Who Benefits the Most From Different Psychological Chronic Pain Treatments? An Exploratory Analysis of Treatment Moderators.

Different psychological chronic pain treatments benefit some individuals more than others. Understanding the factors that are associated with treatment response-especially when those factors differ between treatments-may inform more effective patient-treatment matching. This study aimed to identify variables that moderate treatment response to 4 psychological pain interventions in a sample of adults with low back pain or chronic pain associated with multiple sclerosis, spinal cord injury, acquired amputation, or muscular dystrophy (N = 173). The current study presents the results from secondary exploratory analyses using data from a randomized controlled clinical trial which compared the effects of 4 sessions of cognitive therapy (CT), hypnosis focused on pain reduction (HYP), hypnosis focused on changing pain-related cognitions and beliefs (HYP-CT), and a pain education control condition (ED). The analyses tested the effects of 7 potential treatment moderators. Measures of primary (pain intensity) and secondary (pain interference, depression severity) outcome domains were administered before and after the pain treatments, and potential moderators (catastrophizing, hypnotizability, and electroencephalogram (EEG)-assessed oscillation power across five bandwidths) were assessed at pre-treatment. Moderator effects were tested fitting regression analyses to pre- to post-treatment changes in the three outcome variables. The study findings, while preliminary, support the premise that pre-treatment measures of hypnotizability and EEG brain activity predict who is more (or less) likely to respond to different psychological pain treatments. If additional research replicates the findings, it may be possible to better match patients to their more individually suitable treatment, ultimately improving pain treatment outcomes. PERSPECTIVE: Pre-treatment measures of hypnotizability and EEG-assessed brain activity predicted who was more (or less) likely to respond to different psychological pain treatments. If these findings are replicated in future studies, they could inform the development of patient-treatment matching algorithms.

Pain-related beliefs, cognitive processes, and electroencephalography band power as predictors and mediators of the effects of psychological chronic pain interventions.

ABSTRACT: The current study used data from a clinical trial to identify variables that are associated with and/or mediate the beneficial effects of 4 psychological chronic pain treatments: one teaching patients self-hypnosis to reduce pain intensity (HYP), one teaching self-hypnosis to change thoughts about pain (hypnotic cognitive therapy [HYP-CT]), one teaching cognitive restructuring skills to change thoughts about pain (cognitive therapy [CT]), and one providing education about pain (ED; included as an active control condition). Of 17 possible mechanism variables examined, and with alpha not corrected for multiple comparisons, significant between-group differences were observed for 3. Two of these (changes in beliefs about control over pain and number of days of skill practice) were supported as mediators of the beneficial effects of HYP, CT, or HYP-CT, relative to ED. Six mechanism variables evidenced significant pretreatment to post-treatment changes in the sample as a whole, without showing significant between-group differences. Pretreatment to post-treatment changes in all 6 were associated with improvements in pain interference, pain intensity, or both. In addition, participant ratings of therapeutic alliance at post-treatment were associated significantly with improvements in both pain intensity and pain interference in the sample as a whole. Thus, of the 17 possible mediators examined, there were relatively few that served as mediators for the beneficial effects of specific treatments; a larger number of variables predicted treatment outcome overall. The extent to which these variables are treatment mediators (ie, are responsible for, rather than merely associated with, treatment-related improvements) will require further research.

The chronic pain skills study: Protocol for a randomized controlled trial comparing hypnosis, mindfulness meditation and pain education in Veterans.

OBJECTIVES: To describe the protocol of a randomized controlled trial to evaluate the effectiveness and mechanisms of three behavioral interventions. METHODS: Participants will include up to 343 Veterans with chronic pain due to a broad range of etiologies, randomly assigned to one of three 8-week manualized in-person group treatments: (1) Hypnosis (HYP), (2) Mindfulness Meditation (MM), or (3) Education Control (EDU). PROJECTED OUTCOMES: The primary aim of the study is to compare the effectiveness of HYP and MM to EDU on average pain intensity measured pre- and post-treatment. Additional study aims will explore the effectiveness of HYP and MM compared to EDU on secondary outcomes (i.e., pain interference, sleep, depression, anxiety and PTSD), and the maintenance of effects at 3- and 6-months post-treatment. Participants will have electroencephalogram (EEG) assessments at pre- and post-treatment to determine if the power of specific brain oscillations moderate the effectiveness of HYP and MM (Study Aim 2) and examine brain oscillations as possible mediators of treatment effects (exploratory aim). Additional planned exploratory analyses will be performed to identify possible treatment mediators (i.e., pain acceptance, catastrophizing, mindfulness) and moderators (e.g., hypnotizability, treatment expectations, pain type, cognitive function). SETTING: The study treatments will be administered at a large Veterans Affairs Medical Center in the northwest United States. The treatments will be integrated within clinical infrastructure and delivered by licensed and credentialed health care professionals.

Waking EEG Cortical Markers of Chronic Pain and Sleepiness.

Objective: Spectral power analyses of EEG recordings are reported to distinguish the cortical activity of individuals with chronic pain from those of controls. Further study of these spectral patterns may provide a greater understanding of the processes associated with chronic pain, in addition to providing potential biometric markers of chronic pain for use in both clinical and research settings. However, sleep deprived groups have demonstrated similar characteristics in their spectral power characteristics, particularly in alpha bandwidth power activity. Methods: 103 individuals with chronic pain provided resting awake EEG data in addition to ratings of pain and sleep quality. Two Principal Axis Factor analyses using Promax rotation produced one pain and one sleep factor from relevant questionnaire data provided by participants. These factors were then used to test hypothesized relationships with alpha and theta bandwidth power at the frontal and parietal areas of the cortex. Results: Our findings suggest that reductions in alpha bandwidth power are independently associated with both chronic pain intensity ratings and measures of sleep deficits. Conversely, theta bandwidth power was not found to be associated with either chronic pain or sleep quality measures. Conclusions: This study's findings support that chronic pain intensity and sleep deficits are related to the Alpha spectral bandwidth activity in individuals with chronic pain.

Acuity-independent effects of visual deprivation on human visual cortex.

Visual development depends on sensory input during an early developmental critical period. Deviation of the pointing direction of the two eyes (strabismus) or chronic optical blur (anisometropia) separately and together can disrupt the formation of normal binocular interactions and the development of spatial processing, leading to a loss of stereopsis and visual acuity known as amblyopia. To shed new light on how these two different forms of visual deprivation affect the development of visual cortex, we used event-related potentials (ERPs) to study the temporal evolution of visual responses in patients who had experienced either strabismus or anisometropia early in life. To make a specific statement about the locus of deprivation effects, we took advantage of a stimulation paradigm in which we could measure deprivation effects that arise either before or after a configuration-specific response to illusory contours (ICs). Extraction of ICs is known to first occur in extrastriate visual areas. Our ERP measurements indicate that deprivation via strabismus affects both the early part of the evoked response that occurs before ICs are formed as well as the later IC-selective response. Importantly, these effects are found in the normal-acuity nonamblyopic eyes of strabismic amblyopes and in both eyes of strabismic patients without amblyopia. The nonamblyopic eyes of anisometropic amblyopes, by contrast, are normal. Our results indicate that beyond the well-known effects of strabismus on the development of normal binocularity, it also affects the early stages of monocular feature processing in an acuity-independent fashion.

Effect of Grade I and II intraventricular hemorrhage on visuocortical function in very low birth weight infants.

The neurological outcome for infants with Grade I/II intraventricular hemorrhage (IVH) is debated. The aim of this study was to determine whether very low birth weight infants (VLBW, <1500 g) with Grade I/II (IVH) have altered visuocortical activity compared with infants with no IVH. We assessed the quantitative swept parameter visual evoked potential (sVEP) responses evoked by three different visual stimuli. Data from 52 VLBW infants were compared with data from 13 infants with Grade I or II IVH, enrolled at 5-7 months corrected age. Acuity thresholds and suprathreshold response amplitudes were compared. Grating acuity (GA), contrast sensitivity (CS) and vernier acuity (VA) were each worse in the Grade I/II IVH compared with the no IVH groups (8.24 cpd in IVH group vs. 13.07 cpd in no IVH group for GA; 1.44% vs. 1.18% for CS and 1.55 arcmin vs. 0.58 arcmin for VA). The slopes of the response amplitude for CS and VA were significantly lower in IVH infants. The spatial frequency tuning function was shifted downward on the spatial frequency axis, without a change in slope. These results indicate that Grade I/II IVH are associated with deleterious effects on cortical vision development and function.

Disparity tuning of binocular facilitation and suppression after normal versus abnormal visual development.

PURPOSE: To study the pattern of facilitatory and suppressive binocular interactions in stereodeficient patients with strabismus and in healthy controls. METHODS: Visual evoked potentials were recorded in response to a Vernier onset/offset pattern presented to one eye, either monocularly or paired dichoptically with a straight vertical square-wave grating, which, when fused with the target in the other eye, gave rise to a percept of a series of bands appearing in depth from an otherwise uniform plane or with a grating that contained offsets that produced a standing disparity and the appearance of a constantly segmented image, portions of which moved in depth. RESULTS: Participants with normal stereopsis showed facilitative and suppressive binocular interactions that depended on which dichoptic target was presented. Patients with longstanding, constant strabismus lacked normal facilitative binocular interactions. The response to a normally facilitative stimulus was reduced below the monocular level when it was presented to the dominant eye of patients without anisometropia, consistent with classical strabismic suppression of the nondominant eye. The dominant eye of strabismic patients without anisometropia retained suppressive input from crossed but not uncrossed disparity stimuli presented to the nondominant eye. CONCLUSIONS: Abnormal disparity processing can be detected with the dichoptic VEP method we describe. Our results suggest that suppression in stereoblind, nonamblyopic observers is determined by a binocular mechanism responsive to disparity. In some cases, the sign of the disparity is important, and this suggests a mechanism that can explain diplopia in patients made exotropic after surgery for esotropia.

Figure-ground interaction in the human visual cortex.

Discontinuities in feature maps serve as important cues for the location of object boundaries. Here we used multi-input nonlinear analysis methods and EEG source imaging to assess the role of several different boundary cues in visual scene segmentation. Synthetic figure/ground displays portraying a circular figure region were defined solely by differences in the temporal frequency of the figure and background regions in the limiting case and by the addition of orientation or relative alignment cues in other cases. The use of distinct temporal frequencies made it possible to separately record responses arising from each region and to characterize the nature of nonlinear interactions between the two regions as measured in a set of retinotopically and functionally defined cortical areas. Figure/background interactions were prominent in retinotopic areas, and in an extra-striate region lying dorsal and anterior to area MT+. Figure/background interaction was greatly diminished by the elimination of orientation cues, the introduction of small gaps between the two regions, or by the presence of a constant second-order border between regions. Nonlinear figure/background interactions therefore carry spatially precise, time-locked information about the continuity/discontinuity of oriented texture fields. This information is widely distributed throughout occipital areas, including areas that do not display strong retinotopy.

Abnormalities of coherent motion processing in strabismic amblyopia: Visual-evoked potential measurements.

Coherent motion responses of patients with mild to moderate strabismic amblyopia were compared to those of normals using visual-evoked potentials (VEPs). Responses were elicited by dynamic random-dot kinematograms that alternated at 0.83 Hz between globally coherent (left-right) and incoherent (random) motion states. Tuning curves were measured at the first harmonic of the global motion update rate (0.83 Hz) and at the first harmonic of the dot update rate (20 Hz) for spatial displacements 3.1 to 27.9 arcmin (1.6 to 9.3 deg/s). Responses locked to the changes in the global organization of the local direction vectors were an inverted U-shaped function of displacement/speed in the normal-vision observers and in the fellow eyes of the strabismus patients while the tuning function of the amblyopic eyes was shifted to larger displacements/higher speeds. Responses at the dot update rate were reduced in amplitude and altered in timing in both eyes of the patients. The results are consistent with both local and global deficits in motion processing in strabismic amblyopia.

Sensitivity and configuration-specificity of orientation-defined texture processing in infants and adults.

Here we use textures made up of widely spaced Gabor patches to compare infant and adult sensitivity to the global organization of the elements comprising the textures. Visual Evoked Potentials (VEPs) were recorded to alterations between random images and images containing varying proportions of patches that were of the same orientation. The patches were placed on rectangular, hexagonal or random lattices. Texture-specific responses were robust in adults and their VEP threshold was reached when 1-17% of the patches had the same orientation in the structured image. Infant thresholds were approximately 20-60%. While infants are capable of detecting the global structure of our textures, their sensitivity is low. In adults we found, unexpectedly, that sensitivity and response gain were higher for horizontal compared to vertical global orientations. Infant sensitivity was the same for the two orientations. Comparable orientation anisotropies have not been previously reported for gratings, suggesting that the Gabor-defined textures are tapping different mechanisms. There were small, but measurable effects of the lattice type in adults, with the rectangular lattice producing the largest responses.

Cue-invariant networks for figure and background processing in human visual cortex.

Lateral occipital cortical areas are involved in the perception of objects, but it is not clear how these areas interact with first tier visual areas. Using synthetic images portraying a simple texture-defined figure and an electrophysiological paradigm that allows us to monitor cortical responses to figure and background regions separately, we found distinct neuronal networks responsible for the processing of each region. The figure region of our displays was tagged with one temporal frequency (3.0 Hz) and the background region with another (3.6 Hz). Spectral analysis was used to separate the responses to the two regions during their simultaneous presentation. Distributed source reconstructions were made by using the minimum norm method, and cortical current density was measured in a set of visual areas defined on retinotopic and functional criteria with the use of functional magnetic resonance imaging. The results of the main experiments, combined with a set of control experiments, indicate that the figure region, but not the background, was routed preferentially to lateral cortex. A separate network extending from first tier through more dorsal areas responded preferentially to the background region. The figure-related responses were mostly invariant with respect to the texture types used to define the figure, did not depend on its spatial location or size, and mostly were unaffected by attentional instructions. Because of the emergent nature of a segmented figure in our displays, feedback from higher cortical areas is a likely candidate for the selection mechanism by which the figure region is routed to lateral occipital cortex.

Neural correlates of shape-from-shading.

Visual evoked potentials were recorded during presentation of a single stimulus that generated bi-stable perceptual alternation between two different three-dimensional percepts. One interpretation (asymmetric) changed depth structure from flat to corrugated in depth and the other (symmetric) had the appearance of a flat surface translating laterally behind a set of apertures. Responses during perception of the asymmetric three-dimensional structure contained larger negative components than did responses during perception of the symmetric three-dimensional structure. Control experiments suggest that the interpretation of depth structure is selected after junction information caused by the interplay between shading and object shape is extracted.

Measurement of position acuity in strabismus and amblyopia: specificity of the vernier VEP paradigm.

PURPOSE: An objective measure of positional acuity is desirable in the nonverbal clinical population. This study was conducted to investigate the specificity of the vernier VEP as a measure of positional acuity, evaluating the potential confound of asymmetric motion responses that may be present in some groups of patients. These motion responses could masquerade as position-specific responses, since they occur at the same response frequency as the vernier-related response. METHODS: Twelve observers with early-onset esotropia (EOE), 30 children with untreated amblyopia, and 15 control children underwent swept vernier VEP acuity testing accompanied by a swept motion control stimulus. The control condition was used to detect the presence of artifactual responses not related to position sensitivity. The patients with EOE were selected for high levels of motion asymmetry as documented with oscillating gratings presented monocularly. As a measure of motion confound (penetration), the proportion of first-harmonic responses recorded in the control condition was determined. RESULTS: The penetration rate in the vernier condition in each study group (EOE: 0.93%; amblyopes: 4.26%; normal subjects: 2.40%) and the entire group (2.85%) was acceptably low. The level of penetration was not significantly influenced by the presence of amblyopia. CONCLUSIONS: The vernier VEP paradigm, when applied in the manner described, can be interpreted as a measure of position sensitivity. The presence of motion asymmetry or untreated amblyopia does not affect the validity of vernier measurements made.

Event-related potentials show configural specificity of global form processing.

Glass patterns are a type of moiré created when a random-dot field is overlaid with a rotated, translated or dilated copy. The overall form of the moiré cannot be detected using local processing mechanisms, and because of this, Glass patterns are useful probes of global form processing. Here, we use event-related potentials to show that certain global organizations (concentric structure created by rotation and radial structure produced by dilation) produce much larger brain responses than others (linear structure created by translation). The results are consistent with the existence of specialized form processing mechanisms in the extrastriate cortex.

Suppression of monocular visual direction under fused binocular stimulation: evoked potential measurements.

Visual evoked potentials (VEPs) were recorded in response to a vernier onset/offset target presented to one eye that was combined with matching static targets in the other eye. The monocular response was dominated by a negative peak at 160 ms that occurred after a set of offsets was introduced into a one-dimensional random bar pattern. The static targets produced no discernible VEP response by themselves, but when fused binocularly with the oscillating vernier target, they produced shifts in perceived visual direction that influenced the VEP response. A vernier target fused with static vertical bars was perceived to alternate in depth between a flat surface and one broken into two interleaved surfaces. The response to this "surface-breaking" was as large or larger than the response to the monocular vernier offset. This response was much reduced when the oscillating vernier was fused with a static offset vernier (5' offset) that produced a percept of segregated regions moving in depth. Apparently, the VEP is strongly driven by shifts in visual direction that alter surface, texture, or contour contiguity.

Experience-expectant development of contour integration mechanisms in human visual cortex.

Extended contours are a common feature of natural images. Most previous studies have considered contour integration as a two-dimensional process of linking like-oriented elements along their common orientation axis. Yet contours exist in a three-dimensional world, and one might therefore ask about the relationship between contour integration and binocular vision. Using an event-related potential assay of contour integration, we demonstrate that patients with strabismic amblyopia show a relative insensitivity to Gabor-defined contours in their dominant eyes, all of which had normal acuity. These deficits were not seen in the dominant eyes of patients with anisometropic amblyopia without strabismus, but were present in the amblyopic eyes of patients with either strabismus or anisometropia. Deficits were also found in both eyes of strabismus patients who had normal visual acuity in each eye, but who had strongly reduced or absent stereopsis. These results suggest that the maturation of contour detection mechanisms depends at least in part on the presence of normal binocular interaction during a developmental critical period.

Development of sensitivity to texture and contour information in the human infant.

Texture discrimination and bounding contour extraction are essential parts of the object segmentation and shape discrimination process. As such, successful texture and contour processing are key components underlying the development of the perception of both objects and surfaces. By recording visual-evoked potentials, we investigate whether young infants can detect orientation-defined textures and contours. We measured responses to an organized texture comprised of many Gabor patches of the same orientation, alternated with images containing the same number of patches, but all of random orientation. These responses were compared with a control condition consisting of the alternation between two independently random configurations. Significant difference potentials were found as early as 2-5 months, as were significant odd harmonics in the test conditions. Responses were also measured to Gabor patches organized either as circles (all patches tangent to an imaginary circular path) alternated with pinwheels (all patches having a fixed orientation offset from the path). Infants between 6 and 13 months also showed sensitivity to the global organization of the elements along contours. Differential responses to our texture and contour stimuli and their controls could only have been generated by mechanisms that are capable of comparing the relative orientation of 2 or more patches, as no local information at a single patch distinguished the random and organized textures or the circle and pinwheel configurations.

A VEP measure of the binocular fusion of horizontal and vertical disparities.

PURPOSE: Because of the lateral separation of the orbits, the retinal images differ in the two eyes. These differences are reconciled into a single image through sensory and motor fusional mechanisms. This study demonstrates electrophysiologically the effects that normal horizontal and vertical fusional processes have on the processing of monocular position signals. METHODS: VEPs were recorded in 16 healthy adults in response to a vernier onset-offset target presented to one eye. The vernier offsets appeared and disappeared at 2 Hz and were introduced into bar targets that were oriented either vertically (horizontal offsets) or horizontally (vertical offsets). The magnitude of the offsets was varied over the range of 0.5 to 10 arc min. VEP amplitude was measured as a function of the size of the dynamic offset under monocular viewing conditions and in the presence of two different static targets presented to the other eye. One of the static targets matched the dynamic test, except that it had no vernier offsets. The other static target, the static pedestal, matched the dynamic test, but contained a set of static vernier offsets in locations corresponding to the locations of the dynamic offsets presented to the other eye. RESULTS: VEP amplitude was a monotonically increasing function of vernier offset size under monocular viewing conditions. The addition of the static target without offsets in the other eye resulted in an increased amplitude VEP response. The addition of the static target with vernier offsets resulted in a decrease in VEP amplitude for both horizontal and vertical disparities. CONCLUSIONS: The normal process of fusion results in a single visual direction. To obtain a single visual direction, the visual system must synthesize a binocular visual direction that differs from the monocular components. One of the conditions (the static pedestal with offsets) produces binocular visual direction shifts that degrade the appearance of vernier onset-offset, and reduce VEP amplitude for both horizontal and vertical disparities. This characteristic evoked response marker is a promising tool for measuring binocular fusion objectively in patients with strabismus.

Development of the spatial organization and dynamics of lateral interactions in the human visual system.

Psychophysical thresholds and neuronal responses for isolated stimuli are strongly modified by nearby stimuli in the visual field. We studied the orientation and position specificity of these contextual interactions using a dual-frequency visual-evoked potential technique in developing human infants and adults. One set of small, oriented stimulus elements (targets) was tagged with a temporal frequency f1 of 4.52 Hz. The addition of an abutting second set of similar patches (flankers) tagged at f2 = 2.58 Hz had three effects: (1) The flankers reduced the second and fourth harmonic responses to the targets. This reduction was independent of flanker orientation or position and age. (2) The response to the combination of targets and flankers also contained nonlinear interaction terms (1f1 +/- 1f2) that were tuned for flanker orientation and position in adults, but only for flanker orientation in infants 8-31 weeks of age. (3) Nonlinear interaction terms recorded at 2f1 +/- 2f2 were large and untuned for flanker orientation and position in adults but were nearly absent in the youngest infants. The three forms of nonlinear interaction, thus, have differences in sensitivity to flanker orientation and position and differential growth trends, indicating that they are generated by different mechanisms. These three forms of interaction could serve different functional roles. The first process provides a nonselective gain control that is fully functional in early infancy. The second process, which develops slowly, is selective for the specific form of the stimuli. The third process, which is also immature, pools across orientation.

Temporal dynamics of the human response to symmetry.

Symmetry is a highly salient feature of animals, plants, and the constructed environment. Although the perceptual phenomenology of symmetry processing is well understood, little is known about the underlying neural mechanisms. Here we use visual evoked potentials to measure the time course of neural events associated with the extraction of symmetry in random dot fields. We presented sparse random dot patterns that were symmetric about both the vertical and horizontal axes. Symmetric patterns were alternated with random patterns of the same density every 500 msec, using new exemplars of symmetric and random patterns on each image update. Random/random exchanges were used as a control. The response to updates of random patterns was multiphasic, consisting of P65, N90, P110, N140 and P220 peaks. The response to symmetric/random sequences was indistinguishable from that for random/random sequences up to about 220 msec, after which the response to symmetric patterns became relatively more negative. Symmetry in random dot patterns thus appears to be extracted after an initial response phase that is indifferent to configuration. These results are consistent with the hypothesis (Lee, Mumford, Romero, & Lamme, 1998; Tyler & Baseler, 1998) that the symmetry property is extracted by processing in extrastriate cortex.