Update TRENDS in Cognitive Sciences Vol.8 No.6 June 2004 | Research Focus Human feelings: why are some more aware than others? A.D. (Bud) Craig Atkinson Research Laboratory, Barrow Neurological Institute, 350 West Thomas Rd, Phoenix, AZ 85013, USA A recent article reports that human perception of heartbeat timing is mediated by right (non-dominant) anterior insular cortex, and that the activity and the size of this region is directly correlated with individuals’ subjective awareness of inner body feelings and emotionality. These results support the somatic-marker hypothesis of consciousness (a modern successor to the James–Lange theory of emotion) and the neuroanatomical concept that human awareness is based on a phylogenetically distinct interoceptive pathway. Critchley, Dolan and colleagues have intensively pursued the identification of forebrain regions involved in the neural representation of emotion, primarily using functional imaging [1 –3]. Their recent contribution to this endeavor is an elegant study that matches individuals’ subjective perception of their heartbeat and psychometric measures of their interoceptive awareness and emotionality with a region of the cerebral cortex that appears to be anatomically unique to humans [4]. Their findings solidly confirm that right anterior insula (rAI) is important for explicit subjective awareness and, significantly, offer a substantive anatomical explanation as to why some individuals are more aware of their feelings than others. Their work sets the stage for intimate structural analyses of the very essence of human feelings. Interoceptive feelings We all recognize ‘gut feelings’ that help guide our behavior. The James – Lange theory of emotion proposed that afferent feedback from muscles and viscera, driven by evolutionarily shaped autonomic commands that accompany each emotion, provide the brain with a sensory image, or ‘feeling’, that characterizes the active motivational state. Thus, you feel scared in part because your heart races and your pupils dilate as the growling bear approaches you. Conversely, it is said that quadraplegics with sensory feedback limited to the face have blunted affect [5]; and interestingly, stimulation of the vagus nerve can relieve depression [6]. If an emotion is defined as a motivation and a concurrent characteristic feeling [7], then identifying the part of the brain that provides the image of that subjective feeling (if it can indeed be pinpointed) can show us how we are aware of our selves. Of course, visceral sensation is notoriously vague, and many studies have shown huge variability in subjective awareness of inner feelings, classically Corresponding author: A.D. (Bud) Craig ([email protected]). www.sciencedirect.com referred to as ‘interoception’ [8,9]. Intravenous injections of agents that modulate visceral activity (adrenalin, vasopressin, lactate, insulin, etc.) elicited varying results. However, the heartbeat timing task used by Critchley et al.. [4] is a fairly reliable test of interoception, in terms of reproducibility and covariance with other measures of emotional self-awareness. In this test, a signal is delivered either in synchrony with each QRS wave (or oximeter pulse) or after a fixed delay. Subjects are asked to report simply whether the signal occurs in time with their heartbeat or not. With an average pulse rate of about one per second, a signal that is 500 ms late seems distinctly disparate, if one is aware of one’s pulse at all. A broader concept of interoception as ‘how you feel’ The concept of ‘interoception’ was classically restricted to visceral sensations, but recent neuroanatomical and neurophysiological results indicate that sensations related to the ongoing physiological condition of all organs of the body – muscles, joints, teeth, and skin as well as the viscera – are processed together [10]. The incoming messages are carried in small-diameter primary afferent fibers to lamina I in the spinal dorsal horn and to the solitary nucleus in the medulla (see Figure 1). These pathways represent, respectively, the afferent inputs for the sympathetic and the parasympathetic halves of the autonomic nervous system. They provide the sensory inputs to hierarchically integrative homeostatic mechanisms in the brainstem and hypothalamus that maintain the health of the body. In primates and especially humans, a phylogenetically unique thalamo-cortical extension of these pathways to the insular cortex provides a direct representation of homeostatic afferent activity that engenders the distinct bodily feelings with which we are all so familiar: pain, temperature, itch, muscle burn, visceral sensations, hunger, thirst, taste, and even sensual touch. These feelings represent ‘the material me’, and so this broader concept of interoception converges with the socalled somatic-marker hypothesis of consciousness proposed by Damasio [5]. In this proposal, the afferent sensory representation of the homeostatic condition of the body is the basis for the mental representation of the sentient self. Recursive meta-representations of homeostatic feelings allow the brain to distinguish the inner world from the outer world. Most strikingly, degrees of conscious awareness are related to successive upgrades in the Update 240 TRENDS in Cognitive Sciences Right anterior insular ACC Dorsal posterior insula Thalamus MDvc VMb VMpo Mid brain Pons Medulla NTS Lamina 1 TRENDS in Cognitive Sciences Figure 1. A summary diagram indicating the parallel ascending pathways for small-diameter afferent activity that originate in lamina I and the nucleus of the solitary tract (NTS). These pathways are relayed from the thalamus (by way of VMb and VMpo, the basal and the posterior parts of the ventral medial nucleus) to the dorsal posterior insular cortex, which engenders the interoceptive representation of the physiological condition of the body. This region in humans is rerepresented in the right (non-dominant) anterior insula, which is important for subjective awareness of feelings and emotions. (ACC, anterior cingulate cortex; MDvc, ventro-caudal portion of the medial dorsal nucleus) self-representational maps. That is, individual differences in emotional awareness are predicted to be directly related to differences in the capacity for interoceptive feelings. It is from this perspective that the results of Critchley et al. [4] have deep significance. A revealing experimental design Critchley et al. designed a Latin square using a synchronized or desynchronized heartbeat tone signal, in contrast with a series of ten similarly timed tones that either did or did not include an oddball tone (of matching perceptual difficulty). This enabled ANOVA comparisons of both the main effects of attending to the heartbeat or the auditory cue, as well as comparisons of the interactions between these variables and the timing (synchronized or desynchronized). The subjects recorded their ‘yes/no’ judgments of hearbeat synchronicity with the same finger movements during a relatively short scanning session (15 min), which minimized attention lapses. Interoceptive attention illuminated several forebrain regions, including anterior cingulate (limbic motor cortex), lateral sensorimotor www.sciencedirect.com Vol.8 No.6 June 2004 cortex (a target of visceral afferent activity [11,12]), supplementary motor cortex (involved in manual responses), and bilateral insular cortices. This pattern supports the general view that a network of inter-related forebrain regions is involved in interoceptive attention and emotional feelings [9]. The interaction between desynchronized timing and interoceptive attention also highlighted several regions (including the precuneus) but, strikingly, revealed strong activation mainly in one of the sites illuminated by interoceptive attention: rAI. This indicated a crucial role for rAI in explicit subjective awareness of the mismatched heartbeat signal, confirming previous data showing that a progression of activity to rAI and orbitofrontal cortex is essential for discriminative subjective judgments of interoceptive feelings [10,13]. Their next steps were profoundly revealing. Critchley et al. discovered that activity in rAI was strongly correlated with individual performance accuracy on the heartbeat detection task (didactically normalized by individual performance accuracy in the auditory task). Furthermore, individual anxiety and negative affect (albeit not positive affect; cf. [14]) measured during the task showed a similar correlation with rAI activity, making a firm connection with subjective emotional feeling. Next, using MRI morphometry they found that rAI and the adjacent orbitofrontal region were the only cortical sites for which physical size correlated with individual interoceptive awareness. Finally, in a separate sample, they found that rAI was the only site for which size correlated with self-rated bodily awareness. Thus, their data indicate that both the activation and the size of rAI are uniquely correlated with the subjective awareness of internal feelings of individual humans. The role of rAI in awareness These findings strongly support the composite view of the somatic-marker hypothesis [5] and the primate interoceptive pathway [10] that progressive meta-representations of homeostatic afferent activity in rAI engender the emotional feelings that characterize human sentience. The rAI is activated (selectively or in conjunction with the anterior cingulate) during many emotions, including anger, happiness, sadness, disgust, and lust, as well as by music [10]. The ancillary activation of anterior cingulate cortex is consistent with its proposed role as a behavioral agent, which interacts with rAI and subcortical homeostatic regions to form the hierarchical network representing ‘self ’ [1,5,10,15 – 17]. Although the necessary observations from lesion studies in human patients are still accumulating [18], the reports of pain asymbolia and amusia [19] subsequent to rAI damage are consistent with loss of subjective feelings (in contrast to anosognosia, in which there is loss of spatial reference rather than subjective feelings). Notably, timing disparities between multimodal stimuli also cause graded, selective activation of rAI [20]. This can be accommodated if awareness depends on a capacity for an overview of a quantal series of meta-representations of feelings across time (from the past into the future). Intriguingly, the phrase ‘time stood still’ is often used to describe moments of heightened awareness. Such a Update TRENDS in Cognitive Sciences hypothetical capacity in rAI would readily explain its association with the uniquely human faculty for music (in contrast to prosody) – the rhythmic temporal progression of emotionally laden moments. The activation of cerebellar vermis observed by Critchley et al. might be related to timing as well (or alternatively, to autonomic control). They did report a relative suppression of rAI activity during attention to the desynchronized auditory stimulus; nevertheless, the issue of timing deserves further examination. The morphometric results of Critchley et al. converge with other anatomical findings that associate rAI, orbitofrontal, and anterior cingulate cortices with human sentience [10]. For instance, a novel cell type, the socalled spindle cell, is exclusively located in these regions of the human brain [21]. Recent evidence indicates a trenchant phylogenetic correlation, in that spindle cells are most numerous in aged humans, but progressively less numerous in children, gorillas, bonobos and chimpanzees, and nonexistent in macaque monkeys [22]. Notably, this phylogenetic progression also parallels the results of the mirror test for self-awareness [23]. Evolving awareness The most important implication of this study emerges from the correlation of both activity and physical size of rAI with individual subjective awareness. This implies that individual differences in subjective interoceptive awareness, and by extension emotional depth and complexity, might be expressed in the degree of expansion of rAI and adjacent orbitofrontal cortices. This clearly resembles the relationship between the size of auditory and motor cortices and the pitch and performance ability of musicians, which is partly innate and partly the result of training [24]. A morphological correlation also exists between alexithymia and right anterior cingulate [25]. The rapid development of rAI within a brief evolutionary timescale suggests that nested interoceptive re-representations could be directly related to the advantages of advanced social interaction. The extent to which functional imaging and morphometry, together with other measures of emotional significance such as galvanic skin resistance and heart rate variability, can be related to higher social emotions (such as guilt, empathy, exclusion; e.g. [26]) should receive much more intense study following the objective structural correlation revealed by the work of Critchley et al. Note added in proof: A group in the same laboratory have just reported imaging and morphometric evidence relating rAI and anterior cingulate to empathic pain, a landmark result indicating that the neural basis for subjective feelings also provides the means for awareness of the feelings of others [27]. www.sciencedirect.com Vol.8 No.6 June 2004 241 Acknowledgements I am very grateful to several colleagues for sharing their comments on this manuscript. References 1 Critchley, H.D. et al. (2001) Neuroanatomical basis for first- and second-order representations of bodily states. Nat. Neurosci. 4, 207 – 212 2 Critchley, H.D. et al. (2002) Volitional control of autonomic arousal: a functional magnetic resonance study. Neuroimage 16, 909 – 919 3 Dolan, R.J. (2002) Emotion, cognition, and behavior. Science 298, 1191 4 Critchley, H.D. et al. (2004) Neural systems supporting interoceptive awareness. Nat. Neurosci. 7, 189 – 195 5 Damasio, A.R. 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