Response selection and execution in patients with Parkinson's disease.

Different studies report diverse, sometimes conflicting findings, regarding the ability of Parkinson's disease (PD) patients to benefit from advanced cuing in choice reaction time (RT). Thus, conclusions about the changed state of underlying processes such as set formation, motor programming and motor initiation are not certain. In the present study, visual choice RT testing that utilized brief (100 ms) color signals (red/blue), was followed by auditory choice reaction time (CRT) testing with brief (100 ms) low/high pitch sound stimuli. Response consisted of either index or middle finger flexion. The signals were then combined so that the color stimuli cued the sound stimuli with an 800-ms interstimuli interval. Cuing validity was reduced from 100% during training to 76% during final testing. In addition, the same sound stimuli were presented randomly, without visual cuing, in which case response should have been suppressed. Tested subjects include 19 moderate PD patients, 21 elderly controls and 20 young controls. The patients did not differ from the controls in error rate but were slower to respond, except under 100% congruent cuing, indicating that their extended RT in CRT results from slowed stimulus-response linking and not from impaired motor initiation/execution. In the final condition patients showed no perseverance and demonstrated normal speed of set shifting in incongruent trials.

Recruitment of attentional resources during visuomotor tracking: effects of Parkinson's disease and age.

The ability to recruit attentional resources during distracted tracking was studied in 19 moderate PD patients, 21 healthy elderly subjects and 20 young controls. All subjects tracked a 1-cm circle that moved across a computer screen along a sinusoidal path (training) and along a circular path (testing). Tracking consisted of maintaining a dot cursor within the target by moving an unseen manipulandum across a digitizing tablet. Distraction consisted of adding one or three, colored 12-mm circles that moved around and intersected with the target circle, and one or three dots that moved around and intersected with the subject-controlled cursor. The performance of tasks with a low level of distraction (one dot and one circle distractor) and of tasks with a high level of distraction (three dot and three circle distractors) was compared to performance with no distraction. The elderly and young controls did not differ in the baseline task. Both groups surpassed the patients, who failed to keep pace with the target, despite preserved ability to attain the necessary movement speed. Under a low level of distraction, the ability to adjust the direction of hand movement diminished in both control groups, but task management was unaltered. In the patients adjustment of hand movement direction lowered, as in the controls, but task management reduced significantly. Under a high level of distraction, all groups showed further decrement in both aspects of task performance. We conclude that PD, but not age, significantly reduces the attentional resources required for administrative control of tracking, which are associated with prefrontal function.

Temporal changes in cortical activation during distraction from pain: a comparative LORETA study with conditioned pain modulation.

Methods to cognitively distract subjects from pain and experimental paradigms to induce conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls or DNIC) have each highlighted activity changes in closely overlapping cortical areas. This is the first study, to our knowledge, to compare cortical activation changes during these 2 manipulations in the same experimental set-up. Our study sample included thirty healthy young right handed males capable of expressing CPM. We investigated brief consecutive time windows using 32-channel EEG-based sLORETA, to determine dynamic changes in localized cortical potentials evoked by phasic noxious heat stimuli to the left volar forearm. This was performed under visual cognitive distraction tasks and conditioning hot-water pain to the right hand (CPM), both individually and simultaneously. Previously we have shown that for CPM, there is increased activity in frontal cortical regions followed by reduced activation of the somatosensory areas, suggesting a pain inhibitory role for these frontal regions. We now observed that distraction caused a different extent of cortical activation; greater early activation of frontal areas (DLPFC, OFC and caudal ACC at 250-350 ms post-stimulus), yet lesser reduction in the somatosensory cortices, ACC, PCC and SMA after 350 ms post-stimulus, compared to CPM. Both CPM and distraction reduced subjective pain scores to a similar extent. Combining CPM and distraction further reduced pain ratings compared to CPM and distraction alone, supporting the dissimilarity of the mechanisms of pain modulation under these 2 manipulations. The results are discussed in terms of the differential functional roles of the prefrontal cortex.

Tonic pain and continuous EEG: prediction of subjective pain perception by alpha-1 power during stimulation and at rest.

OBJECTIVE: Pain neurophysiology has been chiefly characterized via event-related potentials (ERPs), which are exerted using brief, phase-locked noxious stimuli. Striving for objectively characterizing clinical pain states using more natural, prolonged stimuli, tonic pain has been recently associated with the individual peak frequency of alpha oscillations. This finding encouraged us to explore whether alpha power, reflecting the magnitude of the synchronized activity within this frequency range, will demonstrate a corresponding relationship with subjective perception of tonic pain. METHODS: Five-minute-long continuous EEG was recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous temperature; and (iii) psychophysically-anchored noxious temperature. Numerical pain scores (NPSs) collected during the application of tonic noxious stimuli were tested for correlation with alpha-1 and alpha-2 power. RESULTS: NPSs and alpha power remained stable throughout the recording conditions (Ps⩾0.381). In the noxious condition, alpha-1 power obtained at the bilateral temporal scalp was negatively correlated with NPSs (Ps⩽0.04). Additionally, resting-state alpha-1 power recorded at the bilateral temporal scalp was negatively correlated with NPSs reported during the noxious condition (Ps⩽0.038). CONCLUSIONS: Current findings suggest alpha-1 power may serve as a direct, objective and experimentally stable measure of subjective perception of tonic pain. Furthermore, resting-state alpha-1 power might reflect individuals' inherent tonic pain responsiveness. SIGNIFICANCE: The relevance of alpha-1 power to tonic pain perception may deepen the understanding of the mechanisms underlying the processing of prolonged noxious stimulation.

Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.

For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala.

Characteristics of response to experimental pain in sexually abused women.

OBJECTIVES: Women with a history of sexual abuse (SA) commonly report greater pain symptoms. It is still unclear whether enhanced pain susceptibility is the result of altered pain processing and response. Therefore, this pilot study aimed to explore pain sensitivity to experimentally induced pain and associated psychology in women with a history of severe SA. METHODS: Twenty-one survivors of severe, long-lasting SA and 21 control women underwent experimentally induced heat pain and completed psychological questionnaires. Pain measures included heat pain thresholds, pain intensity ratings, and pain tolerance in response to contact heat, painful stimulation delivered to the volar forearm. Questionnaires included somatization (Brief Symptom Inventory), personality traits including harm avoidance, novelty seeking, and reward dependence (Cloninger tridimensional personality questionnaire), and levels of dissociation (Dissociative Experiences Scale). RESULTS: SA women had elevated heat pain thresholds (45.7±2.2°C vs. 43.9±3.1°C; P=0.042) and higher pain intensity ratings (on a 0 to 100 scale: 80.0±26.6 vs. 51.2±27.7; P=0.001). In addition, they had lower tolerability to painful tonic stimulation, greater somatization, and larger harm avoidance scores. Regression analyses showed that higher pain intensity ratings in SA women associated with greater tendency for harm avoidance but not with levels of dissociation. DISCUSSION: Women with a history of severe SA seem to have a paradoxical pattern of experimental pain response, characterized by both higher pain thresholds and increased pain intensity ratings. This pattern is associated with the personality trait of harm avoidance. Models that might account for these findings are discussed.

'Pain inhibits pain' mechanisms: Is pain modulation simply due to distraction?

'Diffuse noxious inhibitory controls' (DNIC), a form of supraspinal descending endogenous analgesia, requires a noxious conditioning stimulus for pain attenuation. This may be partly dependent on a distraction effect. The term "conditioned pain modulation" (CPM) has recently been introduced to describe the psychophysical paradigm to test DNIC. The present study aimed to determine whether distraction and tonic heat stimulation inhibit pain through the same or different mechanisms by looking at whether there is a similar or even an additive effect on pain attenuation. Test pain was brief heat stimulation applied to the left volar of 34 healthy volunteers. For conditioning, the right hand was immersed in 46.5 degrees C water. Distraction was provided by three different difficulty levels of continuous cognitive visual tasks. Experimental blocks consisted of test pain: (1) alone; 'baseline', (2) with conditioning pain; 'CPM', (3) with distraction; 'distraction' and (4) with conditioning pain and distraction; 'combined'. They were randomized and repeated three times and pain intensity and unpleasantness rated. Results showed an overall effect of experimental block on test pain intensity (P=0.0125). Post-hoc tests revealed a significant reduction in pain intensity ratings under Combined (21.2+/-2.3; mean+/-SEM) compared to CPM alone (16.0+/-2.3) (P<0.05). Furthermore, at all levels of distraction there were always a few subjects who were not distracted despite expressing CPM. Based on the additive effect of CPM and distraction on pain inhibition, and the cases of no distraction despite CPM, we suggest that CPM acts independently from distraction.

Neurophysiology of the cortical pain network: revisiting the role of S1 in subjective pain perception via standardized low-resolution brain electromagnetic tomography (sLORETA).

UNLABELLED: Multiple studies have supported the usefulness of standardized low-resolution brain electromagnetic tomography (sLORETA) in localizing generators of scalp-recorded potentials. The current study implemented sLORETA on pain event-related potentials, primarily aiming at validating this technique for pain research by identifying well-known pain-related regions. Subsequently, we pointed at investigating the still-debated and ambiguous topic of pain intensity coding at these regions, focusing on their relative impact on subjective pain perception. sLORETA revealed significant activations of the bilateral primary somatosensory (SI) and anterior cingulate cortices and of the contralateral operculoinsular and dorsolateral prefrontal (DLPFC) cortices (P < .05 for each). Activity of these regions, excluding DLPFC, correlated with subjective numerical pain scores (P < .05 for each). However, a multivariate regression analysis (R = .80; P = .024) distinguished the contralateral SI as the only region whose activation magnitude significantly predicted the subjective perception of noxious stimuli (P = .020), further substantiated by a reduced regression model (R = .75, P = .008). Based on (1) correspondence of the pain-activated regions identified by sLORETA with the acknowledged imaging-based pain-network and (2) the contralateral SI proving to be the most contributing region in pain intensity coding, we found sLORETA to be an appropriate tool for relevant pain research and further substantiated the role of SI in pain perception. PERSPECTIVE: Because the literature of pain intensity coding offers inconsistent findings, the current article used a novel tool for revisiting this controversial issue. Results suggest that it is the activation magnitude of SI, which solely establishes the significant correlation with subjective pain ratings, in accordance with the classical clinical thinking, relating SI lesions to diminished perception of pain. Although this study cannot support a causal relation between SI activation magnitude and pain perception, such relation might be insinuated.