Yunhai Qiu

A comparative magnetoencephalographic study of cortical activations evoked by noxious and innocuous somatosensory stimulations

We recorded somatosensory-evoked magnetic fields and potentials produced by painful intra-epidermal stimulation (ES) and non-painful transcutaneous electrical stimulation (TS) applied to the left hand in 12 healthy volunteers to compare cortical responses to noxious and innocuous somatosensory stimulations. Our results revealed that cortical processing following noxious and innocuous stimulations was strikingly similar except that the former was delayed approximately 60 ms relative to the latter, which was well explained by a difference in peripheral conduction velocity mediating noxious (Adelta fiber) and innocuous (Abeta fiber) inputs. The first cortical activity evoked by both ES and TS was in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side. The following activities were in the bilateral secondary somatosensory cortex (SII), insular cortex, cingulate cortex, anterior medial temporal area and ipsilateral SI. The source locations did not differ between the two stimulus modalities except that the dipole for insular activity following ES was located more anterior to that following TS. Both ES and TS evoked vertex potentials consisting of a negativity followed by a positivity at a latency of 202 and 304 ms, and 134 and 243 ms, respectively. The time course of the vertex potential corresponded to that of the activity of the medial temporal area. Our results suggested that cortical processing was similar between noxious and innocuous stimulation in SI and SII, but different in insular cortex. Our data also implied that activities in the amygdala/hippocampal formation represented common effects of noxious and tactile stimulations.

Pain processing within the primary somatosensory cortex in humans

To investigate the processing of noxious stimuli within the primary somatosensory cortex (SI), we recorded magnetoencephalography following noxious epidermal electrical stimulation (ES) and innocuous transcutaneous electrical stimulation (TS) applied to the dorsum of the left hand. TS activated two sources sequentially within SI: one in the posterior bank of the central sulcus and another in the crown of the postcentral gyrus, corresponding to Brodmanns areas 3b and 1, respectively. Activities from area 3b consisted of 20‐ and 30‐ms responses. Activities from area 1 consisted of three components peaking at 26, 36 and 49 ms. ES activated one source within SI whose location and orientation were similar to those of the TS‐activated area 1 source. Activities from this source consisted of three components peaking at 88, 98 and 109 ms, later by 60 ms than the corresponding TS responses. ES and TS subsequently activated a similar region in the upper bank of the sylvian fissure, corresponding to the secondary somatosensory cortex (SII). The onset latency of the SII activity following ES (109 ms) was later by 29 ms than that of the first SI response (80 ms). Likewise, the onset latency of SII activity following TS (52 ms) was later by 35 ms than that of area 1 of SI (17 ms). Therefore, our results showed that the processing of noxious and innocuous stimuli is similar with respect to the source locations and activation timings within SI and SII except that there were no detectable activations within area 3b following noxious stimulation.

Cerebral responses following stimulation of unmyelinated C-fibers in humans: electro- and magneto-encephalographic study.

There are two kinds of pain, a sharp pain ascending through Adelta fibers (first pain) and a second burning pain ascending though C fibers (second pain). By using a novel method, the application of a low intensity CO(2) laser beam to a tiny area of skin using a very thin aluminum plate with numerous tiny holes as a spatial filter, we succeeded in selectively stimulating unmyelinated C fibers of the skin in humans, and could record consistent and clear brain responses using electroencephalography (EEG) and magnetoencephalography (MEG). The conduction velocity (CV) of the C fibers of the peripheral nerve and spinal cord, probably spinothalamic tract (STT), is approximately 1-4 m/s, which is significantly slower than that of Adelta (approximately 10-15 m/s) and Abeta fibers (approximately 50-70 m/s). This method should be very useful for clinical application. Following C fiber stimulation, primary and secondary somatosensory cortices (SI and SII) are simultaneously activated in the cerebral hemisphere contralateral to the stimulation, and then, SII in the hemisphere ipsilateral to the stimulation is activated. These early responses are easily detected by MEG. Then, probably limbic systems such as insula and cingulate cortex are activated, and those activities reflected in EEG components. Investigations of the cortical processing in pain perception including both first and second pain should provide a better understanding of pain perception and, therefore, contribute to pain relief in clinical medicine.

Movements modulate cortical activities evoked by noxious stimulation

&NA; To evaluate the effects of movement on cortical activities evoked by noxious stimulation, we recorded magnetoencephalography following noxious YAG laser stimulation applied to the dorsum of the left hand in normal volunteers. Results of the present study can be summarized as follows: (1) active movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of both primary and secondary somatosensory cortices (SI and SII) in the hemisphere contralateral to the stimulated hand (cSI and cSII). Activity in the hemisphere ipsilateral to the side of stimulation (iSII) was not affected. (2) Active movement of the hand contralateral to the side of noxious stimulation resulted in significant attenuation of cSII. Activity in cSI and iSII was not affected. (3) Passive movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of cSI. Activity in cSII and iSII was not affected. (4) Visual analogue scale (VAS) changes showed a similar pattern to the amplitude changes of cSII. These results suggest that activities in three regions are modulated by movements differently. Inhibition in cSI was considered to be mainly due to an interaction in SI by the signals ascending from the stimulated and movement hand. Inhibition in cSII was considered to be mainly due to particular brain activities relating to motor execution and/or movement execution associated with a specific attention effect. In addition, since VAS changes showed a similar relationship with the amplitude changes of cSII, cSII may play a role in pain perception.

Cerebral activation by the signals ascending through unmyelinated C-fibers in humans: a magnetoencephalographic study

Cerebral processing of first pain, associated with A delta-fibers, has been studied intensively, but the cerebral processing associated with unmyelinated C-fibers, relating to second pain, remains to be investigated. This is the first study to clarify the primary cortical processing of second pain by magnetoencephalography, through the selective activation of C-fibers, by the stimulation of a tiny area of skin with a CO2 laser. In the hemisphere contralateral to the side stimulated, a one-source generator in the upper bank of the Sylvian fissure (secondary somatosensory cortex, SII) or two-source generators in SII and the hand area of the primary somatosensory cortex (SI) were the optimal configurations for the first component 1M. The onset and peak latency of the two sources in SI and SII were not significantly different. In the hemisphere ipsilateral to the stimulation, only one source was estimated in SII, and its peak latency was significantly (approximately 18 ms on average) longer than that of the SII source in the contralateral hemisphere. From our findings we suggest that parallel activation of SI and SII contralateral to the stimulation represents the first step in the cortical processing of C-fiber-related activities, probably related to second pain.

Pain-related magnetic fields evoked by intra-epidermal electrical stimulation in humans.

OBJECTIVES We recently developed a new method for the preferential stimulation of Adelta fibers in humans. The aim of the present study was to examine whether this method can serve as an appropriate stimulus in a magnetoencephalographic study. METHODS We recorded somatosensory-evoked magnetic fields (SEFs) following intra-epidermal electrical stimulation applied to the hand and elbow. Superficial parts of the skin were electrically stimulated through a needle electrode whose tip was inserted in the epidermis. RESULTS In all 13 subjects, the equivalent current dipole was estimated in the secondary somatosensory cortices (SII). In 5 out of 13 subjects, simultaneous activation of the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulation was identified. The mean peak latencies of magnetic fields corresponding to contralateral SI, SII and ipsilateral SII activation following hand stimulation were 162, 158 and 171 ms, respectively. The respective latency following elbow stimulation was 137, 139 and 157 ms, respectively. Estimated peripheral conduction velocity was 15.6m/s. CONCLUSIONS All the results were consistent with previous findings in pain SEF studies. We concluded that our novel intra-epidermal electrical stimulation is useful for pain SEF studies since it does not need special equipment and is easy to control.

Sensory perception during sleep in humans: a magnetoencephalograhic study

We reported the changes of brain responses during sleep following auditory, visual, somatosensory and painful somatosensory stimulation by using magnetoencephalography (MEG). Surprisingly, very large changes were found under all conditions, although the changes in each were not the same. However, there are some common findings. Short-latency components, reflecting the primary cortical activities generated in the primary sensory cortex for each stimulus kind, show no significant change, or are slightly prolonged in latency and decreased in amplitude. These findings indicate that the neuronal activities in the primary sensory cortex are not affected or are only slightly inhibited during sleep. By contrast, middle- and long-latency components, probably reflecting secondary activities, are much affected during sleep. Since the dipole location is changed (auditory stimulation), unchanged (somatosensory stimulation) or vague (visual stimulation) between the state of being awake and asleep, different regions responsible for such changes of activity may be one explanation, although the activated regions are very close to each other. The enhancement of activities probably indicates two possibilities, an increase in the activity of excitatory systems during sleep, or a decrease in the activity of some inhibitory systems, which are active in the awake state. We have no evidence to support either, but we prefer the latter, since it is difficult to consider why neuronal activities would be increased during sleep.

Facilitation of Aδ-fiber-mediated acute pain by repetitive transcranial magnetic stimulation

Background: Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex modulates acute and chronic pain perception. The authors previously showed that rTMS over the primary motor cortex (M1) inhibited capsaicin-induced acute pain ascending through C-fibers. Objective: To investigate the effects of 1-Hz rTMS over M1 on acute experimentally induced pain mediated by Aδ-fibers (i.e., another type of acute pain). Methods: The authors examined whether rTMS over M1 affected laser evoked potentials (LEPs) in 13 normal subjects using thulium: yttrium-aluminum-garnet laser stimulation. Subjective pain-rating scores and LEPs obtained under three different conditions—rTMS, realistic sham stimulation, and a control condition with no stimulation—were compared. Results: The authors found that 1-Hz rTMS over M1 significantly aggravated the subjective pain and enhanced the N2-P2 amplitudes compared with the sham or control sessions. Because the pain-rating scores and the N2-P2 amplitudes correlated positively, the N2-P2 amplitudes in the present study can be regarded as the cortical correlate of subjective pain. Conclusions: Together with the authors’ previous study on C-fiber pain, this facilitatory effect of repetitive transcranial magnetic stimulation on Aδ-fiber-mediated further strengthens the notion of a relationship between repetitive transcranial magnetic stimulation over M1 and pain perception.

Effects of distraction on magnetoencephalographic responses ascending through C-fibers in humans

OBJECTIVE Using magnetoencephalography (MEG), we evaluated the cerebral regions relating to second pain perception ascending through C-fibers and investigated the effect of distraction on each region. METHODS Thirteen normal subjects participated in this study. CO2 laser pulses were delivered to the dorsum of the left hand to selectively activate C-fibers. The MEG responses were analyzed using a multi-dipole model. RESULTS (1) primary somatosensory cortex (SI), and (2) secondary somatosensory cortex (SII)--insula were the main generators for the primary component, 1M, whose mean peak latency was 744 ms. In addition to (1) and (2), (3) cingulate cortex and (4) medial temporal area (MT) were also activated for the subsequent component, 2M, whose mean peak latency was 947 ms. During a mental calculation task (Distraction), all 6 sources were significantly reduced in amplitude, but the SII-insula (P < 0.01) and cingulate cortex (P < 0.001) were more sensitive than the SI (P < 0.05) and MT (P < 0.05). CONCLUSIONS We confirmed that SI in the contralateral hemisphere and SII-insula, cingulate cortex and MT in bilateral hemispheres play a major role in second pain perception, and all sites were much affected by a change of attention, indicating that these regions are related to the cognitive aspect of second pain perception. SIGNIFICANCE The SI, SII, cingulate and MT were activated during the C-fiber-related MEG response, and responses in these regions were significantly diminished during mental distraction.

Effects of attention, distraction and sleep on CO2 laser evoked potentials related to C-fibers in humans

OBJECTIVES The objective of this study is to evaluate the effects of attention, distraction and sleep on CO(2) laser-evoked potentials (LEP) relating to C-fibers (ultra-late LEP). METHODS Non-painful CO(2) laser pulses were delivered to a tiny skin area of the dorsum of the right hand. Ultra-late LEP were recorded from 10 normal subjects in 5 different conditions: control (wakefulness), attention, distraction, drowsiness and sleep (stage 2). RESULTS The amplitude of ultra-late LEP was slightly increased during attention and significantly decreased during distraction, relative to the control. The ultra-late LEP decreased much in amplitude or almost disappeared during sleep. However, significant differences in latency among the conditions were not found. CONCLUSIONS We confirmed that the brain responses relating to signals ascending through C-fibers were much affected by the level of consciousness, being consistent with the findings of late LEP relating to Adelta-fibers. This is the first study to indicate the important characteristics of ultra-late LEP relating to consciousness, suggesting that they include cognitive function and also that one has to be careful of the change in alertness when recording.