Brain activity sustaining the modulation of pain by empathetic comments.

Empathetic verbal feedback from others has been shown to alleviate the intensity of experimental pain. To investigate the brain changes associated with this effect, we conducted 3T-fMRI measurements in 30 healthy subjects who received painful thermal stimuli on their left hand while overhearing empathetic, neutral or unempathetic comments, supposedly made by experimenters, via headsets. Only the empathetic comments significantly reduced pain intensity ratings. A whole-brain BOLD analysis revealed that both Empathetic and Unempathetic conditions significantly increased the activation of the right anterior insular and posterior parietal cortices to pain stimuli, while activations in the posterior cingulate cortex and precuneus (PCC/Prec) were significantly stronger during Empathetic compared to Unempathetic condition. BOLD activity increased in the DLPFC in the Empathetic condition and decreased in the PCC/Prec and vmPFC in the Unempathetic condition. In the Empathetic condition only, functional connectivity increased significantly between the vmPFC and the insular cortex. These results suggest that modulation of pain perception by empathetic feedback involves a set of high-order brain regions associated with autobiographical memories and self-awareness, and relies on interactions between such supra-modal structures and key nodes of the pain system.

Does an observer's empathy influence my pain? Effect of perceived empathetic or unempathetic support on a pain test.

The physiological and behavioural effects of empathy for other's pain have been widely investigated, while the opposite situation, i.e. the influence on one's pain of empathetic feedback from others, remains largely unexplored. Here, we assessed whether and how empathetic and unempathetic comments from observers modulate pain and associated vegetative reactions. In Study 1, conversations between observers of a pain study were recorded by professional actors. Comments were prepared to be perceived as empathetic, unempathetic or neutral, and were validated in 40 subjects. In a subsequent pain experiment (Study 2), changes in subjective pain and heart rate were investigated in 30 naïve participants who could overhear the empathetic or unempathetic conversations pre-recorded in study 1. Subjective pain was significantly attenuated when hearing empathetic comments, as compared to both unempathetic and neutral conditions, while unempathetic comments failed to significantly modulate pain. Heart rate increased when hearing unempathetic remarks and when receiving pain stimuli, but heart acceleration to nociceptive stimulation was not correlated with pain ratings. These results suggest that empathetic feedback from observers has a positive influence on pain appraisal and that this effect may surpass the negative effect of unempathetic remarks. Negative remarks can either trigger feelings of guilt or induce irritation/anger, with antagonistic effects on pain that might explain inter-individual variation. As in basal conditions heart rate and pain perception are positively correlated, their dissociation here suggests that changes in subjective pain were linked to a cognitive bias rather than changes in sensory input.

Presurgical Assessment of the Sensorimotor Cortex Using Resting-State fMRI.

BACKGROUND AND PURPOSE: The functional characterization of the motor cortex is an important issue in the presurgical evaluation of brain lesions. fMRI noninvasively identifies motor areas while patients are asked to move different body parts. This task-based approach has some drawbacks in clinical settings: long scanning times and exclusion of patients with severe functional or neurologic disabilities and children. Resting-state fMRI can avoid these difficulties because patients do not perform any goal-directed tasks. MATERIALS AND METHODS: Nineteen patients with diverse brain pathologies were prospectively evaluated by using task-based and resting-state fMRI to localize sensorimotor function. Independent component analyses were performed to generate spatial independent components reflecting functional brain networks or noise. Three radiologists identified the motor components and 3 portions of the motor cortex corresponding to the hand, foot, and face representations. Selected motor independent components were compared with task-based fMRI activation maps resulting from movements of the corresponding body parts. RESULTS: The motor cortex was successfully and consistently identified by using resting-state fMRI by the 3 radiologists for all patients. When they subdivided the motor cortex into 3 segments, the sensitivities of resting-state and task-based fMRI were comparable. Moreover, we report a good spatial correspondence with the task-based fMRI activity estimates. CONCLUSIONS: Resting-state fMRI can reliably image sensorimotor function in a clinical preoperative routine. It is a promising opportunity for presurgical localization of sensorimotor function and has the potential to benefit a large number of patients affected by a wide range of pathologies.

Mechanical allodynia in neuropathic pain. Where are the brain representations located? A positron emission tomography (PET) study.

BACKGROUND: Brain areas involved in nociception have been repeatedly investigated. Therefore, brain responses to physiological pain conditions are well identified. The same is not true for allodynic pain in patients with neuropathic pain since the cortical reorganizations that are involved in the conversion of non-noxious stimuli into painful sensations still remain unknown. METHODS: The present positron emission tomography (PET) study enrolled 19 patients with dynamic mechanical allodynia to brushing or to cold rubbing of the skin. PET activations during allodynic stimulation were compared to those obtained with the same innocuous stimulation applied outside the neuropathic pain area (control). In a second comparison, they were compared with responses to a noxious heat stimulation applied outside the neuropathic pain area (experimental pain). RESULTS: Common responses to allodynia and control stimulations were found in contralateral SI, SII and insula and in ipsilateral cerebellum. Not surprisingly, heat pain condition was associated with activations in contralateral prefrontal and SII cortices and, bilaterally, in the anterior insular cortices. Distinctive cortical responses between control and allodynic conditions were restricted to one activation within the contralateral anterior insula, a region also activated by experimental heat pain. CONCLUSIONS: The insular subdivision was inappropriately activated considering the innocuous nature of the stimulus, but adequately activated with regard to pain-evoked sensation. Subcortically, the hypothesis of reorganization at any level of the somatosensory and pain pathways underlying such insular activity was supported by the observed shift of thalamic activation from a lateral-posterior to an anterior-medial position.

Modulations of pain sensations.

Representation of time may affect pain perception. We investigated a group of volunteers looking at different clocks while they were being exposed to the same intensity of pain in two experiments. In one case, they saw the actual time, while in the other, they gazed at a clock that made it seem like the stimulation was shortened, even though it wasn't. These results show that simply believing that time is on your side can make anything more bearable. The results were not influenced by the color of the clock (red or green), or the presence of indexes such as (sad or smiling) smileys. The effects were maximal for high intensities of stimulation (pain threshold +1°C) if the stimulation lasted for at least 25s but were absent if the stimulation was short (15 min). These results suggest that pain modulation by time context is mainly available for long and intense painful stimulations. The right upper and posterior parietal cortex may support this effect. These findings are discussed with regard to previous literature of pain modulations but also with regard to the concept of the "pain matrix", its inputs and the temporal dynamics of its constitutive responses.

How the pain of others enhances our pain: searching the cerebral correlates of 'compassional hyperalgesia'.

Observing other people's pain increases our own reports to painful stimuli, a phenomenon that can be defined as 'compassional hyperalgesia' (CH). This functional magnetic resonance imaging study examined the neural correlates of CH, and whether CH could emerge when exposure to the driving stimulus was subliminal. Subjects received electric somatosensory stimuli while observing images of people undergoing painful or enjoyable somatic sensations, presented during a period allowing or not allowing conscious perception. The intensity attributed to painful stimuli increased significantly when these were delivered close to images showing human pain, but only when such images were consciously perceived. The basic core of the Pain Matrix (SI, SII, insula, mid-anterior cingulate) was activated by painful stimuli, but its activation magnitude did not increase during CH. Compassional hyperalgesia was associated with increased activity in polymodal areas involved in emotional tuning (anterior prefrontal, pregenual cingulated) and areas involved in multisensory integration and short-term memory (dorsolateral prefrontal, temporo-parieto-occipital junction). CH appears as a high-order phenomenon needing conscious appraisal of the eliciting visual stimulus, and supported by polymodal areas distinct from the basic Pain Matrix. This suggests that compassion to pain does not result from a mere 'sensory resonance' in pain networks, but rather from an interaction between the output of a first-line processing in the Pain Matrix, and the activity of a high-order network involving multisensory integration (temporo-parietal), encoding of internal states (mid-prefrontal) and short-time memory encoding (dorsolateral prefrontal). The Pain Matrix cannot be considered as an 'objective' correlate of the pain experience in all situations.

Reciprocal thalamocortical connectivity of the medial pulvinar: a depth stimulation and evoked potential study in human brain.

The thalamic medial pulvinar nucleus (PuM) is fully developed only in primates and reaches its greatest extent in humans. To assess the reciprocal functional connectivity between PuM and cortex, we studied intracerebral-evoked responses obtained after PuM and cortical electrical stimulation in 7 epileptic patients undergoing depth electroencephalographic recordings. Cortical-evoked potentials (CEPs) to PuM stimulation were recorded from all explored cortical regions, except striate cortex, anterior cingulated, and postcentral gyrus. Percentages of cortical contacts pairs responding to PuM stimulation (CEPs response rate) ranged from 80% in temporal neocortex, temporoparietal (TP) junction, insula, and frontoparietal opercular cortex to 34% in mesial temporal regions. Reciprocally, PuM-evoked potentials (PEPs) response rates were 14% after cortical stimulation in insula and frontoparietal opercular cortex, 67% in the TP junction, 76% in temporal neocortex, and 80% in mesial temporal regions. Overall, our study of functional PuM connectivity in the human brain converges with most of the data from anatomical studies in monkeys, except for a strong amygdalohippocampal functional projection to PuM and an unexpected imbalance between some of the reciprocal pathways explored. This functional quantitative approach helps to clarify the functional role of PuM as well as its implication in temporal lobe epileptic seizures.

An fMRI study of cortical representation of mechanical allodynia in patients with neuropathic pain.

OBJECTIVE: To investigate cerebral activity associated with allodynia in patients with neuropathic pain. METHODS: The brain responses of 27 patients with peripheral (5), spinal (3), brainstem (4), thalamic (5), lenticular (5), or cortical (5) lesions were studied with fMRI as innocuous mechanical stimuli were addressed to either the allodynic territory or the homologous contralateral region. RESULTS: When applied to the normal side, brush and cold rubbing stimuli did not evoke pain and activated a somatosensory "control" network including contralateral primary (SI) and secondary (SII) somatosensory cortices and insular regions. The same stimuli became severely painful when applied to the allodynic side and activated regions in the contralateral hemisphere that mirrored the "control" network, with, however, lesser activation of the SII and insular cortices. Increased activation volumes were found in contralateral SI and primary motor cortex (MI). Whereas ipsilateral responses appeared very small and restricted after control stimuli, they represented the most salient effect of allodynia and were observed mainly in the ipsilateral parietal operculum (SII), SI, and insula. Allodynic stimuli also recruited additional responses in motor/premotor areas (MI, supplementary motor area), in regions involved in spatial attention (posterior parietal cortices), and in regions linking attention and motor control (mid-anterior cingulate cortex). CONCLUSION: On a background of deafferentation in the hemisphere contralateral to stimuli, enhanced or additional responses to innocuous stimuli in the ipsilateral hemisphere may contribute to the shift of perception from innocuous toward painful and ill-defined sensations.

Orientation discrimination of objects and gratings compared: an fMRI study.

We used functional magnetic resonance imaging to compare the human brain regions involved in orientation discrimination of two-dimensional (2D) objects and gratings. The orientation discrimination tasks, identification and successive discrimination, were contrasted to a dimming detection control condition with identical retinal input. Regions involved in orientation discrimination were very similar for the two types of tasks and for the two types of stimuli and both belonged to the dorsal and ventral visual pathways. They included posterior occipital, lingual, posterior fusiform, inferior temporal, dorsal intraparietal and medial parietal regions. The main difference between the two types of stimuli was a larger activation of precuneus when 2D objects were used compared to gratings. The main difference between discrimination tasks was an enhanced activity, at the group level, in superior frontal sulcus in identification compared to successive discrimination, and at least at the single subject level, a larger activity in right fusiform cortex in successive discriminations compared to identification. Thus, in contradiction to generally accepted views, orientation discrimination of gratings and objects involve largely similar networks including both ventral and dorsal visual regions.

Human brain activity related to the perception of spatial features of objects.

The role of the parietal cortex in visuospatial analysis of object was investigated by cerebral blood flow measurements in seven objects using positron emission tomography. Data were acquired while subjects performed a matching task requiring the discrimination of simultaneously presented objects based on one of their spatial properties. Three properties were studied separately during three scanning conditions repeated twice:surface orientation, principal axis orientation, and size. Scans were also obtained during a sensorimotor control task (similar visual stimulation, same motor action, voluntary saccades toward each object) as well as during rest (no stimulation, eyes closed). Compared to rest, the three property matching tasks showed the same pattern of activation: the whole occipital lobe, the right intraparietal sulcus (IPS), and the right occipitotemporal (OT) junction. Compared to the control condition, only right IPS and OT junction were significantly activated during discrimination of the spatial properties. The IPS focus was located between the superior parietal lobule and the angular gyrus, and the OT activation overlapped the posterior part of the inferior temporal gyrus and the middle occipital gyrus. These results indicate that discrimination of spatial attributes requires the activation of both the parietal and the temporal cortices of the right hemisphere and provide further evidence that the IPS plays a critical role in visuospatial analysis of objects.

Visual working memory for shape and 3D-orientation: a PET study.

In order to determine the neural substrate of working memory for shape and 3D-orientation, regional cerebral blood flow (rCBF) changes were estimated using positron emission tomography (PET). Subjects were scanned during the performance of two delayed-matching-to-sample tasks using flat polydedrical objects of different shapes and 3D-orientations presented in a virtual environment. The shape matching task was associated with activation in the occipito-temporal junction, occipito-parietal cortex and mesial frontal pole of the right hemisphere. During the orientation matching task, rCBF increased in the mesial occipito-temporal cortex, superior temporal gyrus and middle frontal gyrus of the left hemisphere. The right supramarginal gyrus was also activated. These results suggest that both visual pathways are engaged in the processing of objects presented in different orientations. The dorsal stream is involved mainly in working memory of 3D-orientation, while the ventral stream is involved especially in shape working memory.

Visual pathways for object-oriented action and object recognition: functional anatomy with PET.

The purpose of this study was to identify the functional anatomy of the mechanisms involved in visually guided prehension and in object recognition in humans. The cerebral blood flow of seven subjects was investigated by positron emission tomography. Three conditions were performed using the same set of stimuli. In the 'grasping' condition, subjects were instructed to accurately grasp the objects. In the 'matching' condition, subjects were requested to compare the shape of the presented object with that of the previous one. In the 'pointing' condition (control), subjects pointed towards the objects. The comparison between grasping and pointing showed a regional cerebral blood flow (rCBF) increase in the anterior part of the inferior parietal cortex and part of the posterior parietal cortex. The comparison between grasping and matching showed an rCBF increase in the cerebellum, the left frontal cortex around the central sulcus, the mesial frontal cortex and the left inferior parietal cortex. Finally, the comparison between matching and pointing showed an rCBF increase in the right temporal cortex and the right posterior parietal cortex. Thus object-oriented action and object recognition activate a common posterior parietal area, suggesting that some kind of within-object spatial analysis was processed by this area whatever the goal of the task.