Hypnotic induction decreases anterior default mode activity

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Consciousness and Cognition 18 (2009) 848–855

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Consciousness and Cognition journal homepage: www.elsevier.com/locate/concog

Hypnotic induction decreases anterior default mode activity William J. McGeown a, Giuliana Mazzoni a, Annalena Venneri a,b, Irving Kirsch a,* a b

Department of Psychology, University of Hull, UK Department of Neuroscience, University of Modena and Reggio Emilia, Italy

a r t i c l e

i n f o

Article history: Received 27 April 2009 Available online 25 September 2009 Keywords: Hypnosis Suggestion Trance State Default mode Consciousness Functional magnetic resonance imaging (fMRI) Neuroimaging Frontal cortex

a b s t r a c t The ‘default mode’ network refers to cortical areas that are active in the absence of goaldirected activity. In previous studies, decreased activity in the ‘default mode’ has always been associated with increased activation in task-relevant areas. We show that the induction of hypnosis can reduce anterior default mode activity during rest without increasing activity in other cortical regions. We assessed brain activation patterns of high and low suggestible people while resting in the fMRI scanner and while engaged in visual tasks, in and out of hypnosis. High suggestible participants in hypnosis showed decreased brain activity in the anterior parts of the default mode circuit. In low suggestible people, hypnotic induction produced no detectable changes in these regions, but instead deactivated areas involved in alertness. The findings indicate that hypnotic induction creates a distinctive and unique pattern of brain activation in highly suggestible subjects. Ó 2009 Elsevier Inc. All rights reserved.

1. Introduction Our purpose in designing this study was to establish whether the induction of hypnosis produces a unique hypnotic state (Lynn, Kirsch, & Hallquist, 2008) and, if so, to identify its neural correlates. There have been several brain imaging studies on hypnosis, but these have not contributed consistent results, and the neurobiological correlates of the hypnotic induction per se have not been reliably identified (Oakley, 2008). Inconsistency between findings might potentially be accounted for by methodological differences between the studies (Oakley, 2008). In many studies, the hypnotic induction has been confounded with the administration of specific hypnotic suggestions, so that brain activation following a hypnotic suggestion (i.e., a suggested change in experience given after the induction of hypnosis) is compared to activation without either the induction of hypnosis or the suggestion (Faymonville et al., 2000; Grond, Pawlik, Walter, Lesch, & Heiss, 1995; Maquet et al., 1999). The experimental design adopted in these brain imaging experiments does not allow a clear distinction between differences in brain activation that might arise from the induction of hypnosis and those due to task-related suggestion. A better strategy might be to hold suggestion and other task demands constant, so that the only difference would be the presence/absence of hypnotic induction. This strategy has been adopted in a few published studies (Egner, Jamieson, & Gruzelier, 2005; Rainville, Hofbauer, Bushnell, Duncan, & Price, 2002; Rainville et al., 1999). Even in these studies, however, the design was such that the effects of hypnosis on brain physiology per se could not be determined. For example, participants in the Egner et al. (2005) study engaged in a Stroop task, and those in the Rainville et al. (1999, 2002) studies had their hand immersed in warm or painfully hot water. These studies reported modulation of activity in the anterior cingulate cortex due

* Corresponding author. Address: Department of Psychology, University of Hull, Cottingham Road, Hull HU6 7RX, UK. Fax: +44 (0) 1482 465599. E-mail address: [email protected] (I. Kirsch). 1053-8100/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.concog.2009.09.001

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to hypnosis, but they included concomitant tasks (Stroop task/pain) which are also known to involve this area. The differences in brain activity in hypnotic and non-hypnotic conditions might, therefore, be task specific. In addition, in most studies the participants were aware of the purpose of the experiment and what was required of them, which might have influenced brain activity and produced changes that are not specific to hypnosis. Our alternative approach was to scan participants during rest periods following the induction procedure, while they were not performing any specific task and were unaware that assessment had begun. This method minimizes the confounding effects of task, demand characteristics, and performance expectations. The pattern of spontaneous physiological brain activity that is normally detectable during normal resting state is referred to as the ‘default mode’ network of brain function (Raichle et al., 2001). Areas collectively activated during the default mode state involve a set of midline brain structures, including the anterior cingulate, ventral and dorsal medial prefrontal cortex, posterior cingulate and precuneus (Fox & Raichle, 2007; Mason et al., 2007; Raichle et al., 2001). Oakley and Halligan (2009) have suggested that a deviation from the normal default mode activity might provide a neural signature of hypnosis. In the present study, we examined whether any changes occurred to the standard pattern of brain activity during rest after a hypnotic induction. A group of low suggestible participants (i.e. people who do not respond to hypnotic suggestions) were also included to see whether similar alterations to the pattern of spontaneous physiological brain activity occurs in both high and low suggestible people. Changes that are not specific to hypnosis should be found in both groups, whereas changes that are specific to hypnosis should be found only in people who are responsive to hypnosis. In this study, periods of scanning while participants were resting were alternated with periods of passive and active viewing, which participants had been led to believe were the focus of the experiment. Brain activity during these conditions was recorded following a hypnotic induction and also without the induction of hypnosis. By comparing scans acquired during rest periods between hypnosis/non hypnosis runs within subjects in the first level analysis, this experimental procedure minimized the influence of demand characteristics, concurrent tasks, hypnotic suggestions, and performance expectations on brain activity. Instructions were worded in a way that participants had no awareness that scans collected during these resting periods would be used in data analyses. For the passive condition they had to perform a relatively undemanding passive visual perception task (e.g. look at a complex colour or greyscale pattern); for the active condition they had to perform a demanding active visual hallucination task (e.g. draining colour from the colour pattern or adding colour to the greyscale pattern). The aim of this fMRI study was to discover if alterations in the pattern of spontaneous physiological brain activity during rest occur in high and/or low suggestible participants once hypnosis is induced when compared to rest activity out of hypnosis.

2. Method 2.1. Participants Two hundred sixty three potential participants were screened for hypnotic suggestibility on a modified version of the Carleton University Responsiveness to Suggestion Scale (CURSS) (Comey & Kirsch, 1999; Spanos et al., 1983). The CURSS is a widely used group scale for assessing hypnotic suggestibility. It consists of a hypnotic induction followed by seven suggestions requesting ideomotor movements, movement inhibition, and alterations of perception and memory. Participants receive one point for each suggestion to which they respond behaviorally. The Comey and Kirsch (1999) modification of the CURSS has an extended hypnotic induction and introductory instructions that are similar to those of the individually administered Stanford Hypnotic Susceptibility Scale: Form C (Weitzenhoffer & Hilgard, 1962), which is generally considered the gold standard for measuring hypnotic suggestibility. Screening was conducted by university faculty members with groups of participants ranging from 1 to 60 individuals. Individuals who scored in the top (5–7) or bottom range (0–1) were invited for further participation. In a second screening session, participants were asked individually, both in and out of hypnosis, to respond the perceptual alteration suggestions that they were told were the focus of the study. The hypnotic induction was taken from Kirsch, Lynn, and Rhue (1993) and consisted of suggestions for relaxation, pleasant visual imagery, and entry into a hypnotic state. Self report data of these participants’ responses to the perceptual alteration suggestions are reported elsewhere (Mazzoni et al., 2009). Out of these people, eleven highly suggestible participants who succeeded in responding to the perceptual alteration experiences (mean suggestibility rating 5.82 on the CURSS, SD 0.87, range 5–7) and seven low suggestible participants (mean suggestibility rating 0.29, SD 0.49, range 0–1) were included in the fMRI study. 2.2. Procedure Participants were informed that the purpose of the study was to assess what happens in the brain when people respond to suggestions for perceptual alterations both in and out of hypnosis. They were told that while in the scanner, they would see a screen with a fixation point on which they were to focus their eyes, that the fixation point would be followed by a pattern which they had to look at, and that this would then be followed by a signal to alter their perception of the pattern. They were also told that, as in the second screening session, this would be done in and out of hypnosis and that the purpose of the

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study was to compare brain activation when responding to the perceptual alteration suggestion in and out of hypnosis. The focus of the present study, however, was on the eight 20 s intervals during which the fixation point was on the screen before being replaced by the pattern. Given the instructions and the previous screening on the perceptual alteration suggestions and since the experimenter who instructed the participants was also not aware of the true focus of the study at the time of data collection, it seems unlikely that participants would be able to divine that these brief intervals were of any interest. After explaining the experimental procedure, informed consent was obtained for all participants. Subsequent to the fMRI session, high suggestible participants were contacted via email and asked to think back about their experiences and indicate how they differed in and out of hypnosis. All of the responses to this question referred to their experience of the suggestions. None referred to the rest periods or to their experience of hypnosis per se. This supports our supposition that participants understood the perceptual alteration task, rather than the 20 s between-trial pauses (i.e., the resting state periods), to be the focus of the study. Hence, any influence of demand characteristics and performance expectations on the data reported here are most likely negligible. 2.3. fMRI methods Echo planar T2* weighted MRI images were acquired on a 3T Philips Achieva MRI system (TR = 2 s, TE = 35 ms, flip angle a = 80°, voxel dimensions 1.88  1.88  3.00 mm, field of view 240 mm, matrix 128  128  30). Three hundred seventy six volumes of 30 contiguous slices were acquired in each run. Four runs were acquired, two in hypnosis and two out of hypnosis. Hypnosis was induced using an abbreviated version of the induction used during the second screening session. Each run was preceded by 30 s of dummy scans to allow the scanner to reach equilibrium. The experiment followed a block design, alternating the conditions of rest, passive task (view a colour or greyscale pattern), and active task (drain colour from a coloured pattern or add colour to a greyscale pattern). Colour and greyscale trials were counterbalanced across runs. These conditions were repeated four times in each run. The hypnosis/no hypnosis conditions were counterbalanced across the participants with half being imaged under hypnosis first and the other half out of hypnosis first, to ensure that order effects (participant or scanner related) would not affect the findings. The focus of the study was on the fMRI scans acquired over the repeated rest periods (in which participants had no task to perform and no specific requirements). The total scanning time for rest in hypnosis was 320 s and 320 s out of hypnosis (16 epochs in and 16 epochs out of hypnosis for each participant). Suggestions and task instructions were kept constant for the hypnosis and no-hypnosis runs, thus ensuring that the effects of hypnotic induction on brain activation would not be confounded by these factors. This design enabled the within subject comparison of resting brain activation patterns, in and out of hypnosis. At the end of the fMRI session participants were also asked to indicate on a four point scale (normal state, relaxed, hypnotized, and deeply hypnotized) (Hilgard & Tart, 1966) the level of hypnotic state they reached for both the hypnosis runs and the nohypnosis runs. 2.4. fMRI data analysis Imaging data were analyzed using Statistical Parametric Mapping (SPM5) image analysis software (Wellcome Centre for Neuroimaging, London, UK). All volumes from each subject were re-aligned after creating a mean as reference and re-sliced using 4th Degree B-Spline interpolation methods to adjust for residual motion related signal changes. Images were spatially normalized to the standard EPI template available in SPM5 using non-linear estimation of parameters. Normalized images were then spatially smoothed with an 8 mm full width at half maximum isotropic Gaussian kernel to compensate for any residual variability after spatial normalization. A boxcar waveform convolved with a synthetic hemodynamic response function (HRF) was used as the reference waveform for each condition. Image data were high-pass filtered with a set of discrete cosine basis functions with a cut-off period of 128 s. Head motion was less than 3 mm in all volunteers but one, whose scans were not included in the analysis. Head motion was included as a regressor in the first level analyses for the remaining participants. At first level, all four runs for each participant were entered into an analysis using the general linear model. For all conditions (rest, passive, active) contrasts were defined for each condition across scans, i.e. contrasting each condition in the hypnosis runs directly with the same condition in the out of hypnosis runs and vice versa. For example, rest in hypnosis was compared to rest out of hypnosis and the converse comparison was also made. Six contrast images were therefore generated for each participant. For the second level group analysis, random effect analyses were carried out by entering each set of contrast images into one sample t-tests, one for each of the six sets of contrast images. This was repeated for both the high and low suggestible participants. Group comparisons were also carried out for each set of contrast images using an independent sample t-test. Height threshold of significance was set at p < .05 (corrected) for individual group analyses and p < .01 (corrected) for group comparisons. For some group analyses a more liberal uncorrected threshold level was used, primarily to see whether there were any significant clusters in the default mode areas described by previously published studies which were not detected at the chosen threshold level. When that was the case, only significant clusters in areas defined a priori based on published evidence which had an extent of at least 250 voxels and survived small volume correction were taken into account. The type of correction used is detailed in the tables. Anatomical regions were identified using the Talairach Daemon Client (http://ric.uthscsa.edu/projects/tdc/) (Lancaster et al., 2000), following conversion of the Montreal Neurological Institute coordinates extracted from the SPM analyses into Talairach coordinates.

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3. Results During data acquisition, one of the high suggestible participants had excessive movement and was, therefore, excluded from the analyses. This left the high suggestible group with 7 females and 3 males between the ages of 20 and 53 (mean 25.00, SD 10.32). The low suggestible group had 5 females and 2 males between the ages of 20 and 35 (mean 26.86, SD 6.54). 3.1. Effects of hypnosis on the brain in the resting state Immediately after the scanning session, participants were asked to rate their feelings of being hypnotized during both the hypnosis and no-hypnosis part of the session using a 4 point scale with the verbal anchors, normal awake state, very relaxed, mild hypnotic state, and deeply hypnotized. When out of hypnosis, both high and low suggestible people reported that they were either in a normal awake state or very relaxed (mean 1.22, SD 0.44 and mean 1.29, SD 0.49 for highs and lows respectively). After hypnotic induction three highs reported being relaxed and the others reported being mildly or deeply hypnotised (mean 3.00, SD 0.83), while lows rated themselves as being either relaxed or in a normal awake state (mean 1.57, SD 0.53). Wilcoxon signed ranks tests revealed a significant difference between the state rating (before and after hypnosis) in the high suggestible (Z = 2.68; p < .01), but not in the low suggestible (Z = 1.41; ns), indicating that hypnosis had a greater effect on high than low suggestible people. The areas which had significantly reduced levels of activation during hypnosis were identified by comparing the rest period in the no hypnosis condition to the rest period in hypnosis. During hypnosis, high suggestible participants showed reductions in brain activity in the anterior cingulate, medial and superior frontal gyri bilaterally, in addition to the left inferior and middle frontal gyri (see Table 1a, Fig. 1). The converse comparison, hypnosis rest versus no hypnosis rest, which should reveal areas recruited significantly more after the hypnotic induction, found no significant differences. The same analyses yielded a different pattern of changes in low suggestible participants when under hypnosis. These participants showed reductions related to the hypnotic induction during rest, in the posterior cingulate, thalamus, caudate nucleus and insula, bilaterally. Further decreases in activation were seen in the left inferior frontal gyrus, claustrum, lentiform nucleus and right subthalamic nucleus (see Table 1b, Fig. 1). As in the high suggestible participants, low suggestibles showed no areas which were significantly activated to higher levels after the hypnotic induction. A direct comparison of high and low suggestible people showed that when under hypnosis high suggestible participants had lower levels of activation than low suggestibles in the left inferior, middle, superior and medial frontal gyri (Table 1c, Fig 1). No areas were present in which high suggestibles had significantly higher levels of activation than low suggestibles. 3.2. Effects of hypnosis on the brain during passive and active tasks To determine if the hypnosis-induced decreases in prefrontal activation persisted when the participants engaged in tasks, the same comparisons were carried out on the periods when the participants performed the two undemanding visual tasks (passive viewing) and when they performed the two demanding hallucination tasks (active hallucination). No significant group (high versus low suggestible and vice versa) differences in brain activity were found between scans acquired in and out of hypnosis during the passive viewing tasks. For the active tasks, direct group (high versus low suggestible and vice versa) comparisons showed that, when under hypnosis, the high suggestible participants had significantly lower levels of activation in the right middle and superior frontal gyri and in the caudate nucleus than the low suggestible participants (see Table 1d). High suggestible people also had significantly higher levels of activation in the right fusiform and lingual gyrus (see Table 1e). To test whether the reductions that occurred in the high suggestible people when resting under hypnosis were constant across conditions, the voxel that had the greatest reduction in activity (identified in the no hypnosis rest versus hypnosis rest comparison) was determined and the magnitude of the difference in signal in this voxel was then measured across the passive and active tasks, in both high and low suggestible participants. Fig. 2 shows that in the high suggestible participants (but not in the lows) differences between the hypnosis and no hypnosis periods appeared to decrease as task demands increased.

4. Discussion This fMRI study of resting brain activity showed that brain activity decreased significantly in the anterior part of the ‘default mode’ network (prefrontal cortex) in high suggestible participants when hypnotized. No areas had significant increases in activation in this group when in hypnosis. Reduction of spontaneous brain activation in the dorsal and ventromedial prefrontal cortex was not observed in low suggestible people after the hypnotic induction, nor was any area of increased activation detected. Normally, these modifications in the spontaneous physiological resting brain activity, which occurred only in high suggestible individuals after hypnotic induction, would be observable only when people engage in an externally orientated task. In that case, however, reduced activity in anterior default mode areas should also be accompanied by decreases in the posterior section of the default mode network, in addition to concurrent increases in activation in areas related to the task they are attending to. To our knowledge, this study is the first to have observed a reduction in spontaneous default brain activity

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Table 1 Significant differences for the resting state comparisons (a) No hypnosis versus hypnosis in highly suggestible participants, (b) No hypnosis versus hypnosis in low suggestible participants, (c) direct group comparison of high versus low suggestible participants (no hypnosis versus hypnosis). Significant differences for the active state comparisons are shown in (d) the direct group comparison of high versus low suggestible participants (hypnosis versus no hypnosis), and (e) high versus low suggestible participants (no hypnosis versus hypnosis). Brain area – Brodmann’s area (BA)

Left/right

Number of voxels in cluster

Cluster-level p-value (corrected)

Z value at local maximum

Talairach coordinates x

(a) No hypnosis versus hypnosis in high suggestible participants (rest) Superior frontal gyrus (BA 10, 8, 9) L 6803 Middle frontal gyrus (BA 8, 11) L Inferior frontal gyrus (BA 47, 11) L Medial frontal gyrus (BA 8, 11, 10) L Anterior cingulate (BA 32, 25) L Superior frontal gyrus (BA 8) R Medial frontal gyrus (BA 6, 8, 11, 10) R Anterior cingulate (BA 32) R

z

0.000

3.90 3.22 2.60 3.55 2.96 2.77 3.44 2.47

18 34 24 6 0 22 6 4

56 17 20 41 29 35 48 45

25 38 18 40 28 44 36 9

0.001

3.75 3.47 3.06 2.74 3.26 2.96 3.02 2.36 3.02 2.85 2.48 2.48

40 16 6 42 34 18 16 28 24 6 20 8

3 25 22 16 10 12 8 28 33 28 26 14

13 10 27 16 3 14 4 16 9 24 18 4

(c) High versus low suggestible participants (no hypnosis versus hypnosis) (rest) Inferior frontal gyrus (BA 47) L 541 0.002* Middle frontal gyrus (BA 47) L Superior frontal gyrus (BA 9) L 506 0.002* Medial frontal gyrus (BA 8, 6) L

4.03 3.42 3.96 3.35

51 44 20 4

38 35 56 39

7 3 27 42

(d) High versus low suggestible participants (hypnosis versus no hypnosis) (active) Lingual gyrus (BA 18) R 264 0.035* Fusiform gyrus (BA 19) R

3.40 3.27

8 28

84 76

6 10

(e) High versus low suggestible participants (no hypnosis versus hypnosis) (active) Caudate R 859 0.023 Superior frontal gyrus (BA 11) R Middle frontal gyrus (BA 11) R

3.55 3.23 3.08

4 10 18

8 50 36

4 16 10

(b) No hypnosis versus hypnosis in low suggestible participants (rest) Insula (BA 13) L 2670 Thalamus L Posterior cingulate (BA 23, 31) L Inferior frontal gyrus (BA 45) L Claustrum L Caudate L Lentiform nucleus L Insula (BA 13) R Thalamus R Posterior cingulate (BA 23) R Caudate R Subthalamic Nucleus R

*

y

p-value uncorrected, but cluster survives small volume correction.

during a condition of resting state without simultaneous increases in other areas in healthy participants. Therefore, this unique finding might reflect a change in brain state specific to the induction of hypnosis in people who are susceptible to its effects. The region which responded to hypnosis in rest is within the anterior part of the default mode network. As task demands increased across the experimental conditions (i.e. from rest, to passive, and active tasks), the difference in deactivation between hypnosis and no hypnosis in this area became increasingly smaller in the high suggestible participants (see Fig. 2). This latter finding is consistent with previous evidence that activation decreases in default mode areas as task demands increase (Fransson, 2006; Mason et al., 2007). It is not surprising, therefore, that in the passive and active viewing conditions of this study, the decrease in activity in these structures, which might have been due to hypnosis, was not discernable from that induced by progressively more demanding tasks. Changes in default brain activity, like those observed in our study, represent an interesting phenomenon that raises questions about the cognitive mechanisms a hypnotic induction invokes. Knowing exactly what each participant did during the rest blocks is difficult as those periods were not constrained in any way. However, there was no evidence in the data to suggest that as a group the participants engaged in any internally driven goal-directed cognitive task, as significant increases in activation were not detected in any region of the brain. The absence of activation suggests that participants as a group were not performing any single particular task. An interpretation of the mechanisms invoked by hypnotic induction and the relevance of decreased anterior default mode activity in high suggestible people may be attempted by reference to the evidence from studies of changes in default mode activity in healthy and pathological brain states. In normal populations, the default mode has been linked to letting one’s mind wander in the resting state (Mason et al., 2007). In contrast, hypnosis has been linked to a state of readiness to respond

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Fig. 1. Areas of decreased activation due to hypnotic induction in the resting state in high suggestible participants (blue) and low suggestible participants (red). Significant between group differences (greater deactivation in the highs than in lows when directly compared) are shown in yellow. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2. Hypnosis/no hypnosis activity difference (expressed in T values) in the left medial superior frontal gyrus (Talairach voxel coordinates [ 18, 56, 25]) across rest, passive and active tasks, in the high and low suggestible participants.

to whatever suggestions are subsequently given (Kirsch & Lynn, 1998; Tellegen, 1981). Thus, hypnotized individuals may succeed in suspending spontaneous non-goal-directed cognitive activity in preparation for what might be required by future tasks. If this is the case, then one might expect them to exhibit a relative deactivation of the default mode following the induction of hypnosis. Failure to deactivate task irrelevant structures in the default network has been suggested as an explanation of poor cognitive performance in older adults, providing a reason why they are more prone than younger adults to distraction by irrelevant information (Grady, Springer, Hongwanishkul, McIntosh, & Winocur, 2006). In our study, the deactivation of default mode areas in high suggestible people might reflect a state in which irrelevant thought processes are inhibited. Abnormalities in default mode function have been observed in people with autism, a condition in which impaired spontaneous activity in the default mode network has been observed at rest, especially in the anterior ventromedial prefrontal structures which are related to self-directed thoughts, an ability that is particularly impaired in autistic people (Iacoboni, 2006; Kennedy, Redcay, & Courchesne, 2006). Higher levels of activation in medial dorsal and/or ventral prefrontal regions have also been observed while normal healthy people engage in self-referential thought and social-cognitive tasks such as mentalizing about the views of others (Farb et al., 2007; Kelley et al., 2002; Mitchell, Macrae, & Banaji, 2006; Moran, Macrae, Heatherton, Wyland, & Kelley, 2006; Saxe, Moran, Scholz, & Gabrieli, 2006). In addition, a recent review on the default mode network (see Buckner, Andrews-Hanna, & Schacter, 2008) suggests that there might be two main sub-systems that interact within the default mode network; a posterior system which seems associated with memory and is linked extensively to the hippocampal formation, and an anterior system which is activated when participants create self-relevant mental simulations. Consequently, significantly decreased levels of anterior default mode activity during the resting periods in hypnosis suggest that high suggestible participants might be able to suspend spontaneous cognitive activity in the absence of concurrent tasks and may be able to reduce interference from spontaneous self-directed thoughts, possibly in preparation for what might be required by future tasks or in anticipation of whatever instructions they might receive by another agent.

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Decreased activity confined to the anterior cingulate cortex within the anterior default mode network (a region in which decreased activity at rest was seen in this study), has been previously reported in investigations of brain activity during hypnosis (Raz, Fan, & Posner, 2005), but the reported differences were detected while participants exhibited decreased susceptibility to the Stroop interference effect by interpreting visual words as nonsense strings of letters. The finding was interpreted as evidence that the suggestion given in hypnosis decreased activation in brain areas involved in conflict resolution (Oakley, 2008; Raz et al., 2005). This explanation cannot apply to the finding of decreases in the anterior cingulate cortex during rest obtained in the current study, as the effect of suggestion was excluded (i.e., it was the same for the hypnosis and no hypnosis condition). The decreased activation in the anterior cingulate during hypnosis has been discussed in the present paper primarily in terms of its role in the default mode network. However, activity in anterior cingulate cortex has also been detected in studies of conflict resolution, error detection and inhibition (Braver, Barch, Gray, Molfese, & Snyder, 2001; Kiehl, Liddle, & Hopfinger, 2000; Lutcke & Frahm, 2008; Pardo, Pardo, Janer, & Raichle, 1990). Nevertheless, our findings cannot be completely explained in terms of these functions, given the extent of decrease observed in other parts of the anterior default mode network. Instead, the extent of changes in these anterior regions during hypnosis suggests that modulation of a broader area is occurring, such as that involved in the self-referential anterior default mode processing system. Low suggestible people differed from high suggestible individuals in the pattern of changes of rest brain activity during hypnosis. Instead of deactivation in the default mode regions, after hypnotic induction, the low suggestible group showed lowering of activation in the thalamus. Previous evidence shows that changes in thalamic activity are associated with changes in alertness (Sturm & Willmes, 2001) and activation in this area is reduced when people are under general anaesthesia (White & Alkire, 2003). This finding implies that low suggestible individuals enter a state of decreased alertness, which is associated with the thalamus. The effect of hypnotic induction on thalamic activity in the low suggestible participants might be due to the component of the induction which suggested relaxation. Furthermore, the absence of thalamic decreases in the high suggestible participants when resting under hypnosis suggests that the induced state is not simply one of relaxation or of a lowered level of alertness. It is important to note that our findings do not resolve the altered state controversy. Although they are consistent with altered state theories, they are also consistent with Wagstaff’s (1998) contention that the induced ‘state’ is an epiphenomenon. According to Wagstaff, suggestible subjects respond to the suggestion to experience a hypnotic state, just like they do to any other suggestion, and this experience is bound to have neurological correlates. To support the altered state theory, one would have to show a causal connection between the induced state and response to suggestions (Lynn, Kirsch, Knox, Fassler, & Lilienfeld, 2007). That is, it would need to be shown that reducing default mode activity prior to the administration of hypnotic suggestions enhances responsiveness to those suggestions. Also, our study did not include any participants in the medium range of suggestibility. This is important to consider because differences between high and low suggestible individuals could be due to characteristics of low suggestible participants (e.g., low task involvement, anxiety about hypnosis, disinterest) rather than ‘‘state alterations” in the highly suggestible subjects. Indeed, our finding that low suggestibles exhibited signs of decreased alertness is consistent with motivational differences across the suggestibility groups. Future studies on the hypothesized hypnotic state could benefit from the inclusion of moderately suggestible participants. In conclusion, by using a refined experimental design (and a direct within subject comparison of rest epochs across scans, contrasting hypnosis versus non hypnosis directly rather than rest versus another within scan task), this fMRI study has shown that highly suggestible people suspend brain activity in the anterior system of the default mode network in rest following hypnotic induction while this is not the case for low suggestible people. Acknowledgments The authors thank L. Nocetti, P. Nichelli, L. Foan and K. Roberts for their various contributions to this study. This study was partially funded by grants from MIUR to AV and from the BBC to IK and GM. References Braver, T. S., Barch, D. M., Gray, J. R., Molfese, D. L., & Snyder, A. (2001). Anterior cingulate cortex and response conflict: Effects of frequency, inhibition and errors. Cerebral Cortex, 11(9), 825–836. Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). 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