Hypnotizability and sensorimotor gating: a dopaminergic mechanism of hypnosis

Dopaminergic mechanisms have been theorized to influence hypnotizability and sensorimotor gating. In this study, the authors investigated an association between sensorimotor gating, as measured by prepulse inhibition (PPI), and hypnotizability, as assessed by the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C). They found an inverse correlation between the SSHS:C and PPI. This finding, which replicates an earlier study, provides further evidence for a dopaminergic basis for hypnotizability and suggests additional avenues for research, including a method for possibly enhancing hypnotizability through pharmacological interventions.     

Antipsychotic-like properties of phosphodiesterase 4 inhibitors: evaluation of 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO-20-1724) with auditory event-related potentials and prepulse inhibition of startle

Antipsychotic medications function through antagonism of D2 dopamine receptors. Blockade of D2 receptors causes an increase in intracellular cAMP, a ubiquitous second messenger. Inhibition of phosphodiesterase (PDE) activity, a family of enzymes that degrade cyclic nucleotides, causes the same effect. The conceptual linkage between dopamine D2 receptors and PDE activity via cAMP suggests a possible therapeutic potential for PDE inhibitors in schizophrenia. The limited number of studies in support of this hypothesis used rolipram, a specific inhibitor of the PDE4 family. In this study, we investigated the impact of 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (RO-20-1724), another PDE4-specific inhibitor, on auditory event-related potentials (ERPs), prepulse inhibition (PPI) of the startle reflex, and locomotor activity in mice. The ability to reverse amphetamine-induced alterations in ERPs and PPI was used as a model for psychosis. ERPs after RO-20-1724 revealed increased amplitude for the P20 and N40 ERP components. RO-20-1724 reversed the disruptive effect of amphetamines on ERPs and restored gating at a dose that did not impair locomotor activity. However, RO-20-1724 failed to reverse a amphetamine-induced decrease of PPI. Inconsistent results between these two psychosis models suggest that pure sensory processing, as measured with auditory ERPs, may be more sensitive to the effects of intracellular cAMP than sensorimotor effects as assessed with PPI. It remains unclear whether antipsychotic-like properties are a common feature of PDE4 inhibition, or if they are restricted to the pharmacological profile of rolipram. Future studies should examine how PDE4 subtype specificity might contribute to differences between rolipram and RO-20-1724 in sensorimotor gating.     

Frontal-striatal-thalamic mediodorsal nucleus dysfunction in schizophrenia-spectrum patients during sensorimotor gating

Prepulse inhibition (PPI) refers to a reduction in the amplitude of the startle eyeblink reflex to a strong sensory stimulus, the pulse, when it is preceded shortly by a weak stimulus, the prepulse. PPI is a measure of sensorimotor gating which serves to prevent the interruption of early attentional processing and it is impaired in schizophrenia-spectrum patients. In healthy individuals, PPI is more robust when attending to than ignoring a prepulse. Animal and human work demonstrates that frontal–striatal–thalamic (FST) circuitry modulates PPI. This study used functional magnetic resonance imaging (fMRI) to investigate FST circuitry during an attention-to-prepulse paradigm in 26 unmedicated schizophrenia-spectrum patients (13 schizotypal personality disorder (SPD), 13 schizophrenia) and 13 healthy controls. During 3T-fMRI acquisition and separately measured psychophysiological assessment of PPI, participants heard an intermixed series of high- and low-pitched tones serving as prepulses to an acoustic-startle stimulus. Event-related BOLD response amplitude curves in FST regions traced on co-registered anatomical MRI were examined. Controls showed greater activation during attended than ignored PPI conditions in all FST regions—dorsolateral prefrontal cortex (Brodmann areas 46, 9), striatum (caudate, putamen), and the thalamic mediodorsal nucleus. In contrast, schizophrenia patients failed to show differential BOLD responses in FST circuitry during attended and ignored prepulses, whereas SPD patients showed greater-than-normal activation during ignored prepulses. Among the three diagnostic groups, lower left caudate BOLD activation during the attended PPI condition was associated with more deficient sensorimotor gating as measured by PPI. Schizophrenia-spectrum patients exhibit inefficient utilization of FST circuitry during attentional modulation of PPI. Schizophrenia patients have reduced recruitment of FST circuitry during task-relevant stimuli, whereas SPD patients allocate excessive resources during task-irrelevant stimuli. Dysfunctional FST activation, particularly in the caudate may underlie PPI abnormalities in schizophrenia-spectrum patients.     

Structural brain correlates of prepulse inhibition of the acoustic startle response in healthy humans

Neural regions modulating prepulse inhibition (PPI) of the startle response, an operational measure of sensorimotor gating, are well established from animal studies using surgical and pharmacological procedures. The limbic and cortico-pallido-striato-thalamic circuitry is thought to be responsible for modulation of PPI in the rat. The involvement of this circuitry in human PPI is suggested by observations of deficient PPI in a number of neuropsychiatric disorders characterized by abnormalities at some level in this circuitry and recent functional neuroimaging studies in humans. The current study sought to investigate structural neural correlates of PPI in a sample of twenty-four right-handed, healthy subjects (10 men, 14 women). Subjects underwent magnetic resonance imaging (MRI) at 1.5 T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimized volumetric voxel-based morphometry (VBM) implemented in SPM99 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120 ms) to regional grey matter volumes, covarying for sex. Significant positive correlations were obtained between PPI and grey matter volume in the hippocampus extending to parahippocampal gyrus, basal ganglia including parts of putamen, globus pallidus, and nucleus accumbens, superior temporal gyrus, thalamus, and inferior frontal gyrus. These findings identify the relationship between PPI and grey matter availability on a highly spatially localized scale in brain regions shown to be activated in recent functional neuroimaging studies in association with PPI in healthy humans and demonstrate the validity of structural neuroimaging methods in delineating the neural mechanisms underlying human PPI.     

Complementing the Latest APA Definition of Hypnosis: Sensory-Motor and Vascular Peculiarities Involved in Hypnotizability

The aim of this article is to complement the recently revised American Psychological Association (APA) definition of hypnotizability. It (a) lists a few differences in sensorimotor integration between subjects with high (highs) and low (lows) hypnotizability scores in the ordinary state of consciousness and in the absence of suggestions, (b) proposes that hypnotizability-related cerebellar peculiarities may account for them, (c) suggests that the cerebellum could also be involved in cognitive aspects of hypnotizability and (d) explains why the information derived from studies of sensorimotor and cardiovascular aspects of hypnotizability may be relevant to its definition and useful in orienting further experimental research in the field of hypnosis.     

RG3487, a novel nicotinic α7 receptor partial agonist, improves cognition and sensorimotor gating in rodents

Neuronal nicotinic α7 acetylcholine receptors (α7nAChRs) are expressed primarily in the brain and are implicated in modulating many cognitive functions (e.g., attention, working and episodic memory). Not surprisingly, much effort has been committed to the development of molecules acting at α7nAChRs as potential therapies for a variety of central nervous system diseases (e.g., Alzheimer's). N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-1H-indazole-3-carboxamide hydrochloride (RG3487) binds potently to the human α7nAChR (K(i) = 6 nM), in which it acts as a partial agonist (63-69% of acetylcholine) as assessed by whole-cell patch-clamp recordings in both oocytes and QM7 cell lines. RG3487 activates human α7nAChRs with an EC(50) of 0.8 μM (oocytes) and 7.7 μM (QM7 cells). RG3487 also exhibits antagonist properties at the serotonin 3 receptor [IC(50) = 2.8 nM (oocytes), 32.7 nM (N1E-115 cells)]. In vivo, RG3487 improved object recognition memory in rats after acute [minimally effective dose (MED) 1.0 mg/kg p.o.] or repeated (10 day) administration at brain and plasma concentrations in the low-nanomolar range. Spatial learning deficits in age-impaired rats were reversed after RG3487 administration (MED: 0.03 mg/kg i.p.) as evaluated in the Morris water maze task. In the prepulse inhibition (PPI) of startle model of sensorimotor gating, RG3487 improved apomorphine-induced deficits in PPI performance (MED: 0.03 mg/kg i.p.) and reversed phencyclidine-induced impairments in an attentional set-shifting model of executive function (MED: ≤0.03 mg/kg i.p.). Cumulative evidence from these studies indicates RG3487 is a novel and potent α7nAChR partial agonist that improves cognitive performance and sensorimotor gating.     

Estrogen and progesterone prevent disruption of prepulse inhibition by the serotonin-1A receptor agonist 8-hydroxy-2-dipropylaminotetralin

The aim of the present study was to investigate the effect of estrogen and progesterone treatment on 5-hydroxytryptamine (serotonin)-1A (5-HT(1A)) receptor-mediated disruption of prepulse inhibition (PPI) of acoustic startle. The age-at-onset of schizophrenia is later in women than men, and it has been suggested that women may be protected from schizophrenia by the sex steroid hormone estrogen. 5-HT(1A) receptors have been implicated in the development of schizophrenia and the action of antipsychotics. PPI is a model of sensorimotor gating that is deficient in schizophrenia and other illnesses. Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated. Some OVX rats received silastic implants filled with a low dose of estrogen (E20), a high dose of estrogen (E100), progesterone (P), or both the E20- and P-filled (E/P) silastic implants. Two weeks later, the rats were randomly treated with saline, or 0.02 or 0.5 mg/kg of the 5-HT(1A) receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). Treatment with 8-OH-DPAT resulted in a dose-dependent increase in startle amplitude in all rat groups. PPI was significantly reduced after injection of 0.5 mg/kg 8-OH-DPAT in sham-operated rats, untreated OVX rats, E20-treated OVX rats, and P-treated OVX rats. In contrast, in E100- and E/P-treated OVX rats, PPI was not significantly reduced by 0.5 mg/kg 8-OH-DPAT. These data suggest that treatment with a high dose of estrogen, or with a combination of estrogen and progesterone, prevents 8-OH-DPAT-induced disruption of PPI. Thus, these hormones could be protective against sensorimotor gating deficits, at least those induced by 5-HT(1A) receptor stimulation, and may therefore be beneficial against some symptoms of schizophrenia.     

Hypnotizability and blink rate: a test of the dopamine hypothesis

Evidence suggests a role for central dopaminergic activity in determining an individual's level of hypnotizability. The authors measured the correlation between blink rate, which has been shown to correlate with central dopaminergic activity, and hypnotizability. Forty-eight healthy participants were evaluated for hypnotizability by the Harvard Group Scales of Hypnotic Susceptibility and the Stanford Hypnotic Susceptibility Scale: Form C. Blink rate was assessed under conditions of conversation, staring at a cross, listening to music, and resting. Contrary to their hypothesis, the authors found a negative correlation between hypnotizability and blink rate, accounted for primarily by the higher blink rates at rest in medium as compared to high hypnotizables. The results do not provide evidence for a role of dopamine in determining hypnotizability.     

Hypnotizability and Blink Rate: A Test of the Dopamine Hypothesis

Evidence suggests a role for central dopaminergic activity in determining an individual's level of hypnotizability. The authors measured the correlation between blink rate, which has been shown to correlate with central dopaminergic activity, and hypnotizability. Forty-eight healthy participants were evaluated for hypnotizability by the Harvard Group Scales of Hypnotic Susceptibility and the Stanford Hypnotic Susceptibility Scale: Form C. Blink rate was assessed under conditions of conversation, staring at a cross, listening to music, and resting. Contrary to their hypothesis, the authors found a negative correlation between hypnotizability and blink rate, accounted for primarily by the higher blink rates at rest in medium as compared to high hypnotizables. The results do not provide evidence for a role of dopamine in determining hypnotizability.     

CAN SUBJECTIVE RATINGS OF ABSORPTION,DISSOCIATION, AND TIME PERCEPTION DURING “NEUTRAL HYPNOSIS” PREDICT HYPNOTIZABILITY?: An exploratory study

This study explored absorption, dissociation, and time perception on visual analogue scales (VAS) after a neutral hypnosis session to predict hypnotizability. Sixty-two subjects completed the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) and, during a neutral hypnosis session, VAS ratings of absorption, dissociation, and time perception. The findings indicated that 44% of subjects scored high, 35% medium, and 21% low on hypnotizability, as determined by scores on the SHSS:C. Dissociation VAS ratings significantly differed when comparing low to high and medium to high hypnotizable subjects. However, ratings were not significantly different between medium and low subjects. Significant positive correlation was found between dissociation VAS ratings and SHSS:C total scores. Future research is needed to validate this proof-of-concept study.     

Pharmacologic interactions between the muscarinic cholinergic and dopaminergic systems in the modulation of prepulse inhibition in rats

Prepulse inhibition (PPI) of the acoustic startle reflex is a sensorimotor gating process known to be deficient in a number of neurologic and psychiatric conditions, including schizophrenia. Multiple lines of evidence have indicated that the dopaminergic and muscarinic cholinergic systems play an important role in modulating PPI. Moreover, interactions between the dopaminergic and muscarinic cholinergic systems are well known; however, little is known about potential interactions between the two systems in modulating PPI. Therefore, the purpose of the present studies was to determine whether interactions occur between the muscarinic cholinergic and dopaminergic systems in modulating PPI. The efficacy of muscarinic cholinergic receptor agonists in reversing the disruption of PPI induced by apomorphine, a D1/D2 dopamine receptor agonist, was evaluated in male Sprague-Dawley rats. The M1/M4-preferring muscarinic agonist xanomeline and the M2/M4-preferring agonist BuTAC [([5R-[exo]-6-[butylthio]-1,2,5-thiadiazol-3-yl-]-1-azabyciclo-[3.2.1])octane oxalate] reversed the apomorphine-induced disruption of PPI in a manner similar to that produced by the D2-like dopamine receptor antagonists haloperidol and olanzapine. The muscarinic agonists oxotremorine, RS86 [[2-ethyl-8-methyl-2,8-diazaspiro(4.5)decane-1,3-dione] hydrochloride], pilocarpine, milameline, and sabcomeline also reversed the apomorphine-induced disruption of PPI. Moreover, the muscarinic antagonist scopolamine also disrupted PPI, and the D2-like receptor antagonist haloperidol, but not the D1-like receptor antagonist SCH23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], reversed the scopolamine-induced disruption. In addition, xanomeline produced a significant reversal of the disruption in PPI produced by scopolamine. Collectively, the present findings demonstrate that a functional interaction occurs between the muscarinic cholinergic and dopaminergic systems in modulating PPI and that muscarinic cholinergic agonists may be effective in the treatment of the PPI and other cognitive impairments observed in schizophrenia.     

Neonatal intrahippocampal glycoprotein 120 injection: the role of dopaminergic alterations in prepulse inhibition in adult rats

Following neonatal hippocampal administration on postnatal day 1, the dose-response effects of the human immunodeficiency virus 1 protein glycoprotein 120 (gp120) were studied in vivo on prepulse inhibition (PPI) in adulthood. Furthermore, the role of dopaminergic alterations was examined as a within-subject factor. Using a randomized-block design, male and female pups of eight Sprague-Dawley litters were injected bilaterally with either vehicle (1 microl volume) or gp120 (1.29, 12.9, or 129 ng/microl). At 9 months of age, rats were injected s.c. with saline (SAL) (0.1 ml/kg) and tested on preattentive processes, as indexed by sensorimotor gating. Sensorimotor gating was measured by PPI of the auditory startle response (ASR) [interstimulus intervals (ISIs) of 0, 8, 40, 80, 120, and 4000 ms, six trial blocks, Latin square design]. One month later, the animals were treated with a D(1)/D(2) agonist, apomorphine (APO) (0.1 mg/kg) and again tested for PPI. A significant attenuation of the baseline ASR by APO was noted. No significant effects were noted on control ASR trials (ISIs, 0 and 4000 ms). For the SAL condition, response inhibition was significantly reduced as a function of gp120 dose, and the inflection of the inhibition curve was significantly altered for the high-gp120 dose-treated animals. A gp120 treatment x APO drug interaction was evident on amplitude, but not latency, of the response inhibition, with an enhanced inhibition in the APO condition, collapsed across ISIs (08-120 ms) as the neonatal-injected gp120 dose increased. Use of APO to probe integrity of the dopaminergic system suggests long-lasting alterations in neuronal responses consequent to neonatal gp120 exposure.     

Hypnotizability and somatic complaints: a gender-specific phenomenon

The relationship between hypnotizability and somatic illness was measured in 45 college students. Several weeks after completing the Waterloo-Stanford Group C Scale (WSGC), participants filled out a somatic-complaint checklist and measures of psychopathology. Results indicated a positive correlation between hypnotizability and somatic illness, and the relationship was stronger for female participants. In contrast to the quadratic model proposed by Wickramasekera, the current data demonstrated a linear relationship between hypnotizability and somatic complaint. Further analyses showed that somatic complaints were associated with hallucination and imagery items, corresponding to the perceptual-cognitive factor identified in Woody, Barnier, and McConkey's (2005) factor analysis of the Stanford Hypnotic Susceptibility Scale, Form C. The results call into question some claims that high hypnotizability is an adaptive and healthy trait.     

Hypnotizability Is Associated With a Protective but Not Acquisitive Self-Presentation Style

Self-presentation refers to the behavioral strategies a person adopts to convey desired social images of oneself to other people. The Concern for Appropriateness Scale (CAS) measures a defensive and fearful social approach aimed at avoiding social threats whereas the Revised Self-Monitoring Scale (RSMS) measures an active and flexible social approach aimed at gaining power and status. In this study, a significant correlation was found between hypnotizability, as measured by the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) scores and CAS (r = .43, p = .002) but not between hypnotizability and RSMS (r = .070, p = .631). These results suggest that a protective self-presentation style may incline certain individuals to cooperate with hypnotic suggestions.     

Association Between Hypnotizability and the Catechol-O-Methyltransferase (COMT) Polymorphism

Previous studies implicate involvement of dopaminergic systems in hypnotizability and report association with the COMT Val¹⁵⁸Met single nucleotide polymorphism (SNP, rs4680) demonstrating the Val/Met heterozygotes as the most hypnotizable group using the Stanford Hypnotic Susceptibility Scale. This study replicates that association using an independent sample of 127 healthy Hungarian young adults and the Waterloo-Stanford Group C Scale of Hypnotic Susceptibility. Significant association (p = .016) was found between the COMT genotypes and hypnotizability, with a clear additive effect of the Val allele: Hypnotizability scores were highest in Val/Val (5.9), intermediate in Val/Met (4.7), and lowest in Met/Met (4.1). Differences between these results and those of previous studies support recent findings suggesting an inverted-U-shaped relation between dopamine level in the prefrontal cortex and cognitive functioning. The present study replicates association of COMT Val¹⁵⁸Met SNP and hypnotizability and stresses the importance of mediating factors, such as group vs. individual inductions.     

Hypnotizability and absorption in a Danish sample: testing the influence of context

This study tests the validity of a Danish translation of the Tellegen Absorption Scale (TAS) by investigating the correlation between scores on the TAS and a previously validated Danish translation of the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A) in a sample of 168 subjects. Mean TAS and HGSHS:A scores were comparable to those found in U.S. samples. The correlation between absorption and hypnotizability was calculated for scores obtained in the same session (n = 84) and for scores obtained independently in 2 sessions taking place 2 to 12 months apart (n = 84). The results showed a significant relationship between absorption and hypnotizability when absorption was assessed in the hypnotic context. A significant association was also found when absorption and hypnotizability were assessed independently. The findings support the construct validity of the Danish translation of the TAS and reaffirm results of previous studies suggesting that absorption is an important predictor of hypnotizability.     

Hypnotizability and Absorption in a Danish Sample: Testing the Influence of Context

This study tests the validity of a Danish translation of the Tellegen Absorption Scale (TAS) by investigating the correlation between scores on the TAS and a previously validated Danish translation of the Harvard Group Scale of Hypnotic Susceptibility (HGSHS: A) in a sample of 168 subjects. Mean TAS and HGSHS:A scores were comparable to those found in U.S. samples. The correlation between absorption and hypnotizability was calculated for scores obtained in the same session (n = 84) and for scores obtained independently in 2 sessions taking place 2 to 12 months apart (n = 84). The results showed a significant relationship between absorption and hypnotizability when absorption was assessed in the hypnotic context. A significant association was also found when absorption and hypnotizability were assessed independently. The findings support the construct validity of the Danish translation of the TAS and reaffirm results of previous studies suggesting that absorption is an important predictor of hypnotizability.     

The effectiveness of standardized versus individualized hypnotic suggestions: a brief communication

The results of a number of studies indicate that hypnotizability is a relatively stable trait that has some predictive value for therapy outcome. Some authors argue, however, that hypnotizability scores are artifacts of standardized test procedures, and that more people will benefit from hypnosis when a broader range of suggestions is used. The present study was designed to investigate the effectiveness of standardized versus individualized suggestions. In a crossover design, counterbalanced for order of presentation, 48 Ss were tested twice: once with the Stanford Hypnotic Clinical Scale: Adult (SHCS: Adult) of Morgan and J. R. Hilgard (1975) and once with an individualized equivalent of SHCS: Adult. The results of this comparison showed no significant differences between the 2 methods. The present study does not support the concept of hypnotizability scores as artifacts of standardized measurements.     

The Elkins Hypnotizability Scale: Assessment of Reliability and Validity

Measuring hypnotizability is an integral part of hypnosis research and is also relevant for predicting effectiveness of hypnosis-based therapies. The Elkins Hypnotizability Scale (EHS) was designed to meet the needs of modern hypnosis research and clinical practice. Reliability, validity, and normative data were explored by subjecting 230 participants to the EHS and Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C). The EHS demonstrated adequate internal consistency (α = .78), its items showed good discriminating ability, and scores of the two scales were highly correlated (ρ = .86). Results indicate that the EHS is a reliable and valid tool to assess hypnotizability. Further research is needed to establish its role as a surrogate for the SHSS:C.     

Effects of restricted environmental stimulation: enhancement of hypnotizability for experimental and chronic pain control

Enhancement of hypnotizability and pain tolerance has been demonstrated using restricted environmental stimulation therapy (REST) with university students as Ss (A. F. Barabasz, 1982). The purpose of the present study was to determine whether or not similar results could be obtained with chronic pain patients. Ss consisted of outpatients in treatment for conditions in which pain is prominent who also demonstrated low hypnotizability after repeated hypnosis plateau sessions. 2 groups of Ss were exposed to REST. Situational demand characteristics (Orne, 1962) favored an increase in hypnotizability for REST Group 1 (high demand). REST Group 2 (low demand) was exposed to situational demand characteristics designed to disguise the experimental hypothesis. 2 groups of control Ss were exposed to the same alternative demand characteristic manipulations as the experimental groups, but environmental stimulation was maintained. The Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C) of Weitzenhoffer and E. R. Hilgard (1962), including a posthypnotic suggestion for an anesthetic reaction, and an ischemic pain test were administered prior to treatment and again immediately following treatment. After 6 hours of REST, significant increases in SHSS:C scores were found for high-demand and low-demand experimental Ss, as well as for high-demand control Ss. No such increase was found for low-demand controls. Significant decreases in pain scores were found for both high- and low-demand experimental groups. No significant pain score decreases were found for either control group, suggesting a relatively weak effect of demand characteristics. An independent postexperimental inquiry suggested all Ss believed they received active treatments. The inquiry, conducted 10-15 days after the experiment, also revealed a majority of experimental Ss were using hypnosis on a daily basis to reduce pain with a substantial decrease in pain medication. Only 2 control Ss (highest in hypnotizability) reported similar success. Anecdotal reports of pain reduction experiences using hypnosis after REST intervention were supportive of E. R. Hilgard's (1977) neodissociation theory.