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Reflective Self-Awareness and Conscious States: PET Evidence for a Common Midline Parietofrontal Core
NeuroImage 17, 1080 –1086 (2002) doi:10.1006/nimg.2002.1230
RAPID COMMUNICATION Reflective Self-Awareness and Conscious States: PET Evidence for a Common Midline Parietofrontal Core Troels W. Kjaer,* ,1 Markus Nowak,† ,2 and Hans C. Lou* ,3 *John F. Kennedy Institute, DK-2600 Glostrup, Denmark; and †PET and Cyclotron Unit, Rigshospitalet University Hospital, DK-2100 Denmark Received January 17, 2002
A recent meta-analysis has shown precuneus, angular gyri, anterior cingulate gyri, and adjacent structures to be highly metabolically active in support of resting consciousness. We hypothesize that these regions constitute a functional network of reflective self-awareness thought to be a core function of consciousness. Seven normal volunteers were asked to think intensely on how they would describe the personality traits and physical appearance of themselves and a neutral reference person known to all the subjects (the Danish Queen). During each of the four conditions cerebral blood flow distribution was measured by the intravenous H 2 15O PET scanning technique. During scanning, no sensory or motor activity was intended. After each scan, the subjects reported the contents of their thoughts during the scan to ascertain that the instructions had been followed. The results confirmed our hypothesis: Statistical parametric mapping showed differential activity in precuneus and angular gyri during reflection on own personality traits and in anterior cingulate gyri during reflection on own physical traits. Connectivity analysis of synchrony showed these regions to be functionally connected during reflective self-awareness. The commonality between the neural networks of the resting conscious state and self-awareness reflects the phenomenological concept of a fundamental contribution of reflective self-awareness to the contents and coherence of the conscious state. © 2002 Elsevier Science (USA)
INTRODUCTION We have previously presented evidence for a parietofrontal core in two relaxed conscious states: normal 1 Present address: Department of Clinical Neurophysiology, NF3063, Rigshospitalet University Hospital, DK-2100 Denmark. 2 Present address: Department of Clinical Physiology, Bispebjerg Hospital, DK-2400 Copenhagen, Denmark. 3 Present address: PET-Center, Aarhus University Hospital, DK8000 Aarhus, Denmark.
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resting consciousness and the relaxation meditation in Yoga Nidra. This evidence was obtained by principal component analysis of the contribution of cerebral regions to the neural activity pattern of the two states, identifying precuneus and frontopolar regions as the major contributors to both states (Lou et al., 1999, Kjaer and Lou, 2000). It was hypothesized that the joint activities of these regions were contributing to the unity of consciousness by ensuring a continuing activity of high-level posterior association regions in interaction with anterior prefrontal regions. Subsequently, Mazoyer et al., (2001) and Raichle et al., (2001) have drawn attention to the high activity of these medial parietal and prefrontal regions in the resting conscious states, apparent from meta-analysis of a great number of investigations. Of these regions, the precuneus has repeatedly been shown to be active in retrieval of episodic memory, the content of which has varied from study to study (Andreasen et al., 1995; Krause et al., 1999; Kircher et al., 1999). Explicit studies of the activity of precuneus and lateral parietal regions in self-referential agency have more recently been performed by Ruby and Decety (2001) and Vogeley et al. (2001). The former demonstrated precuneus activation in both first and third person perspectives utilizing various pronouns. The latter employed thinking of first person activities in a number of short stories. Here the activation of precuneus was, however, modest in comparison with a number of coactivated regions, including the anterior cingulate gyrus. Thus, there are indications of a role for precuneus in the notion of the self. The same is true for anterior cingulate gyrus with adjacent structures, which repeatedly has been implicated to be activated by voluntary action and self-regulation (Frith et al., 1991; Posner and Rothbart, 1998). From a phenomenological perspective, the prevailing concept is that reflective self-awareness rather than just agency is the common denominator of conscious experience (Tart, 1994). We
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therefore hypothesize that reflective self-awareness and conscious states have a common neural foundation, which includes the precuneus, the angular gyri, and the anterior cingulate gyrus. Hence, according to the hypothesis, the precuneus, the angular gyri, and the anterior cingulate cortex constitute a core of reflective self-awareness, ensuring the unity of conscious experience. We here present PET evidence for such a complementary dichotomy of the neural foundation of reflective self-awareness and show that it is identical to the core of conscious states described above. MATERIALS AND METHODS To test whether precuneus and prefrontal cortex are active in reflective self-awareness we performed H 2 15O PET scans in four conditions, differing by the subject of reflection only: (1) Reflection on one’s own personality traits (2) Reflection on one’s own physical appearance (3) Reflection on the personality traits of the Danish Queen (4) Reflection on the physical appearance of the Danish Queen The Danish Queen was chosen as a neutral third person control, since all our subjects were likely to know of her physical appearance and personality traits, while on the other hand having no first person relation to her and no strong feelings about her. Seven normal healthy volunteers (five males, age range 22–27 years, median 24 years) were scanned three times in each of the four conditions. The order was counterbalanced. Participants performed each reflection task for 2 min, starting 15–25 s before the tracer reached cerebral circulation. During the scans, there were no intended stimuli (subdued light, eye pads, earplugs, etc.) nor any intended motor responses (silent reflections). After cessation of each scan, participants gave an oral report on their thoughts in a free format interview, which was taped. Thus, sensory input and motor activity were minimized during the scans. PET scans were carried out with subjects in supine position using an Advance PET scanner (GE, Milwau-
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kee, WI) operating in 3D mode with collimating septa retracted, producing 35 image slices with a distance of 4.25 mm. The total axial field of view was 15 cm with an approximate in-plane resolution of 5 mm; each subject had an initial 10-min transmission scan followed by 12 intravenous injections of 300 MBq of H 2 15O (Holm et al., 1996). The tracer was administered by an automatic water injection system via the left brachial vein over 30 s followed by 10 ml of isotonic saline for flushing. Data acquisition was triggered by total count rate buildup and began about 40 s after injection start and lasting for 90 s. There was an interval of at least 10 min between repeated emission scans to allow for isotope decay. The subject’s eyes were covered with pads to prevent visual stimulation and to minimize eye movement. The examination room was quiet, with subdued light. Earphones were plugged into both ears. The data were analyzed using SPM99 (Frackowiak et al., 1997). All scans of each subject were realigned, coregistered to individual MRIs, and subsequently projected into a standard stereotactic three-dimensional space. The spatially normalized images of all subjects were smoothed with an isotropic Gaussian filter (full width half-maximum 13 mm). For detection of activated areas, Z scores were calculated comparing the first person and the third person reflections concerning personality traits and physical appearance (Friston et al., 1991). Results from this analysis, namely the spatial extent of the structures identified as the precuneus and the anterior cingulate gyrus, were used to extract average rCBF values from the two respective regions. Thus, a functional definition of the precuneus and the anterior cingulate was used. Then, a second SPM analysis was performed. Here, the above-mentioned rCBF values were used as a covariate in a “covariate-only” analysis to reveal other areas in the brain with similar rCBF responses during the first person perspective. The analysis was based on the responses in the precuneus and the anterior cingulate during the first person perspective, i.e., in the physical appearance and personality traits conditions, as this is the core of our frontalparietal connectivity hypothesis.
TABLE 1 Examples of Comments I am extrovert and talkative, while on the other hand I have sides only my friends know. I am rather loving to my girl friends and my family and that like. And considerate—on the other hand I can be quite cold sometimes. She seems open and forthcoming. She seems like a person with authority—a good representative of Denmark. She appears to be a queen we can be proud of. She is creative and interested in art and in meeting people. I have dark hair and brown eyes. And a quite large nose and big ears. I thought about my lips and how my body is shaped. . . . Er . . . and then there is my belly . . . I have relatively large hands. I thought she must be long-haired even though you never really see it. The hair is always tied in a knot. She has a rather long neck, and a long face, and normal ears.
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TABLE 2 (A) rCBF Clusters Which Differ during Reflections on Own Personality Traits vs Control More active
Less active
Z score
x
y
z
Region
Z score
x
y
z
Region
4.62 4.27 4.13 3.78 3.69 3.49
0 ⫺54 22 ⫺26 56 0
⫺56 ⫺36 28 46 ⫺36 ⫺14
56 32 28 ⫺14 44 76
Precuneus (7)* Inf parietal lobe (40)* Sup front gyr (8)* Middle front gyr (11)* Inf par lobe (40)* Suppl motor area (6)*
4.02 3.77 3.68 3.66 3.60 3.58 3.53 3.49 3.36 3.29
50 26 38 28 ⫺16 ⫺30 2 28 64 38
⫺64 ⫺58 ⫺20 ⫺36 ⫺76 8 ⫺72 ⫺16 ⫺4 20
⫺20 ⫺14 ⫺34 ⫺24 ⫺30 ⫺28 2 74 ⫺20 ⫺30
Cerebellar lobe Cerebellar lobe Fusiform gyr (20) Fusiform gyr (20) Cerebellar lobe Sup temp gyr (36) Ling gyr (18) Front sup gyr (4) Middle temp gyr (21) Fusiform gyr (47)
(B) rCBF Clusters Which Differ during Reflections on Own Physical Appearance vs Control More active
Less active
Z score
x
y
z
Region
Z score
x
y
z
Region
3.86 3.65 3.64 3.49 3.47 3.33
10 2 ⫺22 14 ⫺38 ⫺14
⫺50 42 22 22 32 60
⫺24 12 ⫺16 34 4 4
Cerebellar lobe Ant cing gyr (32)* Middle front gyr (11)* Ant cing gyr (31)* Inf front gyr (45–47)* Sup front gyr (10)*
4.28 4.00 3.46
38 38 22
⫺20 ⫺84 ⫺30
⫺24 38 16
Fusiform gyr (20) Sup occ gyr (19) Sup temp gyr (42)
Note. Coordinates from the Talairach and Tournoux (1988) atlas. Positive values refer to regions to the right of (x), anterior to (y), and superior to (z) the anterior commissure. Numbers in parentheses refer to the Brodmann areas. Clusters with Z-score peaks ⬎3.09 were included (corresponding to P ⬍ 0.001 uncorr.). Only the highest peak is included in the case of several confluent peaks. Regions expected to be active based on the hypothesis are labeled with an asterisk.
RESULTS Before each PET scan, subjects were assigned one of the four tasks mentioned above. After each scan, subjects gave an oral report in free format about their thoughts. Examples are given in Table 1. The results generally confirmed our hypothesis. Reflection on personality traits of oneself showed preferential activity in the precuneus, bilateral temporoparietal regions, and left orbitofrontal cortex, compared to reflections on the neutral third person, the Danish Queen (Table 2A, Fig. 1A). Reflection on the physical appearance of oneself mainly activated the anterior cingulate gyrus, compared to reflections on the neutral third person (Table 2B, Fig. 1B). The reported Z scores are significant without correction for multiple comparisons. The majority of the identified clusters were predicted by the hypothesis (marked with an asterisk in
Table 2). On the other hand, none of the identified clusters in the control comparison (“less active” in Table 2) were in the hypothesized brain region. The major parietal and frontal regions identified by the activation analysis, i.e., the precuneus and the anterior cingulate gyrus, were used as the explaining variables for the covariate analysis (Table 3). Crosscorrelation to whole brain produced the maps presented in Figs. 2 and 3. The data are presented as Z scores. It is seen that precuneus and angular gyrus (posterior and anterior frontal regions) are functionally connected just as predicted. DISCUSSION We here present the novel hypothesis that the neural correlate of reflective self-awareness is similar to the distribution of high metabolic activity in resting con-
FIG. 1. (A) rCBF pattern of reflection on own personality traits vs those of control person, with differential activity mainly in precuneus and bilateral temporoparietal regions. (B) rCBF pattern of reflection on own physical appearance vs that of control person, with differential activity mainly in anterior cingulate gyrus. FIG. 2. Functional connectivity from precuneus to the whole brain during self-reflection. Mainly temporoparietal regions are functionally connected to the precuneus. FIG. 3. Functional connectivity from anterior cingulate gyrus to the whole brain during self-reflection. Mainly adjacent frontal regions and precuneus are functionally connected to the anterior cingulate gyrus.
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TABLE 3 (A) rCBF Clusters Functionally Connected to the Precuneus during Self-Reflection Z score
x
y
z
Region
7.14 4.58 4.58 3.96 3.80 3.68 3.63 3.62 3.59 3.51 3.38
2 ⫺46 60 54 ⫺30 ⫺56 48 ⫺58 36 20 ⫺52
⫺54 ⫺58 ⫺30 ⫺44 ⫺42 ⫺32 ⫺46 ⫺34 0 0 ⫺58
54 12 8 32 ⫺46 ⫺24 ⫺36 30 40 62 ⫺18
Precuneus (7)* Middle temp gyr (37)* Sup temp gyr (22)* Inf par lobe (40)* Cerebellar lobe Inf temp gyr (20) Cerebellar lobe Inf par lobe (40)* Middle front gyr (6) Sup front gyr (6) Inf temp gyr (37)
(B) rCBF Clusters Functionally Connected to the Anterior Cingulate Gyrus during Self-Reflection Z score
x
y
z
Region
6.06 4.14 3.87 3.57 3.50
2 34 ⫺4 ⫺6 ⫺28
42 ⫺40 ⫺52 ⫺34 ⫺38
10 ⫺30 52 ⫺32 ⫺42
Ant cing gyr (32)* Cerebellar lobe Precuneus (7)* Brain stem Cerebellar lobe
Note. Organization similar to that of Table 2. Regions expected to be active based on the hypothesis are labeled with an asterisk.
sciousness, reflecting a fundamental role for selfawareness in the unity of conscious experience. A few years ago, we first presented the idea that precuneus and prefrontal cortex constituted a unifying core of resting conscious state: A “self” (Kjaer and Lou, 2000). A detailed meta-analysis of baseline activity of the brain led Gusnard and Raichle (2001) recently to propose a similar function. We here show, for the first time, that the activity pattern of reflective self-awareness is indistinguishable from the metabolically highly active structures thought to constitute the baseline of conscious states. We also show that this pattern is formed of interconnected structures mainly in the medial parts of posterior and anterior brain. There was no right-hemisphere bias such as was seen in self face recognition (Keenan et al., 1999). As absolute flow was not measured, we cannot be certain whether the difference in activation pattern between self-referential thought and the resting conscious state constituted an actual increase or a less pronounced decrease from rest. The similarity between active self-reference and the resting state patterns is, however, an indication of the phenomenological concept of a core of self-awareness in the resting state, ensuring its unity by functionally integrating posterior and anterior brain. Conscious experiences have often been ascribed to the executive regions of the frontal lobe, especially prefrontal areas, and the cingulate gyrus, while the more posterior sensory regions have been suggested to
be a mere supplier of information to be processed consciously (Mazoyer et al., 2001; Quintana and Fuster, 1999). The executive and sensory regions have very distinct functions at the level of the primary cortices, but they get more functionally integrated at the level of association cortices. The concept behind our work has been that consciousness is complementary, being a function of sensory as well as executive integrative areas. One may conceive it as a summit between anterior and posterior brain. In a previously published study, we identified regions activated and deactivated by meditation compared to resting normal consciousness (Lou et al., 1999) and did a subsequent principal component analysis showing that anterior midline prefrontal cortex and precuneus contributed to both (Kjaer and Lou, 2000). As self-awareness is part of the phenomenology of both states as judged by self-report (Kjaer et al., 2002) and is accompanied by activation of these high-level integrative regions of anterior and posterior brain, their interaction in self-awareness may now be considered to be a core in consciousness. The anatomical connections between the lateral parietal region and frontal cortex are well described. Petrides and Pandya (1984) used autoradiography to demonstrate abundant single-cell connections between precuneus and other regions of the posterior parietal lobe on one hand and frontal areas on the other (Jacobsen and Troganowski, 1977). In contrast, anatomic connections between the medial aspects of posterior and anterior brain have not been studied extensively. However, PET and MR studies have shown functional connectivity between these regions (Schmidt et al., 2002; Krause et al., 1999) during integration of temporal and spatial information and during retrieval of episodic memory. Their functional connectivity was also illustrated in the present work by the syncrony between anterior cingulate gyrus and precuneus. These regions are also involved in executive functions (Quintana and Fuster, 1999). In tasks requiring selection of movement, strong activation was seen, particularly and invariably in the precuneus, but also in the premotor and supplementary motor and in the superior parietal association cortices (Tulving, 1987). Complex sequential finger movements were found to be accompanied by a proportional increase in rCBF in the right dorsal premotor cortex and the right precuneus (Sadato et al., 1996), again demonstrating the close relationship between the frontal cortex and the precuneus in goal-directed action. The activation of the anterior cingulate gyrus during physical self-awareness illustrates that this function is closely related to volition and self-regulation, which all are attributed to the anterior cingulate gyrus (Frith et al., 1991; Posner and Rothbart, 1998). This close sensory–motor interaction may be the foundation for the predictive mechanism in motor control (Blakemore et al., 2000).
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Lesion data specifically concerning the precuneus are not available, but in frontal lobe lesions, a number of syndromes have been described. Of particular importance in the present context are the deficits in both sensory and motor attention and deficiency in perceiving the spatial relationship between the self and the environment. One striking finding in some frontally damaged patients is an apparent decrease in normal self-awareness and, consequently, impaired self-regulation (Stuss and Benson, 1986). Sarazin and colleagues (1998) compared the cognitive and behavioral functions of patients with frontal lesions to the local levels of glucose utilization determined by the 18FDG PET method. They found cognitive functions to be disturbed in hypometabolism of the dorsolateral frontal cortex and behavioral and social skills in ventromedial frontal cortex. Pertinent to the present findings is their demonstration of an association between hypometabolism of the anterior pole (area 10) and global frontal dysfunction, confirming recent activation studies of a coordinated role of all prefrontal functions for this region. These anatomical studies and task-elicited activations have been complemented by the examination of cerebral activity patterns during states of consciousness, such as diverse sleep states, and our own study of the meditative state vs normal consciousness. The sleep states are, like meditation and normal consciousness, characterized by distinct behavioral and electroencephalographic patterns (Rechtschaffen et al., 1966). One characteristic common to the sleep stages is reduced reflective self-awareness (Kahan et al., 1997; Hobson et al., 1998). In REM sleep, rCBF is reduced in precuneus and dorsolateral prefrontal, parietal, and posterior cingulate cortices (Braun et al., 1998). In deep sleep, or slow-wave sleep, a disproportionate flow reduction is seen in precuneus, orbital frontal cortex, basal forebrain, anterior cingulate cortex, basal ganglia, thalami, and dorsal pons (Marquet et al., 1997). Thus, reduction in activity in the precuneus is common to the two sleep stages as predicted if they were instrumental in consciousness of the self in its environment. A more recent study of rCBF during rest and three different depths of anesthesia induced by propofol detected activity changes similar to what has been found during voluntary loss of consciousness (Fiset et al., 1999). In addition to a decrease in global cerebral blood flow, they identified predominantly right-sided regional flow decrements in thalamus, precuneus/cuneus, and frontal cortical regions. These results support a specific hypothesis that anesthetics induce behavioral changes via an effect on specific neuronal networks. The finding supports our concept of a general perception–action cycle in the conscious resting brain, independent of motor activity, involving highlevel integrative cortical regions in anterior and posterior brain.
The ultimate state of conscious incapacity—the vegetative state— has been investigated assessing regional cerebral metabolism using fluorodeoxyglucose positron emission tomography (Laureys et al., 1999). Also, this study identified impaired function of frontal and parietotemporal association areas, including the precuneus. In the present study, we have noted that not only telencephalic structures but also cerebellum seem to be differentially active in reflective self-awareness. Not being included in our initial hypothesis, definitive conclusions on this point was not obtained. It would have required statistical confirmation, corrected for multiple comparisons, and the cerebellum did not pass this test (in fact, of the regions studied here only precuneus did, with a P value of 0.05, corrected for multiple comparisons). In conclusion, we have here demonstrated, for the first time, a midline network of posterior and anterior brain linking self-awareness and conscious experience. ACKNOWLEDGMENTS We are grateful to chief psychologist Anders Gade for discussions on how to design the experimental paradigm. The staff at the PET Center at Rigshospitalet, Copenhagen, is acknowledged for participation. The work is supported by the Lundbeck Foundation. Furthermore, The John and Birthe Meyer Foundation is acknowledged for the donation of the Cyclotron and PET scanner.
REFERENCES Andreasen, N. C., O’Leary, D. S., Cizadlo, T., Arndt, S., Rezai, K., Watkins, G. L., Ponto, L. L., and Hichwa, R. D. 1995. Remembering the past: Two facets of episodic memory explored with positron emission tomography. Am. J. Psychiatry 152: 1576 –1585. Blakemore, S. J., Wolpert, D., and Frith, C. 2000. Why can’t you tickle yourself? NeuroReport 11: R11–16. Braun, A. R., Balkin, T. J., Wesensten, N. J., Gwadry, F., Carson, R. E., Varga, M., et al. 1998. Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep. Science 279: 91–95. Fiset, P., Paus, T., Daloze, T., Plourde, G., Meuret, P., Bonhomme, V., et al. 1999. Brain mechanisms of propofol-induced loss of consciousness in humans: A positron emission tomographic study. J. Neurosci. 19: 5506 –5513. Frackowiak, R. S. J., Friston, K. J., Frith, C. D., Dolan, R. J., and Mazziotta, J. C., Eds. 1997. Human Brain Function. Academic Press, San Diego. Friston, K. J., Frith, C. D., Liddle, P. F., and Frackowiak, R. S. J. 1991. Comparing functional (PET) images: The assessment of significant change. J. Cereb. Blood Flow Metab. 11: 690 – 699. Frith, C. D., Friston, K. J., Liddle, P. F., and Frackowiack, R. S. J. 1991. Willed action and the prefrontal cortex in man: A study with PET. Proc. R. Soc. London B 244: 241–246. Gusnard, D. A., and Raichle, M. E. 2001. Searching for a baseline: Functional imaging and the resting human brain. Nat. Rev. Neurosci. 2: 685– 694. Hobson, J. A., Stickgold, R., and Pace-Schott, E. F. 1998. The neuropsychology of REM sleep dreaming. NeuroReport 9: R1–14.
1086
RAPID COMMUNICATION
Holm, S., Law, I., and Paulson, O. B. 1996. 3D PET activation studies with an H 2 15O bolus injection. In Quantification of Brain Function Using PET. (M. Rea, Ed.), pp. 93–97. Academic Press, San Diego. Jacobsen, S., and Troganowski, J. Q. 1977. Prefrontal granular cortex of the rhesus monkey. Brain Res. 132: 209 –233. Kahan, T. L., La Berge, S., Levitan, L., and Zimbardo, P. 1997. Similarities and differences between dreaming and waking cognition: An exploratory study. Consciousness Cognit. 6: 132–147. Keenan, J. P., McCutcheon, B., Freund, S., Gallup, G. G., Jr., Sanders, G., and Pascual-Leone, A. 1999. Left hand advantage in a self-face recognition task. Neuropsychologia 37: 1421–1425. Kircher, T. T., Senior, C., Phillips, M. L., Benson, P. J., Bullmore, E. T., Brammer, M., Simmons, A., Williams, S. C., Bartels, M., and David, A. S. 2000. Toward a functional neuroanatomy of self processing: Effects of faces and words. Cognit. Brain Res. 10: 133–144. Kjaer, T. W., and Lou, H. C. 2000. Interaction between precuneus and dorsolateral prefrontal cortex may play a unitary role in consciousness. A principal component analysis of rCBF. Consciousness Cognit. 9: S59. Kjaer, T. W., Bertelsen, C., Piccini, P., Brooks, D., Alving, J., and Lou, H. C. 2002. Increased dopamine tone during meditationinduced change of consciousness. Cognit. Brain Res. 13: 255–259. Krause, B. J., Horwitz, B., Taylor, J. G., Schmidt, D., Mottaghy, F. M., Herzog, H., Halsband, U., and Mu¨ ller-Ga¨ rtner, H.-W. 1999. Network analysis in episodic encoding and retrieval of word-pair associates: A PET study. Eur. J. Neurosci. 11: 3293–3301. Laureys, S., Goldman, S., Phillips, C., Van Bogaert, P., Aerts, J., Luxen, A., et al., 1999. Impaired effective cortical connectivity in vegetative state: Preliminary investigation using PET. NeuroImage 9: 377–382. Lou, H. C., Kjaer, T. W., Friberg, L., Wildschiodtz, G., Holm, S., and Nowak, M. 1999. A 15O-H 2O PET study of meditation and the resting state of normal consciousness. Hum. Brain Mapping 7: 98 –105. Marquet, P., Degueldre, C., Aerts, J., Peters, J.-M., Luxen, A., and Franck, G. 1997. Functional neuroanatomy of human slow wave sleep. J. Neurosci. 17: 2807–2812. Mazoyer, B., Zago, L., Mellet, E., Bricogne, S., Etard, O., Houde, O., Crivello, F., Joliot, M., Petit, L., and Tzourio-Mazoyer, N. 2001. Cortical networks for working memory and executive functions sustain the conscious resting state in man. Brain Res. Bull. 54: 287–298.
Petrides, M., and Pandya, D. N. 1984. Projections to the frontal cortex from the posterior parietal region in the rhesus monkey. J. Comp. Neurol. 228: 105–116. Posner, M. I., and Rothbart, M. K. 1998. Attention, self-regulation and consciousness. Philos. Trans. R. Soc. London B. Biol. Sci. 353: 1915–1927. Quintana, J., and Fuster, J. M. 1999. From perception to action: Temporal integrative functions of prefrontal and parietal neurons. Cereb. Cortex. 9: 213–221. Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., Shulman, G. L. 2001. A default mode of brain function. Proc. Natl. Acad. Sci. USA 98: 676 – 682. Rechtschaffen, A., Hauri, P., and Zeitlin, M. 1966. Auditory awakening thresholds in REM and NREM sleep stages. Percept. Mot. Skills 22: 927–942. Ruby, P., and Decety, J. 2001. Effect of subjective perspective taking during simulation of action: A PET investigation of agency. Nat. Neurosci. 4: 546 –550. Sadato, N., Campbell, G., Ibanez, V., Deiber, M., and Hallett, M. 1996. Complexity affects regional cerebral blood flow change during sequential finger movements. J. Neurosci. 16: 2691–2700. Sarazin, M., Pillon, B., Giannakopoulos, P., Rancurel, G., Sanison, Y., and Dubois, B. 1998. Clinico metabolic dissociation of cognitive functions and social behavior in frontal lobe lesions. Neurology 51: 142–148. Schmidt, D., Krause, B. J., Mottaghy, F. M., Halsband, U., Herzog, H., Tellmann, L., and Mu¨ ller-Ga¨ rtner, H.-W.2002. Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities. Neuropsychologia 20: 457– 470. Stuss, D. T., and Benson, D. F. 1986. The frontal lobes. In The Frontal Lobes, pp. 246 –247. Raven Press, New York. Talairach, J., and Tournoux, P. 1988. Co-planar Stereotaxic Atlas of the Human Brain. Thieme, New York. Tart, C. T. 1994. Living the Mindful Life. Shambhala, Boston. Tulving, E. 1987. Elements of Episodic Memory. Oxford Univ. Press, Oxford. Vogeley, K., Bussfeld, P., Newen, A., Herrmann, S., Happe´ , F., Falkai, P., Maier, W., Shah, N. J., Fink, G. R., and Zilles, K. 2001. Mind reading: Neural mechanisms of theory of mind and selfperspective. NeuroImage 14: 170 –181.
RAPID COMMUNICATION Reflective Self-Awareness and Conscious States: PET Evidence for a Common Midline Parietofrontal Core Troels W. Kjaer,* ,1 Markus Nowak,† ,2 and Hans C. Lou* ,3 *John F. Kennedy Institute, DK-2600 Glostrup, Denmark; and †PET and Cyclotron Unit, Rigshospitalet University Hospital, DK-2100 Denmark Received January 17, 2002
A recent meta-analysis has shown precuneus, angular gyri, anterior cingulate gyri, and adjacent structures to be highly metabolically active in support of resting consciousness. We hypothesize that these regions constitute a functional network of reflective self-awareness thought to be a core function of consciousness. Seven normal volunteers were asked to think intensely on how they would describe the personality traits and physical appearance of themselves and a neutral reference person known to all the subjects (the Danish Queen). During each of the four conditions cerebral blood flow distribution was measured by the intravenous H 2 15O PET scanning technique. During scanning, no sensory or motor activity was intended. After each scan, the subjects reported the contents of their thoughts during the scan to ascertain that the instructions had been followed. The results confirmed our hypothesis: Statistical parametric mapping showed differential activity in precuneus and angular gyri during reflection on own personality traits and in anterior cingulate gyri during reflection on own physical traits. Connectivity analysis of synchrony showed these regions to be functionally connected during reflective self-awareness. The commonality between the neural networks of the resting conscious state and self-awareness reflects the phenomenological concept of a fundamental contribution of reflective self-awareness to the contents and coherence of the conscious state. © 2002 Elsevier Science (USA)
INTRODUCTION We have previously presented evidence for a parietofrontal core in two relaxed conscious states: normal 1 Present address: Department of Clinical Neurophysiology, NF3063, Rigshospitalet University Hospital, DK-2100 Denmark. 2 Present address: Department of Clinical Physiology, Bispebjerg Hospital, DK-2400 Copenhagen, Denmark. 3 Present address: PET-Center, Aarhus University Hospital, DK8000 Aarhus, Denmark.
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resting consciousness and the relaxation meditation in Yoga Nidra. This evidence was obtained by principal component analysis of the contribution of cerebral regions to the neural activity pattern of the two states, identifying precuneus and frontopolar regions as the major contributors to both states (Lou et al., 1999, Kjaer and Lou, 2000). It was hypothesized that the joint activities of these regions were contributing to the unity of consciousness by ensuring a continuing activity of high-level posterior association regions in interaction with anterior prefrontal regions. Subsequently, Mazoyer et al., (2001) and Raichle et al., (2001) have drawn attention to the high activity of these medial parietal and prefrontal regions in the resting conscious states, apparent from meta-analysis of a great number of investigations. Of these regions, the precuneus has repeatedly been shown to be active in retrieval of episodic memory, the content of which has varied from study to study (Andreasen et al., 1995; Krause et al., 1999; Kircher et al., 1999). Explicit studies of the activity of precuneus and lateral parietal regions in self-referential agency have more recently been performed by Ruby and Decety (2001) and Vogeley et al. (2001). The former demonstrated precuneus activation in both first and third person perspectives utilizing various pronouns. The latter employed thinking of first person activities in a number of short stories. Here the activation of precuneus was, however, modest in comparison with a number of coactivated regions, including the anterior cingulate gyrus. Thus, there are indications of a role for precuneus in the notion of the self. The same is true for anterior cingulate gyrus with adjacent structures, which repeatedly has been implicated to be activated by voluntary action and self-regulation (Frith et al., 1991; Posner and Rothbart, 1998). From a phenomenological perspective, the prevailing concept is that reflective self-awareness rather than just agency is the common denominator of conscious experience (Tart, 1994). We
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therefore hypothesize that reflective self-awareness and conscious states have a common neural foundation, which includes the precuneus, the angular gyri, and the anterior cingulate gyrus. Hence, according to the hypothesis, the precuneus, the angular gyri, and the anterior cingulate cortex constitute a core of reflective self-awareness, ensuring the unity of conscious experience. We here present PET evidence for such a complementary dichotomy of the neural foundation of reflective self-awareness and show that it is identical to the core of conscious states described above. MATERIALS AND METHODS To test whether precuneus and prefrontal cortex are active in reflective self-awareness we performed H 2 15O PET scans in four conditions, differing by the subject of reflection only: (1) Reflection on one’s own personality traits (2) Reflection on one’s own physical appearance (3) Reflection on the personality traits of the Danish Queen (4) Reflection on the physical appearance of the Danish Queen The Danish Queen was chosen as a neutral third person control, since all our subjects were likely to know of her physical appearance and personality traits, while on the other hand having no first person relation to her and no strong feelings about her. Seven normal healthy volunteers (five males, age range 22–27 years, median 24 years) were scanned three times in each of the four conditions. The order was counterbalanced. Participants performed each reflection task for 2 min, starting 15–25 s before the tracer reached cerebral circulation. During the scans, there were no intended stimuli (subdued light, eye pads, earplugs, etc.) nor any intended motor responses (silent reflections). After cessation of each scan, participants gave an oral report on their thoughts in a free format interview, which was taped. Thus, sensory input and motor activity were minimized during the scans. PET scans were carried out with subjects in supine position using an Advance PET scanner (GE, Milwau-
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kee, WI) operating in 3D mode with collimating septa retracted, producing 35 image slices with a distance of 4.25 mm. The total axial field of view was 15 cm with an approximate in-plane resolution of 5 mm; each subject had an initial 10-min transmission scan followed by 12 intravenous injections of 300 MBq of H 2 15O (Holm et al., 1996). The tracer was administered by an automatic water injection system via the left brachial vein over 30 s followed by 10 ml of isotonic saline for flushing. Data acquisition was triggered by total count rate buildup and began about 40 s after injection start and lasting for 90 s. There was an interval of at least 10 min between repeated emission scans to allow for isotope decay. The subject’s eyes were covered with pads to prevent visual stimulation and to minimize eye movement. The examination room was quiet, with subdued light. Earphones were plugged into both ears. The data were analyzed using SPM99 (Frackowiak et al., 1997). All scans of each subject were realigned, coregistered to individual MRIs, and subsequently projected into a standard stereotactic three-dimensional space. The spatially normalized images of all subjects were smoothed with an isotropic Gaussian filter (full width half-maximum 13 mm). For detection of activated areas, Z scores were calculated comparing the first person and the third person reflections concerning personality traits and physical appearance (Friston et al., 1991). Results from this analysis, namely the spatial extent of the structures identified as the precuneus and the anterior cingulate gyrus, were used to extract average rCBF values from the two respective regions. Thus, a functional definition of the precuneus and the anterior cingulate was used. Then, a second SPM analysis was performed. Here, the above-mentioned rCBF values were used as a covariate in a “covariate-only” analysis to reveal other areas in the brain with similar rCBF responses during the first person perspective. The analysis was based on the responses in the precuneus and the anterior cingulate during the first person perspective, i.e., in the physical appearance and personality traits conditions, as this is the core of our frontalparietal connectivity hypothesis.
TABLE 1 Examples of Comments I am extrovert and talkative, while on the other hand I have sides only my friends know. I am rather loving to my girl friends and my family and that like. And considerate—on the other hand I can be quite cold sometimes. She seems open and forthcoming. She seems like a person with authority—a good representative of Denmark. She appears to be a queen we can be proud of. She is creative and interested in art and in meeting people. I have dark hair and brown eyes. And a quite large nose and big ears. I thought about my lips and how my body is shaped. . . . Er . . . and then there is my belly . . . I have relatively large hands. I thought she must be long-haired even though you never really see it. The hair is always tied in a knot. She has a rather long neck, and a long face, and normal ears.
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TABLE 2 (A) rCBF Clusters Which Differ during Reflections on Own Personality Traits vs Control More active
Less active
Z score
x
y
z
Region
Z score
x
y
z
Region
4.62 4.27 4.13 3.78 3.69 3.49
0 ⫺54 22 ⫺26 56 0
⫺56 ⫺36 28 46 ⫺36 ⫺14
56 32 28 ⫺14 44 76
Precuneus (7)* Inf parietal lobe (40)* Sup front gyr (8)* Middle front gyr (11)* Inf par lobe (40)* Suppl motor area (6)*
4.02 3.77 3.68 3.66 3.60 3.58 3.53 3.49 3.36 3.29
50 26 38 28 ⫺16 ⫺30 2 28 64 38
⫺64 ⫺58 ⫺20 ⫺36 ⫺76 8 ⫺72 ⫺16 ⫺4 20
⫺20 ⫺14 ⫺34 ⫺24 ⫺30 ⫺28 2 74 ⫺20 ⫺30
Cerebellar lobe Cerebellar lobe Fusiform gyr (20) Fusiform gyr (20) Cerebellar lobe Sup temp gyr (36) Ling gyr (18) Front sup gyr (4) Middle temp gyr (21) Fusiform gyr (47)
(B) rCBF Clusters Which Differ during Reflections on Own Physical Appearance vs Control More active
Less active
Z score
x
y
z
Region
Z score
x
y
z
Region
3.86 3.65 3.64 3.49 3.47 3.33
10 2 ⫺22 14 ⫺38 ⫺14
⫺50 42 22 22 32 60
⫺24 12 ⫺16 34 4 4
Cerebellar lobe Ant cing gyr (32)* Middle front gyr (11)* Ant cing gyr (31)* Inf front gyr (45–47)* Sup front gyr (10)*
4.28 4.00 3.46
38 38 22
⫺20 ⫺84 ⫺30
⫺24 38 16
Fusiform gyr (20) Sup occ gyr (19) Sup temp gyr (42)
Note. Coordinates from the Talairach and Tournoux (1988) atlas. Positive values refer to regions to the right of (x), anterior to (y), and superior to (z) the anterior commissure. Numbers in parentheses refer to the Brodmann areas. Clusters with Z-score peaks ⬎3.09 were included (corresponding to P ⬍ 0.001 uncorr.). Only the highest peak is included in the case of several confluent peaks. Regions expected to be active based on the hypothesis are labeled with an asterisk.
RESULTS Before each PET scan, subjects were assigned one of the four tasks mentioned above. After each scan, subjects gave an oral report in free format about their thoughts. Examples are given in Table 1. The results generally confirmed our hypothesis. Reflection on personality traits of oneself showed preferential activity in the precuneus, bilateral temporoparietal regions, and left orbitofrontal cortex, compared to reflections on the neutral third person, the Danish Queen (Table 2A, Fig. 1A). Reflection on the physical appearance of oneself mainly activated the anterior cingulate gyrus, compared to reflections on the neutral third person (Table 2B, Fig. 1B). The reported Z scores are significant without correction for multiple comparisons. The majority of the identified clusters were predicted by the hypothesis (marked with an asterisk in
Table 2). On the other hand, none of the identified clusters in the control comparison (“less active” in Table 2) were in the hypothesized brain region. The major parietal and frontal regions identified by the activation analysis, i.e., the precuneus and the anterior cingulate gyrus, were used as the explaining variables for the covariate analysis (Table 3). Crosscorrelation to whole brain produced the maps presented in Figs. 2 and 3. The data are presented as Z scores. It is seen that precuneus and angular gyrus (posterior and anterior frontal regions) are functionally connected just as predicted. DISCUSSION We here present the novel hypothesis that the neural correlate of reflective self-awareness is similar to the distribution of high metabolic activity in resting con-
FIG. 1. (A) rCBF pattern of reflection on own personality traits vs those of control person, with differential activity mainly in precuneus and bilateral temporoparietal regions. (B) rCBF pattern of reflection on own physical appearance vs that of control person, with differential activity mainly in anterior cingulate gyrus. FIG. 2. Functional connectivity from precuneus to the whole brain during self-reflection. Mainly temporoparietal regions are functionally connected to the precuneus. FIG. 3. Functional connectivity from anterior cingulate gyrus to the whole brain during self-reflection. Mainly adjacent frontal regions and precuneus are functionally connected to the anterior cingulate gyrus.
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TABLE 3 (A) rCBF Clusters Functionally Connected to the Precuneus during Self-Reflection Z score
x
y
z
Region
7.14 4.58 4.58 3.96 3.80 3.68 3.63 3.62 3.59 3.51 3.38
2 ⫺46 60 54 ⫺30 ⫺56 48 ⫺58 36 20 ⫺52
⫺54 ⫺58 ⫺30 ⫺44 ⫺42 ⫺32 ⫺46 ⫺34 0 0 ⫺58
54 12 8 32 ⫺46 ⫺24 ⫺36 30 40 62 ⫺18
Precuneus (7)* Middle temp gyr (37)* Sup temp gyr (22)* Inf par lobe (40)* Cerebellar lobe Inf temp gyr (20) Cerebellar lobe Inf par lobe (40)* Middle front gyr (6) Sup front gyr (6) Inf temp gyr (37)
(B) rCBF Clusters Functionally Connected to the Anterior Cingulate Gyrus during Self-Reflection Z score
x
y
z
Region
6.06 4.14 3.87 3.57 3.50
2 34 ⫺4 ⫺6 ⫺28
42 ⫺40 ⫺52 ⫺34 ⫺38
10 ⫺30 52 ⫺32 ⫺42
Ant cing gyr (32)* Cerebellar lobe Precuneus (7)* Brain stem Cerebellar lobe
Note. Organization similar to that of Table 2. Regions expected to be active based on the hypothesis are labeled with an asterisk.
sciousness, reflecting a fundamental role for selfawareness in the unity of conscious experience. A few years ago, we first presented the idea that precuneus and prefrontal cortex constituted a unifying core of resting conscious state: A “self” (Kjaer and Lou, 2000). A detailed meta-analysis of baseline activity of the brain led Gusnard and Raichle (2001) recently to propose a similar function. We here show, for the first time, that the activity pattern of reflective self-awareness is indistinguishable from the metabolically highly active structures thought to constitute the baseline of conscious states. We also show that this pattern is formed of interconnected structures mainly in the medial parts of posterior and anterior brain. There was no right-hemisphere bias such as was seen in self face recognition (Keenan et al., 1999). As absolute flow was not measured, we cannot be certain whether the difference in activation pattern between self-referential thought and the resting conscious state constituted an actual increase or a less pronounced decrease from rest. The similarity between active self-reference and the resting state patterns is, however, an indication of the phenomenological concept of a core of self-awareness in the resting state, ensuring its unity by functionally integrating posterior and anterior brain. Conscious experiences have often been ascribed to the executive regions of the frontal lobe, especially prefrontal areas, and the cingulate gyrus, while the more posterior sensory regions have been suggested to
be a mere supplier of information to be processed consciously (Mazoyer et al., 2001; Quintana and Fuster, 1999). The executive and sensory regions have very distinct functions at the level of the primary cortices, but they get more functionally integrated at the level of association cortices. The concept behind our work has been that consciousness is complementary, being a function of sensory as well as executive integrative areas. One may conceive it as a summit between anterior and posterior brain. In a previously published study, we identified regions activated and deactivated by meditation compared to resting normal consciousness (Lou et al., 1999) and did a subsequent principal component analysis showing that anterior midline prefrontal cortex and precuneus contributed to both (Kjaer and Lou, 2000). As self-awareness is part of the phenomenology of both states as judged by self-report (Kjaer et al., 2002) and is accompanied by activation of these high-level integrative regions of anterior and posterior brain, their interaction in self-awareness may now be considered to be a core in consciousness. The anatomical connections between the lateral parietal region and frontal cortex are well described. Petrides and Pandya (1984) used autoradiography to demonstrate abundant single-cell connections between precuneus and other regions of the posterior parietal lobe on one hand and frontal areas on the other (Jacobsen and Troganowski, 1977). In contrast, anatomic connections between the medial aspects of posterior and anterior brain have not been studied extensively. However, PET and MR studies have shown functional connectivity between these regions (Schmidt et al., 2002; Krause et al., 1999) during integration of temporal and spatial information and during retrieval of episodic memory. Their functional connectivity was also illustrated in the present work by the syncrony between anterior cingulate gyrus and precuneus. These regions are also involved in executive functions (Quintana and Fuster, 1999). In tasks requiring selection of movement, strong activation was seen, particularly and invariably in the precuneus, but also in the premotor and supplementary motor and in the superior parietal association cortices (Tulving, 1987). Complex sequential finger movements were found to be accompanied by a proportional increase in rCBF in the right dorsal premotor cortex and the right precuneus (Sadato et al., 1996), again demonstrating the close relationship between the frontal cortex and the precuneus in goal-directed action. The activation of the anterior cingulate gyrus during physical self-awareness illustrates that this function is closely related to volition and self-regulation, which all are attributed to the anterior cingulate gyrus (Frith et al., 1991; Posner and Rothbart, 1998). This close sensory–motor interaction may be the foundation for the predictive mechanism in motor control (Blakemore et al., 2000).
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Lesion data specifically concerning the precuneus are not available, but in frontal lobe lesions, a number of syndromes have been described. Of particular importance in the present context are the deficits in both sensory and motor attention and deficiency in perceiving the spatial relationship between the self and the environment. One striking finding in some frontally damaged patients is an apparent decrease in normal self-awareness and, consequently, impaired self-regulation (Stuss and Benson, 1986). Sarazin and colleagues (1998) compared the cognitive and behavioral functions of patients with frontal lesions to the local levels of glucose utilization determined by the 18FDG PET method. They found cognitive functions to be disturbed in hypometabolism of the dorsolateral frontal cortex and behavioral and social skills in ventromedial frontal cortex. Pertinent to the present findings is their demonstration of an association between hypometabolism of the anterior pole (area 10) and global frontal dysfunction, confirming recent activation studies of a coordinated role of all prefrontal functions for this region. These anatomical studies and task-elicited activations have been complemented by the examination of cerebral activity patterns during states of consciousness, such as diverse sleep states, and our own study of the meditative state vs normal consciousness. The sleep states are, like meditation and normal consciousness, characterized by distinct behavioral and electroencephalographic patterns (Rechtschaffen et al., 1966). One characteristic common to the sleep stages is reduced reflective self-awareness (Kahan et al., 1997; Hobson et al., 1998). In REM sleep, rCBF is reduced in precuneus and dorsolateral prefrontal, parietal, and posterior cingulate cortices (Braun et al., 1998). In deep sleep, or slow-wave sleep, a disproportionate flow reduction is seen in precuneus, orbital frontal cortex, basal forebrain, anterior cingulate cortex, basal ganglia, thalami, and dorsal pons (Marquet et al., 1997). Thus, reduction in activity in the precuneus is common to the two sleep stages as predicted if they were instrumental in consciousness of the self in its environment. A more recent study of rCBF during rest and three different depths of anesthesia induced by propofol detected activity changes similar to what has been found during voluntary loss of consciousness (Fiset et al., 1999). In addition to a decrease in global cerebral blood flow, they identified predominantly right-sided regional flow decrements in thalamus, precuneus/cuneus, and frontal cortical regions. These results support a specific hypothesis that anesthetics induce behavioral changes via an effect on specific neuronal networks. The finding supports our concept of a general perception–action cycle in the conscious resting brain, independent of motor activity, involving highlevel integrative cortical regions in anterior and posterior brain.
The ultimate state of conscious incapacity—the vegetative state— has been investigated assessing regional cerebral metabolism using fluorodeoxyglucose positron emission tomography (Laureys et al., 1999). Also, this study identified impaired function of frontal and parietotemporal association areas, including the precuneus. In the present study, we have noted that not only telencephalic structures but also cerebellum seem to be differentially active in reflective self-awareness. Not being included in our initial hypothesis, definitive conclusions on this point was not obtained. It would have required statistical confirmation, corrected for multiple comparisons, and the cerebellum did not pass this test (in fact, of the regions studied here only precuneus did, with a P value of 0.05, corrected for multiple comparisons). In conclusion, we have here demonstrated, for the first time, a midline network of posterior and anterior brain linking self-awareness and conscious experience. ACKNOWLEDGMENTS We are grateful to chief psychologist Anders Gade for discussions on how to design the experimental paradigm. The staff at the PET Center at Rigshospitalet, Copenhagen, is acknowledged for participation. The work is supported by the Lundbeck Foundation. Furthermore, The John and Birthe Meyer Foundation is acknowledged for the donation of the Cyclotron and PET scanner.
REFERENCES Andreasen, N. C., O’Leary, D. S., Cizadlo, T., Arndt, S., Rezai, K., Watkins, G. L., Ponto, L. L., and Hichwa, R. D. 1995. Remembering the past: Two facets of episodic memory explored with positron emission tomography. Am. J. Psychiatry 152: 1576 –1585. Blakemore, S. J., Wolpert, D., and Frith, C. 2000. Why can’t you tickle yourself? NeuroReport 11: R11–16. Braun, A. R., Balkin, T. J., Wesensten, N. J., Gwadry, F., Carson, R. E., Varga, M., et al. 1998. Dissociated pattern of activity in visual cortices and their projections during human rapid eye movement sleep. Science 279: 91–95. Fiset, P., Paus, T., Daloze, T., Plourde, G., Meuret, P., Bonhomme, V., et al. 1999. Brain mechanisms of propofol-induced loss of consciousness in humans: A positron emission tomographic study. J. Neurosci. 19: 5506 –5513. Frackowiak, R. S. J., Friston, K. J., Frith, C. D., Dolan, R. J., and Mazziotta, J. C., Eds. 1997. Human Brain Function. Academic Press, San Diego. Friston, K. J., Frith, C. D., Liddle, P. F., and Frackowiak, R. S. J. 1991. Comparing functional (PET) images: The assessment of significant change. J. Cereb. Blood Flow Metab. 11: 690 – 699. Frith, C. D., Friston, K. J., Liddle, P. F., and Frackowiack, R. S. J. 1991. Willed action and the prefrontal cortex in man: A study with PET. Proc. R. Soc. London B 244: 241–246. Gusnard, D. A., and Raichle, M. E. 2001. Searching for a baseline: Functional imaging and the resting human brain. Nat. Rev. Neurosci. 2: 685– 694. Hobson, J. A., Stickgold, R., and Pace-Schott, E. F. 1998. The neuropsychology of REM sleep dreaming. NeuroReport 9: R1–14.
1086
RAPID COMMUNICATION
Holm, S., Law, I., and Paulson, O. B. 1996. 3D PET activation studies with an H 2 15O bolus injection. In Quantification of Brain Function Using PET. (M. Rea, Ed.), pp. 93–97. Academic Press, San Diego. Jacobsen, S., and Troganowski, J. Q. 1977. Prefrontal granular cortex of the rhesus monkey. Brain Res. 132: 209 –233. Kahan, T. L., La Berge, S., Levitan, L., and Zimbardo, P. 1997. Similarities and differences between dreaming and waking cognition: An exploratory study. Consciousness Cognit. 6: 132–147. Keenan, J. P., McCutcheon, B., Freund, S., Gallup, G. G., Jr., Sanders, G., and Pascual-Leone, A. 1999. Left hand advantage in a self-face recognition task. Neuropsychologia 37: 1421–1425. Kircher, T. T., Senior, C., Phillips, M. L., Benson, P. J., Bullmore, E. T., Brammer, M., Simmons, A., Williams, S. C., Bartels, M., and David, A. S. 2000. Toward a functional neuroanatomy of self processing: Effects of faces and words. Cognit. Brain Res. 10: 133–144. Kjaer, T. W., and Lou, H. C. 2000. Interaction between precuneus and dorsolateral prefrontal cortex may play a unitary role in consciousness. A principal component analysis of rCBF. Consciousness Cognit. 9: S59. Kjaer, T. W., Bertelsen, C., Piccini, P., Brooks, D., Alving, J., and Lou, H. C. 2002. Increased dopamine tone during meditationinduced change of consciousness. Cognit. Brain Res. 13: 255–259. Krause, B. J., Horwitz, B., Taylor, J. G., Schmidt, D., Mottaghy, F. M., Herzog, H., Halsband, U., and Mu¨ ller-Ga¨ rtner, H.-W. 1999. Network analysis in episodic encoding and retrieval of word-pair associates: A PET study. Eur. J. Neurosci. 11: 3293–3301. Laureys, S., Goldman, S., Phillips, C., Van Bogaert, P., Aerts, J., Luxen, A., et al., 1999. Impaired effective cortical connectivity in vegetative state: Preliminary investigation using PET. NeuroImage 9: 377–382. Lou, H. C., Kjaer, T. W., Friberg, L., Wildschiodtz, G., Holm, S., and Nowak, M. 1999. A 15O-H 2O PET study of meditation and the resting state of normal consciousness. Hum. Brain Mapping 7: 98 –105. Marquet, P., Degueldre, C., Aerts, J., Peters, J.-M., Luxen, A., and Franck, G. 1997. Functional neuroanatomy of human slow wave sleep. J. Neurosci. 17: 2807–2812. Mazoyer, B., Zago, L., Mellet, E., Bricogne, S., Etard, O., Houde, O., Crivello, F., Joliot, M., Petit, L., and Tzourio-Mazoyer, N. 2001. Cortical networks for working memory and executive functions sustain the conscious resting state in man. Brain Res. Bull. 54: 287–298.
Petrides, M., and Pandya, D. N. 1984. Projections to the frontal cortex from the posterior parietal region in the rhesus monkey. J. Comp. Neurol. 228: 105–116. Posner, M. I., and Rothbart, M. K. 1998. Attention, self-regulation and consciousness. Philos. Trans. R. Soc. London B. Biol. Sci. 353: 1915–1927. Quintana, J., and Fuster, J. M. 1999. From perception to action: Temporal integrative functions of prefrontal and parietal neurons. Cereb. Cortex. 9: 213–221. Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., Shulman, G. L. 2001. A default mode of brain function. Proc. Natl. Acad. Sci. USA 98: 676 – 682. Rechtschaffen, A., Hauri, P., and Zeitlin, M. 1966. Auditory awakening thresholds in REM and NREM sleep stages. Percept. Mot. Skills 22: 927–942. Ruby, P., and Decety, J. 2001. Effect of subjective perspective taking during simulation of action: A PET investigation of agency. Nat. Neurosci. 4: 546 –550. Sadato, N., Campbell, G., Ibanez, V., Deiber, M., and Hallett, M. 1996. Complexity affects regional cerebral blood flow change during sequential finger movements. J. Neurosci. 16: 2691–2700. Sarazin, M., Pillon, B., Giannakopoulos, P., Rancurel, G., Sanison, Y., and Dubois, B. 1998. Clinico metabolic dissociation of cognitive functions and social behavior in frontal lobe lesions. Neurology 51: 142–148. Schmidt, D., Krause, B. J., Mottaghy, F. M., Halsband, U., Herzog, H., Tellmann, L., and Mu¨ ller-Ga¨ rtner, H.-W.2002. Brain systems engaged in encoding and retrieval of word-pair associates independent of their imagery content or presentation modalities. Neuropsychologia 20: 457– 470. Stuss, D. T., and Benson, D. F. 1986. The frontal lobes. In The Frontal Lobes, pp. 246 –247. Raven Press, New York. Talairach, J., and Tournoux, P. 1988. Co-planar Stereotaxic Atlas of the Human Brain. Thieme, New York. Tart, C. T. 1994. Living the Mindful Life. Shambhala, Boston. Tulving, E. 1987. Elements of Episodic Memory. Oxford Univ. Press, Oxford. Vogeley, K., Bussfeld, P., Newen, A., Herrmann, S., Happe´ , F., Falkai, P., Maier, W., Shah, N. J., Fink, G. R., and Zilles, K. 2001. Mind reading: Neural mechanisms of theory of mind and selfperspective. NeuroImage 14: 170 –181.