Perturbing the activity of the superior temporal gyrus during pain encoding prevents the exaggeration of pain memories: A virtual lesion study using single-pulse transcranial magnetic stimulation.

BACKGROUND: Past studies have shown that pain memories are often inaccurate, a phenomenon known as mnemonic pain bias. Pain memories are thought to play an important role on how future pain is felt. Recent evidence from our laboratory suggests that individuals who exaggerate past pain display increased superior temporal gyrus (STG) activity during the encoding of experimental painful stimulations, suggesting that this brain structure plays an important role in pain memories. OBJECTIVE: /hypothesis. To determine whether a virtual lesion paradigm, targeting the STG during pain encoding, can affect long-lasting pain memories. We hypothesized that interfering with the activity of the STG would attenuate mnemonic bias. METHODS: Randomized double-blind study with two parallel groups. Participants received either sham (n = 21) or real (n = 21) transcranial magnetic stimulation (TMS - virtual lesion paradigm) over the STG during pain encoding (milliseconds after the administration of a painful stimuli). Pain intensity and unpleasantness were evaluated using a visual analog scale (VAS; 0 to 10) immediately after the painful event, and at recall, 2 months later. The mnemonic pain bias (calculated by subtracting the pain scores obtained at recall from the pain score obtained during encoding) was compared between the two groups for both pain intensity and unpleasantness. RESULTS: Participants in both groups did not differ in terms of age and gender (real TMS = 27 years ±â€¯9, 43% female; sham TMS = 25 years ±â€¯4, 49% female; p > 0.64). The mnemonic bias related to pain intensity was similar in both groups (p = 0.83). However, the mnemonic bias related to pain unpleasantness was lower in the real TMS group (p = 0.04). CONCLUSIONS: Our results provide the first evidence that the STG, is causally involved in the formation of biased memories of pain unpleasantness.

Unravelling the effect of experimental pain on the corticomotor system using transcranial magnetic stimulation and electroencephalography.

The interaction between pain and the motor system is well-known, with past studies showing that pain can alter corticomotor excitability and have deleterious effects on motor learning. The aim of this study was to better understand the cortical mechanisms underlying the interaction between pain and the motor system. Experimental pain was induced on 19 young and healthy participants using capsaicin cream, applied on the middle volar part of the left forearm. The effect of pain on brain activity and on the corticomotor system was assessed with electroencephalography (EEG) and transcranial magnetic stimulation (TMS), respectively. Compared to baseline, resting state brain activity significantly increased after capsaicin application in the central cuneus (theta frequency), left dorsolateral prefrontal cortex (alpha frequency), and left cuneus and right insula (beta frequency). A pain-evoked increase in the right primary motor cortex (M1) activity was also observed (beta frequency), but only among participants who showed a reduction in corticospinal output (as depicted by TMS recruitment curves). These participants further showed greater beta M1-cuneus connectivity than the other participants. These findings indicate that pain-evoked increases in M1 beta power are intimately tied to changes in the corticospinal system, and provide evidence that beta M1-cuneus connectivity is related to the corticomotor alterations induced by pain. The differential pattern of response observed in our participants suggest that the effect of pain on the motor system is variable from on individual to another; an observation that could have important clinical implications for rehabilitation professionals working with pain patients.

Effect of pulsed electromagnetic field therapy on experimental pain: A double-blind, randomized study in healthy young adults.

Previous studies suggested that pulsed electromagnetic field (PEMF) therapy can decrease pain. To date, however, it remains difficult to determine whether the analgesic effect observed in patients are attributable to a direct effect of PEMF on pain or to an indirect effect of PEMF on inflammation and healing. In the present study, we used an experimental pain paradigm to evaluate the direct effect of PEMF on pain intensity, pain unpleasantness, and temporal summation of pain. Twenty-four healthy subjects (mean age 22 ± 2 years; 9 males) participated in the experiment. Both real and sham PEMF were administered to every participant using a randomized, double-blind, cross-over design. For each visit, PEMF was applied for 10 minutes on the right forearm using a portable device. Experimental pain was evoked before (baseline) and after PEMF with a 9 cm(2) Pelletier-type thermode, applied on the right forearm (120 s stimulation; temperature individually adjusted to produce moderate baseline pain). Pain intensity and unpleasantness were evaluated using a 0-100 numerical pain rating scale. Temporal summation was evaluated by comparing pain intensity ratings obtained at the end of tonic nociceptive stimulation (120 s) with pain intensity ratings obtained after 60 s of stimulation. When compared to baseline, there was no change in pain intensity and unpleasantness following the application of real or sham PEMF. PEMF did not affect temporal summation. The present observations suggest that PEMF does not directly influence heat pain perception in healthy individuals.

Altered autonomic nervous system reactivity to pain in trigeminal neuralgia.

BACKGROUND: In the past two decades, there has been increasing evidence to suggest that trigeminal neuralgia (TN) may be linked to a dysfunction of the autonomic nervous system (ANS). The aim of the present study was to formally test this hypothesis by comparing the reactivity of the ANS to experimental pain in a population of TN patients and healthy controls. METHODS: Twelve patients diagnosed with classical TN and 12 healthy controls participated in the study. Cardiac activity was assessed while participants were instructed to rest and again during a cold pressor test (CPT). Heart rate variability analyses were performed off-line to obtain parasympathetic (high-frequency) and sympathetic (low-frequency) indices. RESULTS: At baseline, ANS measures did not differ between healthy controls and TN patients, and both groups showed a similar increase in heart rate during the CPT (all p values >0.05). However, TN patients showed a greater increase in cardiac sympathetic activity and a greater decrease in cardiac parasympathetic activity during CPT compared with healthy controls (all p values <0.05). Importantly, changes in sympathetic reactivity, from baseline to CPT, were negatively associated with the number of pain paroxysms experienced each day by TN patients in the preceding week (r=-.58, p<0.05). CONCLUSIONS: These results suggest that TN, like many other short-lasting, unilateral facial pain conditions, is linked to ANS alterations. Future studies are required to determine if the altered ANS response observed in TN patients is a cause or a consequence of TN pain.

Significance of Non-phase Locked Oscillatory Brain Activity in Response to Noxious Stimuli.

BACKGROUND: Although current pain-evoked electroencephalographic (EEG) studies provide valuable information regarding human brain regions involved in pain, they have mostly considered neuronal responses which oscillate in phase following a painful event. In many instances, cortical neurons respond by generating bursts of activity that are slightly out of phase from trial-to-trial. These types of activity bursts are known as induced brain responses. The significance of induced brain responses to pain is still unknown. METHODS: In this study, 23 healthy subjects were given both non-painful and painful transcutaneous electrical stimulations in separate testing blocks (stimulation strength was kept constant within blocks). Subjective intensity was rated using a numerical rating scale, while cerebral activity tied to each stimulation was measured using EEG recordings. Induced brain responses were identified using a time frequency wavelet transform applied to average-removed single trials. RESULTS: Results showed a pain-specific burst of induced theta activity occurring between 180 and 500 ms post-shock onset. Source current density estimations located this activity within the dorsolateral prefrontal cortex (DLPFC, bilaterally), however, only right DLPFC activity predicted a decrease in subjective pain as testing progressed. CONCLUSION: This finding suggests that non-phase locked neuronal responses in the right DLPFC contribute to the endogenous attenuation of pain through time. PERSPECTIVE: This article presents neuroimaging findings demonstrating that, in response to pain, non-phase locked bursts of theta activity located in the right dorsolateral prefrontal cortex are associated with a progressive decrease in subjective pain intensity, which has potentially important implications regarding how humans endogenously control their experiences of pain.

Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures.

Individual differences in pain sensitivity vary as a function of precuneus reactivity.

Although humans differ widely in how sensitive they are to painful stimuli, the neural correlates underlying such variability remains poorly understood. A better understanding of this is important given that baseline pain sensitivity scores relate closely to the risk of developing refractory, chronic pain. To address this, we used a matched perception paradigm which allowed us to control for individual variations in subjective experience. By measuring subjective pain, nociceptive flexion reflexes, and, somatosensory evoked brain potentials (with source localization analysis), we were able to map the brain's sequential response to pain while also investigating its relationship to pain sensitivity (i.e. change in the stimulation strength necessary to experience pain) and spinal cord activity. We found that pain sensitivity in healthy adults was closely tied to pain-evoked responses in the contralateral precuneus. Importantly, the precuneus did not contribute to the actual representation of pain in the brain, suggesting that pain sensitivity and pain representation depend on separate neuronal sub-systems.

Does extent of resection impact survival in patients bearing glioblastoma?

BACKGROUND: The impact of malignant glioma resection on survival is still a matter of controversy. The lack of well-designed prospective studies as well as control of all factors in retrospective studies plays an important role in this debate. Amongst some of these uncontrolled factors, are the inclusion of different histological grades, the lack of objective methods to estimate the extent of resection and unspecified delays in post-operative imaging. METHODS: We retrospectively reviewed 126 consecutive patients with glioblastoma, operated on by the senior authors at the Centre Hospitalier Universitaire de Sherbrooke, who met the following criteria: >18 years of age, newly diagnosed glioblastoma, pre-operative magnetic resonance imaging (MRI) within 2 weeks prior to surgery, and a post-operative MRI within 72 hours after surgery. Extent of tumour resection was calculated using pre and post-operative tumour delimitation on gadolinium-enhanced T1 MRI in a volumetric analysis. RESULTS: Applying stringent specific inclusion criteria, 126 patients were retained in the analysis. The median overall survival was 271 days and the median extent of resection was 65%. Patients with more than 90% of tumour resection had a significantly better outcome, improving median survival from 225 to 519 days (P=0.006). Other factors that significantly improved survival were the use of radiotherapy, the number of regimens and type of chemotherapy used. CONCLUSION: A more aggressive approach combining maximal safe resection and use of salvage chemotherapy seems to confer a survival advantage for glioblastoma patients.

Pain perception in schizophrenia: evidence of a specific pain response profile.

OBJECTIVE: Ever since the characterization of schizophrenia, clinicians have noted abnormal pain sensitivity in their patients. The published literature, however, is inconsistent concerning the nature of the change reported. The objective of this study was to characterize the pain response profile of schizophrenic patients by providing both acute and prolonged (i.e., rapidly repeating) painful stimuli to schizophrenic participants and control subjects. PARTICIPANTS: Twelve schizophrenic subjects and eleven controls were included in the final analysis. Diagnosis was made according to Diagnostic and Statistical Manual of mental disorders-4th edition, text revision (DSM-IV-TR) criteria. METHODS: Intermittent, transcutaneous stimulations of the left sural nerve were administered to all participants. Painful sural nerve stimulations provoked a nociceptive flexion reflex response which was measured using an electromyographic recording of the bicep femoris muscle. Pain ratings were obtained using a 0-10 verbal numerical scale. Among schizophrenic participants, the relationship between subjective pain, reflex amplitude, and clinical features was investigated. The Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, and Subjective Scale to Investigate Cognition in Schizophrenia were used to evaluate clinical features. RESULTS: Compared with controls, schizophrenic subjects showed increased sensitivity to acute pain (i.e., lower pain thresholds; P = 0.019), but decreased subjective pain sensitization (P = 0.027). Group differences in subjective pain sensitization were not accompanied by group differences in nociceptive reflex activity (P = 0.260), suggesting supraspinal origins to the change in pain experienced by schizophrenic subjects. Moreover, positive symptoms correlated negatively with pain threshold values among schizophrenic participants (r = -0.696, P = 0.012), suggesting that distortions of thought and function relate to pain sensitivity in schizophrenic patients. CONCLUSION: Results indicate that schizophrenic subjects present a specific experimental pain response profile, characterized by elevated sensitivity to acute pain but reduced sensitivity to prolonged pain.

High-Grade Gliomas Located in the Right Hemisphere Are Associated With Worse Quality of Life.

BACKGROUND: The impact of glioma location on quality of life (QOL) has not been conclusively studied, possibly due to the prohibitively high sample size that standard statistical analyses would require and the inherent heterogeneity of this disease. By using a novel algorithm, we investigated the impact of tumor location on QOL in a limited set of 53 consecutive patients. METHODS: The glial tumors of 53 consecutive patients were segmented and registered to a standardized atlas. The Euclidian distance between 90 brain regions and each tumor's margin was calculated and correlated to the patient's self-reported QOL as measured by the Sherbrooke Neuro-Oncology Assessment Scale questionnaire. RESULTS: QOL was not correlated to tumor volume, though a significant correlation was observed with its proximity to these areas: right supramarginal gyrus, right rolandic operculum, right superior temporal gyrus, right middle temporal gyrus, right angular gyrus, and right inferior parietal lobule. Interestingly, all identified areas are in the right hemisphere, and localized in the temporoparietal region. We postulate that the adverse relation between proximity to these areas and QOL results from disruption in visuospatial functioning. CONCLUSIONS: Although the areas identified in this study are traditionally considered non-eloquent areas, tumor proximity to these regions showed more impact on QOL than any other brain regions. We postulate that this effect is mediated via an adverse impact on the visuospatial functioning.

Development of a concise QOL questionnaire for brain tumor patients.

BACKGROUND: The purpose of this study was to develop and validate a self-administered questionnaire to measure the health-related quality of life (QOL) of patients with brain cancer. We wanted to assess both core and disease-specific concerns in a single, easy-to-use instrument, thus promoting concision and clinical utility. The questionnaire departs from its predecessors in that it was designed for- and validated among French speaking Canadians. METHODS: A focus group of health professionals was used to develop items for the questionnaire, which was later validated with 105 patients suffering from brain cancer. The underlying structure of the questionnaire was investigated using principal component analysis and confirmed using a principal factor analysis. RESULTS: The final version of the questionnaire contains 30 items. Seven multi-item scales, tapping into distinct dimensions of QOL, were uncovered (i.e., functional well-being, symptom severity/fear of death, social support/acceptance of disease, autonomy in personal care, digestive symptomatology, neurocognitive function, and pain). Assessment of reliability revealed elevated internal consistency for each of the seven scales (Cronbach coefficient alpha .65), whereas known-groups validity (anchor-based approach) revealed that the different dimensions uniquely discriminated between patients with different functional levels (Karnofsky Performance Scores) and clinical status (exposure to neurosurgery, radiotherapy, and use of chemotherapy and anticonvulsants). CONCLUSION: Our QOL questionnaire, the Sherbrooke Neuro-Oncology Assessment Scale, or SNAS, taps into both core and disease-specific issues relevant to neuro-oncology patients. It has good validity and reliability, and clearly reflects the multidimensional nature of QOL. Depending on the research focus, it may be used in clinical trials to track the impact of disease and/or treatment on satisfaction, functional status, and general well-being.

Respiratory effects on experimental heat pain and cardiac activity.

OBJECTIVE: Slow deep breathing has been proposed as an effective method to decrease pain. However, experimental studies conducted to validate this claim have not been carried out. DESIGN: We measured thermal pain threshold and tolerance scores from 20 healthy adults during five different conditions, namely, during natural breathing (baseline), slow deep breathing (6 breaths/minute), rapid breathing (16 breaths/minute), distraction (video game), and heart rate (HR) biofeedback. We measured respiration (rate and depth) and HR variability from the electrocardiogram (ECG) output and analyzed the effects of respiration on pain and HR variability using time and frequency domain measures of the ECG. RESULTS: Compared with baseline, thermal pain threshold was significantly higher during slow deep breathing (P = 0.002), HR biofeedback (P < 0.001), and distraction (P = 0.006), whereas thermal pain tolerance was significantly higher during slow deep breathing (P = 0.003) and HR biofeedback (P < 0.001). Compared with baseline, only slow deep breathing and HR biofeedback conditions had an effect on cardiac activity. These conditions increased the amplitude of vagal cardiac markers (peak-to-valley, P < 0.001) as well as low frequency power (P < 0.001). CONCLUSION: Slow deep breathing and HR biofeedback had analgesic effects and increased vagal cardiac activity. Distraction also produced analgesia; however, these effects were not accompanied by concomitant changes in cardiac activity. This suggests that the neurobiology underlying respiratory-induced analgesia and distraction are different. Clinical implications are discussed, as are the possible cardiorespiratory processes responsible for mediating breathing-induced analgesia.

Fibromyalgia subgroups: profiling distinct subgroups using the Fibromyalgia Impact Questionnaire. A preliminary study.

The main goal of this project was to identify the presence of fibromyalgia (FM) subgroups using a simple and frequently used clinical tool, the Fibromyalgia Impact Questionnaire (FIQ). A total of 61 women diagnosed with FM participated in this study. FM subgroups were created by applying a hierarchical cluster analysis on selected items of the FIQ (pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms). We also tested for group differences on experimental pain, psychosocial functioning and demographic characteristics. Two cluster profiles best fit our data. FM-Type I was characterized by the lowest levels of anxiety, depressive and morning tiredness symptoms, while FM-Type II was characterized by elevated levels of pain, fatigue, morning tiredness, stiffness, anxiety and depressive symptoms. Both FM subgroups showed hyperalgesic responses to experimental pain. These results suggest that pain and stiffness are universal symptoms of the disorder but that psychological distress is a feature present only in some patients.

Infant botulism intoxication and autonomic nervous system dysfunction.

Three infants presenting with severe cases of infantile botulism, occurring at 17, 30, and 180 days of life, respectively, are described in this report. All three infants presented with areflexive flaccid coma or apnoeas requiring prolonged ventilation. In serum, type B botulinum neurotoxin (BoNT/B) was detected in two cases and BoNT/A in the third case, confirming the diagnosis of infantile botulism. Despite constant nursing and monitoring, the recovery of motility was progressive, but finally complete. Dysautonomia, measured by recording heart rate variability (HRV), persisted beyond observable physical recovery. Dysautonomia was assessed using a time-domain analysis of the continuous electrocardiogram response (via non-invasive weekly 24h Holters), which included sympathetic (SDNN) and parasympathetic indices (RMS-SD, pNN50). In all three of our patients, we observed an initial hypotonic period and a major decrease in all HRV indices. Despite observable recovery shortly after extubation, HRV time domain indices remained altered for many weeks. Because of the close monitoring afforded by hospitalization, this change in autonomic function was not accompanied by syncope, complications arising from ventricular arrhythmia, or sudden death. Our observations have important clinical implications since they emphasize the importance of pursuing cardiopulmonary monitoring following apparent functional recovery from the BoNTs.

Pain perception in schizophrenia: no changes in diffuse noxious inhibitory controls (DNIC) but a lack of pain sensitization.

BACKGROUND: Pain is a dynamic phenomenon resulting from the activity of both excitatory (e.g. sensitization) and inhibitory endogenous modulation systems. Preliminary experimental studies have shown diminished pain sensitivity in schizophrenia patients. The objective of the study was to investigate the role of excitatory and inhibitory systems on pain perception in schizophrenia. METHODS: Participants were 23 patients with a schizophrenia-spectrum disorder (DSM-IV criteria) and 29 healthy volunteers, who did not differ in age, sex or ethnicity. Excitatory and inhibitory systems were elicited using a temporal summation test (Peltier thermode) administered before and after activation of the diffuse noxious inhibitory control (DNIC) by means of a cold-pressor test. RESULTS: Time was a significant predictor of pain scores in controls, but not in patients. That is, pain ratings increased during the tonic thermal stimulation among controls but not in schizophrenia patients. When correlation coefficients (between time and pain ratings) for patients and controls were compared, the correlation coefficient emerged as significantly weaker in the schizophrenia group (Z=12.04; p=0.0001), suggesting a lack of sensitization in schizophrenia. DNIC was similar in magnitude in both patients and controls. CONCLUSIONS: Diminished pain sensitivity in schizophrenia may be related to abnormal excitatory mechanisms, but not to DNIC. More studies are needed to better characterize the neurophysiological and neurochemical mechanisms involved in the lack of sensitization in schizophrenia.

An experimental model to measure excitatory and inhibitory pain mechanisms in humans.

Numerous approaches have been used to induce and measure experimental pain perception with the goal of better understanding excitatory and inhibitory pain mechanisms. In this study, the objective was to develop a simple experimental design which would enable us to elicit and measure multiple nociceptive mechanisms that have been reported to play a role in the development and persistency of chronic pain, such as temporal summation (TS) and diffuse noxious inhibitory control (DNIC). Eighty-three healthy subjects (42 men, 41 women) participated in this study where we examined pain perception of two tonic heat pain stimulation (thermode) separated by a 2 minute cold pressor test (CPT) (7 degrees C, 10 degrees C or 12 degrees C) which allowed us to activate DNIC. The heat pain response was characterized by a peak pain during the first 30 s, which was stronger for women (p = 0.001). We also observed a TS phenomenon during the second minute of stimulation. DNIC's analgesia was assessed by measuring the difference in pain ratings between the two thermode procedures, before and after inducing DNIC by a cold pressure test on the opposite arm. We found that the mean pain ratings and peak pain but not TS were significantly reduced by DNIC. No sex differences were observed in DNIC analgesia. Our experimental pain design allowed us to measure several excitatory and inhibitory pain mechanisms in one experimental session. We were able to separate the effect of DNIC on the peak pain and on TS. This method is simple, sensitive and can easily be used in different population of either healthy subjects or chronic pain patients.

Neurophysiological measures of task-set switching: effects of working memory and aging.

We investigated age-related differences in task-switching performance by using behavioral measures and event-related brain potentials. We tested younger and older adults, and we separated older adults into groups with high and low working memory (WM); that is, we separated them into old-high-WM and old-low-WM groups. On average, all participants responded more slowly in mixed-task than in single-task blocks (i.e., reaction time or RT mixing cost). Younger adults and old-high-WM participants had equivalent RT mixing costs and showed larger posterior negative slow-wave activity when preparing for mixed trials than for single-task trials, suggesting that mixed-task trials required trial-to-trial preparation. Old-high-WM participants also showed frontally distributed activity on mixed-task trials, suggesting their use of executive control to offset age-related differences in mixed-task preparation. In contrast, old-low-WM participants had large RT mixing costs and large posterior event-related brain potential negativities during single-task trials, suggesting that they prepare during single- and mixed-task blocks. High WM, therefore, may help older adults offset the age-related difficulties often observed when they are task switching.

Changes in pain perception and descending inhibitory controls start at middle age in healthy adults.

OBJECTIVES: Previous studies have shown a reduction of diffuse noxious inhibitory controls (DNICs) in elderly adults compared with younger adults. Unfortunately, little is known regarding the developmental course of DNIC deficits and so it is still unclear whether middle-aged adults also show a DNIC deficit. The aims of the present study were to better characterize the developmental time course of the change in DNIC response by adding a middle-aged group. The role of expectations was also investigated. METHODS: The pain thresholds (PTs) of 20 young, 20 middle-aged, and 20 healthy elderly volunteers were assessed before and during a cold pressor task (water at 7 degrees C). Acute nociceptive stimuli were administered using a thermode and consisted of a range of painless and painful heat pulses. RESULTS: Analyses showed that thermal PTs increase by middle age but that the DNIC-induced increase in PT dampens progressively with advancing age. DNIC response was negatively correlated with advancing age, however, expectations regarding DNIC efficacy did not vary with age. This suggests that age-related changes in the size of the DNIC response are not best explained by an age-related change in expectation. DISCUSSION: The findings tell us that changes in pain perception and endogenous pain modulation arrive earlier than previously suggested. Studies on aging and pain should include a middle-aged group when comparing pain measures across the adult lifespan.

Unpredictable pain timings lead to greater pain when people are highly intolerant of uncertainty.

BACKGROUND AND PURPOSE: Many psychological factors are known to influence pain perception. Among them, intolerance of uncertainty (IU) may play a key modulating role in situations where uncertainty prevails, especially uncertainty regarding the timing of painful events. The objective of this study was to explore the impact of individual differences in IU on pain perception during predictable and unpredictable stimulation timings. We hypothesized that people with high IU, as opposed to those with low IU, would perceive more pain when the timing of painful stimulations cannot be predicted, as compared to when they can. METHODS: Twenty (20) healthy adults, aged between 18 and 35 years old, were recruited. Painful sensations were provoked using transcutaneous electrical stimulations of the right sural nerve. By measuring IU (Intolerance of Uncertainty Scale) and subjective pain (verbal numerical rating scale), it was possible to test the relationship between IU and pain perception, by simulating predictable and unpredictable painful experiences. This was done through cued shock interval (CSI) blocks, with either variable timing or fixed timings (long or short time frame). Self-administered questionnaires were also used to measure pain hypervigilance, pain catastrophizing, state anxiety, and trait anxiety. RESULTS: Pearson correlations confirmed the presence of an association (r=0.63) between IU and the change in pain intensity provoked by unpredictable stimulation timings. Importantly, this association was significant only for stimulations provided at long CSIs, indicating that higher IU scores predicted higher pain intensity scores when stimulation timings became unpredictable, and when the cued delay was long. No association was found between pain scores and other psychological variables. CONCLUSIONS: Our results show that IU moderately correlates to the change in pain intensity provoked by unpredictable stimulation timings. High IU scores were associated with a worsening of the subjective pain experience, especially during long delays in an unpredictable situation. These observations suggest that IU could be considered as a psychological variable that is able to influence pain perception in certain situations. IMPLICATIONS: Assessing and addressing IU could be an added value in pain-related therapy, especially in chronic pain.

Behavioural and electrophysiological measures of task switching during single and mixed-task conditions.

In order to understand how the brain prepares for and executes a switch in task demand, we measured reaction time (RT), accuracy, and event-related brain potentials associated with performance in single and mixed-task blocks using a cued design. Our results show that trials which repeat in a mixed-task block (repeat trials) were more demanding than trials which repeated in a single-task block, as reflected by the presence of a RT mixing cost and by the presence of a smaller target-locked positivity (P3b) on repeat trials. Within a mixed-task block, repeat and switch trials also differed, where repeat trials showed evidence of greater preparation (larger cue-locked negativity), more efficient target processing (larger target-locked P3b), and shorter RTs. In addition, the cue-locked negativity difference remained despite equating repeat and switch trials on RT, suggesting that this negativity difference is specific to the switching process. Our results are discussed in light of existing models of task switching.