Controllability and hippocampal activation during pain expectation in fibromyalgia syndrome.

To examine the role of perceived control in pain perception, fibromyalgia patients and healthy controls participated in a reaction time experiment under different conditions of pain controllability. No significant differences between groups were found in pain intensity and unpleasantness ratings. However, during the expectation of uncontrollable pain, patients compared to controls showed higher hippocampal activation. In addition, hippocampal activity during the pain expectation period predicted activation of the posterior cingulate cortex (PCC), precuneus and hippocampus during pain stimulation in fibromyalgia patients. The increased activation of the hippocampus during pain expectation and subsequent activation of the PCC/precuneus during the lack of control phase points towards an influence of pain perception through heightening of alertness and anxiety responses to pain in fibromyalgia patients.

Contextual modulation of pain in masochists: involvement of the parietal operculum and insula.

Pain can be modulated by contextual stimuli, such as emotions, social factors, or specific bodily perceptions. We presented painful laser stimuli together with body-related masochistic visual stimuli to persons with and without preferred masochistic sexual behavior and used neutral, positive, and negative pictures with and without painful stimuli as control. Masochists reported substantially reduced pain intensity and unpleasantness in the masochistic context compared with controls but had unaltered pain perception in the other conditions. Functional magnetic resonance imaging revealed that masochists activated brain areas involved in sensory-discriminative processing rather than affective pain processing when they received painful stimuli on a masochistic background. The masochists compared with the controls displayed attenuated functional connectivity of the parietal operculum with the left and right insulae, the central operculum, and the supramarginal gyrus. Masochists additionally showed negative correlations between the duration of interest in masochistic activities and activation of areas involved in motor activity and affective processing. We propose that the parietal operculum serves as an important relay station that attenuates the affective-motivational aspects of pain in masochists. This novel mechanism of pain modulation might be related to multisensory integration and has important implications for the assessment and treatment of pain.

Deficient modulation of pain by a positive emotional context in fibromyalgia patients.

This study aimed to investigate the modulating effects of emotional context on pain perception in 16 patients with fibromyalgia syndrome (FMS) and 16 healthy control (HC) subjects. An infrared laser was used to apply individually adapted painful stimuli to the dorsum of the left hand. The emotional background of the painful stimuli was modulated by concurrent presentations of negative, neutral, and positive picture stimuli selected from the International Affective Picture System. As control conditions, painful stimuli and the pictures were also presented by themselves. During each of the 5 laser-picture trials, subjects received 10 painful stimuli and were asked to rate the average intensity and unpleasantness of the experienced pain. Functional magnetic resonance images were obtained, using a T2(∗) sensitive echo planar sequence. HC subjects showed a linear increase in pain intensity and unpleasantness ratings when painful stimuli were presented during positive, neutral, and negative pictures. In contrast, FMS patients showed a quadratic trend for pain intensity ratings indicating a lack of pain reduction by the positive pictures. In addition, the FMS patients showed less activation in secondary somatosensory cortex, insula, orbitofrontal cortex, and anterior cingulate cortex during the positive picture pain trials. Our results suggest that fibromyalgia patients are less efficient in modulating pain by positive affect and may benefit less from appetitive events than healthy control subjects.

Is the effect of tinnitus on auditory steady-state response amplitude mediated by attention?

OBJECTIVES: Auditory steady-state response (ASSR) amplitude enhancement effects have been reported in tinnitus patients. As ASSR amplitude is also enhanced by attention, the effect of tinnitus on ASSR amplitude could be interpreted as an effect of attention mediated by tinnitus. As N1 attention effects are significantly larger than those on the ASSR, if the effect of tinnitus on ASSR amplitude were due to attention, there should be similar amplitude enhancement effects in tinnitus for the N1 component of the auditory-evoked response. METHODS: MEG recordings which were previously examined for the ASSR (Diesch et al., 2010a) were analyzed with respect to the N1m component. Like the ASSR previously, the N1m was analyzed in the source domain (source space projection). Stimuli were amplitude-modulated (AM) tones with one of three carrier frequencies matching the tinnitus frequency or a surrogate frequency 1½ octave above the audiometric edge frequency in controls, the audiometric edge frequency, and a frequency below the audiometric edge. Single AM-tones were presented in a single condition and superpositions of three AM-tones differing in carrier and modulation frequency in a composite condition. RESULTS: In the earlier ASSR study (Diesch et al., 2010a), the ASSR amplitude in tinnitus patients, but not in controls, was significantly larger in the (surrogate) tinnitus condition than in the edge condition. Patients showed less evidence than controls of reciprocal inhibition of component ASSR responses in the composite condition. In the present study, N1m amplitudes elicited by stimuli located at the audiometric edge and at the (surrogate) tinnitus frequency were smaller than N1m amplitudes elicited by sub-edge tones both in patients and controls. The relationship of the N1m response in the composite condition to the N1m response in the single condition indicated that reciprocal inhibition among component N1m responses was reduced in patients compared against controls. CONCLUSIONS: In the present study, no evidence was found for an N1-amplitude enhancement effect in tinnitus. Compared to controls, reciprocal inhibition is reduced in tinnitus patients. Thus, as there is no effect on N1m that could potentially be attributed to attention, it seems unlikely that the enhancement effect of tinnitus on ASSR amplitude could be accounted for in terms of attention induced by tinnitus.

Structural changes of the corpus callosum in tinnitus.

OBJECTIVES: In tinnitus, several brain regions seem to be structurally altered, including the medial partition of Heschl's gyrus (mHG), the site of the primary auditory cortex. The mHG is smaller in tinnitus patients than in healthy controls. The corpus callosum (CC) is the main interhemispheric commissure of the brain connecting the auditory areas of the left and the right hemisphere. Here, we investigate whether tinnitus status is associated with CC volume. METHODS: The midsagittal cross-sectional area of the CC was examined in tinnitus patients and healthy controls in which an examination of the mHG had been carried out earlier. The CC was extracted and segmented into subregions which were defined according to the most common CC morphometry schemes introduced by Witelson (1989) and Hofer and Frahm (2006). RESULTS: For both CC segmentation schemes, the CC posterior midbody was smaller in male patients than in male healthy controls and the isthmus, the anterior midbody, and the genou were larger in female patients than in female controls. With CC size normalized relative to mHG volume, the normalized CC splenium was larger in male patients than male controls and the normalized CC splenium, the isthmus and the genou were larger in female patients than female controls. Normalized CC segment size expresses callosal interconnectivity relative to auditory cortex volume. CONCLUSION: It may be argued that the predominant function of the CC is excitatory. The stronger callosal interconnectivity in tinnitus patients, compared to healthy controls, may facilitate the emergence and maintenance of a positive feedback loop between tinnitus generators located in the two hemispheres.

Functional and structural aspects of tinnitus-related enhancement and suppression of auditory cortex activity.

The steady-state auditory evoked magnetic field was recorded in tinnitus patients and controls, both either musicians or non-musicians, all of them with high-frequency hearing loss. Stimuli were AM-tones with two modulation frequencies and three carrier frequencies matching the "audiometric edge", i.e. the frequency above which hearing loss increases more rapidly, the tinnitus frequency or the frequency 1 1/2 octaves above the audiometric edge in controls, and a frequency 1 1/2 octaves below the audiometric edge. Stimuli equated in carrier frequency, but differing in modulation frequency, were simultaneously presented to the two ears. The modulation frequency-specific components of the dual steady-state response were recovered by bandpass filtering. In both hemispheres, the source amplitude of the response was larger for contralateral than ipsilateral input. In non-musicians with tinnitus, this laterality effect was enhanced in the hemisphere contralateral and reduced in the hemisphere ipsilateral to the tinnitus ear, especially for the tinnitus frequency. The hemisphere-by-input laterality dominance effect was smaller in musicians than in non-musicians. In both patient groups, source amplitude change over time, i.e. amplitude slope, was increasing with tonal frequency for contralateral input and decreasing for ipsilateral input. However, slope was smaller for musicians than non-musicians. In patients, source amplitude was negatively correlated with the MRI-determined volume of the medial partition of Heschl's gyrus. Tinnitus patients show an altered excitatory-inhibitory balance reflecting the downregulation of inhibition and resulting in a steeper dominance hierarchy among simultaneous processes in auditory cortex. Direction and extent of this alteration are modulated by musicality and auditory cortex volume.

An MR-compatible device for automated and safe application of laser stimuli in experiments employing nociceptive stimulation.

In this paper the establishment of an automatic laser application device that reproducibly delivers laser stimuli in a safe, controlled, and reliable manner is presented. Nociceptive stimulation is widely used in functional magnetic resonance imaging (fMRI) experiments and a number of different methods are employed. One major advantage of laser stimulation as a method to administer painful stimuli is that it selectively activates nociceptors. To avoid damage to the subject's skin, which might occur if the same skin area were stimulated too often, the laser focal spot needs to be repositioned after each stimulus. Here, we describe the design of the mechanical set-up, the functionality, the computation of laser stimulus intensity, the materials used, the monitoring system, and the interface to the control software. Additionally, MR-compatibility and functionality of the device were evaluated and assessed in a 3T MR scanner. Finally, the reliability and validity of the device were tested and demonstrated. It permits easy and investigator-independent use of laser stimulation in the MR scanner.

Reduced volume of Heschl's gyrus in tinnitus.

The neural basis of tinnitus is unknown. Recent neuroimaging studies point towards involvement of several cortical and subcortical regions. Here we demonstrate that tinnitus may be associated with structural changes in the auditory cortex. Using individual morphological segmentation, the medial partition of Heschl's gyrus (mHG) was studied in individuals with and without chronic tinnitus using magnetic resonance imaging. Both the tinnitus and the non-tinnitus group included musicians and non-musicians. Patients exhibited significantly smaller mHG gray matter volumes than controls. In unilateral tinnitus, this effect was almost exclusively seen in the hemisphere ipsilateral to the affected ear. In bilateral tinnitus, mHG volume was substantially reduced in both hemispheres. The tinnitus-related volume reduction was found across the full extent of mHG, not only in the high-frequency part usually most affected by hearing loss-induced deafferentation. However, there was also evidence for a relationship between volume reduction and hearing loss. Correlations between volume and hearing level depended on the subject group as well as the asymmetry of the hearing loss. The volume changes observed may represent antecedents or consequences of tinnitus and tinnitus-associated hearing loss and also raise the possibility that small cortical volume constitutes a vulnerability factor.

Alteration in the response properties of primary somatosensory cortex related to differential aversive Pavlovian conditioning.

The effects of differential aversive Pavlovian conditioning on the functional organization of primary somatosensory cortex (SI) were examined in 17 healthy participants. Neuroelectric source imaging from 60 electrodes was employed while nine subjects received an innocuous electric stimulus (conditioned stimulus, CS) to one finger (left or right) that was followed by painful electric shock to the lower back (unconditioned stimulus, US) and an innocuous stimulus to the other finger that was never followed by pain. Eight subjects received a presentation of the innocuous and painful stimuli with equal probability to both fingers (control group). The data included the electromyogram (EMG) from the left m. corrugator, and judgments of intensity, aversiveness, and CS-US contingency. Only the experimental group displayed EMG conditioning, differential contingency judgments, as well as a change of dipole orientation for the CS and an enhanced dipole moment for the US in the electroencephalogram. Intensity and unpleasantness ratings were altered in a more unspecific manner and did not differ between groups and stimulus conditions. The data suggest that SI contributes to memory processes in associative learning. Pavlovian conditioning of tactile responses might be important in the altered processing of painful stimuli in chronic pain patients where enhanced conditioning has been demonstrated.

Central processing of acute muscle pain in chronic low back pain patients: an EEG mapping study.

The presence of perceptual sensitization and related brain responses was examined in 14 chronic low back pain (CLBP) patients and 13 healthy controls comparable in age and sex. Multichannel EEG recordings and pain ratings were obtained during the presentation of 800 painful electrical intramuscular and intracutaneous stimuli each to the left m. erector spinae and the left m. extensor digitorum. Perception and pain thresholds were not significantly different between the two groups, though patients showed significantly more perceptual sensitization. Across all stimulation conditions, a larger EEG component 80 milliseconds after stimulation was observed in the CLBP group. No significant group differences were found for the N150. The component 260 milliseconds after stimulus onset was significantly smaller in the CLBP group. N80, N150, and perceptual sensitization were significantly positively correlated. These results indicate enhanced perceptual sensitization and enhanced processing of the sensory-discriminative aspect of pain, as expressed in the N80 component, in CLBP patients. This may be one neurophysiologic basis of sensitization and the chronicity process. The lower P260 component in the patients may be explained in terms of tonic pain inhibiting phasic pain or may be related to the affective distress observed in this patient group.

Auditory discrimination training for the treatment of tinnitus.

This paper presents a series of 12 cases of chronic tinnitus patients who participated in 4 weeks of auditory discrimination training either close to or far removed from the tinnitus frequency. The training was based on the assumption that tinnitus is related to a shift of the representation of the tinnitus frequency in auditory cortex outside of the normal tonotopic map and that training close to but not removed from the tinnitus frequency should result in a reduction in the severity of the tinnitus. Tinnitus severity was measured 4 times per day during the entire treatment and other tinnitus-related variables were assessed 1 week before and 1 month posttreatment. The comparison of the training close to as compared to remote from the tinnitus frequency did not yield a statistically significant difference. However, a post hoc analysis revealed that patients who engaged in regular training as compared to those who practiced irregularly were significantly more successful in reducing tinnitus severity independent of the trained frequencies. Treatment success was best predicted by days of training and general activity levels. The data suggest that auditory discrimination training shows a dose response effect irrespective of training location and that treatment success is also related to psychological variables. For more substantial changes in multiple variables an extended training period with additional consideration of emotional variables would be necessary. In addition, controls for nonspecific training effects need to be implemented.

Enhancement of steady-state auditory evoked magnetic fields in tinnitus.

The steady-state auditory evoked magnetic field and the Pbm, the magnetic counterpart of the second frontocentrally positive middle latency component of the transitory auditory evoked potential, were measured in ten tinnitus patients using a 122-channel gradiometer system. The patients had varying degrees of hearing loss. In all patients, the tinnitus frequency was located above the frequency of the audiometric edge, i.e. the location on the frequency axis above which hearing loss increases more rapidly. Stimuli were amplitude-modulated sinusoids with carrier frequencies at the tinnitus frequency, the audiometric edge, two frequencies below the audiometric edge, and two frequencies between the audiometric edge and the tinnitus frequency. Below the audiometric edge, the root-mean-square field amplitude of the steady-state response computed across the whole head as well as the contralateral and the ipsilateral dipole moment decreased as a function of carrier frequency. With carrier frequency above the audiometric edge, the steady-state response increased again. The amplitudes of the transitory Pbm component were patterned in a qualitatively similar way, but without the differences being significant. For the steady-state response, both whole-head root-mean-square field amplitude and the dipole moment of the sources at the tinnitus frequency showed significant positive correlations with subjective ratings of tinnitus intensity and intrusiveness. These correlations remained significant when the influence of hearing loss was partialled out. The observed steady-state response amplitude pattern likely reflects an enhanced state of excitability of the frequency region in primary auditory cortex above the audiometric edge. The relationship of tinnitus to auditory cortex hyperexcitability and its independence of hearing loss is discussed with reference to loss of surround inhibition in and map reorganization of primary auditory cortex.

Parietal activation during visual search in the absence of multiple distractors.

Search for a target object embedded in a visual scene involves the posterior parietal cortex. This region is thought to play a role in visual attention by counteracting the effects of distractors on targets or by inhibiting distractors. Using fMRI, we investigated whether the parietal cortex is also engaged in visual search without distractors. Cortical activation was compared between two 'single object' search tasks differing only in difficulty. Activation differences between both tasks were found in the anterior and inferior part of the intraparietal sulcus, but in neither its posterior part nor the frontal eye fields. Thus a subset of parietal regions participates in the control of visual search even in the absence of distractors.

A perceptual interference account of acquisition difficulties for non-native phonemes.

This article presents an account of how early language experience can impede the acquisition of non-native phonemes during adulthood. The hypothesis is that early language experience alters relatively low-level perceptual processing, and that these changes interfere with the formation and adaptability of higher-level linguistic representations. Supporting data are presented from an experiment that tested the perception of English /r/ and /l/ by Japanese, German, and American adults. The underlying perceptual spaces for these phonemes were mapped using multidimensional scaling and compared to native-language categorization judgments. The results demonstrate that Japanese adults are most sensitive to an acoustic cue, F2, that is irrelevant to the English /r/-/l/ categorization. German adults, in contrast, have relatively high sensitivity to more critical acoustic cues. The results show how language-specific perceptual processing can alter the relative salience of within- and between-category acoustic variation, and thereby interfere with second language acquisition.

Visual feature and conjunction searches of equal difficulty engage only partially overlapping frontoparietal networks.

According to a classical view of visual object recognition, targets are detected "pre-attentively" if they carry unique features, whereas attention has to be deployed serially to object locations for feature binding if the targets can be distinguished from distracters only in terms of their feature conjunctions. Consistent with this view, recent reports suggest a contribution of the posterior parietal cortex (PPC; one major region controlling spatial attention) to conjunction search as opposed to feature search. However, PPC engagement in conjunction search might also reflect feature-based attention or the difficulty of target selection. The present fMRI study compared regions and amplitudes of cortical activity reflecting the attention mechanisms of a conjunction and a feature search of equal difficulty performed during maintenance of fixation. Attention-related activity was assessed by comparing each hard feature and conjunction search with an easy feature search. Hard feature and conjunction search activated overlapping regions in multiple PPC areas and in the frontal eye field (FEF). Most consistent PPC overlaps were located in the anterior and posterior intraparietal sulcus (IPS). The response amplitude of posterior IPS did not differ between both search tasks. However, the IPS junction with the transverse occipital sulcus and the FEF responded at a higher amplitude during conjunction search. Moreover, regions of the prefrontal cortex and the PPC were activated only during either hard feature or conjunction search. These findings suggest that equally difficult visual searches for features and conjunctions are controlled by overlapping frontoparietal networks, but also that both search types involve specific mechanisms.