Spatial attention to thermal pain stimuli in subjects with visual spatial hemi-neglect: extinction, mislocalization and misidentification of stimulus modality

One approach to the study of disordered spatial attention is to carry out tests of extinction, in which stimuli are detected on the left when they are presented on the left alone, but not when both sides are stimulated simultaneously in a dual simultaneous stimulation (DSS) protocol. Extinction has been documented for multiple sensory modalities, but not for thermal pain stimuli, to our knowledge. We now test the hypothesis that subjects with visual spatial neglect (hemi-neglect) will have alterations in thermal pain sensation which are related to abnormal spatial attention. The results demonstrate that thermal pain extinction of hot and cold pain stimuli occurs in a proportion of subjects with hemi-neglect. In the subjects with visual spatial hemi-neglect but without thermal pain extinction, the sensation of the thermal pain stimulus on the affected (left) side was not extinguished but was often localized to the unaffected (right) side, and the submodality of the stimulus (cold or hot) was often misidentified. Ratios indicating the magnitude of extinction, mislocalization and misidentification were significantly larger on the left side of subjects with visual spatial neglect than in healthy controls or in controls with stroke but without hemineglect. The proportion of subjects with thermal pain extinction, mislocalization, or misidentification was significantly higher in subjects with hemi-neglect than those in either control group. These results demonstrate that disordered attention exerts a powerful effect upon the perception of both the location and the quality of thermal pain stimuli.     

Visual imagery of famous faces: effects of memory and attention revealed by fMRI

Complex pictorial information can be represented and retrieved from memory as mental visual images. Functional brain imaging studies have shown that visual perception and visual imagery share common neural substrates. The type of memory (short- or long-term) that mediates the generation of mental images, however, has not been addressed previously. The purpose of this study was to investigate the neural correlates underlying imagery generated from short- and long-term memory (STM and LTM). We used famous faces to localize the visual response during perception and to compare the responses during visual imagery generated from STM (subjects memorized specific pictures of celebrities before the imagery task) and imagery from LTM (subjects imagined famous faces without seeing specific pictures during the experimental session). We found that visual perception of famous faces activated the inferior occipital gyri, lateral fusiform gyri, the superior temporal sulcus, and the amygdala. Small subsets of these face-selective regions were activated during imagery. Additionally, visual imagery of famous faces activated a network of regions composed of bilateral calcarine, hippocampus, precuneus, intraparietal sulcus (IPS), and the inferior frontal gyrus (IFG). In all these regions, imagery generated from STM evoked more activation than imagery from LTM. Regardless of memory type, focusing attention on features of the imagined faces (e.g., eyes, lips, or nose) resulted in increased activation in the right IPS and right IFG. Our results suggest differential effects of memory and attention during the generation and maintenance of mental images of faces.     

Effects of attention on the intensity and unpleasantness of thermal pain

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

Association between language and spatial laterality and cognitive ability: an fMRI study

The interaction between language and spatial laterality and its association with cognitive ability was explored in a group of 42 right-handers and 40 left-handers using functional magnetic resonance imaging. Cognitive ability measures including working memory, verbal comprehension and perceptual organisation were assessed using the Wechsler Adult Intelligence Scale (version III). Left-handers show lower working memory scores than right-handers. Increased rightward language laterality is also associated with decreased working memory performance, which we suggest is related to the involvement of the left inferior frontal gyrus in subvocal rehearsal during working memory tasks. The interaction between language and spatial laterality is associated with performance on verbal comprehension and perceptual organisation, such that when language and spatial laterality are dissociated between the hemispheres a significant increase in verbal comprehension and perceptual organisation performance is found. There is a decrease in performance on the verbal comprehension and perceptual organisation subtests when language and spatial processing are associated to the same hemisphere (i.e. both lateralised to the right hemisphere or both lateralised to the left). This interaction is interpreted in relation to the 'hemispheric crowding' hypothesis, which proposes increased cognitive ability when language and spatial laterality are dissociated.     

Changes in pain from a repetitive thermal stimulus: the roles of adaptation and sensitization

This study examined processes that contribute to the changing painfulness of a repeatedly presented thermal (heat) stimulus. The 3-second pulses were presented to the side of the hand at a rate of 4/min, too slow to engage wind-up. Over the course of 32 trials, pain intensity (measured by verbal report on a 0-100 scale) first declined and then (in most cases) rose again, indicating adaptation and sensitization, respectively. The magnitude of adaptation grew across a series of 3 runs, indicating that adaptation has a slow as well as a fast component. The rate of sensitization depended on stimulus temperature, but not on subjective pain intensity; this result implies that sensitization takes place at an early processing stage. Adaptation and sensitization were comparable in participants with fibromyalgia, temporomandibular disorders, and in healthy controls, indicating that these processes occur before the perceptual amplification that characterizes fibromyalgia and temporomandibular disorders. The ability of vibration to reduce pain has previously been shown to involve segmental inhibition; the finding in the present study that vibratory gating of pain is significantly (inversely) related to the rate of sensitization suggests that the latter also reflects segmental processes. Several lines of evidence thus point to the conclusion that adaptation and sensitization occur at early stages of sensory information processing.     

Receptive field size-dependent attention effects in simultaneously presented stimulus displays

Neurophysiological studies in monkeys show that multiple stimuli presented within the receptive field of a neuron are not processed independently but rather act in a mutually suppressive way. Recently, such suppressive interactions have also been reported in human neuroimaging studies. This is seen as evidence that stimuli compete for neural representation. According to the 'biased competition' approach, attention can bias this competition in favor of the attended stimulus, relieving it of the suppressive influences of the distracters. In this paper, we report data that support these findings. Specifically, the effect of attention on stimuli with different spatial separations was investigated more thoroughly. The biased competition approach would predict that, for a given spatial separation and eccentricity, the difference between attended and unattended displays depends on the receptive field size of an area. In a blocked fMRI experiment, participants viewed four simultaneously presented, colorful pictures under different attention conditions (attended and unattended). Stimuli were separated either 2 degrees , 4 degrees or 7 degrees . In line with previous experiments, we found that the effect of attention correlated with the estimated receptive field size of an area. In areas V1, V2 and VP, where estimated receptive field sizes are small, no significant attention effects were found in any of the spatial separation conditions. In V4, there was a significant difference between attended and unattended conditions for the 2 degrees and 4 degrees spatial separations, but not for 7 degrees . Finally in area TEO, significant differences between attended and unattended conditions were observed for all spatial separations.     

Delayed effects of attention in visual cortex as measured with fMRI

To what extent does attention modulate neural activity in early visual areas? fMRI measurements of attentional modulation in primary visual cortex (V1) show large effects, while single unit recordings show much smaller ones. This discrepancy suggests that fMRI measures of attention may be inflated, perhaps by activity related to other processes. To test whether effects measured with fMRI actually reflect attentional enhancement, we used a rapid acquisition protocol to determine their timing. Subjects were presented with two stimuli on either side of fixation and were cued to attend one and ignore the other. Attended stimuli showed a greater magnitude of response in V1, but this increase was delayed, by roughly one second in time, relative to both unattended responses and response increases due to boosting stimulus contrast. These results suggest that fMRI measurements of attention may primarily depend upon other processes that take a relatively long time to feed back to V1. Our results demonstrate the importance of using the fine timing information available in the fMRI response.     

Taste laterality studied by means of umami and salt stimuli: an fMRI study

Aim of the present study was to investigate laterality of the gustatory system in the human brain for the taste qualities elicited by MSG (monosodium glutamate) and NaCl (sodium chloride). A total of 23 subjects participated in a block-design functional magnetic resonance imaging (fMRI) study. Liquid stimuli were presented at supra-threshold concentrations and delivered by means of a computer controlled gustometer. Left and right sides of the mouth were stimulated separately in order to correlate statistical parametrical maps to both the site of the stimulus and the specific taste quality. Following the effects of the site of stimulation through primary and secondary gustatory cortices an effort was made to explore the laterality of the gustatory pathways. Our results showed for both tastants a predominance of ipsilateral connections at the thalamus level. Insula left and right regions were both involved for both tastants. In these regions we found a high proportion of ipsilateral connection again for both the tastants. Considering orbitofrontal/prefrontal cortex, left-sided stimulation with NaCl or MSG produced left-sided activation of the orbito-frontal cortex clearly indicating the presence of an ipsilateral path. Finally, the hypothesis of frontal operculum as primary gustatory cortex and lateral prefrontal cortex as secondary was also supported by the results from dynamic causal modeling.     

Increased pain sensitivity in fibromyalgia: effects of stimulus type and mode of presentation

Fibromyalgia (FM) is defined in part by sensitivity to blunt pressure. Pressure pain sensitivity in FM is evaluated typically by the use of 'ascending' testing methods such as tender point counts or dolorimetry, which can be influenced by response bias of both the subject and examiner. Methods that present stimuli in a random, unpredictable fashion might minimize the influence of these factors. In this study, we compared the results of ascending and random assessments of both pressure and thermal pain sensitivities in 43 FM patients and 28 age- and gender-matched controls. Even though FM is defined on the basis of pressure sensitivity, this group was also more sensitive to heat stimuli, presented in either ascending or random paradigms. In both the patient and control groups, the pain ratings to painful sensations evoked by both thermal and pressure stimuli were significantly greater in the random, compared with the ascending method. The number of subjects classified as 'expectant' because they rated pain higher in ascending than random paradigms was similar for FM and control groups. Both patients and controls exhibited a similar degree of sensitization to pressure and thermal stimuli. The increased sensitivity to both pressure and thermal stimuli for threshold and suprathreshold stimuli in FM patients is consistent with central augmentation of pain processing.     

The effects of prior pain experience on neural correlates of empathy for pain: An fMRI study

Neuroimaging studies have revealed partially shared neural substrates for both the actual experience of pain and empathy elicited by the pain of others. We examined whether prior pain exposure increased neural activity in the anterior midcingulate cortex (aMCC) and bilateral anterior insula (AI) as a correlate of empathy for pain. Participants (N = 64: 32 women, 32 men) viewed pictures displaying exposure to pressure pain (pain pictures) and pictures without any cue of pain (neutral pictures). Prior to the experiment, half of the participants were exposed to the same pain stimulus as the one seen in the pain pictures (pain exposure condition); the other half had no such experience (touch exposure condition). A balanced sex ratio was kept, to investigate possible sex differences. In the region-of-interest analyses, participants of the pain exposure condition showed decreased activity in the right AI and the aMCC relative to participants of the touch exposure condition. While in men, no differences were found in relation to their exposure condition, women with pain exposure showed decreased activity in the aMCC and additionally, in bilateral AI. Based on the entire sample, whole brain analyses revealed stronger activation in the retrosplenial cortex, dorsomedial prefrontal cortex, and medial prefrontal cortex in the pain exposure condition. In conclusion, prior pain exposure did not increase, but decreased activity in regions regularly associated with empathy for pain. However, pain experience increased activity in regions associated with memory retrieval, perspective taking, and top-down emotion regulation, which might facilitate empathizing with others.     

Detection versus estimation in event-related fMRI: choosing the optimal stimulus timing.

With the advent of event-related paradigms in functional MRI, there has been interest in finding the optimal stimulus timing, especially when the interstimulus interval is varied during the imaging run. Previous works have proposed stimulus timings to optimize either the estimation of the impulse response function (IRF) or the detection of signal changes. The purpose of this paper is to clarify that estimation and detection are fundamentally different goals and to determine the optimal stimulus timing and distribution with respect to both the accuracy of estimating the IRF and the power of detection assuming a particular hemodynamic model. Simulated stimulus distributions are varied systematically, from traditional blocked designs to rapidly varying event related designs. These simulations indicate that estimation of the hemodynamic impulse response function is optimized when stimuli are frequently alternated between task and control states, with shorter interstimulus intervals and stimulus durations, whereas the detection of activated areas is optimized by blocked designs. The stimulus timing for a given experiment should therefore be generated with the required detectability and estimation accuracy.     

Mental motor imagery indexes pain: The hand laterality task

Mental motor imagery is subserved by the same cognitive systems that underlie action. In turn, action is informed by the anticipated sensory consequences of movement, including pain. In light of these considerations, one would predict that motor imagery would provide a useful measure pain‐related functional interference. We report a study in which 19 patients with chronic musculoskeletal or radiculopathic arm or shoulder pain, 24 subjects with chronic pain not involving the arm/shoulder and 41 normal controls were asked to indicate if a line drawing was a right or left hand. Previous work demonstrated that this task is performed by mental rotation of the subject's hand to match the stimulus. Relative to normal and pain control subjects, arm/shoulder pain subjects were significantly slower for stimuli that required greater amplitude rotations. For the arm/shoulder pain subjects only there was a correlation between degree of slowing and the rating of severity of pain with movement but not the non‐specific pain rating. The hand laterality task may supplement the assessment of subjects with chronic arm/shoulder pain.     

Acceptance of the unpleasant reality of chronic pain: effects upon attention to pain and engagement with daily activities

This paper investigates whether acceptance was related to less attention to pain, and to more engagement with daily activities. The results of two studies are reported. In a first cross-sectional study, 501 chronic pain patients completed self-report instruments on pain severity, attention to pain and acceptance. In a second diary study, 62 patients with chronic pain reported pain intensity, attention to pain and characteristics of goal-directed behaviour 8 times a day using an experience sampling method. Acceptance was measured using a self-report instrument. It was found that acceptance was related to less attention to pain (study 1 and study 2), more engagement with daily activities, a higher motivation to complete activities and a better efficacy to perform daily activities (study 2). Results are discussed in terms of how a positive life despite pain may be preserved by a flexible adjustment of personal goals to current limitations and adversities.     

Object representations in ventral and dorsal visual streams: fMRI repetition effects depend on attention and part-whole configuration

The effects of attention and object configuration on the neural responses to short-lag visual image repetition were investigated with fMRI. Attention to one of two object images in a prime display was cued spatially. The images were either intact or split vertically; a manipulation that negates the influence of view-based representations. A subsequent single intact probe image was named covertly. Behavioural priming observed as faster button presses was found for attended primes in both intact and split configurations, but only for uncued primes in the intact configuration. In a voxel-wise analysis, fMRI repetition suppression (RS) was observed in a left mid-fusiform region for attended primes, both intact and split, whilst a right intraparietal region showed repetition enhancement (RE) for intact primes, regardless of attention. In a factorial analysis across regions of interest (ROIs) defined from independent localiser contrasts, RS for attended objects in the ventral stream was significantly left-lateralised, whilst repetition effects in ventral and dorsal ROIs correlated with the amount of priming in specific conditions. These fMRI results extend hybrid theories of object recognition, implicating left ventral stream regions in analytic processing (requiring attention), consistent with prior hypotheses about hemispheric specialisation, and implicating dorsal stream regions in holistic processing (independent of attention).     

An fMRI study of joint attention experience

Although much is now known about eye movement detection, little is known about the higher cognitive processes involved in joint attention. We developed video stimuli which when watched, engender an experience of joint attention in the observer. This allowed us to compare an experience of joint attention to nonjoint attention within an fMRI scanning environment. Joint attention was associated with activity in the ventromedial frontal cortex, the left superior frontal gyrus (BA10), cingulate cortex, and caudate nuclei. The ventromedial frontal cortex has been consistently shown to be activated during mental state attribution tasks. BA10 may serve a cognitive integration function, which in this case seems to utilize a perception-action matching process. The activation we identified in BA10 overlaps with a location of increased grey matter density that we recently found to be associated with autistic spectrum disorder. This study therefore constitutes evidence that the neural substrate of joint attention also serves a mentalizing function. The developmental failure of this substrate in the left anterior frontal lobe may be important in the etiology of autistic spectrum disorder.     

Pain and laterality in a British pain clinic sample

The distribution of pain laterality was investigated in a sample of patients from a British Pain Relief Centre. The findings replicated those previously obtained by Hall et al. [1] in an American Pain Clinic sample. There was no evidence of preferential left lateralization of pain and no evidence that the frequency of left-sided pain varied with the presence or absence of a lesion.     

From Descartes to fMRI. Pain theories and pain concepts

In the seventeenth century the philosopher Rene Descartes was the forerunner by establishing a scientific hypothesis on the origin of pain. Much later, in the nineteenth century, pain hypotheses emerged which explained the pain sensation either on the basis of intense stimulation of any kind of nerve fibers (intensity hypothesis) or on the basis of specific nociceptors (specificity hypothesis). The "gate control theory" established by Melzack and Wall (1964) offered an explanation of modulations of pain sensation by the interaction between nociceptive and non-nociceptive nerve fibers and by descending control in the central nervous system. Though this hypothesis is outdated in its original form, it had - in a more common formulation - a great influence on our understanding of pain.For building a bridge to our present knowledge, the molecular structure of the nociceptor membrane is of particular importance. On this basis also new pain therapies have been developed. On the other hand, the methods of functional imaging allow the identification of brain regions related to pain processing at a macroscopic level. This new technology opened up new ways of understanding chronic pain processes and new possibilities for the control of therapeutic effects.     

Changing channels: an fMRI study of aging and cross-modal attention shifts

Age-related deficits in visual selective attention suggest that the efficiency of inhibitory processes is particularly affected by aging. To investigate whether processing inefficiencies observed in visual attention are similar in auditory attention and when shifting attention across modalities, we conducted an fMRI study with healthy young and older adults using a task that required sustained auditory and visual selective attention and cross-modal attention shifts. Older adults in this study performed as well as the younger adults, but showed age-related differences in BOLD responses. The most striking of these differences were bilateral frontal and parietal regions of significantly increased activation in older adults during both focused and shifting attention. Our data suggest that this increased activation did not reflect new recruitment, but reliance on brain regions typically used by younger adults when task demands are greater. Older adults' activation patterns suggested that even during focused attention conditions they were "shifting" attention to stimuli in the unattended modality. Increased activation during processing of both task-relevant and task-irrelevant information implies age-related loss of processing selectivity. These patterns may reflect both task-specific compensatory neural recruitment and degradation of sensory inhibition.