) Meeting of minds: the medial frontal cortex and specular images by four- and nine-month-old infants. Child Development 73(1). social cognition. Nat Rev Neurosci 7(4): 268–277. 12. Fox PT, Lancaster JL (2002) Opinion: Mapping context and content: the BrainMap model. Nat Rev Neurosci 3(4): 319–321. 37. Zahn R, Moll J, Krueger F, Huey ED, Garrido G, et al. (2007) Social concepts 13. Kober H, Barrett LF, Joseph J, Bliss-Moreau E, Lindquist K, et al. (2008) are represented in the superior anterior temporal cortex. Proc Natl Acad Functional grouping and cortical-subcortical interactions in emotion: a meta- Sci U S A 104(15): 6430–6435. analysis of neuroimaging studies. Neuroimage 42(2): 998–1031. 38. Jimura K, Konishi S, Asari T, Miyashita Y (2010) Temporal pole activity during 14. Laird AR, Eickhoff SB, Kurth F, Fox PM, Uecker AM, et al. (2009) ALE Meta- understanding other persons’ mental states correlates with neuroticism trait. Analysis Workflows Via the Brainmap Database: Progress Towards A Brain Res 1328: 104–112. Probabilistic Functional Brain Atlas. Front Neuroinformatics 3: 23. 39. van den Bos W, van Dijk E, Westenberg M, Rombouts SA, Crone EA (2011) 15. Ochsner KN (2008) The social-emotional processing stream: five core constructs Changing brains, changing perspectives: the neurocognitive development of and their translational potential for schizophrenia and beyond. Biol Psychiatry reciprocity. Psychol Sci 22(1): 60–70. 64(1): 48–61. 40. Grosbras MH, Beaton S, Eickhoff SB (2011) Brain regions involved in human 16. Fleming SM, Weil RS, Nagy Z, Dolan RJ, Rees G (2010) Relating introspective movement perception: A quantitative voxel-based meta-analysis. Hum Brain accuracy to individual differences in brain structure. Science 329(5998): Mapp. 1541–1543. 41. Cavanna AE, Trimble MR (2006) The precuneus: a review of its functional 17. Laird A (2009) Lost in localization: The focus is meta-analysis, Neuroimage 48: anatomy and behavioural correlates. Brain 129: 564–583. 18–20. 42. Leech R, Kamourieh S, Beckmann CF, Sharp DJ (2011) Fractionating the 18. Darwin C (1872) The expression of the emotions in man and animals. London: default mode network: distinct contributions of the ventral and dorsal posterior John Murray. cingulate cortex to cognitive control. J Neurosci 31(9): 3217–3224. 19. James W (1884) What is an emotion? Mind 9: 188–205. 43. Menon V, Uddin LQ (2010) Saliency, switching, attention and control: a 20. Cannon WB (1929) Bodily Changes in Pain, Hunger, Fear and Rage, vol 2. New network model of insula function. Brain Struct Funct 214(5–6): 655–667. York: Appleton. 44. Kurth F, Zilles K, Fox PT, Laird AR, Eickhoff SB (2010) A link between the 21. Ekman P (1982) Emotion in the human face. Cambridge University Press, New systems: functional differentiation and integration within the human insula York. revealed by meta-analysis. Brain Struct Funct 214(5–6): 519–534. 22. Heider F, Simmel M (1944) An experimental study of apparent behavior. 45. Wiech K, Lin CS, Brodersen KH, Bingel U, Ploner M, Tracey I (2010) Anterior American Journal of Psychology 57: 243–259. insula integrates information about salience into perceptual decisions about pain. 23. Meltzoff AN, Moore MK (1977) Imitation of facial and manual gestures by J Neurosci 30(48): 16324–16331. human neonates, Science 198: 75–78. 46. Lamm C, Decety J, Singer T (2011) Meta-analytic evidence for common and 24. Dunbar R (2004) Gossip in evolutionary perspective. Review of General distinct neural networks associated with directly experienced pain and empathy Psychology 8(2): 100–110. for pain. Neuroimage 54(3): 2492–2502. PLoS ONE | www.plosone.org 9 February 2012 | Volume 7 | Issue 2 | e30920 Introspective Minds 47. Legrain V, Iannetti GD, Plaghki L, Mouraux A (2011) The pain matrix 69. Weil RS, Rees G (2010) Decoding the neural correlates of consciousness. Curr reloaded: a salience detection system for the body. Prog Neurobiol 93(1): Opin Neurol 23(6): 649–655. 111–124. 70. Etzel JA, Gazzola V, Keysers C (2008) Testing simulation theory with cross- 48. Craig AD (2009) How do you feel–now? The anterior insula and human modal multivariate classification of fMRI data. PLoS One 3(11): e3690. awareness. Nat Rev Neurosci 10(1): 59–70. 71. Fleming SM, Dolan RJ (in press) The neural basis of accurate metacognition. 49. Craig AD (2010) The sentient self. Brain Struct Funct 214(5–6): 563–577. Philosophical Transactions of the Royal Society B: Biological Sciences. 50. Sohn MH, Albert MV, Jung K, Carter CS, Anderson JR (2007) Anticipation of 72. Shannon BJ, Buckner RL (2004) Functional-anatomic correlates of memory conflict monitoring in the anterior cingulate cortex and the prefrontal cortex. retrieval that suggest nontraditional processing roles for multiple distinct regions Proc Natl Acad Sci U S A 104(25): 10330–10334. within posterior parietal cortex. J Neurosci 24(45): 10084–10092. 51. Schilbach L, Eickhoff SB, Cieslik E, Shah NJ, Fink GR, et al. (2010) Eyes on me: 73. Frith CD (2008) Social cognition. Philosophical Transactions of the Royal an fMRI study of the effects of social gaze on action control. Soc Cogn Affect Society B: Biological Sciences 363(1499): 2033–2039. Neurosci. 74. Mason MF, Norton MI, Van Horn JD, Wegner DM, Grafton ST, et al. (2007) 52. Shackman AJ, Salomons TV, Slagter HA, Fox AS, Winter JJ, et al. (2011) The Wandering minds: the default network and stimulus-independent thought. integration of negative affect, pain and cognitive control in the cingulate cortex. Science 315(5810): 393–395. Nat Rev Neurosci 12(3): 154–167. 75. Allen M, Williams G (2011) Consciousness, plasticity, and connectomics: the role 53. Bzdok D, Langner R, Caspers S, Kurth F, Habel U, et al. (2011) ALE meta- of intersubjectivity in human cognition. Front Psychology 2: 20. analysis on facial judgments of trustworthiness and attractiveness. Brain Struct 76. Lou HC, Luber B, Stanford A, Lisanby SH (2010) Self-specific processing in the Funct 215(3–4): 209–223. default network: a single-pulse TMS study. Exp Brain Res 207(1–2): 27–38. 54. Pessoa L, Adolphs R (2010) Emotion processing and the amygdala: from a ‘low 77. Whitfield-Gabrieli S, Moran JM, Nieto-Castanon A, Triantafyllou C, Saxe R, road’ to ‘many roads’ of evaluating biological significance. Nat Rev Neurosci et al. (2011) Associations and dissociations between default and self-reference 11(11): 773–783. networks in the human brain. Neuroimage 55(1): 225–232. 55. Price JL (2003) Comparative aspects of amygdala connectivity. Ann N Y Acad 78. Burgess PW, Dumontheil I, Gilbert SJ (2007) The gateway hypothesis of rostral Sci 985: 50–58. prefrontal cortex (area 10) function. Trends Cogn Sci 11(7): 290–298. 56. Adolphs R (2010) What does the amygdala contribute to social cognition? 79. Gilbert SJ, Dumontheil I, Simons JS, Frith CD, Burgess PW (2007) Comment Ann N Y Acad Sci 1191: 42–61. on ‘‘Wandering minds: the default network and stimulus-independent thought’’. 57. Bach DR, Behrens TE, Garrido L, Weiskopf N, Dolan RJ (2011) Deep and Science 317(5834): 43; author reply 43. superficial amygdala nuclei projections revealed in vivo by probabilistic 80. Bahrami B, Olsen K, Latham PE, Roepstorff A, Rees G, et al. (2010) Optimally tractography. J Neurosci 31(2): 618–623. interacting minds. Science 329(5995): 1081–1085. 58. Kennedy DP, Glascher J, Tyszka JM, Adolphs R (2009) Personal space 81. Carruthers P (2009) How we know our own minds: the relationship between regulation by the human amygdala. Nat Neurosci 12(10): 1226–1227. mindreading and metacognition. Behavioral and Brain Sciences 32(2): 121–138. 59. Kennedy DP, Adolphs R (2010) Impaired fixation to eyes following amygdala 82. Cleeremans A (2011) The radical plasticity thesis: how the brain learns to be damage arises from abnormal bottom-up attention. Neuropsychologia 48(12): conscious. Front Psychology 2: 86. 3392–3398. 83. Timmermans B, Schilbach L, Pasquali A, Cleeremans A (in press) Higher-Order 60. Gosselin F, Spezio ML, Tranel D, Adolphs R (2010) Asymmetrical use of eye Thoughts in Action: Consciousness as an unconscious redescription process. information from faces following unilateral amygdala damage. Soc Cogn Affect Philosophical Transactions of the Royal Society B: Biological Sciences. Neurosci. 84. Fransson P, Skio¨ld B, Horsch S, Nordell A, Blennow M, et al. (2007) Resting- 61. Bickart KC, Wright CI, Dautoff RJ, Dickerson BC, Barrett LF (2011) Amygdala state networks in the infant brain. Proc Natl Acad Sci U S A 25;104(39): volume and social network size in humans. Nat Neurosci 14(2): 163–164. 15531–6. 62. Sanfey AG (2007) Social decision-making: insights from game theory and 85. Hagmann P, Cammoun L, Gigandet X, Meuli R, Honey CJ, et al. (2008) neuroscience. Science 318(5850): 598–602. Mapping the structural core of human cerebral cortex. PLoS Biol 6(7): e159. 63. Schilbach L, Wilms M, Eickhoff SB, Romanzetti S, Tepest R, et al. (2010) Minds 86. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default made for sharing: initiating joint attention recruits reward-related neurocircui- network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124: try. J Cogn Neurosci 22(12): 2702–2715. 1–38. 64. Balleine BW, Delgado MR, Hikosaka O (2007) The role of the dorsal striatum in 87. Fransson P, Marrelec G (2008) The precuneus/posterior cingulate cortex plays a reward and decision-making. J Neurosci 27(31): 8161–8165. pivotal role in the default mode network: Evidence from a partial correlation 65. Toro R, Fox PT, Paus T (2008) Functional coactivation map of the human network analysis. Neuroimage 42(3): 1178–1184. brain. Cereb Cortex 18(11): 2553–2559. 88. Margulies DS, Vincent JL, Kelly C, Lohmann G, Uddin LQ, et al. (2009) 66. Nagano-Saito A, Liu J, Doyon J, Dagher A (2009) Dopamine modulates default Precuneus shares intrinsic functional architecture in humans and monkeys. Proc mode network deactivation in elderly individuals during the Tower of London Natl Acad Sci U S A 106(47): 20069–20074. task. Neurosci Lett 458(1): 1–5. 89. Glahn DC, Winkler AM, Kochunov P, Almasy L, Duggirala R, et al. (2010) 67. Andrews-Hanna JR, Reidler JS, Huang C, Buckner RL (2010) Evidence for the Genetic control over the resting brain. Proc Natl Acad Sci U S A 107(3): Default Network’s Role in Spontaneous Cognition. J Neurophysiol 104: 1223–1228. 322–335. 90. Rosenthal D (2005) Consciousness and Mind. Oxford: Clarendon Press. 68. Christoff K, Gordon AM, Smallwood J, Smith R, Schooler JW (2009) 91. Pasquali A, Timmermans B, Cleeremans A (2010) Know thyself: Metacognitive Experience sampling during fMRI reveals default network and executive system networks and measures of consciousness. Cognition 117: 182–190. contributions to mind wandering. Proc Natl Acad Sci U S A 106(21): 92. Lau H, Maniscalco B (2010) Should confidence be trusted? Science 329(5998): 8719–8724. 1478–1479. PLoS ONE | www.plosone.org 10 February 2012 | Volume 7 | Issue 2 | e30920