Gary H. Duncan

A GENERAL STATISTICAL ANALYSIS FOR FMRI DATA

We propose a method for the statistical analysis of fMRI data that seeks a compromise between efficiency, generality, validity, simplicity, and execution speed. The main differences between this analysis and previous ones are: a simple bias reduction and regularization for voxel-wise autoregressive model parameters; the combination of effects and their estimated standard deviations across different runs/sessions/subjects via a hierarchical random effects analysis using the EM algorithm; overcoming the problem of a small number of runs/session/subjects using a regularized variance ratio to increase the degrees of freedom.

Dissociation of sensory and affective dimensions of pain using hypnotic modulation.

Understanding the complex nature of pain perception requires the ability to separately analyze its psychological dimensions and their interaction, and relate them to specific variables and responses. The present study, therefore, attempted to selectively modulate the sensory and affective dimensions of pain, using a cognitive intervention, and to assess the possible relationship between these psychological dimensions of pain and changes in physiological responses to the noxious stimuli. In three experiments, normal subjects trained in hypnosis rated pain intensity and pain unpleasantness produced by a tonic heat-pain stimulus (1-min immersion of the hand in 45.0-47.5 degrees C water). Two experiments were designed to test hypnotic suggestions to decrease (Experiment one (Section 2.5.1)), or increase and decrease (Experiment two (Section 2.5.2)) pain affect. Suggestions in Experiment three (Section 2.5.3) were directed towards an increase or decrease in pain sensation. In Experiments one and two (Sections 2.5.1 and 2.5.2), the significant modulation in pain unpleasantness ratings was largely independent of variations in perceived pain intensity. Moreover, in Experiment two (Section 2.5.2), there was a significant correlation between the stimulus-evoked heart-rate increase and ratings of pain unpleasantness, but not of pain intensity, suggesting a direct functional interaction between pain affect and autonomic activation. In Experiment three (Section 2.5.3), suggestions to modulate the sensory aspect of pain produced significant modulation of pain intensity ratings, with secondary changes in pain unpleasantness ratings. Hypnotic susceptibility (Stanford Hypnotic Susceptibility Scale form A) was specifically correlated to pain unpleasantness modulation in Experiment two (Section 2.5.2) and to pain intensity modulation in Experiment three (Section 2.5.3), suggesting that this factor relates to the primary process toward which hypnotic suggestions are directed. The specific pain dimension on which hypnotic suggestions act depends on the content of the instructions and is not a characteristic of hypnosis itself. Results are consistent with a successive-stage model of pain perception (e.g. Wade JB, Dougherty LM, Archer CR, Price DD. Assessing the stages of pain processing: a multivariate analytical approach. Pain 1996;68:157-167) which provides a conceptual framework necessary to study the cerebral representation of pain perception.

Cerebral Mechanisms of Hypnotic Induction and Suggestion

The neural mechanisms underlying hypnotic states and responses to hypnotic suggestions remain largely unknown and, to date, have been studied only with indirect methods. Here, the effects of hypnosis and suggestions to alter pain perception were investigated in hypnotizable subjects by using positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) and electroencephalographic (EEG) measures of brain electrical activity. The experimental conditions included a restful state (Baseline) followed by hypnotic relaxation alone (Hypnosis) and by hypnotic relaxation with suggestions for altered pain unpleasantness (Hypnosis-with-Suggestion). During each scan, the left hand was immersed in neutral (35C) or painfully hot (47C) water in the first two conditions and in painfully hot water in the last condition. Hypnosis was accompanied by significant increases in both occipital rCBF and delta EEG activity, which were highly correlated with each other (r = 0.70, p < 0.0001). Peak increases in rCBF were also observed in the caudal part of the right anterior cingulate sulcus and bilaterally in the inferior frontal gyri. Hypnosis-related decreases in rCBF were found in the right inferior parietal lobule, the left precuneus, and the posterior cingulate gyrus. Hypnosis-with-suggestions produced additional widespread increases in rCBF in the frontal cortices predominantly on the left side. Moreover, the medial and lateral posterior parietal cortices showed suggestion-related increases overlapping partly with regions of hypnosis-related decreases. Results support a state theory of hypnosis in which occipital increases in rCBF and delta activity reflect the alteration of consciousness associated with decreased arousal and possible facilitation of visual imagery. Frontal increases in rCBF associated with suggestions for altered perception might reflect the verbal mediation of the suggestions, working memory, and top-down processes involved in the reinterpretation of the perceptual experience. These results provide a new description of the neurobiological basis of hypnosis, demonstrating specific patterns of cerebral activation associated with the hypnotic state and with the processing of hypnotic suggestions.

Effects of attention on the intensity and unpleasantness of thermal pain.

&NA; Both experimental and clinical studies have shown that psychological manipulations, such as hypnosis, behavioral modification and cognitive‐behavioral therapy, can reduce reports of pain. Although these are complex procedures, one important variable common to each is direction of attention. We have previously demonstrated in both humans and monkeys a method for monitoring and manipulating attention toward or away from a painful stimulus and have shown that changes in the direction of attention alter the ability to discriminate noxious heat stimuli. The present study assessed whether these changes in discrimination were accompanied by changes in the perception of pain intensity and/or unpleasantness. These data confirm that both the speed and accuracy of detecting changes in noxious heat stimuli are decreased when the subject attends to another stimulus modality. In addition, they show that direction of attention affects the perceived intensity and unpleasantness of painful stimuli in a similar manner. Our previous findings of attention‐related modulation of nociceptive neuronal activity in the medullary dorsal horn suggest that these attention‐dependent changes in sensory‐discriminative and affective components of pain are mediated at early stages of sensory processing.

A Psychophysical Comparison of Sensory and Affective Responses to Four Modalities of Experimental Pain

It is generally accepted that the sensory and affective components of pain may be differentially associated with various acute and chronic diseases, and that some treatment regimens are best directed toward certain aspects of the pain experience. In addition, experimental animal models have been described that presume to assess either the sensory-discriminative aspects of phasic pain or the affective responses associated with tonic pain. The present psychophysical experiment directly compares the perceived intensity and unpleasantness of sensations evoked by four types of experimental noxious stimuli: contact heat, electric shock, ischemic exercise, and cold-pressor pain. A novel pain measurement technique is described that incorporates unbounded magnitude-estimation/category scales; this technique allows precise ratio responses, while minimizing within- and between-subject variability. We observe that, relative to the perceived intensity of the individual stimuli, subjects consistently differentiate among the degrees of unpleasantness evoked by the four stimulus modalities. Ischemic exercise and cold-pressor pain evoke higher estimates of unpleasantness, and thus may better mimic the pain of chronic disease. The relative unpleasantness produced by contact heat is significantly less than that of the other modalities tested, and therefore contact heat stimuli may be ideally suited for assessing sensory-discriminative aspects of pain perception. Possible neurophysiological mechanisms underlying the observed differences in perceived unpleasantness are discussed in relation to the growing body of literature concerning tonic and phasic pain stimuli.

Hypnosis Modulates Activity in Brain Structures Involved in the Regulation of Consciousness

The notion of consciousness is at the core of an ongoing debate on the existence and nature of hypnotic states. Previously, we have described changes in brain activity associated with hypnosis (Rainville, Hofbauer, Paus, Duncan, Bushnell, & Price, 1999). Here, we replicate and extend those findings using positron emission tomography (PET) in 10 normal volunteers. Immediately after each of 8 PET scans performed before (4 scans) and after (4 scans) the induction of hypnosis, subjects rated their perceived level of mental relaxation and mental absorption, two of the key dimensions describing the experience of being hypnotized. Regression analyses between regional cerebral blood flow (rCBF) and self-ratings confirm the hypothesized involvement of the anterior cingulate cortex (ACC), the thalamus, and the ponto-mesencephalic brainstem in the production of hypnotic states. Hypnotic relaxation further involved an increase in occipital rCBF that is consistent with our previous interpretation that hypnotic states are characterized by a decrease in cortical arousal and a reduction in cross-modality suppression (disinhibition). In contrast, increases in mental absorption during hypnosis were associated with rCBF increases in a distributed network of cortical and subcortical structures previously described as the brains attentional system. These findings are discussed in support of a state theory of hypnosis in which the basic changes in phenomenal experience produced by hypnotic induction reflect, at least in part, the modulation of activity within brain areas critically involved in the regulation of consciousness.

Sex differences in the perception of noxious heat stimuli

&NA; This study compared pain perception in young male and female subjects, using experimental noxious heat stimuli. During 2 sessions, each of 40 subjects rated the magnitude of 120 heat stimuli, ranging from 45°C to 50°C. The study included a comparison of visual analogue and magnitude matching rating procedures, as well as a test of simulated analgesia, in which the range of stimuli presented during the 2 experimental sessions was shifted by 1°C. We found that females rated noxious heat stimuli as more intense than did males, independent of the gender of the experimenter or the type of rating scale. In addition, the data suggest that females discriminate among the painful heat intensities better than males. For example, female subjects showed significant between‐session discrimination of noxious heat stimuli, while male subjects did not, and females produced steeper within‐session stimulus‐response functions than did males. These observed differences in nociceptive discrimination between males and females indicate that the sex‐related variation in pain perception is probably related to sensory factors rather than differences in attitude or emotional response.

Cortical Thickness and Pain Sensitivity in Zen Meditators

Zen meditation has been associated with low sensitivity on both the affective and the sensory dimensions of pain. Given reports of gray matter differences in meditators as well as between chronic pain patients and controls, the present study investigated whether differences in brain morphometry are associated with the low pain sensitivity observed in Zen practitioners. Structural MRI scans were performed and the temperature required to produce moderate pain was assessed in 17 meditators and 18 controls. Meditators had significantly lower pain sensitivity than controls. Assessed across all subjects, lower pain sensitivity was associated with thicker cortex in affective, pain-related brain regions including the anterior cingulate cortex, bilateral parahippocampal gyrus and anterior insula. Comparing groups, meditators were found to have thicker cortex in the dorsal anterior cingulate and bilaterally in secondary somatosensory cortex. More years of meditation experience was associated with thicker gray matter in the anterior cingulate, and hours of experience predicted more gray matter bilaterally in the lower leg area of the primary somatosensory cortex as well as the hand area in the right hemisphere. Results generally suggest that pain sensitivity is related to cortical thickness in pain-related brain regions and that the lower sensitivity observed in meditators may be the product of alterations to brain morphometry from long-term practice.

Sensory and affective aspects of pain perception: is medial thalamus restricted to emotional issues?

SummaryLateral and medial thalamus are traditionally thought to have separate roles in pain processing, with lateral lemniscal regions transmitting discriminative information about location and intensity, while medial nonspecific regions are involved in emotional responses. Contrary to this view, the present study shows that some single neurons in medial thalamus of alert monkey discriminate changes in the intensity of noxious stimuli that are equal to or below the monkeys own discrimination threshold. Since these neurons are also modulated by anesthesia and attentional factors, we suggest that parts of medial thalamus may participate in both discriminative and affective dimensions of pain.

Comparison of verbal and visual analogue scales for measuring the intensity and unpleasantness of experimental pain

&NA; Although the multidimensional nature of pain is now well recognized, there are, nevertheless, very few quantitative tests to measure the separate dimensions of pain and little data concerning their relative sensitivity. The present study compares 2 currently available methods, verbal descriptor and visual analogue scales. Eight subjects rated painful and near‐painful heat stimuli by using visual analogue scales for intensity or unpleasantness and by choosing the most appropriate phrases from lists of intensity or unpleasantness descriptors. In the intensity dimension, the relationship between perception and stimulus temperature was essentially identical whether calculated from the visual analogue or verbal descriptor scales. However, data derived from the verbal descriptor scales revealed that subjects rated the painful temperatures as relatively more intense than unpleasant; this difference could not be detected using the visual analogue scales. These results confirm that both visual analogue and verbal descriptor techniques successfully quantify sensory intensity and affective aspects of pain, but that verbal descriptors may provide the more sensitive tool for separating intensity and unpleasantness.