Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.

Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via the descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in the rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA injection into the hindpaw after the FS shows significantly enhanced thermal hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos-immunoreactive neurons in the left AIC and PIC were significantly lower in the FS+CFA group (L AIC, 95.9±6.8; L PIC, 181.9±23.1) than those in the naive group (L AIC, 151.1±19.3, p<0.05; L PIC, 274.2±37.3, p<0.05). These findings suggest a neuroplastic change in the IC after FS, which may be involved in the enhancement of CFA-induced thermal hyperalgesia through dysfunction of the descending pain modulatory system.

Effects of restraint stress on glial activity in the rostral ventromedial medulla.

Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. Postmortem studies of patients with stress-related psychiatric disorders have demonstrated a decrease in the number of astrocytes and the level of glial fibrillary acidic protein (GFAP), a marker for astrocyte, in the cerebral cortex. Since astrocytes play vital roles in maintaining neuroplasticity via synapse maintenance and secretion of neurotrophins, damage of astrocytes is thought to be involved in the neuropathology. In the present study we examined GFAP, S100ß and CD11b protein levels in the rostral ventromedial medulla (RVM) after the subacute and chronic restraint stresses to clarify changes in descending pain modulatory system in the rat with stress-induced hyperalgesia. Chronic restraint stress (6h/day for 3 weeks), but not subacute restraint stress (6h/day for 3 days), caused a marked mechanical hypersensitivity. Subacute and chronic restraint stresses induced a significant decrease of GFAP protein level in the RVM (21.9 ± 3.6%, p<0.01 and 18.2 ± 5.1%, p<0.05 vs. control group, respectively). In the chronic stress group, the GFAP protein level in the RVM was positively correlated with the mechanical threshold (p<0.05). The immunohistochemical analysis revealed that chronic restraint stress induced a significant decrease in GFAP-immunoreactivity in the nucleus raphe magnus, a part of the RVM, compared to subacute restraint stress. In contrast there was no significant difference in the S100ß and CD11b protein levels between the control and stress groups. These findings suggest that the long-lasting decrease of GFAP protein induced by chronic restraint stress causes dysfunction of astrocytes, which may be involved in the impairment of the RVM that plays pivotal roles in pain modulation.

Distinctions in burst spiking between thalamic reticular nucleus cells projecting to the dorsal lateral geniculate and lateral posterior nuclei in the anesthetized rat.

Thalamic cell activity is under a significant influence of inhibition from the thalamic reticular nucleus (TRN) that is composed of domains connected with first and higher order thalamic nuclei, which are thought to subserve transmission of sensory inputs to the cortex and cortico-thalamo-cortical transmission of cortical outputs, respectively. Provided that TRN cells have distinct activities along with their projections to first and higher order thalamic nuclei, TRN cells could shape cell activities of the two thalamic nuclei in different manners for the distinct functions. In anesthetized rats, visual response and spontaneous activity were recorded from TRN cells projecting to the dorsal lateral geniculate (first order) and lateral posterior (higher order) nuclei (TRN-DLG and TRN-LP cells), using juxta-cellular recording and labeling techniques. TRN-DLG cells had a higher propensity for burst spiking and exhibited bursts of larger numbers of spikes with shorter inter-spike intervals as compared to TRN-LP cells in both visual response and spontaneous activity. Sustained effects of visual input on burst spiking were recognized in recurrent activation of TRN-DLG but not of TRN-LP cells. Further, the features of burst spiking were related with the locations of topographically connected cell bodies and terminal fields. The difference in burst spiking contrasts with the difference between thalamic cells in the DLG and LP, which show low and high levels of burst spiking, respectively. The synergy between thalamic and TRN cell activities with their contrasting features of burst spiking may compose distinctive sensory processing and attentional gating functions of geniculate and extra-geniculate systems.

Chronic restraint stress decreases glial fibrillary acidic protein and glutamate transporter in the periaqueductal gray matter.

Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. Postmortem studies of stress-related psychiatric disorders have demonstrated a decrease in the number of astrocytes and the level of glial fibrillary acidic protein (GFAP), a marker for astrocyte, in the cerebral cortex. Since astrocytes play vital roles in maintaining neuroplasticity via synapse maintenance and secretion of neurotrophins, impairment of astrocytes is thought to be involved in the neuropathology. In the present study we examined GFAP and excitatory amino acid transporter 2 (EAAT2) protein levels in the periaqueductal gray matter (PAG) after subacute and chronic restraint stresses to clarify changes in descending pain modulatory system in the rat with stress-induced hyperalgesia. Chronic restraint stress (6h/day for 3 weeks), but not subacute restraint stress (6h/day for 3 days), caused a marked mechanical hypersensitivity and aggressive behavior. The chronic restraint stress induced a significant decrease of GFAP protein level in the PAG (32.0 ± 8.9% vs. control group, p<0.05). In immunohistochemical analysis the remarkable decrease of GFAP was observed in the ventrolateral PAG. The EAAT2 protein level in the 3 weeks stress group (79.6 ± 6.8%) was significantly lower compared to that in the control group (100.0 ± 6.1%, p<0.05). In contrast there was no significant difference in the GFAP and EAAT2 protein levels between the control and 3 days stress groups These findings suggest a dysfunction of the PAG that plays pivotal roles in the organization of strategies for coping with stressors and in pain modulation after chronic restraint stress.

Sub-threshold cross-modal sensory interaction in the thalamus: lemniscal auditory response in the medial geniculate nucleus is modulated by somatosensory stimulation.

Recent studies have highlighted cross-modal sensory modulations in the primary sensory areas in the cortex, suggesting that cross-modal sensory interactions occur at early stages in the hierarchy of sensory processing. Multi-modal sensory inputs from non-lemniscal thalamic nuclei and cortical inputs from the secondary sensory and association areas are considered responsible for the modulations. On the other hand, there is little evidence of cross-sensory modal sensitivities in lemniscal thalamic nuclei. In the present study, we were interested in a possibility that somatosensory stimulation may affect auditory response in the ventral division (MGV) of the medial geniculate nucleus (MG), a lemniscal thalamic nucleus that is considered to be dedicated to auditory uni-modal processing. Experiments were performed on anesthetized rats. Transcutaneous electrical stimulation of the hindpaw, which is thought to evoke nociception and seems unrelated to auditory processing, modulated unit discharges in response to auditory stimulation (noise bursts). The modulation was observed in the MGV and non-lemniscal auditory thalamic nuclei such as the dorsal and medial divisions of the MG. The major effect of somatosensory stimulation was suppression. The most robust suppression was induced by electrical stimuli given simultaneously with noise bursts or preceding noise bursts by 10 to 20 ms. The results indicate that the lemniscal (MGV) and non-lemniscal auditory nuclei are subject to somatosensory influence. In everyday experience intense somatosensory stimuli such as pain interrupt our ongoing hearing or interfere with clear recognition of sound. The modulation of lemniscal auditory response by somatosensory stimulation may underlie such cross-modal disturbance of auditory perception as a form of cross-modal switching of attention.

Visual motion direction is represented in population-level neural response as measured by magnetoencephalography.

We investigated whether direction information is represented in the population-level neural response evoked by the visual motion stimulus, as measured by magnetoencephalography. Coherent motions with varied speed, varied direction, and different coherence level were presented using random dot kinematography. Peak latency of responses to motion onset was inversely related to speed in all directions, as previously reported, but no significant effect of direction on latency changes was identified. Mutual information entropy (IE) calculated using four-direction response data increased significantly (>2.14) after motion onset in 41.3% of response data and maximum IE was distributed at approximately 20 ms after peak response latency. When response waveforms showing significant differences (by multivariate discriminant analysis) in distribution of the three waveform parameters (peak amplitude, peak latency, and 75% waveform width) with stimulus directions were analyzed, 87 waveform stimulus directions (80.6%) were correctly estimated using these parameters. Correct estimation rate was unaffected by stimulus speed, but was affected by coherence level, even though both speed and coherence affected response amplitude similarly. Our results indicate that speed and direction of stimulus motion are represented in the distinct properties of a response waveform, suggesting that the human brain processes speed and direction separately, at least in part.

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.

A first comparison of the human multifocal visual evoked magnetic field and visual evoked potential.

Our objectives were to determine the feasibility of recording reliable multifocal visual evoked magnetic fields (mfVEFs), to investigate the maximum stimulus eccentricity for which the mfVEF responses can be obtained, and to study how this changes with checksize (spatial frequency tuning). Using a checksize of 30', we recorded 8-channel pattern-onset mfVEFs three times to obtain responses from 19 channels located around the inion. Multifocal visual evoked potentials (mfVEPs) were recorded under the same conditions. Eccentricity changes with spatial frequency were studied using checksizes from 7.5' to 60'. We obtained, for the first time, reliable mfVEFs, and found they could be elicited from more peripheral stimulus elements than could mfVEPs. The larger the checksize, the greater the eccentricity reached.

Human visual motion areas determined individually by magnetoencephalography and 3D magnetic resonance imaging.

We used magnetoencephalography to study inter-individual locational difference in the extrastriate region which responds to visual motion. Magnetic responses to visual motion onset from the right temporo-occipital area were recorded from 12 subjects. All the subjects had clear responses to apparent or random dot coherent motion. The origins of these responses was investigated by use of the single equivalent current dipole model. The nearest scalp to the origin also was identified for each subject, which may be useful in transcranial stimulation studies. Although the magnetic responses of all the subjects should have the same functional properties; be related to neural activities synchronized exclusively to the onset of motion, the estimated origins varied greatly among the subjects. The location of origin could be classified as one of three types: temporo-occipital, occipital, or parietal, according to the sulcal anatomy investigated in the individual's three-dimensional magnetic resonance image. Temporo-occipital types were found for seven subjects, and anatomically the regions were around human MT/V5. Two subjects had the occipital type, with regions posterior to the anatomical MT/V5 and corresponding to V3A anatomically. The other three subjects had origins classified as the parietal type dorso-rostral to the anatomical MT/V5, with regions around the posterior end of the superior temporal sulcus. Although all these cortical regions appear to be related to the neural process of visual motion, whether they correspond functionally to the same names or migrated MT/V5 must now be determined.

Perception of apparent motion is related to the neural activity in the human extrastriate cortex as measured by magnetoencephalography.

To determine the neural correlate of apparent motion perception, we measured magnetic responses to visual stimuli in apparent motion and compared the results with subjective rating of the quality of perceived motion with varied stimulus timing. The latency of the magnetic response was about 150 ms, and its origin was estimated to be in the occipito-parieto-temporal junction. The strength of the first component in the response varied with the stimulus timing, the maximum value being at the interval 0. The change could not be explained by the simple summation of onset and offset responses and this value was related to the subjective rating of quality (smoothness) of motion measured of the stimulus. Results indicate there is a localized cortical region of neural activity which is closely related to the subjective assessment of quality of perceived motion.

Asymmetry of the human visual field in magnetic response to apparent motion.

Predominance of the lower visual field has been shown in various visual tasks, but whether the upper visual field is involved in a specific neural process is unknown. We used magnetoencephalography to study the effect of orientation and direction on the responses of five subjects to apparent motion from the human extrastriate cortex. The first magnetic response always was the largest, and the peak latency of about 200 ms did not change with the stimulus conditions. Amplitudes of the first responses were highest when motions were oriented at the horizontal meridian, decreasing with the degree of the angle between motion orientation and the horizontal meridian. There was no difference in amplitude between the two directions in the lower visual field, whereas the value of the response to downward motion in the upper visual field was significantly larger than that to upward motion. These amplitude changes are not due to differences in the anatomical distribution of neural activities because the estimated origins for the first responses always were in the same cortical area (around the occipito-parieto-temporal region) and the directions of the current vectors did not change with the stimulus conditions, and the estimated current strength changed with the stimulus conditions as did the response amplitude. These findings suggest that the human extrastriate cortex has a directional preference for downward versus upward motion in the upper visual field.

Magnetic response of human extrastriate cortex in the detection of coherent and incoherent motion.

Although direction selectivity is a cardinal property of neurons in the visual motion detection system, movement of numerous elements without global direction (incoherent motion) has been shown to activate human and monkey visual systems, as does coherent motion which has global direction. We used magnetoencephalography to investigate the neural process underlying responses to these types of motions in the human extrastriate cortex. Both motions were created using a random dot kinematogram and four speeds (0, 0.6, 9.6 and 25 degrees /s). The visual stimuli were composed of two successive motions at different speeds; a coherent motion at a certain speed that changed to incoherent motion at another speed or vice versa. Magnetic responses to the change in motion consisted of a few components, the first of which was always largest. The peak latency of the first component was inversely related to the speed of the preceding motion, but for both motions it was not affected by the speed of the subsequent motion. For each subject, the estimated origin of the first component was always in the extrastriate cortex, and this changed with the speed of the preceding motion. For both motions, the location for the slower preceding motion was lateral to that for the faster preceding motion. Although the latency changes of the two motions differed, their overall response properties were markedly similar. These findings show that the speed of incoherent motion is represented in the human extrastriate cortex neurons to the same degree as coherent motion. We consider that the human visual system has a distinct neural mechanism to perceive random dots' motion even though they do not move in a specific direction as a whole.

Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus.

Microelectrode recording was performed in the basal ganglia of 3 patients with generalized dystonia and 1 patient with hemiballismus secondary to a brainstem hemorrhage. Neuronal activity was recorded from the internal and external segments of the globus pallidus and assessed for mean discharge rate and pattern of spontaneous activity. The responses of neurons in the internal segment of the globus pallidus to passive and active movements were also evaluated. Mean discharge rates of neurons in both segments of the pallidum in patients with dystonia and the patient with hemiballismus were considerably lower than those reported for patients with idiopathic Parkinson's disease. In addition, the pattern of spontaneous neuronal activity was highly irregular, occurring in intermittent grouped discharges separated by periods of pauses. Although receptive fields in the dystonia patients were widened and less specific than those reported in normal monkeys, neuronal responses to movement were uncommon in the hemiballismus patient. Before surgery, patients with dystonia experienced abnormal posturing and involuntary movements. Coactivation of agonist-antagonist muscle groups was observed both at rest and during the performance of simple movements. After pallidotomy there was a significant reduction in the involuntary movement associated with these disorders and a more normal pattern of electromyographic activity during rest and movement. Given the improvement in dystonic and hemiballistic movements in these patients after ablation of the sensorimotor portion of the internal segment of the globus pallidus, we suggest that pallidotomy can be an effective treatment for patients with dystonia and also for patients with medically intractable hemiballismus. Based on the finding of decreased neuronal discharge rates in pallidal neurons, we propose that physiologically dystonia most closely resembles a hyperkinetic movement disorder. A model for dystonia is proposed that incorporates the observed changes in the rate and pattern of neuronal activity in the pallidum with data from neuroimaging with positron emission tomography and 2-deoxyglucose studies.

Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia.

Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia. Studies of CNS electrophysiology have suggested an important role for oscillatory neuronal activity in sensory perception, sensorimotor integration, and movement timing. In extracellular single-unit recording studies in awake, immobilized rats, we have found that many tonically active neurons in the entopeduncular nucleus (n = 15), globus pallidus (n = 31), and substantia nigra pars reticulata (n = 31) have slow oscillations in firing rate in the seconds-to-minutes range. Basal oscillation amplitude ranged up to +/-50% of the mean firing rate. Spectral analysis was performed on spike trains to determine whether these multisecond oscillations were significantly periodic. Significant activity in power spectra (in the 2- to 60-s range of periods) from basal spike trains was found for 56% of neurons in these three nuclei. Spectral peaks corresponded to oscillations with mean periods of approximately 30 s in each nucleus. Multisecond baseline oscillations were also found in 21% of substantia nigra dopaminergic neurons. The dopamine agonist apomorphine (0.32 mg/kg iv, n = 10-15) profoundly affected multisecond oscillations, increasing oscillatory frequency (means of spectral peak periods were reduced to approximately 15 s) and increasing the regularity of the oscillations. Apomorphine effects on oscillations in firing rate were more consistent from unit to unit than were its effects on mean firing rates in the entopeduncular nucleus and substantia nigra. Apomorphine modulation of multisecond periodic oscillations was reversed by either D1 or D2 antagonists and was mimicked by the combination of selective D1 (SKF 81297) and D2 (quinpirole) agonists. Seventeen percent of neurons had additional baseline periodic activity in a faster range (0.4-2.0 s) related to ventilation. Multisecond periodicities were rarely found in neurons in anesthetized rats (n = 29), suggesting that this phenomenon is sensitive to overall reductions in central activity. The data demonstrate significant structure in basal ganglia neuron spiking activity at unexpectedly long time scales, as well as a novel effect of dopamine on firing pattern in this slow temporal domain. The modulation of multisecond periodicities in firing rate by dopaminergic agonists suggests the involvement of these patterns in behaviors and cognitive processes that are affected by dopamine. Periodic firing rate oscillations in basal ganglia output nuclei should strongly affect the firing patterns of target neurons and are likely involved in coordinating neural activity responsible for motor sequences. Modulation of slow, periodic oscillations in firing rate may be an important mechanism by which dopamine influences motor and cognitive processes in normal and dysfunctional states.

Effects of visual and auditory stimulation on somatosensory evoked magnetic fields.

DESIGN AND METHODS: We investigated the effects of continuous visual (cartoon and random dot motion) and auditory (music) stimulation on somatosensory evoked magnetic fields (SEFs) following electrical stimulation of the median nerve on 12 normal subjects using paired t test and two way ANOVA for the statistics. RESULTS: In the hemisphere contralateral to the stimulated nerve, the middle-latency components (35-60 ms in latency) were significantly enhanced by visual, but not by auditory stimulation. The dipoles of all components within 60-70 ms following stimulation were estimated to be very close each other, around the hand area of the primary sensory cortex (SI). In the ipsilateral hemisphere, the middle-latency components (70-100 ms in latency), the dipoles of which were estimated to be in the second sensory cortex (SII), were markedly decreased in amplitude by both the visual and auditory stimulation. CONCLUSIONS: These changes in waveform by visual and auditory stimulation are thought to be due to the effects of the activation of polymodal neurons, which receive not only somatosensory but also visual and/or auditory inputs, in areas 5 and/or 7 as well as in the medial superior temporal region (MST) and superior temporal sulcus (STS), although a change of attention might also be a factor causing such findings.

Pain processing traced by magnetoencephalography in the human brain.

The temporal and spatial processing of pain perception in human was traced by magnetoencephalography (MEG). We applied a painful CO2 laser beam to the forearm of 11 normal subjects, and estimated the activated areas using a single equivalent current dipole (ECD) at each time point, and a brain electric source analysis (BESA) as a spatio-temporal multiple source analysis method. The four-source model was found to be the most appropriate; sources 1 and 2 at the secondary sensory cortex (SII) contralateral and ipsilateral to the stimulation, and sources 3 and 4 at the anterior medial temporal area (probably the amygdalar nuclei or hippocampal formation) contralateral and ipsilateral to the stimulation, respectively. Activities in all 4 areas were temporally overlapped. Activity in the primary sensory cortex (SI) contralateral to the stimulated site was not identified. Activity in the cingulate cortex was also not clearly identified. These results are probably due to one or more of the following factors; (1) the cingulate cortex is too deep, (2) the ECDs generated in the cingulate cortex are mainly oriented radially, and (3) the ECDs generated in bilateral hemispheres interfere with each other. No significant or consistent magnetic fields were recorded after 500 msec following the stimulation, probably due to the complicated spatial and temporal overlapping of activities in multiple areas.

Microelectrode-guided pallidotomy: technical approach and its application in medically intractable Parkinson's disease.

OBJECT: The authors describe the microelectrode recording and stimulation techniques used for localizing the caudal sensorimotor portion of the globus pallidus internus (GPi) and nearby structures (internal capsule and optic tract) in patients undergoing GPi pallidotomy. METHODS: Localization is achieved by developing a topographic map of the abovementioned structures based on the physiological characteristics of neurons in the basal ganglia and the microexcitable properties of the internal capsule and optic tract. The location of the caudal GPi can be determined by "form fitting" the physiological map on relevant planes of a stereotactic atlas. A sensorimotor map can be developed by assessing neuronal responses to passive manipulation or active movement of the limbs and orofacial structures. The internal capsule and optic tract, respectively, can be identified by the presence of stimulation-evoked movement or the patient's report of flashes or speckles of light that occur coincident with stimulation. The optic tract may also be located by identifying the neural response to flashes of light. The anatomical/physiological map is used to guide lesion placement within the sensorimotor portion of the pallidum while sparing nearby structures, for example, the external globus pallidus, nucleus basalis, optic tract, and internal capsule. The lesion location and size predicted by using physiological recording together with thin-slice high-resolution magnetic resonance imaging reconstructions of the lesion were confirmed in one patient on histological studies. CONCLUSIONS: These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.

Timing of motion representation in the human visual system.

Visual stimulus in apparent motion evokes a magnetic field from the extrastriate cortex in humans. To investigate what this magnetic field represents, we measured the latencies of the responses in three subjects to the stimuli in apparent motion at various spatial separations. These different latencies were inversely related to the spatial separations of the stimuli (range of 74 to 182 ms) and correlated with each subject's reaction time. The direction of motion affected neither the latency of the magnetic response nor the reaction times. Estimations of the origins of the evoked magnetic fields showed they were always in the same area. In two subjects, the sites were around the meeting point of the ascending limb of the inferior temporal sulcus and the lateral occipital sulcus. In the third subject, the site was in the vicinity of the angular gyrus. The difference between the magnetic response and reaction time was fairly constant (about 64 ms) among the subjects. We consider the magnetic response to be related to the generation of a motion image: First, the response clearly corresponded to human reaction times to the same stimuli: Second, the fact that the magnetic response was related to the spatial separations but independent of the direction of motion is not explained if the response is evoked simply by both the onset and offset of the object in the stimulus. Furthermore, individual reaction times were mainly delayed by the speed of the process that generated the motion image.

Random dots blinking: a new approach to elucidate the activities of the extrastriate cortex in humans.

To investigate cortical activities related to the visual recognition of characters, we recorded the magnetoencephalography (MEG) in six normal subjects who were encouraged to discriminate capital English letters displayed for a brief period. To reduce the primary responses evoked by the luminance change in the striate cortex (V1), we used a novel stimulus method, random dots blinking (RDB), by means of the temporal changes of patterns using a large number of small random dots. Along with the MEG recording, we also measured the discrimination accuracy rate (%) to know how well the subjects recognized the letters. One clear component, about 300 ms in peak latency, was identified in all six subjects. Its peak amplitude and the discrimination accuracy rate increased similarly as the character display duration became longer. Its signal source was estimated in the extrastriate cortex, around the fusiform gyrus, in the right hemisphere. We suspect that the activity in these cortical areas has strong relation to the conscious perception of characters.