The role of area 17 in visual imagery: Convergent evidence from PET and rTMS

Science

Volumn 284, Issue 5411, 1999, Pages 167-170

  Kosslyn, S M ^a,b   Pascual Leone, A ^c   Felician, O ^c,d   Camposano, S ^c   Keenan, J P ^c   Thompson, W L ^a   Ganis, G ^a   Sukel, K E ^a   Alpert, N M ^b  

^a HARVARD UNIVERSITY   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d TIMONE HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; BRAIN MAPPING; CONTROLLED STUDY; HUMAN; IMAGERY; NORMAL HUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; TASK PERFORMANCE; TRANSCRANIAL MAGNETIC STIMULATION; VISUAL CORTEX; VISUAL MEMORY;

ADULT; BRAIN MAPPING; HUMANS; IMAGINATION; MAGNETICS; MALE; MEMORY; TOMOGRAPHY, EMISSION-COMPUTED; VISUAL CORTEX; VISUAL PERCEPTION;

EID: 0033515885     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.284.5411.167     Document Type: Article

References (42)

1. S. M. Kosslyn, Image and Mind (Harvard Univ. Press, Cambridge, MA, 1980); Image and Brain: The Resolution of the Imagery Debate (MIT Press, Cambridge, MA, 1994); M. Tye, The Imagery Debate (MIT Press, Cambridge, MA, 1991).
2. S. M. Kosslyn, Image and Mind (Harvard Univ. Press, Cambridge, MA, 1980); Image and Brain: The Resolution of the Imagery Debate (MIT Press, Cambridge, MA, 1994); M. Tye, The Imagery Debate (MIT Press, Cambridge, MA, 1991).
3. S. M. Kosslyn, Image and Mind (Harvard Univ. Press, Cambridge, MA, 1980); Image and Brain: The Resolution of the Imagery Debate (MIT Press, Cambridge, MA, 1994); M. Tye, The Imagery Debate (MIT Press, Cambridge, MA, 1991).
4. These areas are spatially organized, both physically and functionally [see, for example, P. T. Fox et al., Nature 323, 806 (1986); R. B. H. Tootell, M. S. Silverman, E. Switkes, R. L. De Valois, Science 218, 902 (1982)]. Thus, patterns of activation within them are themselves laid out in space and serve to depict information.
5. These areas are spatially organized, both physically and functionally [see, for example, P. T. Fox et al., Nature 323, 806 (1986); R. B. H. Tootell, M. S. Silverman, E. Switkes, R. L. De Valois, Science 218, 902 (1982)]. Thus, patterns of activation within them are themselves laid out in space and serve to depict information.
6. For reviews, see E. Mellet, L Petit, B. Mazoyer, M. Denis, N. Tzourio, NeuroImage 8, 129 (1998); W. L. Thompson and S. M. Kosslyn, in Brain Mapping: The Systems, A. W. Toga and J. C. Mazziotta, Eds. (Academic Press, San Diego, in press).
7. For reviews, see E. Mellet, L Petit, B. Mazoyer, M. Denis, N. Tzourio, NeuroImage 8, 129 (1998); W. L. Thompson and S. M. Kosslyn, in Brain Mapping: The Systems, A. W. Toga and J. C. Mazziotta, Eds. (Academic Press, San Diego, in press).
8. For example, in some tasks no behavior is assessed and subjects need not use imagery [for example, M. D'Esposito et al., Neuropsychologia 35, 725 (1997)], whereas in others the subjects are asked to perform spatial tasks, which may rely primarily on the parietal lobes [E. Mellet, N. Tzourio, M. Denis, B. Mazover, J. Cognit. Neurosci. 7, 433 (1995)]. However, activation in Area 17 is probably not simply a consequence of needing high spatial resolution (see E. Mellet et al., NeuroImage, in press).
9. For example, in some tasks no behavior is assessed and subjects need not use imagery [for example, M. D'Esposito et al., Neuropsychologia 35, 725 (1997)], whereas in others the subjects are asked to perform spatial tasks, which may rely primarily on the parietal lobes [E. Mellet, N. Tzourio, M. Denis, B. Mazover, J. Cognit. Neurosci. 7, 433 (1995)]. However, activation in Area 17 is probably not simply a consequence of needing high spatial resolution (see E. Mellet et al., NeuroImage, in press).
10. For example, in some tasks no behavior is assessed and subjects need not use imagery [for example, M. D'Esposito et al., Neuropsychologia 35, 725 (1997)], whereas in others the subjects are asked to perform spatial tasks, which may rely primarily on the parietal lobes [E. Mellet, N. Tzourio, M. Denis, B. Mazover, J. Cognit. Neurosci. 7, 433 (1995)]. However, activation in Area 17 is probably not simply a consequence of needing high spatial resolution (see E. Mellet et al., NeuroImage, in press).
11. S. M. Kosslyn, K. E. Sukel, B. M. Bly, Mem. Cognit., in press. As illustrated in Fig. 1, sets of four stripes were created (with Aldus SuperPaint, Aldus Corporation, San Diego, CA). Forty-eight sound files also were created with Soundedit 1.6 (Macromedia, San Francisco, CA). Each sound file contained numbers that named two quadrants, followed by the name of a property of the stripes, such as "1, 2, Length." The numbers specified which two quadrants were to be compared, and the property name indicated the comparison the subject was to make (length, width, orientation, or spacing between the stripes). For half the comparisons of each type, the stripes in the quadrant named first had more of the specified dimension, whereas for the other half the stripes in the quadrant named second were greater along this dimension. All of the cues were a single syllable (the word "tilt" cued orientation discriminations and "space" cued spacing discriminations). We created two sets of cues; one of them asked subjects to compare length or width and the other asked subjects to compare spacing or orientation. Half the subjects received one set of cues, and half received the other. The subjects were not aware of the possible comparisons while they studied and memorized the stimuli. For the baseline in the PET study, two additional words ("depth" and "height") were used so that the subjects would not have any idea of how they were to study the stimuli, once these were presented to them in the learning phase. The cues were presented with software on a Macintosh computer with an RGB monitor (Apple Computer, Cupertino, CA). The trial sequence within each block was random, except that the same number (which labeled a quadrant) and the same type of discrimination could not appear more than three times in succession.
12. Eight right-handed male students or professionals from the Boston area, aged 20 to 36 years (mean, 27 years), volunteered to participate in the PET study. All reported being in good health and free of any psychoactive medication. They were all unaware of the hypotheses of the experiment at the time of testing.
13. 2 began, and continued for 70 s, at which point the PET camera was turned off, and subjects were instructed to stop performing the task. All other aspects of the procedure were the same as in (5). The mean response time in the imagery condition was 2704 ms, and the mean error rate was 21.5%.
14. The baseline condition was always presented first, before subjects had seen the stimuli or knew about the nature of the task. We were concerned that if subjects had participated in the imagery task, they might have visualized stimuli even during the baseline condition. In the baseline condition, the subjects closed their eyes and listened to the auditory stimuli that were prepared for that condition. They were told that they would be hearing sets of three words (the names of two numbers followed by another word), and that they were to respond as soon as they heard the third word. They were instructed to not pay attention to or try to assign meaning to any of the words they heard. They were asked to alternate the side of each response.
15. SPM95 (Wellcome Department of Cognitive Neurology, London, UK), which is based on the theories presented in K. J. Friston et al., J. Cereb. Blood Flow Metab. 11, 690 (1991); Hum. Brain Map 2, 189 (1995); K. J. Worsley, A. C. Evans, S. Marrett, P. Neelin, J. Cereb. Blood Flow Metab. 12, 900 (1992). For further details on the PET analysis, see S. M. Kosslyn et al., Psychophysiology 35, 1 (1998).
16. SPM95 (Wellcome Department of Cognitive Neurology, London, UK), which is based on the theories presented in K. J. Friston et al., J. Cereb. Blood Flow Metab. 11, 690 (1991); Hum. Brain Map 2, 189 (1995); K. J. Worsley, A. C. Evans, S. Marrett, P. Neelin, J. Cereb. Blood Flow Metab. 12, 900 (1992). For further details on the PET analysis, see S. M. Kosslyn et al., Psychophysiology 35, 1 (1998).
17. SPM95 (Wellcome Department of Cognitive Neurology, London, UK), which is based on the theories presented in K. J. Friston et al., J. Cereb. Blood Flow Metab. 11, 690 (1991); Hum. Brain Map 2, 189 (1995); K. J. Worsley, A. C. Evans, S. Marrett, P. Neelin, J. Cereb. Blood Flow Metab. 12, 900 (1992). For further details on the PET analysis, see S. M. Kosslyn et al., Psychophysiology 35, 1 (1998).
18. SPM95 (Wellcome Department of Cognitive Neurology, London, UK), which is based on the theories presented in K. J. Friston et al., J. Cereb. Blood Flow Metab. 11, 690 (1991); Hum. Brain Map 2, 189 (1995); K. J. Worsley, A. C. Evans, S. Marrett, P. Neelin, J. Cereb. Blood Flow Metab. 12, 900 (1992). For further details on the PET analysis, see S. M. Kosslyn et al., Psychophysiology 35, 1 (1998).
19. In addition to the findings shown in Fig. 2, other regions were found to be activated in the PET study during the imagery condition, relative to the baseline condition. In the left hemisphere, we found activation in superior parietal cortex, cerebellum, parahippocampal gyrus, superior frontal cortex, and dorsolateral prefrontal cortex; in the right hemisphere, we found activation in Areas 18/19, the occipito-parietal sulcus, cerebellum, inferior temporal cortex, thalamus, two points in Brodmann's Area 10 of the dorsolateral prefrontal cortex, and at the junction of the inferior frontal and dorsolateral prefrontal cortices. All areas were activated with a Z score greater than 3.09 (P < 0.001, uncorrected for multiple comparisons). Although Area 17 was activated along the midline, activation in other relatively early visual areas was tateralized to the right hemisphere. Marsolek and colleagues [for example, for a review see C. J. Marsolek and E. D. Burgund, in Cerebral Asymmetries in Sensory and Perceptual Processing, S. Christman, Ed. (Elsevier, Amsterdam, 1997)] have provided much evidence that visual memories for specific stimuli (as opposed to prototypes or categories) are stored and processed more effectively in the right hemisphere, whereas visual memories of categories and prototypes are stored and processed more effectively in the left hemisphere. The lateralization found here may reflect such specialization.
20. L. G. Cohen et al., Nature 389, 180 (1997); E. M. Wassermann, J. Grafman, T. Paus, Trends Cognit. Neurosci. 1, 199 (1997); A. Pascual-Leone et al., Neuropsychologia 37, 207 (1999).
21. L. G. Cohen et al., Nature 389, 180 (1997); E. M. Wassermann, J. Grafman, T. Paus, Trends Cognit. Neurosci. 1, 199 (1997); A. Pascual-Leone et al., Neuropsychologia 37, 207 (1999).
22. L. G. Cohen et al., Nature 389, 180 (1997); E. M. Wassermann, J. Grafman, T. Paus, Trends Cognit. Neurosci. 1, 199 (1997); A. Pascual-Leone et al., Neuropsychologia 37, 207 (1999).
23. V. E. Amassian et al., Electroencephalogr. Clin. Neurophysiol. 74, 458 (1989).
24. For recent reviews on TMS applications in studies on visual pathways, see V. E. Amassian et al., J. Clin. Neurophysiol. 15, 288 (1998); V. Walsh and A. Cowey, Trends Cognit. Neurosci. 2, 103 (1998).
25. For recent reviews on TMS applications in studies on visual pathways, see V. E. Amassian et al., J. Clin. Neurophysiol. 15, 288 (1998); V. Walsh and A. Cowey, Trends Cognit. Neurosci. 2, 103 (1998).
26. A. Pascual-Leone, M. Hallett, J. Grafman, in New Horizons in Cognitive Neuroscience, M. Shugishita, Ed. (Elsevier, Amsterdam, 1994);
27. A. Pascual-Leone et al., in Handbook of Neuropsychology, J. Grafman and F. Boiler, Eds. (Elsevier, Amsterdam, 1996), vol. 11.
28. R. Chen et al., Neurology 48, 1398 (1997); A. Pascual-Leone et al., J. Clin. Neurophysiol. 15, 333 (1998).
29. R. Chen et al., Neurology 48, 1398 (1997); A. Pascual-Leone et al., J. Clin. Neurophysiol. 15, 333 (1998).
30. Repetitive TMS was performed with a Magstim Super Rapid stimulator (Magstim, Whitland, UK) with a Magstim Double 70-mm figure-of-eight coil. The coil was firmly maintained in a constant position with a specially designed coil holder. A three-dimensional reconstructed MRI of each subject was used to determine the optimal coil placement to target the occipital pole, at the tip of the calcarine fissure. During real rTMS. the center of the coil was held tangentially to the scalp and symmetrically across the midline of the occipital pole, targeting the tip of the calcarine fissure. During sham rTMS, the coil was lowered by 3 cm and rotated so that the edge of the two wings of the coil rested at 90° on the scalp. In this sham rTMS condition, the induced magnetic field did not enter the brain, although the touch on the scalp, the sound of the coil being activated, and the induced muscle twitching are comparable to those in the real rTMS condition. Intracerebral measurements of the induced voltages by TMS with various coil orientations in primates document the appropriateness of the sham TMS condition used here [S. H. Lissanby et al., Electroencephalogr. Clin. Neurophysiol. 107, 79P (1998)]. Repetitive TMS was delivered at 90% of the subject's motor threshold at 1-Hz stimulation frequency, in a single train of 10 min duration. Our hypothesis was that underlying cortical activity would be affected for at least 10 min after rTMS. To avoid carry-over effects between conditions, there was a pause of 30 min between tasks and thus between rTMS trains. Overall, each subject received 600 stimuli per train, and a total of 2400 stimuli (1200 real and 1200 sham stimuli). Stimulation was performed in accordance with current safety recommendations [E. M. Wassermann, Electroencephalogr. Clin. Neurophysiol. 108, 1 (1998)] using a protocol approved by the local investigational review board and with an investigational device exemption from the Food and Drug Administration.
31. Repetitive TMS was performed with a Magstim Super Rapid stimulator (Magstim, Whitland, UK) with a Magstim Double 70-mm figure-of-eight coil. The coil was firmly maintained in a constant position with a specially designed coil holder. A three-dimensional reconstructed MRI of each subject was used to determine the optimal coil placement to target the occipital pole, at the tip of the calcarine fissure. During real rTMS. the center of the coil was held tangentially to the scalp and symmetrically across the midline of the occipital pole, targeting the tip of the calcarine fissure. During sham rTMS, the coil was lowered by 3 cm and rotated so that the edge of the two wings of the coil rested at 90° on the scalp. In this sham rTMS condition, the induced magnetic field did not enter the brain, although the touch on the scalp, the sound of the coil being activated, and the induced muscle twitching are comparable to those in the real rTMS condition. Intracerebral measurements of the induced voltages by TMS with various coil orientations in primates document the appropriateness of the sham TMS condition used here [S. H. Lissanby et al., Electroencephalogr. Clin. Neurophysiol. 107, 79P (1998)]. Repetitive TMS was delivered at 90% of the subject's motor threshold at 1-Hz stimulation frequency, in a single train of 10 min duration. Our hypothesis was that underlying cortical activity would be affected for at least 10 min after rTMS. To avoid carry-over effects between conditions, there was a pause of 30 min between tasks and thus between rTMS trains. Overall, each subject received 600 stimuli per train, and a total of 2400 stimuli (1200 real and 1200 sham stimuli). Stimulation was performed in accordance with current safety recommendations [E. M. Wassermann, Electroencephalogr. Clin. Neurophysiol. 108, 1 (1998)] using a protocol approved by the local investigational review board and with an investigational device exemption from the Food and Drug Administration.
32. Mindful of the possibility of carry-over effects (practice or fatigue), we tested a different set of volunteers in the PET and TMS conditions. Three men and two women, aged 19 to 41 years (mean 29 years), volunteered to participate as paid subjects in the rTMS experiment. All were right-handed according to the Edinburgh Handedness Scale. All were medication free, had normal neurological and physical exams, and had no personal or family history of neurological disorder, including seizures. Subjects provided written informed consent before entering the study.
33. Although it remains unclear whether the effects of TMS to the occipital pole are due to direct intracortical effects or interference with connections from the affected area, functional disruption of Area 17 is well documented (12). Nevertheless, given the limitations in focality of TMS, interference with contiguous portions of Area 18 is likely [see, for example, G. F. Potts et al., J. Clin. Neurophysiology. 15, 344 (1998)]. However, the PET results did not show that this task activates contiguous parts of Area 18 but rather a part of Area 18 over 4 cm away, which is unlikely to have played a functional role in task performance (as noted below).
34. The same task as in the PET experiment was administered [see (5)], and subjects again were asked to respond as quickly and accurately as possible (by pressing two different keys with the middle and index finger of their dominant hand). Response time was measured from the time of stimulus onset to the key response; error rates were also measured. Subjects learned the stimulus display as before. However, because response times and error rates were our only dependent measures, we included 24 practice trials before the study to ensure that there would not be a ceiling effect; if the task was too challenging, it would have been difficult to detect differences among the conditions.
35. The same task was used in the imagery and perception conditions, but in the perception condition the entire stimulus display appeared for 500 ms immediately after the auditory cue was presented. Before each experimental task (imagery or perception), sham or real rTMS was applied. The subject received rTMS while sitting in front of the computer to be used for testing (Macintosh 17-inch RGB monitor, Apple Computer, Cupertino, CA). The task was initiated immediately after the end of the last magnetic stimulus. Therefore, each subject received a total of four sessions of rTMS. To control for potential learning effects, the subjects were randomly assigned to receive sham (n = 2) or real rTMS (n = 3) first. The imagery task was always conducted first to prevent the subjects from overlearning the stimuli (and thus not having to use imagery later), which may have occurred if the perceptual task was presented first.
36. Repetitive TMS was tolerated welt by all subjects, without undesirable side effects. No pre-or post-TMS differences in neurological status or visual acuity were noted in any of the subjects. None reported phosphenes during the stimulation.
37. For example, G. Beckers and V. Homberg, [Exp. Brain Res. 87, 421 (1991)] and G. Beckers and S. Zeki [Brain, 118, 49 (1995)] showed that TMS over the presumed site of Area VS impaired motion perception, but left color perception and shape perception unchanged; in contrast, TMS to V1 (Area 17) disrupted detection of visual stimuli without affecting motion perception. Areas V5 and V1 are interconnected, and therefore, if the effects of TMS on a given cortical area were secondary to transsynaptic effects, TMS to V1 should disrupt motion perception (by remote effects onto V5) and TMS to V5 should disrupt visual perception in general (by remote effects onto V1). This was not the case. Although transsynaptic effects of TMS on distant cortical and subcortical areas are possible [for example, R. J. Ilmoniemi et al., Neuroreport 8, 3537 (1997); T. Paus et al., J. Neurosci. 17, 3178 (1997)], these effects have not been found to produce significant changes in behavior within the time span studied here. TMS effects appear to originate from disruption of the same cortical areas that show activation on functional imaging studies, and originate primarily from disruption of the directly targeted cortical region. Among the areas activated in our study [see (10]], the one closest to Area 17 (where TMS was delivered) was Areas 18/19, which was at a distance of 43.3 mm; the closest other areas that were activated were the cerebellum, 43.7 mm from Area 17, and the occipito-parietal sukus, 45.3 mm from Area 17. Given the previous findings with TMS noted above, it is unlikely that TMS delivered to medial occipital cortex had its effects by disrupting one of the more remote areas that were activated during the task.
38. For example, G. Beckers and V. Homberg, [Exp. Brain Res. 87, 421 (1991)] and G. Beckers and S. Zeki [Brain, 118, 49 (1995)] showed that TMS over the presumed site of Area VS impaired motion perception, but left color perception and shape perception unchanged; in contrast, TMS to V1 (Area 17) disrupted detection of visual stimuli without affecting motion perception. Areas V5 and V1 are interconnected, and therefore, if the effects of TMS on a given cortical area were secondary to transsynaptic effects, TMS to V1 should disrupt motion perception (by remote effects onto V5) and TMS to V5 should disrupt visual perception in general (by remote effects onto V1). This was not the case. Although transsynaptic effects of TMS on distant cortical and subcortical areas are possible [for example, R. J. Ilmoniemi et al., Neuroreport 8, 3537 (1997); T. Paus et al., J. Neurosci. 17, 3178 (1997)], these effects have not been found to produce significant changes in behavior within the time span studied here. TMS effects appear to originate from disruption of the same cortical areas that show activation on functional imaging studies, and originate primarily from disruption of the directly targeted cortical region. Among the areas activated in our study [see (10]], the one closest to Area 17 (where TMS was delivered) was Areas 18/19, which was at a distance of 43.3 mm; the closest other areas that were activated were the cerebellum, 43.7 mm from Area 17, and the occipito-parietal sukus, 45.3 mm from Area 17. Given the previous findings with TMS noted above, it is unlikely that TMS delivered to medial occipital cortex had its effects by disrupting one of the more remote areas that were activated during the task.
39. For example, G. Beckers and V. Homberg, [Exp. Brain Res. 87, 421 (1991)] and G. Beckers and S. Zeki [Brain, 118, 49 (1995)] showed that TMS over the presumed site of Area VS impaired motion perception, but left color perception and shape perception unchanged; in contrast, TMS to V1 (Area 17) disrupted detection of visual stimuli without affecting motion perception. Areas V5 and V1 are interconnected, and therefore, if the effects of TMS on a given cortical area were secondary to transsynaptic effects, TMS to V1 should disrupt motion perception (by remote effects onto V5) and TMS to V5 should disrupt visual perception in general (by remote effects onto V1). This was not the case. Although transsynaptic effects of TMS on distant cortical and subcortical areas are possible [for example, R. J. Ilmoniemi et al., Neuroreport 8, 3537 (1997); T. Paus et al., J. Neurosci. 17, 3178 (1997)], these effects have not been found to produce significant changes in behavior within the time span studied here. TMS effects appear to originate from disruption of the same cortical areas that show activation on functional imaging studies, and originate primarily from disruption of the directly targeted cortical region. Among the areas activated in our study [see (10]], the one closest to Area 17 (where TMS was delivered) was Areas 18/19, which was at a distance of 43.3 mm; the closest other areas that were activated were the cerebellum, 43.7 mm from Area 17, and the occipito-parietal sukus, 45.3 mm from Area 17. Given the previous findings with TMS noted above, it is unlikely that TMS delivered to medial occipital cortex had its effects by disrupting one of the more remote areas that were activated during the task.
40. For example, G. Beckers and V. Homberg, [Exp. Brain Res. 87, 421 (1991)] and G. Beckers and S. Zeki [Brain, 118, 49 (1995)] showed that TMS over the presumed site of Area VS impaired motion perception, but left color perception and shape perception unchanged; in contrast, TMS to V1 (Area 17) disrupted detection of visual stimuli without affecting motion perception. Areas V5 and V1 are interconnected, and therefore, if the effects of TMS on a given cortical area were secondary to transsynaptic effects, TMS to V1 should disrupt motion perception (by remote effects onto V5) and TMS to V5 should disrupt visual perception in general (by remote effects onto V1). This was not the case. Although transsynaptic effects of TMS on distant cortical and subcortical areas are possible [for example, R. J. Ilmoniemi et at., Neuroreport 8, 3537 (1997); T. Paus et al., J. Neurosci. 17, 3178 (1997)], these effects have not been found to produce significant changes in behavior within the time span studied here. TMS effects appear to originate from disruption of the same cortical areas that show activation on functional imaging studies, and originate primarily from disruption of the directly targeted cortical region. Among the areas activated in our study [see (10]], the one closest to Area 17 (where TMS was delivered) was Areas 18/19, which was at a distance of 43.3 mm; the closest other areas that were activated were the cerebellum, 43.7 mm from Area 17, and the occipito-parietal sukus, 45.3 mm from Area 17. Given the previous findings with TMS noted above, it is unlikely that TMS delivered to medial occipital cortex had its effects by disrupting one of the more remote areas that were activated during the task.
41. J. Talairach and P. Toumoux, Co-planar Stereotaxic Atlas of the Human Brain, M. Rayport, transl. (Thieme, New York. 1988).
42. This research was supported in part by grants from the Human Frontiers Science Program, National Eye Institute (RO1 EY12091). and the National Institute for Mental Health (RO1 MH57980). S.C. was a visiting scientist from the Department of Pediatrics, Division of Neurology, Faculty of Medicine, University of Chile. Subjects were tested according to American Psychological Association rules and regulations. After the general purpose and possible risks of the experiment were explained, informed consent was obtained from each subject before the experimental procedure began. This research was approved by the respective Institutional Review Boards of the sponsoring institutions.