Negative motor networks: Electric cortical stimulation and diffusion tensor imaging.

INTRODUCTION: This study investigated the networks of Negative motor areas (NMAs) using electric cortical stimulation and diffusion tensor imaging (DTI). METHODS: Twelve patients with intractable focal epilepsy, in which NMAs were identified by electrical cortical stimulation, were enrolled in this study. Electric stimulation at 50Hz was applied to the electrodes during motor tasks to identify the NMAs. DTI was used to identify the subcortical fibers originating from the NMAs found by electrical stimulation. RESULTS: NMAs were found in lateral frontal areas (premotor area (PM) and precentral gyrus) in all 12 patients, in pre-supplementary motor areas (pre-SMAs) in four patients, and in posterior parietal cortices (PPCs) in four. DTI detected fibers connecting to the ipsilateral PMs, PPCs and temporal regions via U-fibers, superior longitudinal fasciculus (SLF), and arcuate fasciculus (AF) from the lateral frontal NMAs. Pre-SMA-NMAs had connections with ipsilateral PMs and contralateral pre-SMAs via the frontal aslant tract and transcallosal commissural fibers, and PPC-NMAs with ipsilateral PMs via SLF and AF. CONCLUSION: This study found the characteristic cortical network of each NMA, and especially revealed new insight of pre-SMA-NMA and PPC NMA. These NMAs might be associated with different mechanism of negative motor response.

Hemispheric asymmetry of the arcuate fasciculus: a preliminary diffusion tensor tractography study in patients with unilateral language dominance defined by Wada test.

OBJECTIVE: Lateralization of language function is a prominent feature of human brain function, and its underlying structural asymmetry has been recently reported in normal right-handed subjects. By means of diffusion tensor tractography (DTT), we investigated the asymmetry of the language network, namely, the arcuate fasciculus in patients in whom the unilateral language dominance was defined by Wada test. METHODS: DTT was performed in 24 patients with a focal lesion or an epileptic focus outside the C-shaped segment of the arcuate fasciculus. The arcuate fasciculus was reconstructed by placing two regions-of-interest in the deep white matter lateral to the corona radiata. The pathway was then divided into one terminating in the temporal lobe (FT tract) and the other in the parietal lobe (FP tract). The relative number and volume of the FT and FP tracts in each hemisphere were submitted to repeated measure ANOVA separately, with the hemisphere as a within-subject factor and with the side of pathology as a between subject factor. RESULTS: The FT tract showed a significantly larger number and volume in the language dominant hemisphere than in the non-dominant hemisphere, while, for the FP tract, no significant hemispheric difference was observed in the relative number or volume. There was a tendency that the FT tract was less lateralized when the pathology was located in the dominant hemisphere than in the non-dominant hemisphere. CONCLUSION: Dominance of the FT tract in the language dominant hemisphere was demonstrated for the first time in a patient population and implicated a clinical utility of DTT for non-invasive evaluation of language lateralization. Our preliminary study might indicate reorganization of the language network in conjunction with pathology.

Diffusion tensor fiber tractography for arteriovenous malformations: quantitative analyses to evaluate the corticospinal tract and optic radiation.

BACKGROUND AND PURPOSE: We hypothesized that diffusion tensor fiber tractography would be affected by intracranial arteriovenous malformation (AVM). The purpose of the present study was to evaluate the influence of intracranial AVM on corticospinal tract and optic radiation tractography. MATERIALS AND METHODS: The subject group comprised 34 patients with untreated intracranial AVM. Hemorrhage was present in 13 patients and absent in 21 patients. Perinidal fractional anisotropy (FA) and number of voxels along the reconstructed corticospinal and optic radiation tracts were measured, and left-to-right asymmetry indices (AIs) for those values were quantified. Patients were assigned to 1 of 3 groups: tracts distant from nidus, tracts close to nidus without neurologic symptoms, and tracts close to nidus associated with neurologic symptoms. One-way analysis of variance was used to compare differences in AI between groups. Hemorrhagic and nonhemorrhagic groups were assessed separately. RESULTS: In patients without hemorrhage, AI of optic radiation volume (P<.0001), AI of perinidal FA along corticospinal tract (P=.006), and optic radiation (P=.01) differed significantly between groups. In patients associated with hemorrhage, AI of corticospinal tract volume (P=.01), AI of perinidal FA along corticospinal tract (P=.04), and optic radiation (P=.004) differed significantly between groups. CONCLUSIONS: Corticospinal tract and optic radiation tractography were visualized in patients with AVM. In patients with both hemorrhagic and nonhemorrhagic AVM, the 2 fiber tracts close to the nidus were less visualized in the affected hemisphere than those distant from the nidus. Tracts were less visualized in patients with neurologic symptoms than in asymptomatic patients.

Cortical myoclonus: sensorimotor hyperexcitability.

Cortical or cortical reflex myoclonus is characterized by abnormally enlarged cortical somatosensory evoked potentials (giant SEPs), which most likely reflect pathologically hyperexcitable sensorimotor cortex. To clarify the pathogenesis of myoclonus of cortical origin, we simultaneously recorded SEPs and whole head somatosensory evoked magnetic fields (SEFs) following electric stimulation of the median nerve at the wrist in six patients with cortical myoclonus. N20m and enlarged P30m were observed in all patients and were localized at the posterior bank of the central sulcus (Brodmann area 3b of the primary somatosensory cortex). In addition, P25m and N35m components of SEFs were recognized in five and four patients, respectively. P25m component, that is, the magnetic counterpart of P25 in EEG, was the earliest cortical component showing enhancement in patients. Multidipole analysis combined with magnetic resonance imaging (MRI) coregistration revealed that the generators of P25m were in the precentral gyrus in four patients and in the postcentral gyrus in one patient. The second SEFs around 200 msec after the single stimulus were recorded in three patients at area 3b (repetitive SEFs); two of whom showed negative as well as positive myoclonus. The importance of motor cortex for the generation of cortical reflex myoclonus was thus demonstrated. The pathologic features of SEFs suggest abnormal excitability of primary sensorimotor cortex.

EEG change in the conscious rat during immobility induced by psychological stress.

EEG changes in the conscious rat under conditions of stress were quantitatively analyzed. After conditioning the rat to expect an electroshock when placed in the test box, the rat assumed a catatonia-like immobility when placed in the box even though the electroshock was not applied. While in this state relative brain-wave activity over the range 7.5--13.0 Hz significantly increased in the cortex and the hippocampus, but not in the amygdaloid and the caudate nuclei. The immobility accompanied by changes in the EEG disappeared when the animal was returned to the home cage and immediately reappeared after the rat was retransferred to the test box. Diazepam (10 mg/kg, PO), CS-386 (5 mg/kg, PO), nicotinamide (1 mg/kg, IP), and chlorpromazine (10 mg/kg, PO) significantly suppressed the augmented activity under the same stress condition. The difference between drug-induced catatonia or catalepsy and the catatonia-like immobility under the stress condition was discussed.

Decreased calmodulin-NR1 co-assembly as a mechanism for focal epilepsy in cortical dysplasia.

The NMDA receptor is one of the ionotropic glutamate receptors essential for excitatory neurotransmission. The NMDAR1 subunit is inactivated by direct interaction with calmodulin. The protein levels of calmodulin, NMDAR1 and their complex were quantified in tissue resected from epileptogenic and non-epileptogenic cortical areas as determined by chronic subdural electrode recordings from three patients (aged 6, 14 and 18 years) with focal epilepsy associated with cortical dysplasia. In all patients, the co-assembly of calmodulin and NMDAR1 was decreased in epileptogenic dysplastic cortex compared with normal appearing non-epileptogenic cortex, while there was no significant difference in the total protein levels of calmodulin or NMDAR1 between the two EEG groups. These results suggest that decreased calmodulin-NMDAR1 co-assembly is a cellular mechanism that contributes to hyperexcitability in dysplastic cortical neurons and in focal seizure onsets.

Postnatal expressions of non-phosphorylated and phosphorylated neurofilament proteins in the rat hippocampus and the Timm-stained mossy fiber pathway.

Neurofilament proteins (NFPs), the cytoskeletal proteins that are essential for axogenesis and maintenance of neuron shape in the nervous system, were studied for their spatial distributions at nine postnatal days (PN 3, 5, 7, 10, 14, 17, 21, 28, and 120). Simultaneously non-phosphorylated (SMI-32; 150/200 kDa; Sternberger) and phosphorylated (SMI-31; 200 kDa) NFP immunoreactivity in the entire developing rat hippocampus was studied, quantified, and compared to that of mossy fiber (MF) axons and terminals using Neo-Timm's histochemistry, the most selective, sensitive, and reproducible technique. Differential developmental expressions were observed between the two NFP states. SMI-32 was initially expressed on PN 3 only in the perikarya of pyramidal neurons in CA3. As early as PN 5, SMI-31 appeared in the MF pathway, in parallel to the growth of MF axons. By contrast, SMI-32 did not appear at any age in the MF pathway, including the MF terminal zone of stratum lucidum. At PN 14, the distribution of both NFPs in the MF system (MFs and their target neurons, i.e., CA3/CA4 pyramidal neurons and hilar neurons) was nearly complete; however, the peak densities of SMI-32 and SMI-31 were later at PN 21 and statistically equal to the most adult level (PN 120). The temporal regulation and maximal levels of SMI-32 and SMI-31 expressions on MF target neurons (CA3: SMI-32) and in the MF terminal zone (stratum lucidum: SMI-31) were nearly parallel to the progressive and rapid PN growth of the MF axons and terminals occurring between PN 14 and PN 17, suggesting that the mechanisms for maturation of MF synaptogenesis occur after PN 17.

Serial processing of the somesthetic information revealed by different effects of stimulus rate on the somatosensory-evoked potentials and magnetic fields.

In order to evaluate information processing in the somatosensory cortex, the effect of two different stimulus rates was investigated by simultaneously recording somatosensory-evoked potentials (SEPs) and magnetic fields (SEFs) in nine healthy adults. During electric stimulation of the median nerve at the wrist, SEFs were recorded with the helmet-shaped whole-head coverage magnetometer array with 122 first-order planar gradiometers while SEPs were simultaneously recorded from seven scalp positions. Interstimulus intervals (ISIs) of 0.9 s and 4 s were compared. In all subjects, N20 as well as its magnetic counterpart, N20m, was clearly demonstrated over the contralateral somatosensory area. Subsequent deflections around 80-200 ms did not make any clear peak and were smaller than those at 20-60 ms (P30m, P40m, N50m and P60m). After 200 ms, SEFs were negligible, whereas SEPs had larger amplitude than those of shorter latencies, constituting a peak around 250 ms (P250). Both SEF and SEP deflections later than 40 ms were decreased in responses at the shorter ISI; this diminution was most prominent for P250. Therefore, it is concluded that the tangential currents in the somatosensory cortex (area 3b) mainly contribute to responses during the first 200 ms after the stimulus, whereas the radially oriented currents (most likely in the crown of the postcentral gyrus) take over for subsequent information processing.

A short episode of seizure activity protects from status epilepticus-induced neuronal damage in rat brain.

Kainic acid (KA)-induced status epilepticus (SE) in adult rats results in extensive neuronal damage throughout the limbic system and the loss of selectively vulnerable neuronal populations, particularly CA3 neurons. We investigated the effects of a short episode of seizure activity on neuronal death elicited by a subsequent prolonged SE episode. A short episode of seizure activity was produced by sub-cutaneous (s.c.) injection of KA followed after 1 h by pentobarbital administration. Twenty-four hours later, KA was administered again, and animals were sacrificed 3 days later. Neuronal damage was estimated by visual analysis of neuronal density. Our results show that a short episode of seizure activity did not produce neuronal damage but almost completely protected vulnerable neurons from KA-induced neuronal damage. These results extend to epileptic tolerance the notion of tolerance previously described in the case of ischemia.

Subregions of human MT complex revealed by comparative MEG and direct electrocorticographic recordings.

OBJECTIVE: To locate the visual motion complex (MT+) and study its response properties in an epilepsy surgery patient. METHODS: A 17-year-old epilepsy patient underwent invasive monitoring with subdural electrodes in the right temporo-parieto-occipital area. MT+ was investigated by cortical electric stimulation and by epicortical visual evoked potentials time-locked to motion onset of sinusoidal gratings (motion VEP). Motion-related visual evoked magnetic field (motion VEF) was also recorded before the electrode implantation to complement the invasive recording. RESULTS: Motion VEPs revealed two subregions within MT+, generating early and late potentials respectively. The early activity with a peak around 130 ms was localized at a single electrode situated immediately caudal to the initial portion of the ascending limb of the superior temporal sulcus (AL-STS). The late activity, peaking at 242-274 ms, was located ventro-rostrally over three electrodes. Among the four electrodes with motion VEPs, cortical stimulation at the most caudal pair elicited motion-in-depth perception involving the whole visual field. In addition to two subregions revealed on the gyral crown, magnetoencephalography (MEG) demonstrated another subregion with a late motion VEF in AL-STS immediately rostral to the electrode with the early motion VEP. CONCLUSIONS: In combination with MEG recording, the present invasive exploration demonstrated human MT+ in a focal area of the temporo-parieto-occipital junction and delineated possible three subregions as indicated by the different latencies and distributions of the motion VEP/VEFs. SIGNIFICANCE: Comparative MEG and direct electrocorticographic recordings delineated possible subregions within the human MT complex.

Increased NR1-NR2A/B coassembly as a mechanism for rat chronic hippocampal epilepsy.

The N-methyl-D-aspartate receptors (NMDAR) produce physiologically functional channels for enhanced excitatory neurotransmission when they exist as heteromeric complexes containing the NMDAR1 subunit combined with NMDAR2. We examined the expressions of NMDAR1 and 2A/B protein in the kainic acid induced rat chronic epileptic hippocampus. Immunoreactivities of both NMDAR1 and NDMAR2A/B were increased in the inner molecular layer of the dentate gyrus, while they were decreased in the hilar and CA3/4 pyramidal zones. Immunoblot analysis demonstrated that the overall level of NMDAR1-2A/B coassembly was increased in the whole hippocampus. These results indicate that the increase of the NMDAR1-2A/B complex in the inner molecular layer is a significant cellular mechanism that contributes to focal hyperexcitability in rat chronic hippocampal epilepsy.

Bilateral kainic acid lesions in the rat hilus induce non-linear additive mossy fiber neoinnervation.

Kainic acid (KA) lesions of the rat hilus model hippocampal sclerosis and temporal lobe epilepsy. Unilateral hilar cell loss denervates the associational afferents normally projecting to the inner molecular layer (IML) granule cell dendrites, followed by ipsilateral mossy fiber (MF) sprouting. Hilar neurons also project through the hippocampal commissure to the contralateral IML. This study compared densities of IML MF sprouting following unilateral versus bilateral low dose KA lesions, using Neo-Timm stain 30 days later. Unilateral KA (0.4 microg) caused only dense ipsilateral MF sprouting. Bilateral lesions with lower doses of KA (0.1 with 0.2 or 0.3 microg) induced dense bilateral MF sprouting. However, the same low doses of KA injected unilaterally did not induce significant sprouting ipsilaterally or contralaterally. These data show that denervations of both associational and commissural afferents to the same IML dendritic zones of granule cells induce non-linear, additive bilateral MF neoinnervations.

Time course of transient expression of GDNF protein in rat granule cells of the bilateral dentate gyri after unilateral intrahippocampal kainic acid injection.

We examined the time course of expression of glial cell line-derived neurotrophic factor (GDNF) protein in the granule cells of the dentate gyrus following unilateral intrahippocampal injection of kainic acid (KA). Recurrent behavioral seizures were observed approximately 1 h after KA injection, which lasted for 4-6 h. GDNF immunoreactivity began to increase bilaterally in the granule cells within 3 h after KA injection, continued to increase until post-injection day (PID) 4, and returned to the control level by PID 7. The results suggest that the increase of GDNF protein in the granule cells may be ascribable to seizures induced by the KA injection. The increase of GDNF protein might promote survival of the granule cells after the intrahippocampal KA injection.

NMDAR2 upregulation precedes mossy fiber sprouting in kainate rat hippocampal epilepsy.

Following intrahippocampal (hilar) kainic acid (KA) lesions in rats, NMDAR2A/B receptor proteins are upregulated significantly in the inner molecular layer (IML) of the dentate gyrus by post-injection day 5. By contrast, the aberrant mossy fibers which reinnervate the IML remained in the subgranular zone before sprouting and synapsing in the IML, which occurs at approximately post-KA day 17. For 40 days thereafter, this mossy fiber ingrowth progressed, while the increased NMDAR2A/B (receptors) immunoreactivity remained at the same densities. These results suggest that new NMDAR2A/B proteins in granule cell dendrites are limited to the IML, which is the eventual site for MF hyperinnervation, neosynaptogenesis, and recurrent synaptic hyperexcitability.

Frontopolar ictal epileptiform discharges on scalp electroencephalogram in temporal lobe epilepsy.

We report 3 patients with medically intractable complex partial seizures (CPS) arising from the temporal lobe judged by surgical outcome, in whom scalp electroencephalogram (EEG) showed ictal epileptiform discharges at the frontopolar region. In all patients, results of cranial magnetic resonance imaging (MRI), positron emission tomography (PET), and ictal single photon emission computed tomography (SPECT) were consistent with those of temporal lobe epilepsy (TLE). The epileptogenic area was defined in the temporal lobe by chronic subdural recording in 2 patients. After surgical treatment (amygdalohippocampectomy, anterior temporal lobectomy, and temporal lesionectomy, respectively), all 3 patients became seizure-free and the interictal frontopolar epileptiform discharges on scalp EEG disappeared. Patients with TLE may show ictal scalp EEG with frontopolar onset. This is most likely explained by direction of dipolar orientation of epileptiform discharges in 1 of our patients; rapid spread of ictal activity to the frontopolar area can also be considered in the 2.

Limited value of interictal brain perfusion SPECT for detection of epileptic foci: high resolution SPECT studies in comparison with FDG-PET.

Accurate localization of epileptic foci is important for pre-surgical evaluation of patients with medically intractable epilepsy, and F-18 FDG PET has been proved to be a valuable method for this purpose. To examine the clinical value with interictal brain perfusion SPECT, we performed brain perfusion SPECT of Tc-99m HMPAO by means of a high resolution SPECT camera, and compared the results with F-18 FDG PET images and MRI in 10 patients with medically intractable epilepsy. In 9 of 10 patients (90%), FDG PET images showed focal hypo-metabolism in the area corresponding with the results of electroencephalography (EEG). SPECT images, however, demonstrated hypo-perfused lesions which corresponded with hypo-metabolic lesions on FDG PET images in only 6 cases (60%). Although MRI showed abnormal findings in 8 cases, the lesions were not directly related to epileptic foci in 2 cases. In conclusion, FDG PET is a valuable tool for accurate localization of epileptic foci. Brain perfusion SPECT, however, may not always be paralleled to metabolism visualized on FDG PET images.

[Spinal cord stab injury by acupuncture needle: a case report].

It is very rare for neurosurgeons to encounter cases of spinal cord injury caused by a broken acupuncture needle. A 45-year-old man was referred to our clinic because of urinary retention about two weeks after acupuncture therapy (a needle was broken during treatment). The patient showed no motor weakness, or sensory disturbance. The needle was seen transversely stabbing the spinal cord at C1/2 on CT imaging and X-ray film. In all of the reported seven cases of longitudinal stab injuries (posterior puncture), sensorimotor disturbances were present. In transverse stab injuries (lateral puncture), however, two cases did not show motor weakness but sensory disturbance. The centrifugal pathway for micturition in the spinal cord lies in the middle one third of the lateral columns and in the width of the central canal. The patient complained of urinary retention because the bilateral descending fibers might have been stabbed by the needle. Surgical treatment relieved the patient from his complaint.