Neural basis of stable perception of an ambiguous apparent motion stimulus.

Although it has been shown that an alternative dominant percept induced by an ambiguous visual scene has neural correlates in various cortical areas, it is not known how such a dominant percept is maintained until it switches to another. We measured the primary visual response to the two-frame bistable apparent motion stimulus (stroboscopic alternative motion) when observers continuously perceived one motion and compared this with the response for another motion using magnetoencephalography. We observed a response component at around 160 ms after the frame change, the amplitude of which depended on the perceived motion. In contrast, brain responses to less ambiguous and physically unambiguous motions in both the horizontal and vertical directions did not evoke such a component. The differential response evoked by the bistable apparent motion is therefore distinct from directionally-selective visual responses. The results indicate the existence of neural activity related to establish and maintain one dominant percept, the magnitude of which is related to the ambiguity of the stimulus. This is in the line with the currently proposed idea that dominant percept is established in the distributed cortical areas including the early visual areas. Further, the existence of the neural activity induced only by the ambiguous image suggests that the competitive neural activities for the two possible percepts exist even when one dominant image is continuously perceived.

Neural processes of attentional inhibition of return traced with magnetoencephalography.

Inhibition of return (IOR) is a phenomenon that involves reaction times (RTs) to a spatially cued target that are longer than RTs to an uncued target when the interval between the cue and target is prolonged. Although numerous studies have examined IOR, no consensus has yet been reached regarding the neural mechanisms responsible for it. We used magnetoencephalography (MEG) and measured the human neural responses underlying the time course of IOR, applying a typical spatial cueing paradigm. The cue-target interval was 600+/-200 ms. Three experimental conditions were employed. Cued; the cue and target were presented at the same location. Uncued; the two stimuli were presented at opposite locations. Neutral; the cue stimulus was presented bilaterally. We found differences in the amplitudes of signals in the postero-temporal and bilateral temporal areas, and peak latencies in a central area between the cued and uncued conditions. These signals were localized to the extrastriate cortex, bilateral temporal-parietal junction (TPJ), and primary motor cortex, respectively. Bilateral TPJ activities are related to the identification of salient events in the sensory environment both within and independent of the current behavioral context and may play an important role in IOR in addition to extrastriate and the primary motor cortex.

Recommendations for the clinical use of somatosensory-evoked potentials.

The International Federation of Clinical Neurophysiology (IFCN) is in the process of updating its Recommendations for clinical practice published in 1999. These new recommendations dedicated to somatosensory-evoked potentials (SEPs) update the methodological aspects and general clinical applications of standard SEPs, and introduce new sections dedicated to the anatomical-functional organization of the somatosensory system and to special clinical applications, such as intraoperative monitoring, recordings in the intensive care unit, pain-related evoked potentials, and trigeminal and pudendal SEPs. Standard SEPs have gained an established role in the health system, and the special clinical applications we describe here are drawing increasing interest. However, to prove clinically useful each of them requires a dedicated knowledge, both technical and pathophysiological. In this article we give technical advice, report normative values, and discuss clinical applications.

Warm-, hot- and pain-related neural activities depending on baseline skin temperatures.

BACKGROUND: This study investigated the characteristics of temperature-related evoked neural activities to baseline skin temperatures on target and adjacent sites using contact heat evoked potentials (CHEPs). METHODS: Contact heat evoked potentials were recorded from 12 normal subjects during three stimuli: target temperatures for "warm", "hot" and "pain" were set at 41, 46 and 51 °C, respectively. The baseline temperature was separately set at 30, 35 and 40 °C under all conditions, and a heat pulse was delivered over the right forearm at 41 °C under the warm condition, at 46 °C under the hot condition and at 51 °C under the pain condition. RESULTS: The N2-P2 amplitude was significantly larger at the 40 °C baseline than at the 30 and 35 °C baselines during the pain condition, whereas no significant differences were observed during the hot and warm conditions. In addition, the effects of an interference warm stimulation to adjacent sites were examined; however, no significant effects were observed. CONCLUSIONS: These results suggest that the priming effects of temperature on CHEPs were only observed under the pain condition, indicating the specificity of thermal pain, as well as a difference in the neural mechanisms responsible for thermal noxious and innocuous processing in human brains. SIGNIFICANCE: This study using CHEPs shows the importance of baseline and target skin temperatures to investigate the characteristics of temperature-related neural activities. This measure may contribute to understanding of warm-, hot-, and pain-related neural activities in human brains.

Characteristics of sensori-motor interaction in the primary and secondary somatosensory cortices in humans: a magnetoencephalography study.

We studied sensori-motor interaction in the primary (SI) and secondary somatosensory cortex (SII) using magnetoencephalography. Since SII in both hemispheres was activated following unilateral stimulation, we analyzed SIIc (contralateral to stimulation) as well as SIIi (ipsilateral to stimulation). Four tasks were performed in human subjects in which a voluntary thumb movement of the left or right hand was combined with electrical stimulation applied to the index finger of the left or right hand: L(M)-L(S) (movement of the left thumb triggered stimulation to the left finger), L(M)-R(S) (movement of the left thumb triggered electrical stimulation to the right finger), R(M)-R(S) (movement of the right thumb triggered electrical stimulation to the right finger), and R(M)-L(S) (movement of the right thumb triggered electrical stimulation to the left finger). Stimulation to the index finger only (S condition) was also recorded. In SI, the amplitude of N20m and P35m was significantly attenuated in the R(M)-R(S) and L(M)-L(S) tasks compared with the S condition, but that for other tasks showed no change, corresponding to a conventional gating phenomenon. In SII, the R(M)-L(S) task significantly enhanced the amplitude of SIIc but reduced that of SIIi compared with the S condition. The L(M)-L(S) and R(M)-R(S) tasks caused a significant enhancement only in SIIi. The L(M)-R(S) task enhanced the amplitude only in SIIc. The laterality index showed that SII modulation with voluntary movement was more dominant in the hemisphere ipsilateral to movement but was not affected by the side of stimulation. These results provided the characteristics of activities in somatosensory cortices, a simple inhibition in SI but complicated changes in SII depending on the side of movement and stimulation, which may indicate the higher cognitive processing in SII.

Backward-masking: the effect of the duration of the second stimulus on recognition of the first stimulus.

OBJECTIVE: We recorded event-related magnetic fields following a target stimulus followed by a masking stimulus to investigate the visual backward masking effect using a helmet-type magnetoencephalography system in humans. METHODS: In the target stimulus with masking stimulus conditions, duration of the target stimulus was constant at 16 ms, and duration of the masking stimulus was altered (16, 48 and 144 ms). The target stimulus was masked by the 144-ms masking stimulus, but not by the 16-ms masking stimulus, and was obscured by the 48-ms masking stimulus. For control conditions (Single-condition), event-related magnetic fields were recorded following the sole presentation of the masking stimulus for 32, 64 or 160 ms. RESULTS: One major response was obtained at 180 ms after the onset of the stimulation in each condition. The equivalent current dipole of one major response was estimated to lie in the occipital lobe, but there was a relatively large inter-individual difference. There was no significant difference in latency between the target stimulus with masking stimulus conditions and Single-conditions. In the target stimulus with masking stimulus conditions with the 48- and 144-ms masking stimulus, the root mean square value did not differ from that in the respective Single-condition, while the root mean square value for the target stimulus with masking stimulus conditions with the 16-ms masking stimulus was significantly smaller than that in the Single-condition with the 32-ms masking stimulus, but not different from that in the Single-condition with the 16-ms masking stimulus. CONCLUSIONS: The peak latency of one major response depended on the onset of the first stimulus for both the target stimulus with masking stimulus conditions and Single-condition, but the root mean square value depended on the duration of the masking stimulus. We concluded that the temporal information for the target stimulus was preserved during the masking effect, while the figural information was interrupted by the masking stimulus. Our results suggested that temporal factors for the stimulus were processed differently from those responsible for the object's recognition during backward masking.

The somatosensory evoked magnetic fields.

Averaged magnetoencephalography (MEG) following somatosensory stimulation, somatosensory evoked magnetic field(s) (SEF), in humans are reviewed. The equivalent current dipole(s) (ECD) of the primary and the following middle-latency components of SEF following electrical stimulation within 80-100 ms are estimated in area 3b of the primary somatosensory cortex (SI), the posterior bank of the central sulcus, in the hemisphere contralateral to the stimulated site. Their sites are generally compatible with the homunculus which was reported by Penfield using direct cortical stimulation during surgery. SEF to passive finger movement is generated in area 3a or 2 of SI, unlike with electrical stimulation. Long-latency components with peaks of approximately 80-120 ms are recorded in the bilateral hemispheres and their ECD are estimated in the secondary somatosensory cortex (SII) in the bilateral hemispheres. We also summarized (1) the gating effects on SEF by interference tactile stimulation or movement applied to the stimulus site, (2) clinical applications of SEF in the fields of neurosurgery and neurology and (3) cortical plasticity (reorganization) of the SI. SEF specific to painful stimulation is also recorded following painful stimulation by CO(2) laser beam. Pain-specific components are recorded over 150 ms after the stimulus and their ECD are estimated in the bilateral SII and the limbic system. We introduced a newly-developed multi (12)-channel gradiometer system with the smallest and highest quality superconducting quantum interference device (micro-SQUID) available to non-invasively detect the magnetic fields of a human peripheral nerve. Clear nerve action fields (NAFs) were consistently recorded from all subjects.

Heat stress-induced phosphorylation of FoxO3a signalling in rat skeletal muscle.

AIM: A recent study demonstrated that FoxO3a was directly induced by the overexpression of Hsp72 in rat soleus muscle. However, whether heat stress treatment induces FoxO3a phosphorylation in rat skeletal muscle remains unclear. This study examined the effects of heat stress on the regulation of the FoxO3a signalling pathway in rat skeletal muscle. METHODS: Thirty-two male Wistar rats (15 weeks old) were randomly assigned into two groups; sedentary control group (Sed, n = 8) and experimental group (n = 24). After an overnight fast, one leg of each rat (HS leg) in the experimental group was immersed in hot water (43 °C) for 30 min, and the soleus and plantaris muscles in both legs were removed immediately (0 min), 30 min, 60 min, or 24 h after the heat stress (n = 6 each group). The contralateral, non-heated leg in the experimental group served as an internal control (CT leg). RESULTS: Heat stress treatment resulted in a significant increase in FoxO3a phosphorylation (Ser253) in the soleus and plantaris muscles of heat-stressed legs after 24 h. Hsp72 expression in heat-stressed legs was significantly higher at 60 min and 24 h in these muscles. Activation of the PTEN/Akt and MEK/ERK pathways was also observed in these muscles immediately after stress, but not at 24 h. There were no differences in FoxO1 and AMPKα phosphorylation in either muscle. CONCLUSION: Heat stress in rat skeletal muscle induces phosphorylation of FoxO3a signalling, and it may be related to Hsp72 upregulation, and the activation of the PTEN/Akt and MEK/ERK pathways.

Treatment of essential tremor with arotinolol.

We investigated the effect of arotinolol, a new peripherally acting beta-adrenergic blocker, in 15 patients with essential tremor. The patients received 30 mg per day of arotinolol for 8 weeks. Accelerometer readings showed a significant reduction in amplitude of postural tremor after treatment. Action tremor also improved to essentially the same degree as postural tremor. The present findings support the view that the therapeutic effect of beta-blockers in essential tremor is mediated by peripheral beta-adrenergic receptors.

Peripheral and central nerve conduction in subacute myelo-optico-neuropathy.

Five patients with subacute myelo-optico-neuropathy (SMON) were studied by short-latency somatosensory evoked potentials (SEPs) in response to electrical stimulation of the median nerve and the posterior tibial nerve. SEPs with median nerve stimulation were normal in all cases, but SEPs with posterior tibial nerve stimulation were abnormal in two patients with severe sensory loss in the legs. Abnormalities suggested normal peripheral conduction but a marked attenuation of the cortical component and delayed central conduction. These findings were in conformity with postmortem morphometric analysis, which showed marked reduction of myelinated fibers in the gracile fascicle but only slight reduction of large myelinated fibers in the sural nerve. The pathophysiology of SMON appears to be mainly a central distal axonopathy.

Accelerated aging of the brain in Werner's syndrome.

We report the electrophysiologic examination of a 55-year-old woman with Werner's syndrome. Needle EMG and peripheral conduction studies were normal. In contrast, EEG was moderately abnormal, the N20 and P25 potentials of SEPs were delayed and enlarged, and the event-related potential, P300, was delayed. These characteristic findings indicated accelerated aging of the brain, as in the other organs, in Werner's syndrome.

Neuroepithelial cyst presenting as recurrent aseptic meningitis.

A 41-year-old man had three episodes of acute aseptic meningitis from the age of thirty-six. With each episode he had severe occipital headache associated with a mononuclear pleocytosis and an increase in CSF protein. He had a neuroepithelial cyst originating from the choroid plexus of the right cerebellomedullary cistern. Spontaneous ruptures of the cyst probably caused recurrent chemical meningitis. A neuroepithelial cyst must be considered in the differential diagnosis of intracranial cystic tumors presenting with aseptic meningitis.

Numb chin syndrome secondary to Burkitt's cell acute leukemia.

We describe a case of Burkitt's cell acute lymphoblastic leukemia presenting with the bilateral numb chin syndrome as the initial symptom of the disease. Postmortem study of the trigeminal nerve showed heavy infiltrations of leukemic cells and destruction of axon and myelin by leukemic cells in the mandibular nerve.

Cortical tremor: a variant of cortical reflex myoclonus.

Two patients with action tremor that was thought to originate in the cerebral cortex showed fine shivering-like finger twitching provoked mainly by action and posture. Surface EMG showed relatively rhythmic discharge at a rate of about 9 Hz, which resembled essential tremor. However, electrophysiologic studies revealed giant somatosensory evoked potentials (SEPs) with enhanced long-loop reflex and premovement cortical spike by the jerk-locked averaging method. Treatment with beta-blocker showed no effect, but anticonvulsants such as clonazepam, valproate, and primidone were effective to suppress the tremor and the amplitude of SEPs. We call this involuntary movement "cortical tremor," which is in fact a variant of cortical reflex myoclonus.

Human neurolymphomatosis by adult T-cell leukemia.

We report a case of adult T-cell leukemia presenting with sensorimotor polyneuropathy with persistent severe pain. The patient died without treatment after 4 months. Autopsy showed infiltration of peripheral nerves by leukemia with no involvement of the CNS. This case closely resembles Marek's disease of fowls, a virus-induced T-cell lymphoma associated with neurolymphomatosis.

Reading of Japanese Kanji (morphograms) and Kana (syllabograms): a magnetoencephalographic study.

Magnetoencephalograms were recorded from six healthy Japanese subjects in order to investigate the areas in the cortices which are involved in the recognition of Japanese characters (Kanji and Kana). Forty-four Kanji (morphograms), 44 Kana (syllabograms) and 20 alphabet letters were used as stimuli. They were presented randomly and the subjects were required to read each stimulus and count the number of letters. The magnetic responses were recorded with dual 37-channel SQUID (Superconducting Quantum Interference Device) gradiometers from the temporal, parietal and occipital areas of the brain. The magnetic responses to Kanji and Kana were similar and consequently the locations of equivalent current dipoles (ECDs) to Kanji and those to Kana did not differ at any recording site. In all the subjects, ECDs were found in the posterior inferior temporal (PIT) areas approximately corresponding to Brodmann area 37 in the latency range of 150-300 msec. These activities were found in both hemispheres without consistent laterality. The location of the ECD moved forward from posterior to anterior in the PIT area as the latency increased in all but one subject. Only one subject showed activities in the left angular gyrus. Since activities in PIT areas were also found in alphabet letters, the bilateral PIT areas are considered to play an essential role in reading.

Cortical activity related to cue-invariant shape perception in humans.

We used magnetoencephalography to search spatio-temporally for cortical activity related to the perception of shape defined by various visual cues in humans. The visual stimuli were three kinds of two-dimensional figures: two had fixed shapes (Diamond and Cross), the other did not (Noise). These figures were defined by three visual cues: difference of flicker, texture or luminance between the foreground and the background in the random dot pattern. Using this stimulus, we recorded the magnetic responses from the temporo-occipital regions of nine healthy subjects. Additionally, we measured the reaction time for the subjects to detect the figure by button-pressing. A magnetic component was identified in the responses. The properties of the first magnetic component differed for stimulus condition. The peak latency of the first magnetic component was different for the cues (270 ms for flicker, 360 ms for texture and 250 ms for luminance), but not for the figures. In contrast, the peak amplitude of the first magnetic component was different for the figures (96-144 fT for Diamond or Cross and 52-80 fT for Noise), but not for the cues. The signal source of the first magnetic component was estimated to lie on the ventral side of the extrastriate cortex: In the posterior part of the inferior temporal cortex, probably in the fusiform gyrus in four subjects, and in the lateral part of the occipital cortex which was outside of the primary visual cortex (visual area 1) in one subject. The signal source location was different inter-individually, but almost the same within each subject. Reaction time was 471 ms for flicker, 569 ms for texture and 426 ms for luminance, but the interval between the reaction time and the peak latency was constant (about 200 ms) for each cue. The first magnetic component was more clearly recorded from the right hemisphere than from the left.We found that the shape defined by the different visual cues activates the same localized site in the lateral extrastriate cortex. This spatial convergence suggests that there is a restricted locus that processes the visual shape regardless of the difference of the visual cue. The correspondence between the peak latency and the reaction time suggests that the activity of the area is responsible for the perception of visual shape. The inter-hemispheric difference suggests a dominance of the right hemisphere in visual shape processing.

The spatiotemporal dynamics of the face inversion effect: a magneto- and electro-encephalographic study.

The neurophysiological basis of the face inversion effect was studied with magneto- and electro-encephalography in 10 normal subjects. Spatiotemporal analyses using dipole modeling was performed on combined evoked magneto and electro-encephalography data to hemifield presentation of upright and inverted faces and objects. Inferior temporal cortex, i.e. fusiform gyrus, and lateral temporal cortex near the superior temporal sulcus were activated simultaneously, but independently, at 140-200 ms post-stimulus to upright and inverted unfamiliar faces. Right hemisphere inferior temporal cortex and lateral temporal cortex were active in all subjects, and in the left hemisphere in half the subjects. Latencies to inverted relative to upright faces were longer in the right hemisphere, and shorter in the left hemisphere. For right hemifield stimulation ipsilateral activation delay was around 18-19 ms for both upright and inverted faces and was calculated from all 10 subjects. For left hemifield stimulation, and the data from 7 of 10 subjects, it was 22 and 29 ms to upright and inverted faces, respectively. In sum, the methods used in this study did not identify clear differences in anatomical location of activated regions to upright and inverted faces. We believe, however, that the differences in processing upright versus inverted faces are attributable to temporal processing differences rather than to processing of information by different brain regions.

Attention and visual interference stimulation affect somatosensory processing: a magnetoencephalographic study.

In our previous study, continuous visual (cartoon and random dot motion) and auditory (music) stimulation changed the somatosensory evoked magnetic fields following electrical stimulation of the median nerve in human subjects. They enhanced the middle-latency components (3M and 4M) generated in the contralateral primary somatosensory cortex, and reduced the MI component generated in the ipsilateral secondary somatosensory cortex. We speculated that such interference effects were caused by activation of polymodal neurons in areas 5 and/or 7 of the parietal lobe as well as in the medial superior temporal region and superior temporal sulcus. However, we could not exclude the effect of attention on such interference effects. In the present study, to know the effect of attention on visual and auditory interference in these changes, we stimulated the bilateral median nerves unilaterally in a random order, and asked subjects to count the number of times the left median nerve was stimulated while visual or auditory interference was applied. Five components (1M-5M) were identified in the hemisphere contralateral to the stimulated nerve and only one component (MI) was found in the ipsilateral hemisphere. The 3M and 4M components (33-75 ms in latency) were enhanced by both attention and visual interference stimulation but not by auditory stimulation. The 5M component (70-115 ms) and MI component (70-133 ms) were enhanced by attention, but were not changed by attention together with visual or auditory interference. Summarizing the results of our previous study and the present study, (1) visual interference alone enhanced the 3M and 4M but reduced the MI, and (2) attention alone also enhanced the 3M and 4M, and enhanced the 5M and MI. As a result, (3) visual interference with attention enhanced the 3M and 4M more, and showed no significant change of the 5M and MI. This was compatible with a summation of the effects caused by visual interference alone and attention alone, but some interactions between visual interference and attention might have taken place. The locations of dipoles of all components were not significantly changed by attention or any interference stimulation. These findings support the idea that there are significant interactions of activities relating to somatosensory stimulation, visual stimulation and cognitive function, in both the primary and the secondary somatosensory cortex in humans.

The auditory evoked magnetic fields to very high frequency tones.

We studied the auditory evoked magnetic fields (AEFs) in response to pure tones especially at very high frequencies (from 4000 Hz to 40,000 Hz). This is the first systematic study of AEFs using tones above 5000 Hz, the upper audible range of humans, and ultrasound. We performed two experiments. In the first, AEFs were recorded in 12 subjects from both hemispheres under binaural listening conditions. Six types of auditory stimulus (pure tones of five different frequencies: 4000 Hz, 8000 Hz, 10,000 Hz, 12,000 Hz, 14,000 Hz, and a click sound as the target stimulus) were used. In the second experiment, we used 1000 Hz, 15,000 Hz, and two ultrasounds with frequencies of 20,000 Hz and 40,000 Hz. The subjects could detect all stimuli in the first experiment but not the ultrasounds in the second experiment. We analyzed N1m, the main response with approximately 100 ms in peak latency, and made the following findings. (1) N1m responses to the tones up to 12,000 Hz were clearly recorded from at least one hemisphere in all 12 subjects. N1m for 14,000 Hz was identified in at least one hemisphere in 10 subjects, and in both hemispheres in six subjects. No significant response could be identified to ultrasounds over 20,000 Hz. (2) The amplitude of the N1m to the tones above 8000 Hz was significantly smaller than that to 4000 Hz in both hemispheres. There was a tendency for the peak latency of the N1m to be longer for the tones with higher frequencies, but no significant change was found. (3) The equivalent current dipole (ECD) of the N1m was located in the auditory cortex. There was a tendency for the ECD for the tones with higher frequencies to lie in more medial and posterior areas, but no significant change was found. (4) As for the interhemispheric difference, the N1m amplitude for all frequency tones was significantly larger and the ECDs were estimated to be located more anterior and medial in the right hemisphere than the left. The priority of the right hemisphere, that is the larger amplitude, for very high frequency tones was confirmed. (5) The orientation of the ECD in the left hemisphere became significantly more vertical the higher the tones. This result was consistent with previous studies which revealed the sensitivity of the frequency difference in the left hemisphere. From these findings we suggest that tonotopy in the auditory cortex exists up to the upper limit of audible range within the small area, where the directly air-conducted ultrasounds are not reflected.