Electrophysiological evidence for sequential discrimination of positive and negative facial expressions.

OBJECTIVE: To elucidate the differences in temporal processing between positive and negative facial expressions by using event-related potentials (ERPs) with spatially filtered images. METHODS: Based on the traits of parallel visual pathways, four types of facial expression images (happiness, fear, anger and neutral) with low, high and broadband spatial frequencies (LSF, HSF and BSF, respectively) were carefully created with the consideration of luminance, contrast and emotional intensity. These images were pseudo-randomly presented to 13 healthy subjects to record ERPs. Twenty recording electrodes were placed over the scalp according to the International 10-20 system. For emotion-relevant late negative components with latencies of 190-390 ms, the amplitude differences among the four facial expressions were analyzed for sequential 20-ms time windows by ANOVA. RESULTS: There were significant amplitude differences between positive and negative LSF facial expressions in the early time windows of 270-310 ms at the occipitotemporal region. Subsequently, the amplitudes among negative HSF facial expressions differed significantly in the later time windows of 330-390 ms. CONCLUSIONS: Discrimination between positive and negative facial expressions precedes discrimination among different negative expressions in a sequential manner based on parallel visual channels. SIGNIFICANCE: ERPs with spatially filtered images have provided the first evidence for sequential discrimination of positive and negative facial expressions.

Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats.

Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal diseases resulting in adult blindness caused by mutations of various genes. Although it is difficult to cure the blindness that results from these diseases, delaying the disease progression may be of great benefit, since the majority of RP diseases are seen in middle age or later. To test a gene therapy strategy for RP using a neurotrophic factor gene, we assessed the effect of simian lentivirus (SIV)-mediated subretinal gene transfer of pigment epithelium-derived factor (PEDF), a potent neurotrophic factor, during the disease progression in Royal College of Surgeons (RCS) rats, a well-accepted animal model of RP. Regional gene transfer via SIV into the peripheral subretinal space at the nasal hemisphere was performed in all animals to monitor site-specific transgene expression as well as the therapeutic effect in each retina. Gene transfer of lacZ and PEDF was observed in the regional pigment epithelium corresponding to the regional gene transfer. Histologically, PEDF gene transfer significantly protected the loss of photoreceptor cells (PCs) corresponding to the regions of the gene transfer, compared to those of control groups during the course of the experiment. The antiapoptotic effect of PEDF on PCs is likely to be a related mechanism, because a significant reduction of terminal dUTP-nicked end labeling-positive PC numbers was found in PEDF-treated eyes compared to those of the control group (P<0.05). PEDF-treated eyes also retained a significant sensitivity to light flash during the experimental course. These findings clearly show that neuroprotective gene therapy using PEDF can protect retinal degeneration and functional defects in individuals with RP.

Simian immunodeficiency virus-based lentivirus vector for retinal gene transfer: a preclinical safety study in adult rats.

Although lentivirus vectors hold promise for ocular gene therapy, they also have potential safety issues, particularly in the case of the current human immunodeficiency virus-based vectors. We recently developed a novel lentivirus vector derived from the nonpathogenic simian immunodeficiency virus from African green monkeys (SIVagm) to minimize these potentials. In this preclinical study, we evaluated whether SIV vector could be efficiently and safely applicable to retinal gene transfer by assessing the transgene expression, retinal function and histology over a 1-year period following subretinal injection in adult rats. The functional assessment via electroretinogram after both titers of SIV-lacZ (2.5 x 10(7) or 2.5 x 10(8) transducing units/ml) injection revealed both the dark and light adaptations to soon be impaired, in a dose-dependent manner, after a buffer injection as well, and all of them recovered to the control range by day 30. In both titers tested, the retinas demonstrated a frequent transgene expression mainly in the retinal pigment epithelium; however, the other retinal cells rarely expressed the transgene. Retinas exposed to a low titer virus showed no significant inflammatory reaction throughout the observation period, and also maintained the transgene expression over a 1-year period. In the retinas exposed to a high titer virus, however, mononuclear cell infiltration persisted in the subretinal area, and the retina that corresponded to the injected area finally underwent degeneration by around day 90. No retinal neoplastic lesions could be found in any animals over the 1-year period. We thus propose that SIV-mediated stable gene transfer might be useful for ocular gene transfer; however, more attention should be paid to avoiding complications when administering high titer lentivirus to the retina.

History of allergic disorders in common neurologic diseases in Japanese patients.

OBJECTIVE: To clarify the association between past and present history of allergic disorders and neurologic diseases. METHODS: The past and present history of common allergic disorders together with family history was prospectively studied in all out-patients at the Department of Neurology at Kyushu University Hospital from March 1998 to February 2000. RESULTS: Among 3113 out-patients, 2152 (69.1%) completed a questionnaire. Myelitis showed a statistically significant increase of concomitant atopic dermatitis (P=0.006) and concomitant and past atopic dermatitis (P=0.014), as compared with neurologically healthy controls. Moreover, patients with lower motoneuron disease (LMND) had a statistically significant increase of past and concomitant asthma (P=0.007). None of the other common neurologic diseases showed any increase of allergic disorders when compared with controls. CONCLUSIONS: The present study supports the significant association between allergic disorders and such spinal cord diseases as myelitis and LMND in Japanese patients.

The soleus late response elicited by transcranial magnetic stimulation reflects agonist-antagonist postural adjustment in the lower limbs.

OBJECTIVES: We studied the origin and underlying mechanism of the soleus late response (SLR) at a mean latency of 90 ms following transcranial magnetic stimulation. METHODS: The soleus primary response (SPR) and SLR were recorded from the soleus (SOL) muscle in 27 normal subjects under various conditions using a double-cone coil. We also tested 28 patients demonstrating neurological disorders with postural disturbance. RESULTS: The amplitude of the SPR gradually increased and its latency gradually decreased against the voluntary contraction (0-80%) of the tibialis anterior (TA) muscle. In contrast, the SLR amplitude was the greatest at a 20% TA contraction while the SLR latency was the shortest at a 40% TA contraction. The preactivation of SOL enhanced the SPR response but did not evoke the SLR. The SPR amplitude was significantly augmented while standing, however, the SLR amplitude tended to decrease. The SLR was never obtained following the stimulation of the brainstem, lumbar roots and peroneal nerve. The SLR was abnormal in patients with cerebellar ataxia and Parkinson's disease while the SPR was normal. CONCLUSIONS: A lack of any correlation between the SPR and SLR suggests that the SLR does not originate in the corticospinal tract. The SLR may thus be a polysynaptic response related to the postural control of the agonist and antagonist organization between the TA and SOL.

A magnetoencephalographic study on development of the somatosensory cortex in infants.

In order to examine the sensori-motor correlation in infants, we recorded the somatosensory evoked magnetic fields to tactile stimulation by using a 37-channel magnetoencephalograph. Twelve healthy infants were examined at palmar grasp stage and pincers grasp stage. Air-tapping stimulation of the right thumb was performed. Three distinct components (W1-3) emerged, W3, with a latency of approximately 100 ms, being the most prominent. As infants grew up, the correlation coefficient and the amplitude of the equivalent current dipole of W3 for the thumb increased. These developmental changes may be attributable to increases in the stability and reproducibility of the cortex in response to somesthetic inputs. Moreover, this change along with motor development supports the presence of a sensori-motor correlation in infants.

[A variant form of septo-optic-pituitary dysplasia (SOPD) complicated with acute optic neuritis].

We herein report a case of a variant form of septo-optic-pituitary dysplasia (SOPD). A 40-year-old man was admitted due to sudden occurrence of left blurred vision and lasting polyuria. He showed short statue of height of 144 cm and the neurological examination revealed hypesthesia of the left trigeminal nerve and temporal pallor in the left fundus oculi. Brain MR imaging demonstrated agenesis of the septum pellucidum and hypoplasia of the corpus callosum with subcortical spotty lesions, but optic nerve hypoplasia was not detected. The left eye showed a prolonged P100 latency of pattern reversal VEPs. He was diagnosed as having hypopituitarism since growth hormone-releasing factor did not stimulate growth hormone secretion and restriction of water-intake did not induce secretion of antidiuretic hormone. Thus we regarded this case as a variant form of SOPD. The mutation of HESX 1 gene, however, was not detected in the case. P100 of the left eye showed a reduction in latency four months after discharge. This case was considered to be a variant form of SOPD complicated by acute optic neuritis.

Magnesium deficiency differentially affects the retina and visual cortex of intact rats.

To determine the influence of magnesium (Mg) on the visual system, electroretinograms (ERG) and visual evoked potentials (VEP) were recorded under dark-(DA) and light-adapted (LA) conditions in intact rats. Weanling rats were fed either a Mg-deficient (Mg-D) or a control diet for 17 d before the tests, and ERG, VEP and immunohistopathological analyses of retinae and cortices were made. In the Mg-D rats, ear congestion, hair loss and loss of body weight were observed, and serum Mg concentration was approximately 25% of that in the control rats (P < 0.01). The amplitudes of the DA a-wave and the second positive peak of the oscillatory potentials (OP2) of the ERG, and the negative component of the VEP (N1) in Mg-D rats were significantly greater than those of control rats. However, the amplitudes of the DA b-wave, LA 2 Hz b-wave, the 20 Hz flicker responses and the implicit times of all response components did not differ between the two groups. The immunohistopathologic results also were not altered in the Mg-D rats. We suggest that the functional abnormalities induced by Mg deficiency may depend not only on the hyperactivity of the N-methyl-D-aspartate (NMDA) receptor, but also on the behavior of the Ca(2+) and Mg(2+) ions in the intact eye.

Myelitis associated with atopic disorders in Japan: a retrospective clinical study of the past 20 years.

OBJECTIVE: To clarify the clinical features of myelitis associated with atopic disorders in Japanese patients. SUBJECTS AND METHODS: We retrospectively studied the clinical, immunological and electrophysiological features of 68 consecutive patients with myelitis of acute or subacute onset diagnosed at Kyushu University Hospital during the past 20 years. RESULTS: While only 2 of 28 (7%) patients with myelitis diagnosed between 1979 and 1993 had either atopic dermatitis (AD) or bronchial asthma (BA), 19 of 40 (48%) patients with myelitis diagnosed between 1994 and 1998 did. Among the 40 patients with myelitis diagnosed between 1994 and 1998, 19 patients with either AD or BA as well as 21 patients without either disease showed a significantly higher level of serum total IgE, higher frequency of hyperIgEaemia and higher frequency of mite antigen-specific IgE than 82 healthy controls. Myelitis patients with AD presenting as persistent paresthesia/dysesthesia in all four limbs showed cervical cord lesions on MRI and abnormalities in upper limb motor evoked potentials but no abnormalities in the cerebrospinal fluid (CSF), while myelitis patients with BA showed preferential involvement of the lower motor neurons clinically and electromyographically. In addition, 12 patients with myelitis who had hyperIgEaemia and mite antigen-specific IgE but neither AD nor BA showed incomplete transverse myelitis with mild motor disability and few CSF abnormalities. CONCLUSION: The clinical features of myelitis associated with atopic disorders were in part distinguished by the type of preceding atopic disorder, and also were different from those of hyperIgEaemic myelitis with no preceding atopic disorders.

Sporadic amyotrophic lateral sclerosis showing abnormal somatosensory evoked potentials: a report of three cases.

OBJECTIVE: Although dysfunction of the sensory systems in sporadic amyotrophic lateral sclerosis (ALS) has been reported, the clinical characteristics of such cases still remain unknown. We therefore performed a clinico-electrophysiological analysis of sporadic ALS patients. MATERIAL AND METHODS: Twelve ALS patients (aged 36-66 years), who had their somatosensory evoked potentials (SEPs) evaluated, were reviewed and their clinical characteristics were delineated. In addition, needle EMG, sensory nerve conduction velocities, motor evoked potentials (MEPs) and cervical MRI or plain X-ray of the neck were also recorded. RESULTS: Three cases were segregated from the other 9 patients because of predominant upper motor neuron signs with pseudobulbar palsy and abnormal posterior tibial nerve and/or median nerve SEPs. The MEPs were also abnormal in these 3 patients and the brainstem auditory evoked potentials were abnormal in one patient. EMG revealed less involvement in the lower motor neurons. CONCLUSION: Sporadic ALS with a predominant upper motor neuron sign and also demonstrating pseudobulbar palsy with abnormal SEPs, may therefore form a clinical subtype of ALS.

[A patient with restless legs syndrome/periodic limb movement successfully treated by wearing a lumbar corset].

We report a 77-year-old woman with restless legs syndrome(RLS) and periodic limb movement(PLM). From 62 years of age, she was awakened by tingling and involuntary movement in her legs during sleep. There symptoms disappeared when she stood up and walked. She was treated with clonazepam (2.5 mg/day) and valproate (400 mg/day) at 77 years of age, and the symptoms clearly ameliorated. However, she developed mild truncal ataxia and was referred to our hospital. On admission, neurological examination revealed Babinski and Chaddock signs bilaterally with depressed tendon reflexes in the lower limbs, mild truncal ataxia and horizontal gaze nystagmus. She did not present with involuntary movement of the legs while taking the anti-epileptic drugs. Cessation of these drugs alleviated the truncal ataxia and nystagmus, but reexacerbated abnormal sensation with involuntary movement in her legs during sleep. The involuntary movements in her legs were slower than myoclonus and resembled a Babinski reflex (duration about 1 second), and they appeared periodically (around every 30 seconds) in I-II sleep stages. Neither brain MRI nor EEG detected any abnormality. Cervical MRI revealed focal compression of the spinal cord by osteophytes at C5-C6 (more severe on the left side). Motor evoked potentials with transcranial magnetic stimulation revealed a mild delay in the central conduction time (CCT), which was more prolonged on the left side. She was thus diagnosed as having RLS/PLM with involvement of the bilateral pyramidal tracts. Although nerve conduction studies did not detect any abnormality in the peripheral nerves, RLS/PLM of the left leg was induced by electric stimulation of the left tibial nerve. Because she did not want medication any more, we treated her with a lumbar corset, hoping that wearing a lumbar corset might induce contraction of the truncal muscles that would mimic standing and walking or might produce additional sensory input that would induce a 'sensory trick'. Consequently, her abnormal sensation and involuntary movement during sleep as well as the stimulation of the tibial nerve disappeared. Wearing a lumbar corset may inhibit the excitability of the spinal cord that generates RLS/PLM, though the level of sensory input by the corset was higher than the input level of abnormal sensation in her legs. A lumbar corset may be a useful alternative choice for patients with RLS/PLM, who cannot tolerate either anti-epileptic or dopaminergic drugs.

Different vulnerability of rat retinal cells to methylmercury exposure.

We tested the hypothesis that methylmercury chloride (MMC) caused a selective vulnerability in rat retinal cells during the intact preparation. MMC was injected subcutaneously daily at 3 different doses (0.25, 0.70 or 1.50 mg/kg/day) for 30 days. The electroretinograms under dark- and light-adaptation were recorded before and at 10-day intervals during the treatment period. With the lowest dose of MMC, only the amplitude of the light-adapted (LA) 20 Hz response significantly decreased on Day 30. At the intermediate dose, amplitude reductions were observed on Day 20 for the LA 20 Hz response and dark-adapted (DA) a-wave, while reductions in the LA 2 Hz b-wave and DA b-wave were noted only on Day 30. At the highest dose, these changes occurred earlier during the course of treatment. However, the amplitude of the DA second positive oscillatory potentials and the implicit times of any response components remained unchanged at all dosages. These results suggest that the cones are more sensitive than the rods, bipolar cells and Müller cells to MMC. However, amacrine cells were found to be relatively insensitive. Therefore, each retinal cell was found to have a different vulnerability to MMC.

[A case of Gerstmann-Sträussler-Scheinker syndrome (GSS) with late onset--a haplotype analysis of Glu219Lys polymorphism in PrP gene].

We report a 74-year-old man with late onset Gerstmann-Sträussler-Scheinker syndrome (GSS). In this family, 3 out of 6 siblings and his father developed cerebellar ataxia and mental deterioration in their fifth decades. He complained of unsteady walking and tingling pain in the legs at the age of 70. Neurological examination revealed moderate truncal ataxia, mild limb ataxia, ataxic speech, sensory impairment, paresthesia and areflexia in the lower extremities. CSF examination showed elevated CSF and 14-3-3 proteins with a normal cell count. EEG and brain MRI demonstrated no abnormality. Somatosensory evoked potential (SEP) study showed delayed N13-N20 interpeak latencies in the upper extremities and delayed N20 at 12th thoracic spinous process, indicating dysfunction of the posterior roots or columns of the spinal cord including the dorsal horns and proximal peripheral nerve. Analysis of the prion protein gene demonstrated a Pro102Leu amino acid substitution, which is compatible with classical GSS. Haplotype analysis of the PrP gene identified a Glu219Lys polymorphism on another allele. Recently, it was confirmed that protein X, which accelerates the conversion of the normal type of PrP (PrPC) into a pathological type of PrP (PrPSc), binds to the 219th amino acid residue of PrP. Therefore, the 219Lys polymorphism theoretically inhibited formation of PrPSc and may thus have delayed the onset of the disease in this patient.

Recovery of brain dysfunction after methylmercury exposure in rats.

We studied the time course of central nervous system (CNS) involvement after the termination of methylmercury exposure to rats, in order to investigate whether or not the involvement still progresses even after the termination of exposure. Methylmercury chloride (MMC), at a dose of 2 mg/kg/day, was subcutaneously injected for 25 consecutive days in 12 adult male Sprague-Dawley rats. Six of them were sacrificed on the final day of exposure (group A) after completing the observations of behavioral changes and determining the local cerebral glucose utilization (LCGU) as an indicator of cerebral neuronal activities. Histological examinations of the brain and the sciatic nerve were done. The other six rats were further followed up for 90 days after the termination of exposure (group B). In addition, six rats that received physiological saline served as a control. Group A showed a significant reduction of LCGU without any accompanying cerebral histological alterations and a moderate loss of myelinated fibers in the sciatic nerve. Group B showed normal LCGU rates while severe axonal degeneration of the sciatic nerve was found on the final day of the 90-day follow-up period. The present results demonstrate that a transient involvement of the CNS can occur after MMC exposure. In addition, a complete recovery may occur when the process is mild enough not to cause histological alterations. In contrast, the involvement of the peripheral nerve is much more severe than that of the CNS and it was observed to progress even after the cessation of MMC exposure. Therefore, it seems unlikely, at least in rats, that a steadily progressive course occurs in the CNS but not in the peripheral nerves over a long period of time after MMC exposure.

Chronic effects of methylmercury on the cerebral function in rats.

We studied the effects of the long-term and small-dose administration of methylmercury chloride (MMC) on the cerebral function in rats. MMC, at a dose of 0.7 mg/kg/day, was subcutaneously injected for 85 consecutive days in nine adult male Sprague-Dawley rats. They were then sacrificed on the final day of exposure (MMC group) after both completing observations on behavioral changes and also determining the local cerebral glucose utilization (LCGU) as an indicator of the cerebral neuronal activities. Histological examinations of the brain and the sciatic nerve were also performed. In addition, seven rats who received physiological saline also served as a control. LCGU significantly decreased in the visual cortex, lateral geniculate nucleus and medial geniculate nucleus without any accompanying histological alterations. Severe axonal degeneration of the sciatic nerve was also observed, which corresponded to the previously described crossed leg phenomenon. The present results suggest that the damage to the peripheral nerve was much more severe than that to the brain, which caused behavioral changes. Although no cerebral morphological changes were observed, brain dysfunction showed a selective involvement of the visual and auditory systems. This finding suggests that LCGU is a sensitive method for detecting the subclinical cerebral dysfunction caused by long-term and small-dose MMC intoxication in the rat brain.

Reorganization of the primary somatosensory area in epilepsy associated with focal cortical dysplasia.

A 5-year-old boy with focal cortical dysplasia was referred to our hospital because of epileptic seizures. He showed mild weakness of the left hand without sensory disturbance. Brain MRI revealed extensive cortical dysplasia with pachygyria and microgyria around the right central sulcus. On EEG examination, interictal spikes were noted over the right fronto/centro/parietal region. A 37-channel magnetometer revealed that the sources of the spikes were in a small, restricted region of the normal frontal lobe adjacent to the dysplastic brain. Somatosensory evoked magnetic fields indicated that the location of the current source of N2O was in the same area. Our patient shows a unique case of plasticity and reorganization of the somatosensory function due to cortical dysplasia.

[A case of chronic toluene intoxication presenting stimulus-sensitive segmental spinal myoclonus].

We reported a 48-year-old male who showed stimulus-sensitive spinal myoclonus due to chronic toluene intoxication. He has been exposed to thinner for more than 30 years as a painter, and occasionally experienced an episode of headache, nausea and dizziness because of acute thinner intoxication. He noted tremor of his hands 10 years ago. He also noticed memory disturbance since the end of 1997. Neurological examination revealed postural tremor of his fingers on the bilateral sides and the left arm. In addition, rhythmic myoclonic jerks were induced in the right upper limb muscles by a tendon tap given on the right brachioradialis muscles. Surface EMG revealed repetitive grouping discharges in those two muscles approximately 100 msec after the tendon tap which continued for about 30-50 msec. A long loop reflex (C-reflex) and giant SEPs were not observed in his right upper limb, and EEG showed no spike. Urinary excretion of N-benzoylglycine, which was a metabolite of toluene was increased (1.17 g/l). Therefore, he was diagnosed as a case of chronic toluene intoxication. His myoclonic jerks were considered to be stimulus-sensitive spinal myoclonus, because they were induced segmentally and because cortical hyperexcitability was not seen. This is the first report to describe the occurrence of stimulus-sensitive spinal myoclonus in the case of chronic toluene intoxication.

Differential interaction of somatosensory inputs in the human primary sensory cortex: a magnetoencephalographic study.

OBJECTIVE: Somatosensory evoked magnetic fields (SEFs) were recorded to investigate the interaction of the somatosensory inputs using the modality of electrical finger stimulation in 6 normal subjects. METHODS: Electrical stimuli were given to the index (II), middle (III) or little (V) fingers individually, and also to pairs of either the II and III simultaneously, or the II and V simultaneously. The interaction ratio (IR) was calculated as the ratio of the SEF amplitude by simultaneous two-finger stimulation to the arithmetically summed SEF amplitudes of two individual-finger stimulations. RESULTS: SEFs showed 3 major components: N22m, P30m and P60m. The N22m and P60m revealed a clear somatotopic organization in the primary sensory cortex (S1) in the sequence of II, III and V, while the P30m showed a cluster with medial location compared with N22m and P60m in S1. The N22m had a significantly greater IR in II and III stimulation compared to that in II and V stimulation. The P60m also showed a similar trend in the IR but was greater than that of N22m. In contrast, the IR in P30m showed no such tendency. CONCLUSION: The interaction of S1 was most influenced when adjacent receptive fields were activated in the modality of electrical finger stimulation. Our results were consistent with the concept that the Brodmann's areas in S1 which produce the 3 components of the SEFs have different functional organization.

Effects of stimulus orientation on spatial frequency function of the visual evoked potential.

Visual performance is better in response to vertical and horizontal stimuli than oblique ones in many visual tasks; this is called the orientation effect. In order to elucidate the electrophysiological basis of this psychophysical effect, we studied the effects of stimulus orientation on the amplitudes and latencies of visual evoked potentials (VEPs) over different spatial frequencies of the visual stimulation. VEPs to sinusoidal gratings at four orientations (vertical, horizontal, and oblique at 45 degrees and 135 degrees) with eight spatial frequencies (0.5-10.7 cycles/deg) at reversal rates of 1 Hz and 4 Hz were recorded in nine subjects. At 1-Hz stimulation, the amplitude and latency of P100 were measured. At 4-Hz stimulation, VEPs were Fourier-analyzed to obtain phase and amplitude of the second harmonic response (2F). At 1-Hz stimulation, P100 latencies were decreased for oblique stimuli compared with those for horizontal and vertical stimuli at lower spatial frequencies. Conversely, those for oblique stimuli were increased compared with those for horizontal and vertical stimuli at higher spatial frequencies. At 4-Hz stimulation, spatial tuning observed in 2F amplitude of the oblique gratings shifted to lower spatial frequencies when compared with those of vertical stimulation. The alteration of the VEP spatial frequency function caused by the oblique stimuli was in good agreement with the orientation effect observed in psychophysical studies. Our study may have a clinical implication in that VEP testing with stimuli in more than one orientation at slow and fast temporal modulations can be useful in evaluating neurological disease affecting the visual system.

Differential temporal coding of the vibratory sense in the hand and foot in man.

OBJECTIVE: We studied the difference in the temporal tuning function of the vibratory senses between the hand and foot in man by using steady-state somatosensory evoked potentials (S-SEPs) to vibratory stimulation. METHODS: Vibratory stimuli were applied to the palm and sole, and the S-SEPs were then recorded in 8 normal subjects. A total of 200 responses were recorded from 4 electrodes including the ipsi-and contralateral somatosensory areas of the hand and foot. The amplitude of the first harmonic component (1F) was obtained by a Fourier analysis. The effect of modulation frequency (17-30 Hz) on the 1F at a stimulus intensity of 0.05 N was studied. RESULTS: The amplitudes of the S-SEPs were the greatest in the contralateral hand and foot areas. The mean 1F amplitudes of the palm S-SEPs as a function of the modulation frequency showed a narrow tuning curve with a peak near 21 Hz while those of the sole demonstrated a broad tuning curve. CONCLUSION: Our results suggest the differential temporal coding of the vibratory sense in the hand and foot areas of the somatosensory cortex in man. This is probably caused by the different characteristics in the receptors situated in the hand and foot.