Effects of distraction on pain perception: magneto- and electro-encephalographic studies

After a painful CO2 laser stimulation to the skin, the magnetoencephalography (MEG) response (164 ms in average peak latency) was not affected by distraction, but the sequential electroencephalography (EEG) responses (240-340 ms), probably generated by a summation of activities in multiple areas, were markedly affected. We suspect that the MEG response, whose dipole is estimated in the bilateral second somatosensory cortex (SII) and insula, reflects the primary activities of pain in humans.     

Comparison between SI and SII responses as a function of stimulus intensity

In this MEG study we investigated the differences in responses to somatosensory electrical stimuli between primary (SI) and secondary (SII) sensory cortices using 10 different levels of stimulus intensity, starting from below the sensory threshold up to a weak painful level. SI dipole source linearly increased in amplitude as the stimulus intensity raised up to a strong motor level and then saturated at higher stimulation levels. The contralateral and ipsilateral SII dipole source strengths followed the stimulus intensity growing up to the motor threshold, but showed a decrease at the strong motor level, followed by an increase as the stimulus intensity raised towards the weak painful threshold. These results suggest different responses of SI and SII cortices as the intensity of stimulation rises from non-painful to painful values.     

Dipolar source modeling of somatosensory evoked potentials to painful and nonpainful median nerve stimulation

Dipolar source modeling might help in clarifying whether somatosensory evoked potentials (SEPs) after electrical stimulation at painful intensity contain any information related to the nociceptive processing. SEPs were recorded after left median nerve stimulation at three different intensities: intense but nonpainful (intensity 2); slightly painful (pain threshold; intensity 4); and moderately painful (intensity 6). Scalp SEPs at intensities 2, 4, and 6 were fitted by a five-dipole model. When the strength modifications of the source activities up to 40 ms were examined across the different stimulus intensities, no significant difference was found. In the later epoch (40-200 ms), a posterior parietal dipole and two bilateral sources probably located in the second somatosensory (SII) areas increased significantly their dipole moments when the stimulus was increased from 2 to 4 and became painful. Since no difference was found when the stimulus intensity was increased from 4 to 6, the observed increase of the dipolar strengths is probably related to a variation of the stimulus quality (nonpainful vs. painful), rather than of the stimulus intensity per se. Our findings lead us to conclude that a large convergence of nociceptive and non-nociceptive afferents probably occurs bilaterally in the SII areas.     

Cortical correlates of false expectations during pain intensity judgments--a possible manifestation of placebo/nocebo cognitions

We investigated the effects of expectation on intensity ratings and somatosensory evoked magnetic fields and electrical potentials following painful infrared laser stimuli in six healthy subjects. The stimulus series contained trials preceded by different auditory cues which either contained valid, invalid or no information about the upcoming laser intensity. High and low intensities occurred equally probable across cue types. High intensity stimuli induced greater pain than low intensity across all cue types. Furthermore, laser intensity significantly interacted with cue validity: high intensity stimuli were perceived less painful and low intensity stimuli more painful following invalid compared to valid cues. The amplitude of the evoked magnetic field localized within the contralateral secondary somatosensory cortex (SII) at about 165 ms after laser stimuli varied also both with stimulus intensity and cue validity. The evoked electric potential peaked at about 300 ms after laser stimuli and yielded a single dipole source within a region encompassing the caudal anterior cingulate cortex and posterior cingulate cortex. Its amplitude also varied with stimulus intensity, but failed to show any cue validity effects. This result suggests a priming of early cortical nociceptive sensitivity by cues signaling pain severity. A possible contribution of the SII cortex to the manifestation of nocebo/placebo cognitions is discussed.     

Magnetic source imaging of tactile input shows task-independent attention effects in SII

We investigated whether attention to different stimulus attributes (location, intensity) has different effects on the activity of the secondary (SII) somatosensory cortex. Tactile stimuli were applied to the left index finger and somatosensory evoked fields (SEFs) were recorded using a whole-head magnetoencephalography (MEG) system. Two oddball paradigms with stimuli varying in location or intensity were performed in an ignore and an attend condition. Brain sources were estimated by magnetic source imaging. No attention effect was observed for the primary SI area. However, attention enhanced SII activity bilaterally from 55 to 130 ms by 52% in the spatial and 64% in the intensity discrimination task. SII attentional enhancement was very similar in both paradigms and occurred both for deviants and standards.     

Magnetoencephalography in the detection of focal lesions in West syndrome.

BACKGROUND: According to the international classification of epilepsy syndromes, West syndrome (WS) is a form of generalized epilepsy. However, it is known that localized lesions can induce WS and that patients with WS often subsequently develop focal seizures. We evaluated such patients using magnetoencephalography (MEG). METHOD: Fourteen patients of 3 months to 6 years of age who had or who had previously had WS were examined. MEGs were recorded using a laying-type whole-cortex MEG system with a 160-channel first-order gradiometer. Twelve-channel electroencephalography (EEG) and one-channel electrocardiography (ECG) were simultaneously recorded. Equivalent current dipoles were estimated at the point of spikes on the EEG. RESULTS: Patients were classified by magnetic resonance imaging (MRI) findings into a focal lesion group (group F, n=7) and a non-focal lesion group (group N, n=7). The dipoles estimated from the MEG were classified into three groups: W, with the dipoles distributed over a wide brain area (n=7); WC, dipoles distributed over a wide area along with a dense dipole distribution in a specific cortical area (n=3); and C, closed dipole distribution in a unilateral cerebral focal area (n=4). Patients were also classified by the stage of the disease during which the MEG was recorded, and by the type of seizure they experienced. Those with hypsarrhythmia examined early in the disease all had pattern W regardless of their lesion group, whereas those examined later exhibited more diverse dipole patterns that corresponded to seizure type. CONCLUSIONS: Dipoles were distributed widely over bilateral cerebral cortex when patients had infantile spasms with hypsarrhythmia whether or not they had focal lesions. The dipole distribution pattern in MEG changed according to changes in seizure type.     

Functional localization of the somatomotor area by magnetoencephalography]

Precise localization of the current dipole by the magnetoencephalography (MEG) has enabled us to combine the functional information onto the anatomical landmarks. This merit can be best exhibited when the dipole is situated in the superficial cortex and directed parallel to the skull surface. However, before utilizing MEG extensively as a clinical tool, it is inevitable to confirm the precision of the source localization by comparing the estimation with the actual sources. Somatosensory evoked field (SEF) following the electric shock to the peripheral nerve and movement-related cortical field (MRCF) associated with self-paced movement can show us the estimated sources at the postcentral and precentral cortex, respectively, with somatotopic organization. These localizations were confirmed by the direct recordings from the human brain surface during the operation, even if the corresponding areas were anatomically distorted by some lesion occupying the central area. In addition, MEG can localize second somatosensory area (SII) over the superior bank of the Sylvian fissure as well as posterior parietal cortex (PPC), which are difficult to be detected by the EEG recording. These reliable estimation enables us to apply MEG to clarification of pathogenesis of various diseases and source localization for higher brain function.     

A study of dipole localization accuracy for MEG and EEG using a human skull phantom

Objective: To investigate the accuracy of forward and inverse techniques for EEG and MEG dipole localization.Design and Methods: A human skull phantom was constructed with brain, skull and scalp layers and realistic relative conductivities. Thirty two independent current dipoles were distributed within the `brain' region and EEG and MEG data collected separately for each dipole. The true dipole locations and orientations and the morphology of the brain, skull and scalp layers were extracted from X-ray CT data. The location of each dipole was estimated from the EEG and MEG data using the R-MUSIC inverse method and forward models based on spherical and realistic head geometries. Additional computer simulations were performed to investigate the factors affecting localization accuracy.Results: Localization errors using the relatively simpler locally fitted sphere approach are only slightly greater than those using a BEM approach. The average localization error over the 32 dipoles was 7–8 mm for EEG and 3 mm for MEG.Conclusion: The superior performance of MEG over EEG appears to be because the latter is more sensitive to errors in the forward model arising from simplifying assumptions concerning the conductivity of the skull, scalp and brain.     

Neuromagnetic activation of primary and secondary somatosensory cortex following tactile-on and tactile-off stimulation

ObjectiveMagnetoencephalography (MEG) recordings were performed to investigate the cortical activation following tactile-on and tactile-off stimulation.MethodsWe used a 306-ch whole-head MEG system and a tactile stimulator driven by a piezoelectric actuator. Tactile stimuli were applied to the tip of right index finger. The interstimulus interval was set at 2000 ms, which included a constant stimulus of 1000 ms duration.ResultsProminent somatosensory evoked magnetic fields were recorded from the contralateral hemisphere at 57.5 ms and 133.0 ms after the onset of tactile-on stimulation and at 58.2 ms and 138.5 ms after the onset of tactile-off stimulation. All corresponding equivalent current dipoles (ECDs) were located in the primary somatosensory cortex (SI). Moreover, long-latency responses (168.7 ms after tactile-on stimulation, 169.8 ms after tactile-off stimulation) were detected from the ipsilateral hemisphere. The ECDs of these signals were identified in the secondary somatosensory cortex (SII).ConclusionsThe somatosensory evoked magnetic fields waveforms elicited by the two tactile stimuli (tactile-on and tactile-off stimuli) with a mechanical stimulator were strikingly similar. These mechanical stimuli elicited both contralateral SI and ipsilateral SII activities.SignificanceTactile stimulation with a mechanical stimulator provides new possibilities for experimental designs in studies of the human mechanoreceptor system.     

Human magnetic auditory evoked fields.

Magnetoencephalographic (MEG) averaged auditory evoked fields to click stimuli (N = 512) were recorded from four human subjects. The MEG was recorded with an asymmetric second derivative SQUID gradiometer located in an aluminum shielded room. Unlike conventional EEG auditory evoked potentials, which have a widespread distribution, evoked magnetic fields appear to be localized to the general area of the primary auditory cortex and diminish rapidly in amplitude as the gradiometer is moved away in any direction.     

Primary somatosensory cortex is actively involved in pain processing in human

We recorded somatosensory evoked magnetic fields (SEFs) by a whole head magnetometer to elucidate cortical receptive areas involved in pain processing, focusing on the primary somatosensory cortex (SI), following painful CO(2) laser stimulation of the dorsum of the left hand in 12 healthy human subjects. In seven subjects, three spatially segregated cortical areas (contralateral SI and bilateral second (SII) somatosensory cortices) were simultaneously activated at around 210 ms after the stimulus, suggesting parallel processing of pain information in SI and SII. Equivalent current dipole (ECD) in SI pointed anteriorly in three subjects whereas posteriorly in the remaining four. We also recorded SEFs following electric stimulation of the left median nerve at wrist in three subjects. ECD of CO(2) laser stimulation was located medial-superior to that of electric stimulation in all three subjects. In addition, by direct recording of somatosensory evoked potentials (SEPs) from peri-Rolandic cortex by subdural electrodes in an epilepsy patient, we identified a response to the laser stimulation over the contralateral SI with the peak latency of 220 ms. Its distribution was similar to, but slightly wider than, that of P25 of electric SEPs. Taken together, it is postulated that the pain impulse is received in the crown of the postcentral gyrus in human.     

Difference in somatosensory evoked fields elicited by mechanical and electrical stimulations: Elucidation of the human homunculus by a noninvasive method

We recently recorded somatosensory evoked fields (SEFs) elicited by compressing the glabrous skin of the finger and decompressing it by using a photosensor trigger. In that study, the equivalent current dipoles (ECDs) for these evoked fields appeared to be physiologically similar to the ECDs of P30m in median nerve stimulation. We sought to determine the relations of evoked fields elicited by mechanically stimulating the glabrous skin of the great toe and those of electrically produced P40m. We studied SEFs elicited by mechanical and electrical stimulations from the median and tibial nerves. The orientations of dipoles from the mechanical stimulations were from anterior-to-posterior, similar to the orientations of dipoles for P30m. The direction of the dipole around the peak of N20m from median nerve electrical stimulation was opposite to these directions. The orientations of dipoles around the peak of P40m by tibial nerve stimulation were transverse, whereas those by the compression and decompression stimulation of the toe were directed from anterior-to-posterior. The concordance of the orientations in ECDs for evoked fields elicited by mechanical and electrical stimulations suggests that the ECDs of P40m are physiologically similar to those of P30m but not to those of N20m. The discrepancy in orientations in ECDs for evoked field elicited by these stimulations in the lower extremity suggests that electrical and compression stimulations elicit evoked fields responding to fast surface rubbing stimuli and/or stimuli to the muscle and joint.     

Pain-related somatosensory evoked magnetic fields induced by controlled ballistic mechanical impacts.

The purpose of this study was to investigate cortical processing of painful compared with tactile mechanical stimulation by means of magnetoencephalography (MEG) using the novel technique of mechanical impact loading. A light, hard projectile is accelerated pneumatically in a guiding barrel and elicits a brief sensation of pain when hitting the skin in free flight. Controllable noxious and innocuous impact velocities facilitate the generation of different, predetermined stimulus intensities. The authors applied painful as well as tactile mechanical impacts to the dorsum of the second, third, and fourth digit of the nondominant hand. Pain-related somatosensory evoked magnetic fields (SSEFs) were compared with those following tactile stimulation in seven healthy volunteers. Contralateral primary sensory cortical area activation was observed within the first 70 msec after tactile as well as painful stimulus intensities. Only painful impacts elicited SSEF responses assigned to the bilateral secondary sensory cortical regions and to the middle part of the contralateral cingulate gyrus, which were active at latency ranges of 55 to 155 msec and 90 to 220 msec respectively. Additional long-latency responses occurred in these cortical areas as long as 280 msec after painful stimulation in three subjects. In contrast to tactile stimulation, painful mechanical impacts elicited SSEF responses in cortical areas demonstrated to be involved in central pain processing by previous MEG and neuroimaging studies. Because of its similarity to natural noxious stimuli and the possibility of adjustable painful and tactile impact velocities, the technique of mechanical impact loading provides a useful method for the neurophysiologic evaluation of cortical pain perception.     

Magnetoencephalographic evaluation of anterior corpus callosotomy for intractable epilepsy in a patient with lennox-gastaut syndrome

We analyzed the preoperative and postoperative interictal magnetoencephalographic (MEG) patterns in a 32-year-old woman with Lennox-Gastaut syndrome who underwent an anterior corpus callosotomy (CC). A 37-channel biomagnetometer was used for the simultaneous recording of electroencephalogram (EEG) and MEG. Preoperatively, interictal EEG demonstrated a bilaterally synchronous spike and slow wave bursts with a maximum amplitude on the bifrontal region. The waveforms of the MEG were similar but did not completely correspond to those of the EEG. The estimated equivalent current dipoles (ECDs) originating from bilaterally synchronous paroxysmal discharges formed a dense cluster on the bilateral frontal lobes, especially on the deep midfrontal region. After anterior CC, MEG disclosed a marked reduction of the number of ECDs. The preoperative MEG patterns were thought to be representative of interhemispheric synchrony as a large dipole orientation, and these MEG paterns were partly disrupted by anterior CC.     

Neural substrates underlying evaluation of pain in actions depicted in words

Previous research has shown that evaluation of pain shown in pictures is mediated by a cortical circuit consisting of the primary and secondary somatosensory cortex (SI and SII), the anterior cingulate cortex (ACC), and the insula. SI and SII subserve the sensory-discriminative component of pain processing whereas ACC and the insula mediate the affective-motivational aspect of pain processing. The current work investigated the neural correlates of evaluation of pain depicted in words. Subjects were scanned using functional magnetic resonance imaging (fMRI) while reading words or phrases depicting painful or neutral actions. Subjects were asked to rate pain intensity of the painful actions depicted in words or counting the number of Chinese characters in the words. Relative to the counting task, rating pain intensity induced activations in SII, the insula, the right middle frontal gyrus, the left superior temporal sulcus and the left middle occipital gyrus. Our results suggest that both the sensory-discriminative and affective-motivational components of the pain matrix are engaged in the processing of pain depicted in words.     

Benefit of simultaneous recording of EEG and MEG in dipole localization

PURPOSE: In this study, we tried to show that EEG and magnetoencephalography (MEG) are clinically complementary to each other and that a combination of both technologies is useful for the precise diagnosis of epileptic focus. METHODS: We recorded EEGs and MEGs simultaneously and analyzed dipoles in seven patients with intractable localization-related epilepsy. MEG dipoles were analyzed by using a BTI Magnes 148-channel magnetometer. EEG dipoles were analyzed by using a realistically shaped four-layered head model (scalp-skull-fluid-brain) built from 2.0-mm slice magnetic resonance imaging (MRI) images. RESULTS: (a) In two of seven patients, MEG could not detect any epileptiform discharges, whereas EEG showed clear spikes. However, dipoles estimated from the MEG data corresponding to the early phase of EEG spikes clustered at a location close to that of the EEG-detected dipole. (b) In two of seven patients, EEG showed only intermittent high-voltage slow waves (HVSs) without definite spikes. However, MEG showed clear epileptiform discharges preceding these EEG-detected HVSs. Dipoles estimated for these EEG-detected HVSs were located at a location close to that of the MEG-detected dipoles. (c) Based on the agreement of the results of these two techniques, surgical resection was performed in one patient with good results. CONCLUSIONS: Dipole modeling of epileptiform activity by MEG and EEG sometimes provides information not obtainable with either modality used alone.     

Evoked magnetic fields from primary and secondary somatosensory cortices: A reliable tool for assessment of cortical processing in the neonatal period

Objective

To determine interhemispheric differences and effect of postmenstrual age (PMA), height, and gender on somatosensory evoked magnetic fields (SEFs) from the primary (SI) and secondary (SII) somatosensory cortices in healthy newborns.

Methods

We recorded SEFs to stimulation of the contralateral index finger (right in 46 and left in 12) healthy fullterm newborns and analyzed the magnetic responses with equivalent current dipoles.

Results

Activity from both the SI and SII was consistently detectable in the contralateral hemisphere of the newborns during quiet sleep. No significant interhemispheric differences existed in SI or SII response peak latencies, source strengths, or location (n = 8, quiet sleep). SI or SII response peak latency or source strength were not significantly affected by PMA, height, or gender.

Conclusions

During the neonatal period (PMA 37–44 weeks), activity from the contralateral SI and SII can be reliably evaluated with MEG. The somatosensory responses are similar in the left and right hemispheres and no corrections for exact PMA, height, or gender are necessary for interpreting the results. However, the evaluation should be conducted in quiet sleep.

Significance

The reproducibility of the magnetic SI and SII responses suggests clinical applicability of the presented MEG method.     

Different laterality between the thumb and index finger in human SII activities

We compared the ipsilateral and contralateral evoked activities in the secondary somatosensory cortex (SII) of four human subjects. Magnetic cortical fields, evoked by electrical stimulation of the distal interphalangeal joint of either the thumb or the index finger, were recorded by an 80-channel whole head type magnetoencephalography system (MEG). We calculated the ratio of the equivalent current dipole (ECD) moment of the ipsilateral area to that of the contralateral area. The mean ratio for the thumb across the subjects was 0.43 +/- 0.13, while that for the index finger was 0.77 +/- 0.20 (mean +/- s.d). The ratio for the index finger was significantly higher than that for the thumb (p = 0.039, two tailed t-test). These results show that the cortical index finger area is activated more bilaterally than the thumb area.     

急性脑梗死脑磁图脑诱发磁场发生源空间位置特征研究

目的:研究急性脑梗死患者体感皮层中枢和听觉皮层中枢脑磁图(MEG)变化特征。方法:对15例急性脑梗死患者于发病后3-4周进行体感诱发磁场(SEFs)和听觉诱发磁场(AEFs)检测,同时检测健康志愿者作为对照。SEFs电刺激部位为腕部正中神经处,电流脉冲宽度0.3ms,刺激间隔0.5s。AEFs采用双耳纯音刺激,频率2KHz,声音强度90dB,刺激间隔ls,持续时间8ms,脑磁图检查后进行MRI超薄扫描。结果:SEFs的最主要波峰为M20,其ECD均位于体感皮层中枢,AEFs为M100,位于两侧颞横回。两侧ECD位置三维不对称性由(△X2+△Y2+△Z2)1-2表示,SEFs和AEFs测定患者组均较正常对照组不对称性增大。结论:MEG可灵敏地检测出急性脑梗死患者皮层中枢功能损伤。     

Implanted medical devices or other strong sources of interference are not barriers to magnetoencephalographic recordings in epilepsy patients

ObjectiveLocalization accuracy in magnetoencephalography (MEG) recordings is highly dependent on signal to noise ratio, which is difficult to control.MethodsWe have post-processed our data in order to reduce noise to a level permitting adequate source localization with equivalent current dipole methods. In 30 consecutive epilepsy patients, MEG was recorded using a whole-head MEG system consisting of 204 planar gradiometer and 102 magnetometers, with simultaneous EEG. Data were reviewed to identify interictal spikes. The initial analysis was done after employing a spatiotemporal signal space separation (tSSS) method. A total of 18 dipole clusters in 15 patients were reanalyzed without tSSS, to compare the number, goodness of fit, and locations of acceptable dipoles before and after processing.ResultsIn 8 of 18 clusters, although acceptable dipole clusters were captured before processing, there was a clear improvement of all parameters with tSSS. In another 5 clusters, all from patients with vagus nerve stimulators, there were few or no acceptable dipoles before processing, but sufficient dipole clusters were obtained with tSSS.ConclusionIn contrast to volunteer research subjects, clinical patients cannot be expected to cooperate as fully, and their MEG data are likely to include more interference. This study demonstrates that processing the MEG data with a method to eliminate artifact arising from outside the brain significantly improves the data.SignificanceIn some cases, this improvement can mean the difference between satisfactory dipole fits vs no possible localization.