Effects of Direct and Indirect Suggestions for Analgesia: The Role of Hypnotizability and Expectation of Pain Relief.

Among the methods for cognitive control of pain, the suggestions for analgesia-direct or indirect-have been widely and successfully used in experimental and clinical trials. The primary aim of this study was to contribute to the debate about the difference in the effectiveness of indirect and direct suggestions for the management of experimental pain in the ordinary state of consciousness. The secondary aim of the study was to ascertain the role of hypnotizability and expectation of pain relief in the suggestions' effect. A sample of 65 healthy participants with different levels of direct (Harvard Group Scale of Hypnotic Susceptibility: A score) and indirect suggestibility level (Alman-Wexler Indirect Hypnotic Susceptibility Scale score) and different levels of declared expectation of pain relief was submitted to direct and indirect suggestions for analgesia during cold pressure test. The results showed that both direct and indirect suggestions increase the threshold of experimental pain and that the expectation of pain relief is relevant only to the effect of direct suggestions. PERSPECTIVE: Although the reported findings cannot be extended to clinical pain, they suggest that indirect suggestions can be effective independently from the expectation of pain relief, thus evading the possible negative effects of traits such as catastrophism or reactance. Thus, indirect suggestions should be preferred in clinical contexts.

Interoception as a function of hypnotizability during rest and a heartbeat counting task.

The hypnotizability-related differences in morpho-functional characteristics of the insula could at least partially account for the differences in interoceptive accuracy (IA) observed between high and low hypnotizable individuals (highs, lows). Our aim was to investigate interoceptive processing in highs, lows, and medium hypnotizable individuals (mediums), who represent most of the population, during a 10-minute open eyes relaxation condition (Part 1) and three repetitions of consecutive 2-minute open eyes, closed eyes, and heartbeat counting conditions, followed by a 2-minute post-counting condition (Part 2). Electrocardiogram and electroencephalogram were recorded in 14 highs, 14 mediums, and 18 lows, classified according to the Stanford Hypnotic Susceptibility Scale: Form A. Heartbeat-evoked cortical potentials (HEP) were extracted throughout the entire session, and IA index was obtained for the heartbeat counting task (HCT). In Part 1, significant hypnotizability-related differences were observed in the right central region in both early and late HEP components, with lows showing positive amplitudes and highs/mediums showing negative amplitudes. In Part 2, the same group differences were limited to the early component. Moreover, in the left frontal regions, only mediums modified their HEP during the counting task with respect to the open/closed eyes conditions, whereas highs displayed HEP differences between counting and post-counting rest. HCT did not show significant group differences. In conclusion, highs and mediums seem to be more similar than mediums and lows regarding HEP, despite the absence of significant differences in HCT. Nonetheless, a negative correlation between hypnotizability scores and HEP amplitudes was observed in the regions showing group differences.

Hypnotizability-related risky experience and behavior.

Risk is the probability of an adverse event. The proneness to take a risk and the risk taking behavior differ among the general population. Hypnotizability is a stable psychophysiological trait expressing the individual proneness to modify perception, memory and behavior following specific suggestions also in the ordinary state of consciousness. Some hypnotizability-related neurophysiological and behavioral correlates suggest that hypnotizability level, measured by standard scales classifying individuals as low (lows), medium (mediums) and high hypnotizable (highs) subjects, can be related to risk propensity and risk-taking. To study whether hypnotizability modulates risk propensity and behavior, we recruited healthy participants, classified through the Standford Hypnotic Susceptibility scale, form A, and compared lows' (n = 33), mediums' (n = 19) and highs'(n = 15) experiential and behavioral risk perception and propensity variables through the Domain-specific risk-taking scale and the Balloon Analogue Risk Task. MANOVA results indicated that different hypnotizability levels are not associated with different risky behavior and experience, except for higher expected financial benefits from risky behavior in lows. However, hypnotizability-related risk profiles were identified through correlational analyses. In fact, highs exhibited a negative association between risk perception and propensity to risk-taking, whereas mediums and lows displayed a positive association between risk propensity and expected benefit. In conclusion, the highs' profile indicates a more automatic behavior with respect to mediums and lows.

Physiological Correlates of Hypnotizability: Hypnotic Behaviour and Prognostic Role in Medicine.

Studies in the field of experimental hypnosis highlighted the role of hypnotizability in the physiological variability of the general population. It is associated, in fact, with a few differences which are observable in the ordinary state of consciousness and in the absence of suggestions. The aim of the present scoping review is summarizing them and indicate their relevance to the neural mechanisms of hypnosis and to the prognosis and treatment of a few medical conditions. Individuals with high, medium and low hypnotizability scores display different cerebral functional differences-i.e., functional equivalence between imagery and perception/action, excitability of the motor cortex, interoceptive accuracy-possibly related to brain structural and functional characteristics, and different control of blood supply at peripheral and cerebral level, likely due to different availability of endothelial nitric oxide. These differences are reviewed to support the idea of their participation in hypnotic behaviour and to indicate their prognostic and therapeutic usefulness in a few medical conditions.

Modulation of the heartbeat evoked cortical potential by hypnotizability and hypnosis.

Hypnotizability is a psychophysiological trait measured by scales and associated with several differences, including interoceptive accuracy and the morpho-functional characteristics of interoception-related brain regions. The aim of the study was to assess whether the amplitude of the heartbeat evoked cortical potential (HEP), a correlate of interoceptive accuracy, differs in participants with low (lows) and high (highs) hypnotizability scores (assessed by the Stanford Hypnotic Susceptibility Scale, Form A) before and after the induction of hypnosis. ECG and EEG were monitored in 16 highs and 15 lows during an experimental session, including open eyes baseline (B), closed eyes relaxation (R), hypnotic induction (IND), neutral hypnosis (NH), and post session baseline (Post). No significant difference was observed between groups and conditions in autonomic variables. The HEP amplitude was lower in highs than in lows at the right parietal site, likely due to hypnotizability related differences in the functional connection between the right insula and parietal cortex. It increased in highs and decreased in lows across the session, possibly due to the highs' preeminently internally directed attention and to the lows' possible disengagement from the task. Since interoception is involved in several cognitive-emotional functions, its hypnotizability related differences may contribute to the variability of experience and behavior in daily life.

Is hypnotic assessment relevant to neurology?

Studies conducted in healthy subjects have clearly shown that different hypnotic susceptibility, which is measured by scales, is associated with different functional equivalence between imagery and perception/action (FE), cortical excitability, and information processing. Of note, physiological differences among individuals with high (highs), medium (mediums), and low hypnotizability scores (lows) have been observed in the ordinary state of consciousness, thus independently from the induction of the hypnotic state, and in the absence of specific suggestions. The potential role of hypnotic assessment and its relevance to neurological diseases have not been fully explored. While current knowledge and therapies allow a better survival rate, there is a constant need to optimize rehabilitation treatments and quality of life. The aim of this paper is to provide an overview of hypnotizability-related features and, specifically, to discuss the hypothesis that the stronger FE, the different mode of information processing, and the greater proneness to control pain and the activity of the immune system observed in individuals with medium-to-high hypnotizability scores have potential applications to neurology. Current evidence of the outcome of treatments based on hypnotic induction and suggestions administration is not consistent, mainly owing to the small sample size in clinical trials and inadequate control groups. We propose that hypnotic assessment may be feasible in clinical routine and give additional cues into the treatment and rehabilitation of neurological diseases.

Well-Being in Highly Hypnotizable Persons.

Both hypnotizability and well-being are relevant to health. This study aimed to investigate whether high hypnotizability was positively associated with well-being and whether the latter was related to the activity of the behavioral inhibition/approach system (BIS/BAS). ANOVA revealed significantly higher scores on the General Well-Being Index (PGWBI) in highly hypnotizable (highs, n = 31) compared with low hypnotizable participants (lows, n = 53), with medium hypnotizable participants (mediums, n = 41) exhibiting intermediate values. This finding was discussed in relation to other hypnotizability-related traits, such as morpho-functional brain characteristics, equivalence between imagery and perception, and interoceptive sensitivity. A secondary finding was a nonsignificant gender difference in scores on the PGWBI. The highs' higher well-being could be considered a favorable prognostic factor for physical and mental health.

Heartbeat-Evoked Cortical Potential during Sleep and Interoceptive Sensitivity: A Matter of Hypnotizability.

Individuals with different hypnotizability display different interoceptive sensitivity/awareness (IS) and accuracy (IA), likely sustained by morphofunctional differences in interoception-related brain regions and, thus, possibly also observable during sleep. We investigated the heartbeat-evoked cortical potential amplitude (HEP) during sleep, its association with IS, and the role of hypnotizability in such association. We performed a retrospective analysis of polysomnographic recordings of 39 healthy volunteers. Participants completed the Multidimensional Assessment of Interoceptive Awareness (MAIA), measuring IS and IA, and underwent hypnotic assessment via the Stanford Hypnotic Susceptibility Scale, form A. The amplitude of the early and late HEP components was computed at EEG frontal and central sites. In both regions, the early HEP component was larger in N3 than in N2 and REM, with no difference between N2 and REM. Greater HEP amplitude at frontal than at central sites was found for the late HEP component. HEP amplitudes were not influenced by the autonomic state assessed by heart rate variability in the frequency and time domains. We report for the first time a positive correlation between the central late HEP component and MAIA dimensions, which became non-significant after removing the effects of hypnotizability. Our findings indicate that hypnotizability sustains the correlation between IS and HEP amplitude during sleep.

Interoceptive Accuracy as a Function of Hypnotizability.

This study aimed to measure the interoceptive accuracy (IA) of individuals with high (highs), medium (mediums), and low hypnotizability (lows) through the heartbeat-counting task during 3 relaxation trials. Participants completed the Multidimensional Assessment of Interoceptive Awareness (MAIA), ECG and skin conductance (SC) were monitored, and the experienced difficulty in counting was reported. Results showed similar counting difficulty and number of actual heartbeats in highs, mediums, and lows. SC decreased in highs during all trials, in mediums and lows only in the third trial. IA measured as [1 - (ǀrecorded heartbeats-counted heartbeatsǀ)/recorded heartbeats] was negatively correlated with hypnotizability and not correlated with interoceptive sensitivity (IS) measured by MAIA scales. Among mediums, IA was higher in males than in females.

An evolutionary approach to hypnotizability.

We propose here an evolutionary interpretation of the presence of highly hypnotizable persons (highs) among the general population. Current experimental evidence suggests the presence of stronger functional equivalence between imagery and perception, non-opioid cognitive control of pain, favorable cardiovascular asset, and greater interoceptive sensitivity in highs. We hypothesize that these characteristics were greatly relevant to our ancestors' survival, and that they may have facilitated the natural selection of individuals who are now named "highs" due to one of their side effects - the proneness to accept suggestions - as part of the reported physiological features. Unfortunately, our theoretical hypothesis cannot be currently experimentally proven. We believe, however, that looking at hypnotizability in a naturalistic, evolutionary perspective may emphasize the importance of its physiological correlates in daily life and in the prediction of the outcome of medical treatments.

Linear and non linear measures of pupil size as a function of hypnotizability.

Higher arousal and cortical excitability have been observed in high hypnotizable individuals (highs) with respect to low hypnotizables (lows), which may be due to differences in the activation of ascending activating systems. The present study investigated the possible hypnotizability-related difference in the cortical noradrenergic tone sustained by the activity of the Locus Coeruleus which is strongly related to pupil size. This was measured during relaxation in three groups of participants-highs (N = 15), lows (N = 15) and medium hypnotizable individuals (mediums, N = 11)-in the time and frequency domains and through the Recurrence Quantification Analysis. ECG and Skin Conductace (SC) were monitored to extract autonomic indices of relaxation (heart interbeats intervals, parasympathetic component of heart rate variability (RMSSD) and tonic SC (MeanTonicSC). Most variables indicated that participants relaxed throughout the session. Pupil features did not show significant differences between highs, mediums and lows, except for the spectral Band Median Frequency which was higher in mediums than in lows and highs at the beginning, but not at the end of the session.Thus, the present findings of pupil size cannot account for the differences in arousal and motor cortex excitability observed between highs and lows in resting conditions.

Multisensory Integration Is Modulated by Hypnotizability.

This study investigated multisensory integration in 29 medium-to-high (mid-highs) and 24 low-to-medium (mid-lows) hypnotizable individuals, classified according to the Stanford Hypnotic Susceptibility Scale, Form A. Participants completed a simultaneity judgment (SJ) task, where an auditory and a visual stimulus were presented in close proximity to their body in a range of 11 stimulus onset asynchronies. Results show that mid-highs were prone to judge audiovisual stimuli as simultaneous over a wider range of time intervals between sensory stimuli, as expressed by a broader temporal binding window, when the visual stimulus precedes the auditory one. No significant difference was observed for response times. Findings indicate a role of hypnotizability in multisensory integration likely due to the highs' cerebellar peculiarities and/or sensory modality preference.

Postural effects of interoceptive imagery as a function of hypnotizability.

The aim of the study was to investigate the effects of pleasant and unpleasant interoceptive imagery on postural control in participants with different hypnotizability, interoceptive sensibility and ability of imagery. Forty-one healthy individuals classified as high (highs), medium (mediums) and low hypnotizables (lows) according to the Stanford Hypnotic Susceptibility Scale, form A (SHSS, A) were characterized for Interoceptive Sensitivity (IS) through the Multisensory Assessment of Interoceptive Awareness (MAIA) and for organic mental imagery (ORG) through Betts' questionnaire. The experimental session included baseline closed eyes conditions preceding tasks of pleasant (P) and unpleasant imagery (U) and a neutral cognitive task (NT) while standing on a stabilometric platform. Subjective reports of vividness and pleasantness/unpleasantness of mental images were collected. Postural variables, ECG and pneumogram were acquired. Highs exhibited greater vividness of imagery than mediums/lows and larger Area of the Centre of Pressure (CoP), while mediums and lows decreased it during all tasks with respect to baseline conditions. Significant differences moderated by IS and ORG were found between highs and lows in the CoP Area. In all groups significant task related differences in the CoP Area were moderated only by IS. Cardiovascular variables were similar in the three groups, but differed among tasks and were influenced by IS and ORG. Our findings extend earlier observations on the role of hypnotisability in the postural correlates of sensorimotor imagery to interoceptive imagery, support the hypothesis that interoceptive sensibility moderates postural control and cardiorespiratory variables during interoceptive imagery, and confirm earlier reports of the absence of hypnotisability-related modulation of cardiorespiratory variables during emotional tasks.

Hypnotizability-Related Effects of Pain Expectation on the Later Modulation of Cortical Connectivity.

This study examined hypnotizability-related modulation of the cortical network following expected and nonexpected nociceptive stimulation. The electroencephalogram (EEG) was recorded in 9 high (highs) and 8 low (lows) hypnotizable participants receiving nociceptive stimulation with (W1) and without (noW) a visual warning preceding the stimulation by 1 second. W1 and noW were compared to baseline conditions to assess the presence of any later effect and between each other to assess the effects of expectation. The studied EEG variables measured local and global features of the cortical connectivity. With respect to lows, highs exhibited scarce differences between experimental conditions. The hypnotizability-related differences in the later processing of nociceptive information could be relevant to the development of pain-related individual traits. Present findings suggest a lower impact of nociceptive stimulation in highs than in lows.

Association of hypnotizability and deep sleep: any role for interoceptive sensibility?

The aim of the study was to investigate the possible association of hypnotizability and deep sleep (N3) duration, and whether the interoceptive sensibility influences this association. This was motivated by the proneness of highly hypnotizable individuals to easily change their psychophysiological state, i.e., from wakefulness to hypnosis and sleep, and by the positive association observed between hypnotizability and interoceptive sensibility. Forty-seven healthy participants previously enrolled in a polysomnographic night sleep study completed the questionnaire for Multidimensional Assessment of Interoceptive Awareness (MAIA) and underwent hypnotic assessment through the Stanford Hypnotic Susceptibility Scale, form A (SHSS,A). Results showed that N3 duration is not linearly correlated with hypnotizability. Controlling for a few MAIA scales did not modify the relation between hypnotizability and deep sleep. A polynomial relation indicates that N3 duration and N3 percentage of the total sleep time increase with hypnotizability in the low-to-medium range of hypnotizability and decrease in the medium-to-high range. In conclusion, hypnotic assessment predicts N3 duration and their association is not modified by interoceptive awareness/sensitivity.

High Motor Cortex Excitability in Highly Hypnotizable Individuals: A Favourable Factor for Neuroplasticity?

Hypnotizability is a psychophysiological trait associated with morphofunctional brain peculiarities and with several cognitive, sensorimotor and cardiovascular correlates. Behavioral and EEG studies indicate stronger functional equivalence (FE) between motor imagery and action in the individuals with high hypnotizability scores (Highs). We hypothesized that stronger FE leading to greater proneness to ideomotor behavior could be due to greater cortical excitability of the motor cortex. The aim of the study was to evaluate the motor cortical excitability through measurements of the muscle potentials (MEPs) evoked in the left abductor pollicis brevis by transcranial magnetic stimulation (TMS) of the right motor cortex in 10 Highs, 10 medium (Mediums) and 10 low hypnotizable individuals (Lows) classified according to the Stanford Hypnotic Susceptibility Scale, form A (SHSS). They were studied in basal conditions (B) and during motor imagery (MI). Results showed significant, negative correlations (i) between hypnotizability and MEPs Resting Motor Threshold (RMT) in basal conditions, and (ii) between hypnotizability and both MEPs RMT and suprathreshold (I1mv) stimulation intensities during MI. ANOVA revealed significantly lower stimulation intensities in Highs than in Lows, with Mediums exhibiting intermediate values. Thus, the Highs' greater cortical excitability could sustain their greater FE and proneness to ideomotor behavior. In cognitive neuroscience these findings are relevant to the physiological interpretation of the response to sensorimotor suggestions by participants in the ordinary state of consciousness. In the clinical field they can predict the efficacy of mental training based on motor imagery and, possibly, the degree of imagery-induced cortical plasticity.

HYPNOTIZABILITY-RELATED FAAH C385A POLYMORPHISM: POSSIBLE ENDOCANNABINOID CONTRIBUTION TO SUGGESTION-INDUCED ANALGESIA.

Fatty acid amide hydrolase (FAAH) degrades the endogenous endocannabinoid (eCB) anandamide and might be involved in the response to suggestions of analgesia in subjects with high hypnotizability scores (highs). Since the A allele of the FAAH C385A polymorphism (rs324420) is associated with lower FAAH activity, it was studied in 21 highs, 66 low hypnotizable individuals (lows), and 172 individuals not selected for hypnotizability (controls) representing the general population. No significant difference was observed among groups, but the A allele frequency showed a significant trend to increase from lows to controls and from controls to highs. Since eCB small differences can be amplified by eCB interactions with other neurotransmitters, a contribution of the FAAH polymorphism to the highs' analgesia should not be excluded.

RESPONDING TO SENSORIMOTOR SUGGESTIONS: From Endothelial Nitric Oxide to the Functional Equivalence Between Imagery and Perception.

The reduced cerebellar gray matter (GM) volume observed in highly hypnotizable individuals (highs) is likely due to the excessive release of endothelial nitric oxide in the brain and could account for their behavioral (postural and visuomotor control) and physiological (paradoxical pain control after cerebellar anodal stimulation) characteristics. Reduced cerebellar GM can induce low inhibition of the cerebral cortex, thus stronger functional equivalence (FE) between imagery and perception and greater proneness to respond to sensorimotor suggestions. In fact, stronger FE suggested in highs by behavioral studies has been confirmed by topological data analysis of EEG signals recorded during sensorimotor and imagery tasks. The authors' hypothesis cannot be applied to obstructive suggestions likely sustained by mechanisms related to socio-cognitive factors, i.e., oxytocin availability.

Does hypnotic assessment predict the functional equivalence between motor imagery and action?

Motor imagery is influenced by individual and contextual factors. We investigated whether the psychophysiological trait of hypnotisability modulates its subjective experience and cortical correlates similarly to what was previously shown for head postures mental images. EEG was acquired in 18 high (highs) and 15 low (lows) hypnotizable subjects (Stanford Hypnotic Susceptibility Scale, A). The experimental conditions were: baseline, a complex arm/hand movement, visual (1st person) and kinesthetic imagery of the movement. After each imagery condition, participants scored the vividness and easeness of their performance and their ability to mantain the requested modality of imagery. Subjective reports, chronometric visual/kinesthetic indices, absolute beta and fronto-central midline alpha powers were analyzed. Findings confirmed earlier reports of better kinestetic imagery ability in highs than in lows and better visual than kinesthetic imagery in lows, as well as smaller restructuring of the cortical activity in highs than in lows, during all tasks. Also, they show that hypnotisability accounts for most of the correlations between brain regions for both alpha and beta changes. Thus, imagined and actual movements were less demanding processes in highs at subjective and cortical levels. Finally, hypnotic assessment assists to plan personalized mental training for neuro-rehabilitation and sports and predict their efficacy.

Topology highlights mesoscopic functional equivalence between imagery and perception: The case of hypnotizability.

The functional equivalence (FE) between imagery and perception or motion has been proposed on the basis of neuroimaging evidence of large spatially overlapping activations between real and imagined sensori-motor conditions. However, similar local activation patterns do not imply the same mesoscopic integration of brain regions, which can be described by tools from Topological Data Analysis (TDA). On the basis of behavioral findings, stronger FE has been hypothesized in the individuals with high scores of hypnotizability scores (highs) with respect to low hypnotizable participants (lows) who differ between each other in the proneness to modify memory, perception and behavior according to specific imaginative suggestions. Here we present the first EEG evidence of stronger FE in highs. In fact, persistent homology shows that the highs EEG topological asset during real and imagined sensory conditions is significantly more similar than the lows. As a corollary finding, persistent homology shows lower restructuring of the EEG asset in highs than in lows during both sensory and imagery tasks with respect to basal conditions. Present findings support the view that greater embodiment of mental images may be responsible for the highs greater proneness to respond to sensori-motor suggestions and to report involuntariness in action. In addition, findings indicate hypnotizability-related sensory and cognitive information processing and suggest that the psycho-physiological trait of hypnotizability may modulate more than one aspect of the everyday life.