Hisaji Imamura

Left anterior temporal cortex actively engages in speech perception: A direct cortical stimulation study

Recent neuroimaging studies proposed the importance of the anterior auditory pathway for speech comprehension. Its clinical significance is implicated by semantic dementia or pure word deafness. Neurodegenerative or cerebrovascular nature, however, precluded precise localization of the cortex responsible for speech perception. Electrical cortical stimulation could delineate such localization by producing transient, functional impairment. We investigated engagement of the left anterior temporal cortex in speech perception by means of direct electrical cortical stimulation. Subjects were two partial epilepsy patients, who underwent direct cortical stimulation as a part of invasive presurgical evaluations. Stimulus sites were coregistered to presurgical 3D-MRI, and then to MNI standard space for anatomical localization. Separate from the posterior temporal language area, electrical cortical stimulation revealed a well-restricted language area in the anterior part of the superior temporal sulcus and gyrus (aSTS/STG) in both patients. Auditory sentence comprehension was impaired upon electrical stimulation of aSTS/STG. In one patient, additional investigation revealed that the functional impairment was restricted to auditory sentence comprehension with preserved visual sentence comprehension and perception of music and environmental sounds. Both patients reported that they could hear the voice but not understand the sentence well (e.g., heard as a series of meaningless utterance). The standard coordinates of this restricted area at left aSTS/STG well corresponded with the coordinates of speech perception reported in neuroimaging activation studies in healthy subjects. The present combined anatomo-functional case study, for the first time, demonstrated that aSTS/STG in the language dominant hemisphere actively engages in speech perception.

Intracranially recorded ictal direct current shifts may precede high frequency oscillations in human epilepsy.

OBJECTIVE We assessed the temporal-spatial characteristics of ictal direct current (DC) shifts (or infraslow activity) and high frequency oscillations (HFOs) in 16 patients with intractable focal epilepsy. METHODS The underlying etiology consisted of cortical dysplasia, glioma, hippocampal sclerosis, and low-grade neuroepithelial tumor in nine, four, two, and one patients, respectively. The median number of analyzed seizure events was 8.0 per patient (range: 2-10). Chronic electrocorticographic recording was performed with (1) a band-pass filter of 0.016-600Hz (or 0.016-300Hz) and a sampling rate of 2000Hz (or 1000Hz). RESULTS Ictal DC shifts and a sustained form of ictal HFOs were observed in 75.0% and 50.0% of the patients, and 71.3% and 46.3% of the analyzed seizures. Visual assessment revealed that the onset of ictal DC shifts preceded that of ictal HFOs with statistical significance in 5/7 patients. The spatial extent of ictal DC shifts or HFOs was smaller than that of the conventionally defined seizure onset zone in 9/12 patients. CONCLUSION Both ictal DC shifts and HFOs might represent the core of tissue generating seizures. SIGNIFICANCE The early occurrence of ictal DC shifts warrants further studies to determine the role of glia (possibly mediating ictal DC shifts) in seizure generation.

Increased cortical hyperexcitability and exaggerated myoclonus with aging in benign adult familial myoclonus epilepsy

The clinical implications of enlarged early cortical components of somatosensory evoked potentials in benign adult familial myoclonus epilepsy remain unknown. Somatosensory evoked potentials following electrical stimulation of the median nerve at the wrist were studied in 16 patients with a clinical diagnosis of benign adult familial myoclonus epilepsy (7 men and 9 women; mean age, 51 ± 18 years) and 19 age‐matched apparently healthy control subjects (11 men and 8 women; mean age, 49 ± 18 years). Giant somatosensory evoked potentials were observed in 13 of the 16 patients. P25 and N35 amplitudes in the patient group were 11.4 ± 6.1 and 19.2 ± 11.5 μV, respectively, and both were significantly larger compared with those in control subjects (P = 0.008 for P25 and P < 0.0001 for N35). There was a significant positive relationship between age at somatosensory evoked potential examination and N20, P25, and N35 amplitudes, both in the patient and in the control groups (P < 0.05). The linear regression gradient of the N35 amplitude with respect to age was significantly larger in the patient group than in the control group (P = 0.04). Furthermore, regression analysis showed a significant positive relationship between the myoclonus rating scale and age at time of somatosensory evoked potential examination (R = 0.645, P = 0.007). Somatosensory evoked potential amplitude increased with age in patients with benign adult familial myoclonus epilepsy to a greater extent than in the control subjects, which suggests a progressive increase in cortical excitability based on progressive pathophysiology in benign adult familial myoclonus epilepsy.

Network specific change in white matter integrity in mesial temporal lobe epilepsy

OBJECTIVES To identify the specific change of white matter integrity that occurs in the brain network related to epileptic activity in patients with mesial temporal lobe epilepsy (MTLE). METHODS We recruited 18 patients with MTLE and 18 healthy subjects. In MTLE patients, the remote functional-deficit zone was delineated using fluorodeoxyglucose positron emission tomography as an extratemporal region showing glucose hypometabolism. Using diffusion magnetic resonance imaging tractography, we defined a seizure propagation tract (PT) as a white matter pathway that connects the focus with a remote functional deficit zone. We also used the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF) as control tracts in the hemisphere ipsilateral to the focus. Fractional anisotropy (FA), mean diffusivity (MD), and volume of the tracts were compared among PT, CST, and ILF. RESULTS Tractographic analysis identified the uncinate fasciculus, arcuate fasciculus, and fornix as PTs. A decrease in FA was found in MTLE patients compared with healthy subjects in all tracts, but PTs showed a more significant decrease in FA than did the two control tracts. Although the change in MD was also found in MTLE patients compared with healthy controls, a tract-specific change was not observed. Although white-matter damage was observed in all candidate tracts examined, the integrity of white matter was most significantly decreased in PTs in MTLE. CONCLUSION The change in white matter integrity occurs specifically in the pathways that connect the focus and remote functional deficit zones in patients with MTLE, i.e., the pathways that are assume to be associated with seizure propagation.

Increased clinical anticipation with maternal transmission in benign adult familial myoclonus epilepsy in Japan

We recently reported clinical anticipation in Japanese families with benign adult familial myoclonus epilepsy (BAFME). However, it remains unknown whether clinical anticipation is predominantly associated with paternal or maternal transmission. We investigated the relationship between gender of the transmitting parent and clinical anticipation in nine BAFME families. Clinical anticipation regarding either cortical tremor or generalised seizures was observed in all 12 parent/child pairs (8 mother/child pairs and 4 father/child pairs). Moreover, a higher degree of clinical anticipation was associated with maternal transmission than with paternal transmission (p=0.03). Although a causative gene for BAFME still remains unknown, our finding suggests that BAFME and diseases with unstable expanding repeats, including those in non-coding regions, might share a similar molecular mechanism because such diseases often show clinical anticipation with maternal transmission.

Magnetoencephalography with temporal spread imaging to visualize propagation of epileptic activity

OBJECTIVE We describe temporal spread imaging (TSI) that can identify the spatiotemporal pattern of epileptic activity using Magnetoencephalography (MEG). METHODS A three-dimensional grid of voxels covering the brain is created. The array-gain minimum-variance spatial filter is applied to an interictal spike to estimate the magnitude of the source and the time (Ta) when the magnitude exceeds a predefined threshold at each voxel. This calculation is performed through all spikes. Each voxel has the mean Ta () and spike number (Nsp), which is the number of spikes whose source exceeds the threshold. Then, a random resampling method is used to determine the cutoff value of Nsp for the statistically reproducible pattern of the activity. Finally, all the voxels where the source exceeds the threshold reproducibly shown on the MRI with a color scale representing . RESULTS Four patients with intractable mesial temporal lobe epilepsy (MTLE) were analyzed. In three patients, the common pattern of the overlap between the propagation and the hypometabolism shown by fluorodeoxyglucose-positron emission tomography (FDG-PET) was identified. CONCLUSIONS TSI can visualize statistically reproducible patterns of the temporal and spatial spread of epileptic activity. SIGNIFICANCE TSI can assess the statistical significance of the spatiotemporal pattern based on its reproducibility.

S17-3. Clinical significance of ictal direct current shifts: Is it made by glia?

To assess clinical usefulness of ictal direct current (DC) shifts and also high frequency oscillations (HFO) for delineating epileptogenic zone in human partial epilepsy, we analyzed subdurally recorded EEG in 16 patients, and correlated the findings with pathology. 4, 9, 1 and 2 patients had the diagnosis of glioma, focal cortical dysplasia, low grade neuroepithelial tumor and hippocampal sclerosis, respectively. As the results, ictal DC shifts occurred in 75%, and ictal HFO in 44% of patients. 2 patients with glioma accompanied with focal cortical dysplasia showed ictal DC shifts and ictal HFO with good reproducibility. Ictal DC shifts occurred earlier than or as early as ictal HFO. Both of ictal DC shifts and HFO or either occurred in more restricted areas than conventional ictal changes. We conclude that both ictal DC shifts and HFO finally complementarily contributed to delineate core epileptogenic zone. Earlier occurrence of ictal DC shifts than HFO suggests an active role of glia in seizure generation. A tendency of ictal DC shifts and HFO to occur more in glioma with focal cortical dysplasia may reflect decreased threshold for abnormal depolarization of pyramidal neurons due to glial dysfunction.

34. Comparison between ictal DC shifts and high frequency oscillation (HFO) recorded from subdural electrodes in epilepsy

electoromyograms (EMGs) were simultaneously recorded from the bilateral deltoid muscles. In each ictal event, artifact-free segment of 5 s before and after EMG onset of spasm was selected to analyze the power spectrum by multiple band frequency analysis (MBFA). Each power spectrum of spasms in a series was averaged by triggering EMGs. Ictal 45–110 Hz HFOs preceding each PSs were captured in all patients, and they presented over the area around the lesions on MRI. The resection of the lesion including the area of HFOs stopped PSs in one patient. Incomplete resection of area of ictal HFOs in the other 2 patients remained PSs. The area of ictal HFOs by averaging on scalp EEG during PSs represented the epileptogenic zone.

P15-5 Ictal slow shift and high frequency oscillation as revealed by intracranial wideband recording in human neocortical epilepsy

the ambiguous stimulus (e.g., human face/house) through red and green filter glasses, thus they perceived one of the two pictures at a time while the other was suppressed. Subjects were instructed to report when their dominant percept changed clearly by pressing the buttons. The numbers of button press for each category were analyzed. EEGs were recorded by a 128-ch high density EEG machine and analyzed by time-frequency analysis. “Human faces” were perceived more frequently than “monkey face” or “house”. However, the number of button press for “monkey face” and “house” were comparable. There was also no significant difference between “green” and “red” stimuli. High density EEGs revealed that gamma-band amplitudes were increased over the left fronto-temporal region when one recognized “human face” than the other categories before the button press. Our psychophysical data revealed that human face recognition could dominate over the other categories during the perception of binocular rivalry. An increase in the amplitude of the gamma-band also suggested that the presence of the neural network specific for human face perception, while the rivalrous stimulus remained to be constant by presented.

P23-13 Progression of benign adult familial myoclonus epilepsy (BAFME) with aging: clinical implication of somatosensory evoked potentials

Objective: To investigate to which extent posterior auricular muscle (PAM) was affected in hemifacial spasm accompanied by auricular symptom and the role of botulinum toxin A injection in the PAM. Methods: There were 265 consecutive HFS patients between July, 2009 and January, 2010; And 63 patients who met the inclusion criteria were enrolled. 33 of 63 patients were given the standard treatment plan of botulinum toxin A (conventional group), 4 units of botulinum toxin A was injected to PAM to 30 patients in addition to the routine HFS treatment plan (PAM group). Before injection, the blink reflex activity and lateral spread of blink reflex to orbicularis oris and PAMs were recorded; Clinical and electrophysiological studies were reviewed at least 4 weeks later (29.47±2.53 days) at the follow-up visit. Results: (1) Compared with those before injection, partial patients of both groups reported that their previous auricular symptoms subsided, the remission rate were 45.5% (15/33), 76.7% (23/30) respectively, the symptoms of PAM group subsided better (c2 = 6.40, P = 0.011). (2) Compared with those before injection, the AMR amplitudes of PAM (390.00±53.58) vs (72.00±9.67), t = 6.011, P = 0.000; and orbicularis oris (405.33±66.71) vs (106.67±10.54), t = 4.383, P = 0.001; of both groups decreased, the AMR amplitudes of PAM in PAM group decreased more obviously (t = 4.237, P = 0.001). There is no obvious difference on the AMR amplitudes of orbicularis oris between both groups (t = 1.127, P = 0.269). Conclusions: Electrophysiological study contributes to the treatment in patients who developed auricular symptoms on the symptomatic side; Those patients may benefit from botulinum toxin injection in the PAM in addition to the routine HFS treatment plan.