Yoshiki Kaneoke

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 Parkinsons 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. Ann Neurol 1999;46:22–35

Burst and oscillation as disparate neuronal properties

We have developed methods to detect and discern burst and oscillatory patterns of neuronal activity. In them, a burst period is defined as an interval in which there are a significantly higher number of spikes as compared to other intervals in the spike train. Oscillation is defined as a spike train in which significant periodicity is detected in its autocorrelogram. The main feature of our burst detection method is that discharge density (i.e., the number of spikes in a short interval) is used instead of the interspike interval. This enables one to assess the likelihood of having burst periods in a spike train. We use the Lomb periodogram to detect periodicity in an autocorrelogram. This method gives one significance of periodicity detected and enables the detection of multiple frequencies in an autocorrelogram. The advantage of these methods is discussed in comparison with the other methods used to detect bursting and oscillatory activity.

Human cortical area responding to stimuli in apparent motion.

APPARENT motion is the perception of the realistic smooth motion of an object which flashes first at one place then at another. To investigate human cortical responses to stimuli in apparent motion, we used a multi-channel biomagnetometer to record the magnetic fields evoked by these stimuli in four normal subjects. The results showed the presence of a localized cortical area exclusively sensitive to apparent motion stimuli that is identical to that for smooth motion. In three subjects this area corresponded to the human homologue of MT/V5. Moreover, the same region in the extrastriate cortex was involved in the short range (0.1°) apparent motion process as well as the long range (1.0°) process.

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.

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 individuals 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. Hum. Brain Mapping 11:33–45, 2000.

Visual detection of motion speed in humans : spatiotemporal analysis by fMRI and MEG

Humans take a long time to respond to the slow visual motion of an object. It is not known what neural mechanism causes this delay. We measured magnetoencephalographic neural responses to light spot motion onset within a wide speed range (0.4–500°/sec) and compared these with human reaction times (RTs). The mean response latency was inversely related to the speed of motion up to 100°/sec, whereas the amplitude increased with the speed. The response property at the speed of 500°/sec was different from that at the other speeds. The speed‐related latency change was observed when the motion duration was 10 msec or longer in the speed range between 5 and 500°/sec, indicating that the response is directly related to the speed itself. The source of the response was estimated to be around the human MT+ and was validated by functional magnetic imaging study using the same stimuli. The results indicate that the speed of motion is encoded in the neural activity of MT+ and that it can be detected within 10 msec of motion observation. RT to the same motion onset was also inversely related to the speed of motion but the delay could not be explained by the magnetic response latency change. Instead, the reciprocal of RT was linearly related to the reciprocal of the magnetic response latency, suggesting that the visual process interacts with other neural processes for decision and motor preparation. Hum. Brain Mapping 16:104–118, 2002.

Somatosensory evoked magnetic fields following passive finger movement

The somatosensory evoked magnetic field (SEF) following passive finger movement and electrical stimulation of finger was studied in 10 normal subjects. Four main components were identified in SEFs recorded at the hemisphere contralateral to the moved finger: 1M(P), 2M(P), 3M(P) and 4M(P). The 1M(P) was clearly identified only in three subjects and was smaller than other components. The equivalent current dipoles (ECDs) of 1M(P) were located around the finger area of the primary sensorimotor cortex and oriented either posteriorly or anteriorly. We speculate that it was generated in areas 3a or 2 of the primary sensory cortex. The 2M(P) and 3M(P) were usually combined as one large deflection with two peaks. Because the ECDs of 2M(P) and 3M(P) were located around the finger area of the sensorimotor cortex and both oriented posteriorly, they were considered to be generated in area 4 and/or 3b, and their activities have temporal overlapping. The 4M(P) has large inter-individual difference in terms of amplitude and latency. The ECD of 4M(P) was also located around the finger area of the primary sensorimotor cortex, and oriented anteriorly. The 4M(PI), the main component recorded from the hemisphere ipsilateral to the moved finger, was located in the upper bank of the sylvian fissure, probably the second sensory cortex (SII). Five components, 1M(E), 2M(E), 3M(E), 4M(E) and 4M(EI), corresponding to 1M(P), 2M(P), 3M(P), 4M(P) and 4M(PI), were identified following electrical stimulation of the same finger. However, SEFs following passive movement were clearly different from SEFs following electrical stimulation, in terms of waveforms and source locations, probably due to differences of ascending fibers and receptive fields.

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.

Human cortical responses to coherent and incoherent motion as measured by magnetoencephalography

To investigate the detail response properties for the incoherent motion of the human visual system, we measured the magnetoencephalographic neural responses to both coherent and incoherent motions at various speeds (from 0.65 to 20.6 degrees /s). The peak latency of the first component of the response from the extrastriate area was inversely related to the speed of motion (from 228 to 155 ms in mean) and there was no significant difference in the latency change between the two types of motion. There were significant differences in the peak amplitude change with the motion speed and a difference in the distribution of the magnetic fields of the responses was seen in six of the seven subjects. The results show that the speed of the incoherently moving dots is represented in the human visual system in the same manner as that of coherently moving dots. The differences in the magnetic fields between the two responses indicate that the same speed-related response changes can occur with different neural populations responsible for both motions.

Brain Regions Responsible for Tinnitus Distress and Loudness: A Resting-State fMRI Study

Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC) strength is affected by the regional autocorrelation coefficient (AC). In this study, we used resting-state functional MRI (fMRI) and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC) and with taking into account the effect of AC (rGCa) to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.