Masutaro Kanda

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.

Functional localization of pain perception in the human brain studied by PET.

TO elucidate the functional localization and somatotopic organization of pain perception in the human cerebral cortex, we studied the regional cerebral blood flow using positron emission tomography during selective painful stimulation in six normal subjects. Response to a painful stimulus was elicited using a special CO2 laser, which selectively activates nociceptive receptors, to the hand and foot. Multiple brain areas, including bilateral secondary somatosensory cortices (SII) and insula, and the frontal lobe and thalamus contralateral to the stimulus side, were found to be involved in the response to painful stimulation. While our data indicate that the bilateral SII play an important role in pain perception, they also indicate that there is no pain-related somatotopic organization in the human SII or insula.

Pain-related and cognitive components of somatosensory evoked potentials following CO2 laser stimulation in man

We recorded cortical potentials evoked by painful CO2 laser stimulation (pain SEP) employing an oddball paradigm in an effort to demonstrate event-related potentials (ERP) associated with pain. In 12 healthy subjects, frequent (standard) pain stimuli (probability 0.8) were delivered to one side of the dorsum of the left hand while rare (target) pain stimuli (probability 0.2) were delivered to the other side of the same hand. Subjects were instructed to perform either a mental count or button press in response to the target stimuli. Two early components (N2 and P2) of the pain SEP demonstrated a Cz maximal distribution, and showed no difference in latency, amplitude or scalp topography between the oddball conditions or between response tasks. In addition, another positive component (P3) following the P2 was recorded maximally at Pz only in response to the target stimuli with a peak latency of 593 msec for the count task and 560 msec for the button press task. Its scalp topography was the same as that for electric and auditory P3. The longer latency of pain P3 can be explained not only by its slower impulse conduction but also by the effects of task difficulty in the oddball paradigm employing the pain stimulus compared with electric and auditory stimulus paradigms. It is concluded that the P3 for the pain modality is mainly related to a cognitive process and corresponds to the P3 of electric and auditory evoked responses, whereas both N2 and P2 are mainly pain-related components.

Generator mechanism of pain-related evoked potentials following CO2 laser stimulation of the hand: scalp topography and effect of predictive warning signal.

In order to clarify the generator mechanism of pain-related evoked potentials (pain EPs), we studied the scalp topography of the pain EPs following CO2 laser stimulation of hand dorsum by using balanced sternovertebral electrodes as the noncephalic reference in 11 normal volunteers. We also examined the effects of predictive warning signal (light-emitting diode) on the pain EPs. In both the warned and unwarned conditions, all of the 22 hand stimulations showed a large negative component (N2) at the peak latency of about 213 ms followed by a large positive component (P2) at the peak latency of about 329 ms. A preceding small negative component (N1) at the peak latency of about 148 ms was detected in 12 of the 22 hand stimulations in the warned condition and in 13 of the 22 hand stimulations in the unwarned condition. P2 was significantly larger and occurred earlier in the warned condition than in the unwarned condition, whereas other components did not differ between the two conditions, suggesting that an increased attention of the subject to the stimulus influenced the generator mechanism of the P2 component. With regards to the scalp topography, N2 was maximal at Cz and widespread transversely to both sides, whereas P2 was maximal at Cz or Pz and spread more posteriorly than N2. These findings suggest that P2 is generated by a different mechanism from N2 and is most likely associated with pain-related cognitive function. N1 was localized to the contralateral central and midtemporal areas, confirming that the nociceptive inputs are perceived in the sensory cortex in humans. The question as to whether the N1 component is generated in the hand area of the primary somatosensory cortex or in the secondary somatosensory cortex, or in both areas, remains to be solved.

A brainstem variant of reversible posterior leukoencephalopathy syndrome

Reversible posterior leukoencephalopathy syndrome (RPLS) is caused by various heterogeneous factors, the commonest being hypertension, followed by nonhypertensive causes such as eclampsia, renal diseases and immunosuppressive therapy. Patients with RPLS exhibit bilateral white and gray matter abnormalities in the posterior aspects of the cerebral hemispheres. However, this syndrome may affect the brainstem predominantly, and these cases are designated as hypertensive brainstem encephalopathy. We present here two patients with reversible brainstem encephalopathy: one with hypertension and the other without hypertension. These patients presented with swelling and diffuse hyperintensities of the brainstem in fluid-attenuated inversion-recovery (FLAIR) and T2-weighted MRI, but with relatively mild clinical symptoms. They recovered without major neurological deficits, but had residual lacunar lesions in the pons. Reversible brainstem encephalopathy with characteristic MRI features was found in both hypertensive and nonhypertensive patients. These patients were diagnosed with a brainstem variant of RPLS, which is potentially fully reversible after an adequate treatment, and therefore should be carefully differentiated from other brainstem disease conditions.

Functional and Morphological Changes in the Hippocampal Neuronal Circuits Associated with Epileptic Seizures

Summary:  Purpose: We review what is currently known about functional and morphologic plasticity of hippocampal neuronal circuits in animal epilepsy models.

Pain-related somatosensory evoked potentials can quantitatively evaluate hypalgesia in Wallenberg's syndrome.

In 6 patients with Wallenbergs syndrome who showed a dissociated loss of pain sense, we recorded pain‐related somatosensory evoked potentials following CO2 laser stimulation of the hand dorsum (pain SEPs). Two components, N2 and P2, were recorded by stimulation of the unaffected hand, whereas on the affected side they were absent or decreased in proportion to the severity of hypalgesia which was evaluated by both needle test and CO2 laser stimulation. Latency of either component, if appeared, was longer in the affected hand stimulation than that in the unaffected one. In contrast, N20 of the conventional electrically‐stimulated SEPs (electric SEPs) showed no difference between the two sides. It is concluded that, unlike other electrophysiological methods, pain SEPs following CO2 laser stimulation can quantitatively evaluate functional impairment of the spinothalamic tract in Wallenbergs syndrome.

Cortical mechanisms underlying point localization of pain spot as studied by event-related potentials following CO2 laser stimulation in man

Abstract To elucidate cortical mechanisms underlying point localization of a pain spot, we investigated event-related potentials (ERPs) while using a CO2 laser beam to apply a pain stimulus to the hand dorsum in 16 healthy men. The stimulus spot (pain spot) was shifted for each stimulus, while the subject was requested to identify the stimulated spot as accurately as possible and to use a pointer in the non-stimulated hand to indicate the corresponding spot on a figure of a hand that was projected onto a screen (localization condition). For the control condition, the subject pointed to a single predetermined spot, regardless of the location of the stimulation (control motor task condition). Electroencephalograms were recorded from 21 electrodes, referenced to the linked earlobes, and were averaged time-locked to the stimulus onset for each task separately. Under the control rest condition (neither point localization nor motor task), only two early components (N2 and P2) were recorded. During the control motor task condition (no point localization), in addition to N2 and P2, a steep negative-going slope was recorded at the fronto-central region. Exclusively during the localization condition, a positive peak (647 ms, 5.6 µV for the left and 634 ms, 5.7 µV for the right hand stimulation) was identified; this was maximal at the midline centro-parietal area and distributed symmetrically over the scalp. It is suggested that the late positive component detected exclusively during the localization task is related to the somatotopic point localization of the pain spot. From the distribution of this ERP, the task most likely involves bilateral activation of the superior parietal cortices.

Increased cortical hyperexcitability and exaggerated myoclonus with aging in benign adult familial myoclonus epilepsy

The clinical implications of enlarged early cortical components of somatosensory evoked potentials in benign adult familial myoclonus epilepsy remain unknown. Somatosensory evoked potentials following electrical stimulation of the median nerve at the wrist were studied in 16 patients with a clinical diagnosis of benign adult familial myoclonus epilepsy (7 men and 9 women; mean age, 51 ± 18 years) and 19 age‐matched apparently healthy control subjects (11 men and 8 women; mean age, 49 ± 18 years). Giant somatosensory evoked potentials were observed in 13 of the 16 patients. P25 and N35 amplitudes in the patient group were 11.4 ± 6.1 and 19.2 ± 11.5 μV, respectively, and both were significantly larger compared with those in control subjects (P = 0.008 for P25 and P < 0.0001 for N35). There was a significant positive relationship between age at somatosensory evoked potential examination and N20, P25, and N35 amplitudes, both in the patient and in the control groups (P < 0.05). The linear regression gradient of the N35 amplitude with respect to age was significantly larger in the patient group than in the control group (P = 0.04). Furthermore, regression analysis showed a significant positive relationship between the myoclonus rating scale and age at time of somatosensory evoked potential examination (R = 0.645, P = 0.007). Somatosensory evoked potential amplitude increased with age in patients with benign adult familial myoclonus epilepsy to a greater extent than in the control subjects, which suggests a progressive increase in cortical excitability based on progressive pathophysiology in benign adult familial myoclonus epilepsy.

Brief A morphological filter for extracting waveform characteristics of single-sweep evoked potentials

A morphological filter was designed for extracting the waveform characteristics of pain SEP from the single-sweep record. The properties of the basic operations for the morphological filter; erosion, dilation, opening and closing were clarified in order to design an appropriate filter. The morphological filter was designed by selecting the structuring elements, which represented the features of the pain SEP waveform. The designed morphological filter was evaluated using the simulation data, and applied to the pain SEP data obtained from a normal adult with satisfactory results.